CHAPTER 30

Somatosensory System Jon H. Kaas Vanderbilt University, Nashville, Tennessee, USA

OUTLINE

Introduction 1075 Ventroposterior Superior Nucleus 1088 Ventroposterior Inferior Nucleus 1088 Receptor Types and Afferent Pathways 1076 The Posterior Group and the Posterior Ventromedial Low-Threshold Afferents Nucleus 1088 from the 1077 Anterior Pulvinar, Medial Pulvinar, and Lateral The SA-I Afferent or the Non-Pacinian Iii Posterior Nucleus 1089 (NP Iii) Channel 1077 The RA-I Afferent or the Non-Pacinian I Anterior Parietal 1089 (NPI) Channel 1078 Anterior Parietal Cortex in Monkeys 1089 The SA-II Afferent or Non-Pacinian II (NP II) Area 3b 1090 Channel 1078 Area 1 1090 The RA-II Afferent or Pacinian (PC) Channel 1079 Area 2 1091 Cutaneous Receptor Afferents of the Hairy 1079 Area 3a 1091 Deep Receptor Afferents 1080 Subcortical Projections 1091 C-Fiber and A-delta Afferents Mediating Anterior Parietal Cortex in 1091 , Itch, , and Touch 1080 Architectonic Fields 1091 Afferent Pathways 1081 Maps in 3a, 3b, 1, and 2: Evidence from Scalp Terminations of Peripheral Afferents in the and Surface Recordings 1092 and 1081 Sensory and Perceptual Impairments Following Ascending Spinal Cord Pathways 1082 Lesions 1094 The Dorsal (Posterior) Column System 1082 Somatosensory Cortex of the Lateral (Sylvian) Second-Order of the Dorsolateral Sulcus Including Insula 1095 Spinal Cord (The Spinomedullothalamic System) 1083 Organization of Cortex of the Lateral Sulcus in The Spinothalamic Pathways 1084 Monkeys 1095 Relay Nuclei of the Medulla and Upper Lateral and Insular Parietal Cortex in Humans 1096 Spinal Cord 1084 Posterior Parietal Cortex 1097 Dorsal ColumneTrigeminal Nuclear Complex 1084 Posterior Parietal Cortex in Monkeys 1097 Lateral Cervical Nucleus, Nuclei X and Z, Area 5a (PE) 1097 External Cuneate Nucleus, and Clarke’s Area 5b (PEc) 1098 Column 1085 Area 7b (PF and PFG) 1098 Lateral Cervical Nucleus 1085 Area 7a (PG) 1098 Nuclei X and Z 1085 Areas of the Intraparietal Sulcus: AIP, , External Cuneate Nucleus 1085 CIP, VIP, MIP, and PIP 1098 Clarke’s Nucleus or Column 1085 Posterior Parietal Cortex Function in Humans 1100 Somatosensory Regions of the Midbrain 1085 Somatosensory Cortex of the Medial Wall: The Somatosensory 1086 Supplementary Sensory Area and Cingulate Ventroposterior Nucleus (VP) 1086 Cortex 1101

The Nervous System, Third Edition DOI: 10.1016/B978-0-12-374236-0.10030-6 1074 Copyright Ó 2012 Elsevier Inc. All rights reserved. INTRODUCTION 1075

are only briefly mentioned here, as they are reviewed INTRODUCTION elsewhere (e.g., Chapter 32). The basic parts and pathways of the somatosensory This chapter outlines the organization of the somato- system of humans are shown in Figure 30.1. In brief, sensory system of humans. The emphasis is on the peripheral nerve afferents related to receptors in the components of this system that are important in identi- skin, muscles, and course centrally past their cell fying objects and features of surfaces by touch. Even bodies in the dorsal root and cranial nerve ganglia to though small shapes can be perceived with information enter the spinal cord and brainstem. These afferents solely from tactile receptors, most discriminations synapse on neurons in the dorsal horn of the spinal involve an active process of tactile exploration and cord, or on equivalent neurons in the brainstem, and multiple contacts on the skin, and an integration of cuta- send a collateral to the dorsal column–trigeminal neous and proprioceptive information as well as efferent nuclear complex. Most of the second-order neurons in control. Thus, this chapter concentrates on the pathways this complex have axons that cross to the contralateral and neural centers for processing information from the lower brainstem to form the column low-threshold of the skin that of axons that ascend to the somatosensory thalamus. provide information about touch, and the deeper recep- Second-order neurons representing the teeth and tors in joints and muscles that provide information project both ipsilaterally and contralaterally to the thal- about position. Conclusions are based on both studies amus (see Chapter 32). Other second-order neurons in humans and studies in other , especially in the dorsal horn of the spinal cord and in the brainstem the frequently studied macaque monkeys. At least the send axons to the contralateral side to form the early stages of processing are likely to be similar in anterolateral spinothalamic ascending pathway (see humans and monkeys, but humans appear to have Figure 30.4). The low-threshold mechanoreceptor infor- a more expanded cortical network for processing mation from the skin and the information from muscle somatosensory information. The important subsystems spindle receptors and joints course in the medial dealing with afferents coding for pain and temperature lemniscus to terminate in nuclei of the ventroposterior

FIGURE 30. 1 The basic components of the shown on a posterolateral view of a . Receptors in the skin project to the or the trigeminal nuclei to form the dorsal column trigeminal complex. The trigeminal complex in the brainstem provide second-order afferents, representing the , that join those from the dorsal column nuclei, representing the body, to terminate in the contralateral ventroposterior complex of the thalamus. Third-order neurons in the thalamus project to anterior parietal cortex, where information is distributed to posterior and lateral parietal cortex.

VI. SYSTEMS 1076 30. SOMATOSENSORY SYSTEM thalamic complex. The spinothalamic pathway carries VPI and Pa project widely to areas of somatosensory information about pain, temperature, and touch to infe- cortex, and LP projects to posterior parietal cortex. Areas rior and caudal parts of the ventroposterior complex. 3b, l, and 2 form a hierarchical sequence of processing, The somatosensory thalamus has been subdivided in while area 3a relates especially to motor cortex. All various ways (e.g., Chapter 19; Hirai and Jones, 1989; four areas project to somatosensory cortex of the lateral Mai et al., 1997; Morel et al., 1997; Jones, 2007). Because sulcus (lateral parietal cortex), especially the second some of the earlier parcellations of thalamic nuclei were somatosensory area, S2, and a more recently discovered based solely in cytoarchitectonic and myeloarchitectonic parietal ventral somatosensory area, PV (Krubitzer et al., criteria (e.g., Ha¨ssler, 1959), and because they do not 1995). These and other areas of the lateral sulcus relate to reflect the many recent advances in understanding motor areas of cortex to guide action, and to perirhinal based on microelectrode recordings, studies of connec- cortex to engage the hippocampus in object recognition tions, and chemoarchitecture, we use more recently and memory (Mishkin, 1979). Other connections of area proposed subdivisions stemming from studies largely 2 and subdivisions of lateral parietal cortex are with in monkeys (see Kaas, 2008 for review). Thus, the relay subdivisions of posterior parietal cortex that are of afferents from the skin via the medial lemniscus is involved with the early stages of forming movement to the ventroposterior nucleus (VP), which has been intentions and sensory guidance for motor actions (Des- traditionally subdivided into a ventroposterior medial murget et al., 2009). Subdivisions of the posterior pari- subnucleus (VPM) representing the face and a ventro- etal cortex project to premotor and motor areas of the posterior lateral subnucleus (VPL) representing the frontal lobe (e.g., Tanne-Gariepy et al., 2002; Stepniew- body. The receptor inputs are relayed ska et al., 2009b). Projections from the posterior parietal to a dorsal or superior part of the ventroposterior cortex also involve the medial limbic cortex of the pari- complex that is often included in VPM and VPL. We etal lobe in producing motivational and possibly distinguish this representation of deep body receptors emotional states. as the ventroposterior superior nucleus (VPS). Many of the spinothalamic afferents terminate in a ventroposte- rior inferior nucleus (VPI). Other spinothalamic affer- RECEPTOR TYPES AND AFFERENT ents end in a caudal part of the VP complex that is PATHWAYS often included in VPI or end in the posterior group of nuclei, part of which has been distinguished as a distinct In humans, the hand is the most important tactile relay nucleus for pain and temperature, the ventrome- for object identification (Darian-Smith, 1984). dial posterior nucleus (VMpo) (Dostrovsky and Craig, Receptors in the hand must convey information about 2008). The somatosensory thalamus also includes nuclei texture and shape. This is done primarily from the finger without ascending somatosensory inputs. The anterior pads during active exploration; consequently, finger pulvinar (Pa) and the lateral posterior complex (LP) position and temporal sequence are important. The receive inputs from somatosensory cortex and project glabrous (hairless) skin of the hand has the highest back to somatosensory cortex. innervation density and tactile acuity of any body The somatosensory cortex has also been variously surface (Darian-Smith, 1984). Hairy skin is less impor- subdivided into proposed subdivisions of functional tant in object identification, and hairy skin is less sensi- significance. Most investigators recognize four subdivi- tive to touch and vibration (Hamalainen and Jarvilehto, sions of the cortex of the , areas 3a, 1981). However, the hairs themselves provide an 3b, 1, and 2, stemming from the early architectonic increased sensitivity to air movement and other stimuli studies of Brodmann (1909) and the Vogts (Vogt and that displace hairs (Hamalainen et al., 1985). Vogt, 1919, 1926). While all four areas were once consid- Psychophysical, physiological, and anatomical ered parts of a single functional area, primary somato- studies on humans and other primates support the or S1, it has been clear for over 25 years view that sensations of touch from the glabrous skin of that each constitutes a separate representation of the the hand are almost completely mediated by four body. Area 3b corresponds to S1 of cats and rats (Kaas, different types of myelinated, rapidly conducting mech- 1983). Areas 3b and 1 correspond to parallel somatotopic anoreceptive afferents (Figure 30.2). The afferent classes representations of cutaneous inputs, while areas 3a and from the glabrous skin include two types of slowly 2 integrate cutaneous and deep receptor inputs. Yet, the adapting afferents and two types of rapidly adapting term “S1” is commonly used to refer to all four areas in afferents. All of these types have been extensively monkeys and humans. To avoid confusion, the architec- studied physiologically in monkeys and related to tonic terms for the four fields are used here. Thalamic receptor types. In addition, the response properties of projections to areas 3b and 1 are largely from VP, these afferents have been characterized during record- while VPS provides driving inputs to areas 3a and 2. ings in humans, and sensations have been evoked by

VI. SYSTEMS RECEPTOR TYPES AND AFFERENT PATHWAYS 1077

FIGURE 30.2 Receptor types (right) and afferent classes (left) of the glabrous skin of humans. Four main classes of low-threshold, rapidly conducting afferents have been described as slowly adapting type I (SA-I) and type II (SA-II), rapidly adapting type I (RA-I) and type II (RA-II) or (PC). Each relates to a specialized receptor complex in the skin. Based on Johansson (1978), Johansson and Vallbo (1983), and Vallbo et al. (1984). The ramp in the adaptation column marks a short period of skin indentation, and the vertical lines represent action potentials recorded during the indentation. electrical stimulation of these afferents. Muscle spindle suprathreshold sensations are typically the result of receptors, perhaps aided by other deep receptors in activity in two or more channels. joints and tendons and by receptors in the skin, play a significant role in the position of limbs and The SA-I Afferent or the Non-Pacinian Iii (NP Iii) fingers. This sense is critical in the ability to recognize Channel the form of objects. Afferents that are thin and slowly In the superficial glabrous skin, the type I class of conducting relate to the sensations of cold, warm, slowly adapting afferents (SA-I) is activated at receptor pain, and crude touch. Other thin afferents are related sites termed Merkel disks (see Rice and Albrecht, to the sensations of itch and tickle (see Craig, 2002 for 2008). Each receptor site includes a specialized Merkel review). This review concentrates on the afferents from cell that is distinct from adjacent skin cells and a number the skin used in touch and the muscle spindle and of disk-like nerve terminals originating from a - skin receptors used in (kinaesthesia or ated (7–12 mm diameter) afferent fiber. Merkel cells position sense). appear to be essential for responses to light touch (Maricich et al., 2009). SA-I receptors are densely distrib- Low-Threshold Mechanoreceptor Afferents uted in the skin of the distal glabrous phalanges of the from the Hand human hand, and they constitute about one-fourth of the 17 000 tactile units of the hand (Johansson and Four types of low-threshold mechanoreceptors are Vallbo, 1979). Microelectrode recordings indicate that found in the glabrous skin of primates, and afferents the SA-I afferents respond throughout a period of from these four types have been studied electrophysio- a skin indentation, even when the indentation is sus- logically in humans (Johansson, 1976, 1978; Jarvilehto tained for many seconds. Thus, they are slowly adapting et al., 1981; Vallbo, 1981; Johansson et al., 1982; to a maintained . Depending on the rate of the Johansson and Vallbo, 1983; Ochoa and Torebjork, indentation, a large transient response also occurs 1983; Torebjork et al., 1984; Vallbo et al., 1984; Westling during onset. The SA-I fibers have small, circumscribed and Johansson, 1987; Edin and Abbs, 1991; Birznieks receptive fields and seem especially responsive when et al., 2009). These results, together with psychophysical the edge of an object indents skin within the receptive information on touch from humans, have led to a four- field. When stimulated by a train of electrical pulses, channel model of cutaneous mechanoreception the single SA-I afferent signals the sensation of light, (Bolanowski et al., 1994, 1988). Tactile experience, uniform pressure at a skin location corresponding to according to the model, depends on various combina- the receptive field. Single electrical impulses are not tions of neural activity in the four channels, with partic- felt, and increases in stimulation frequency result in feel- ular channels providing the critical information for some ings of increased pressure. Thus, SA-I afferents are sensations. Stimuli at threshold levels are signaled by thought to be very important in mediating sensations the channel that is most sensitive to these stimuli, but of static pressure and providing information about the

VI. SYSTEMS 1078 30. SOMATOSENSORY SYSTEM locations of edges and textures of held objects. SA-I afferents best preserve information about moving Braille-like dot patterns on the skin (Johnson and Lamb, 1981). After correlating human discrimination of skin indentation with the response profiles of skin afferents in monkeys, Srinivasan and LaMotte (1987) concluded that static discriminations of shape are based primarily on the spatial configuration of the active and the inactive SA-I afferents. In addition, under static conditions, the SA-I afferents provide most of the inten- sity information. Form and surface texture appears to be dominated by the SA-I system (Johnson and Hsiao, 1992; Hsiao and Bensmaia, 2008).

The RA-I Afferent or the Non-Pacinian I (NPI) Channel The predominant receptor afferent of the skin is the rapidly adapting RA-I fiber. Nearly half of the tactile afferents from the hand are of the RA-I type (Johansson and Vallbo, 1983). RA-I afferents innervate Meissner FIGURE 30.3 Changes in the sensitivity to tactile stimuli with corpuscles, which are located in dermal papillae distance across the receptive field for four classes of afferents from the protruding into the . Meissner corpuscles are glabrous skin of the human hand. Threshold levels on the vertical particularly dense in the glabrous skin of the distal scale are arbitrary and do not indicate different thresholds. The rapidly adapting RA-I and the slowly adapting SA-I afferents have phalanges; they are less common on the palm and are small receptive fields with sharp boundaries, while Pacinian (PC) or rare in hairy skin, being replaced by RA-I afferents rapidly adapting RA-II and slowly adapting SA-II afferents have large related to hair shafts. The corpuscles consist of a core receptive fields with poorly defined boundaries and a gradual change of nerve terminal disks and lamellae of Schwann cells in sensitivity across the skin. Based on Johansson (1978). surrounded by connective tissue extensions of the endo- neural sheath. Meissner corpuscles are elongated moved across the skin, and of course in the sensation of (100–500 mm) perpendicular to the skin, and the outer flutter. Because RA-I afferents are frequently located collagen fibers of the corpuscles are linked with fibrils near a on the back of the hand, and they respond of adjacent epidermal cells, which allow skin deforma- to skin deformation during finger movements, they tions to stretch the corpuscle. Most corpuscles are inner- may also have a role in kinesthesia (Edin and Abbs, 1991). vated by two to six myelinated axons, and each innervates a tight group of corpuscles, providing a small The SA-II Afferent or Non-Pacinian II (NP II) receptive field of almost uniform sensitivity and sharp Channel boundaries (Figure 30.3). RA-I afferents respond only A second class of slowly adapting afferents, SA-II, are to changes in skin indentation, and not to steady inden- thought to innervate Ruffini-like endings that respond tation. The RA-I afferents are thought to be responsible to tension in collagen fibers coursing in the skin. In for the detection of low-frequency vibrations, movement humans, they are especially prevalent around the finger between the skin and a surface, and surface texture nails where they provide information about stress distri- (Johnson and Hsiao, 1992). They appear to detect micro- bution across the finger tips (see Birznieks et al., 2009). scopic slips between manipulated objects and skin to Ruffini or Ruffini-like receptors are also found in provide signals for grip control. RA-I afferents are deep tissues, including joint capsules, ligaments and capable of providing shape information during active tendons. Each Ruffini corpuscle contains an elongated touch (see LaMotte and Srinivasan, 1987). Single electri- (500–1000 mm  200 mm) capsule of four to five layers cal impulses on RA-I afferents from the human hand of lamellar cells covered with a membrane, and a core often result in the detectable sensation of a light tap at of nerve fiber branches and longitudinally aligned a location corresponding to the receptive field. Low- collagen fibrils. Movement of the skin results in frequency stimulation produces a sensation of a series stretching of the corpuscle because it is attached to of taps; at higher frequencies the taps merge into a flut- surrounding tissue. Such stretching results in deforma- tering sensation (Macefield et al., 1990). No increase in tion and activation of the innervating axon. Each Ruffini the magnitude of the sensation follows increases in stim- corpuscle is innervated by one A-beta myelinated fiber, ulation rate. These observations suggest that RA-I units which may also innervate several other adjacent corpus- are especially important in discriminations of textures cles. In the human hand, the SA-II class of afferents

VI. SYSTEMS RECEPTOR TYPES AND AFFERENT PATHWAYS 1079 constitutes about one-fifth of the tactile units (Johansson not sharp (Figure 30.3). PC units typically can be acti- and Vallbo, 1979). SA-II fibers have large, poorly defined vated by gently blowing on the skin, and they respond receptive fields (Figure 30.3), often located near the nail to vibrations produced by tapping the table surface on bed or near skin folds on the digits or palm. These affer- which a skin surface rests. PC afferents, like RA-I fibers, ents are extremely sensitive to skin stretch, and often respond to the indentation and release of the skin they are sensitive to the direction of skin stretch. Normal produced by a probe (Figure 30.2), but fail to respond movements of digits and limbs are very effective in acti- during steady indentation. The responses of Pacinian vating these neurons. Electrical stimulation of single SA- afferents follow the cycle of a sinusoidal vibratory stim- II afferents may not be felt (Macefield et al., 1990), or is ulus. However, unlike RA-I afferents that respond with reported as producing a buzzing sensation (Bolanowski lowest thresholds in the 30–40 Hz range, PC afferents et al., 1994), so uncertainty remains about the role of SA- have lowest thresholds in the 250–350 Hz range. Thus, II afferents in tactile . However, there is PC afferents appear to be the only afferents capable of psychophysical evidence that SA-II channels participate subserving the sensation of high-frequency vibration. in the sense of touch (Bolanowski et al., 1988). In addi- For most frequencies, PC and RA-I afferents both tion, inputs from these skin stretch receptors may contribute to the perceived vibrotactile intensity combine with sensory inputs from muscles and joints (Hollins and Roy, 1996). Electrical stimulation of PC to provide limb and digit position and movement afferents in the human hand are not felt at low stimula- signals (e.g., McCloskey, 1978; Edin and Abbs, 1991). tion rates, but a sensation of vibration or tickle occurs at These cutaneous mechanoreceptors appear to contribute high stimulation rates. Often, the sensation is restricted to a movement sense but not to an of the to a part of the large, diffuse receptive field. PC afferents static-position of a joint (see Clark et al., 1986; Collins poorly resolve moving texture patterns (Johnson and et al., 2005). Also, SA-II units are sensitive to skin Lamb, 1981), and they are apparently unimportant in shearing, and thus they might provide information object identification. Therefore, their major role seems about the weight of objects (McCloskey, 1974). Overall, to be detecting and roughly locating sudden skin defor- SA-II afferents seem well-suited for a role in motor guid- mations produced by ground and air vibrations, and by ance and control (Westling and Johansson, 1987). They skin contact. would not be suitable for representing the details of objects, such as a Braille pattern (Phillips et al., 1992).

The RA-II Afferent or Pacinian (PC) Channel Cutaneous Receptor Afferents of the Hairy Skin Rapidly adapting RA-II afferents innervate Pacinian (PC) corpuscles (Bell et al., 1994). These corpuscles are As in the glabrous skin, the hairy skin has SA-I, SAII, much less common than other receptor endings in the RA-I, and RA-II afferents. However, some modifications skin of the hand (10–15%), and they are also found in in the receptor mechanisms exist. First, deeper tissues (see Johansson and Vallbo, 1979; Darian- disks of the SA-I receptor are often aggregated in small Smith, 1984). Only about 200 corpuscles may be found in (0.25–0.5 mm) diameter touch domes that are slightly the human finger, where they are distributed within elevated from surrounding skin and can be visualized deeper skin, subcutaneous fat, and tendonous attach- with a dissecting microscope. The Merkel touch spot ments of the ventral but not the dorsal parts of the finger. or Haarscheibe is innervated by a single, large The PC corpuscles are large (0.3–1.5 mm  0.2–0.7 mm) (7–12 mm) myelinated fiber that branches to terminate ovoids consisting of a central nerve fiber surrounded in a number of disks associated with Merkel cells. Iso- by an inner core of 60 or so layers of concentrically wrap- lated Merkel cells are rare. Second, some RA-I and ped lamellar cells, a space filled with fluid, and an outer SA-I afferents relate to the shafts of hairs. The SA-I affer- capsule of up to 30 less densely packed lamellae. The ents seem to be activated by Merkel-type endings corpuscle acts as a mechanical filter, relaying high- around hair follicles, and the RA-I afferents may have frequency and attenuating low-frequency components the equivalent of Meissner-type endings in glabrous of skin compression to the axon terminal. The PC affer- skin. Third, the hairy skin does not have Pacinian ents allow the detection of distant events via the trans- corpuscles, but instead relies on a scattering of Pacinian mission of high-frequency vibrations through objects corpuscles located in deep tissue around blood vessels and surfaces. PC afferents are extremely sensitive to and muscles (Bolanowski et al., 1994). Thus, hairy skin transient indentations of the skin over large areas such is less sensitive to vibrations. Fourth, it is not yet clear as a complete digit and part of the palm. Thus, informa- how or if the SA-I afferents in hairy skin contribute to tion is transmitted in the tissue to the region of the tactile sensation; in contrast, SA-II afferents may receptor. Sensitivity gradually decreases with distance mediate sensations of pressure in hairy skin but not in from the receptor, and receptive field boundaries are glabrous skin (Bolanowski et al., 1994). The hairy skin

VI. SYSTEMS 1080 30. SOMATOSENSORY SYSTEM of humans also has C-mechanoreceptive afferents (see (Figure 30.4), and to contribute to a sense of posture below). and movement (Goodwin et al., 1971; McCloskey, 1978; Burgess et al., 1982; Clark et al., 1986; Jones, 1994). For static limb position, Clark et al. (1986), proposed that Deep Receptor Afferents the nervous system computes joint angles and thus As noted earlier, SA-II type afferents associated with limb position from muscle spindle information about Ruffini-like endings are found not only in the skin, the lengths of the muscles that set the positions of joints. where they signal stretch, but also in deep tissues where Muscle spindle afferents are activated when the muscles they also signal stretch. The receptors are Ruffini corpus- relax due to the lengthening of the muscle while cles and Golgi tendon organs. Deep SA-II afferents muscle contractions activate tendon afferents. Microsti- provide information about joint extension and tissue mulation of muscle spindle afferents rarely produces compression. Joint afferents may have a role in the a perception of movement or joint position (Macefield conscious awareness of joint movement (Macefield et al., 1990). et al., 1990). However, joint position sense survives joint removal and replacement (Cross and McCloskey, C-Fiber and A-delta Afferents Mediating 1973). Temperature, Itch, Pain, and Touch Other important deep receptors are the muscle spindle receptors, which were once thought to partici- Other afferents in the skin and deeper tissues relate to pate only in reflexes via spinal cord pathways and motor the sensations of temperature, pain, itch, and crude control via a relay to the cerebellum. Muscle spindle touch. These include several types of mechano-heat afferents are now known to also relay to the cortex , cold nociceptors, polymodal nociceptors

FIGURE 30.4 A more detailed overview of the basic components of the human somatosensory system. Inputs from the four main classes of cutaneous receptors (see Figure 30.2) enter the spinal cord branch and terminate on neurons in the dorsal brain of the spinal cord and in the ipsilateral dorsal column nuclei of the lower brain- stem. Muscle spindle afferents branch in a similar manner with the ascending branch coursing in the dorsal columns or more laterally to terminate in the gracile and cuneate subnuclei as well as the external cuneate nucleus. Other more slowly conducting afferents related to pain, touch, and temperature terminate on dorsal horn neurons that project contralaterally to form the spino- thalamic pathway. Afferents from the face enter the brainstem to terminate in the principal trigeminal nuclei for cutaneous and muscle spindle afferents and the spinal trigeminal nuclei for pain, temperature, and touch afferents. The gracile nucleus represents the hindlimb and lower body; the cuneate nucleus, the forelimb; and the principal trigeminal nucleus, the face for cutaneous inputs. These inputs activate second-order neurons that project via the medial lemniscus to the contralateral thalamus. Nuclei in the thalamus include the ven- troposterior (VP) nucleus with ventroposterior medial (VPM) and ventroposterior lateral (VPL) subnuclei for the face and body representations, respectively. The cutaneous afferents from the foot, hand, and face are represented in a lateromedial sequence in VP. The ven- troposterior superior (VPS) nucleus represents muscle spinal inputs in a similar somatotopic order, while the ventroposterior inferior nucleus receives spinothalamic axons. These nuclei project to subdivisions of anterior parietal and lateral parietal cortex (see text). The second somatosensory area (S2), the parietal ventral area (PV), the parietal rostral area (PR) and caudal and rostral divisions of the ventral somatosensory (VS) complex are indicated. Brodmann’s areas are numbered.

VI. SYSTEMS RECEPTOR TYPES AND AFFERENT PATHWAYS 1081

(Mense, 2008) responsive to heat, pinch, and cooling humans, together with the results from other primates, (HPC), and the wide-dynamic range (WDR) afferents allow several conclusions: (1) the field of each root is (Chapter 32; Willis and Coggeshall, 1991). Specific noci- continuous, and tends to form a strip perpendicular to ceptors conduct in the A-delta range and mediate prick- the spinal cord; (2) adjacent dorsal root distributions ing pain, while the multi-modal afferents conduct in the overlap extensively; (3) there is little overlap at the C range and mediate burning pain. A specific receptor ventral and dorsal body midlines; (4) there is consider- and a C-fiber pathway for itch appears likely (Sun able variability across individuals. et al., 2009). Warm receptor afferents conduct in the C Within dorsal roots, studies in monkeys indicate that range while responding at body and there is some crude organization of afferent fibers higher, but not at noxious levels of heat. according to skin location, with distal receptive fields One class of unmyelinated afferents from the skin located caudal in the dorsal root, while fibers with prox- (C-tactile) respond well to slow stroking of the hairy imal receptive fields tend to be rostral (Werner and skin (Olausson et al., 2002, 2008; Bjo¨rnsdotter et al., Whitsel, 1967). These studies also indicate that 2009). Observations on a patient who lacks large myelin- ascending branches of axons entering the spinal cord ated afferents while having C-afferents intact indicate in the dorsal columns (Figure 30.4) tend to preserve their that the C-tactile afferents allow a soft brush stimulus order of entry so that axons from lower spinal roots are to be detected and localized to a body quadrant. These medial to those from upper spinal roots (Whitsel et al., afferents are thought to signal pleasant touch, and serve 1972). In monkeys, inputs from muscle spindles branch an affiliative function in social body contact. These and and join the cuneate fasciculus for the upper limb, but other slowly conducting afferents synapse on neurons terminate in the spinal cord for the lower limb. Some in the dorsal horn of the spinal cord that project contral- afferent fibers with cell bodies in the dorsal root ganglia aterally to form the spinothalamic pathway. turn and enter the ventral root and then turn and retrace a path back to the dorsal root, as if correcting an error Afferent Pathways (see Willis, 1985). These sensory fibers in the ventral root are largely unmyelinated axons, and many are Afferents course from skin receptor and deep nociceptors. receptor locations to combine in nerve fascicles that join other fascicles to form the peripheral . The Terminations of Peripheral Nerve Afferents in peripheral nerves branch and segregate into dorsal the Spinal Cord and Brainstem sensory roots and ventral motor–sensory roots. The afferents that enter the dorsal roots terminate on Afferent fibers entering the spinal cord either simply neurons in the dorsal horn of the spinal cord. One terminate on neurons in the dorsal horn of the spinal branch of these afferents may ascend to terminate on cord or branch and send a collateral toward the brain- neurons in the dorsal column nuclear complex at the stem to terminate either in the dorsal horn at higher junction of the medulla and spinal cord (Figure 30.1; levels or in the dorsal column–trigeminal nuclear Chapters 7 and 8). complex of the lower brainstem. Figure 30.4 depicts A number of investigators have attempted to deter- sensory terminations in the spinal cord and relays to mine the skin regions subserved by the nerves in each the medulla–spinal cord junction. Termination patterns spinal root in humans and other mammals (see Dykes of peripheral afferents have been investigated in and Terzis, 1981 for review). Dissections have been monkeys and other mammals (see Chapter 7), and used to reveal the gross patterns of these dermatomal some rather consistent features can be assumed to apply distributions, but additional methods include using to humans. First, the axons of specific types of afferents the zone of remaining sensibility after section of dorsal have different characteristic termination patterns in the roots above and below the one studied, electrical dorsal horn of the spinal cord. Second, afferents from recording or stimulation, interruptions of function different skin regions terminate to form a somatotopic produced by ruptured disks, and data from herpes zos- map in the spinal cord. Third, afferents ascending to ter eruptions. For humans, the extensive dermatomal the dorsal column nuclei terminate somatotopically. maps are those of Head (1920), based on skin regions The termination patterns of individual axons that affected by herpes zoster; Foerster (1933), from clinical have been physiologically identified and labeled with cases where spinal roots were sectioned for the relief horseradish peroxidase are known from studies on of pain; and Keegan (1943), from cases of local sensory cats (see Brown, 1981). All four types of cutaneous affer- loss subsequent to ruptures of intervertebral disks. ents bifurcate as they enter the cord to send rostral and Dykes and Terzis (1981) point out that these three caudal branches that further branch to form a sagittally maps of dermatomes differ considerably, and they arranged series of terminal arbors in the dorsal horn. suggest that none is accurate. However, the maps in Individual RA-I collaterals form a separate arbor of

VI. SYSTEMS 1082 30. SOMATOSENSORY SYSTEM about 500 mm in the sagittal plane and 50–300 mm in the region terminate in rostrocaudally elongated zones. transverse plane in layers III and IV. Collaterals of PC or Thus, body parts are represented in rostrocaudal slabs RA-II axons terminate in several sagittally elongated of cells. While different classes of afferents activate arbors (400–750 mm) that extend vertically from layers different groups of spinal cord cells, the single zones III and IV to layers V and VI. SA-I axon collaterals give of label for each digit indicate that the dorsal horn cells rise to spherical arbors (250–700 mm) that distribute in activated from a given skin region are grouped together. layers II, III, IV, and the dorsal margin of V. SA-II axon collaterals terminate over layers III, IV, V, and part of VI in rostrocaudally thin sheets (100–300 mm). While all Ascending Spinal Cord Pathways types differ in the details of distribution, the results indi- Traditionally, the ascending somatosensory pathways cate that inputs from single receptive fields on the skin from the spinal cord include the dorsal column pathway relate to rostrocaudal rows of cells in the dorsal horn. and a ventrolateral pathway (Figure 30.4). The dorsal How axons from specific skin regions terminate in the column pathway includes the axons of first-order dorsal spinal cord is known for a range of mammals, including root ganglion neurons coursing ipsilaterally to the monkeys. Similarities across species suggest that the dorsal column nuclei. The ventrolateral pathway (see termination pattern in humans is similar. Figure 30.5 below) originates from second-order neurons of the shows that the terminations from the skin of the digits dorsal horn, crosses to the opposite ventrolateral white of the hand are arranged in a rostrocaudal row in the matter of the spinal cord, and ascends to brainstem medial dorsal horn of the cervical spinal cord of and thalamic targets, including the ventroposterior infe- macaque monkeys (see Florence et al., 1988, 1989). rior nucleus of the thalamus. The ipsilateral dorsal More proximal parts of the limb are represented more column system is thought to largely deal with epicritic laterally in the dorsal horn, and inputs from the foot functions such as position sense and light touch, demonstrate a similarly orderly arrangement. As for while the crossed spinothalamic system is thought to the single axons, groups of axons from a limited skin mediate protopathic sensibilities of crude touch, pain, and temperature. More recent research has complicated this story by indicating that (1) second-order neurons also contribute to the ipsilateral dorsal columns; (2) additional ipsilateral pathways from second-order neurons exist, including a spinocervical system that is reduced in primates; (3) pathways from the upper and lower limbs differ; (4) crossed spinothalamic pathways vary in location; and (5) descending axons are mixed with ascending axons. Of course, these conclusions are based on anatomical studies in non-human primates and other mammals, but findings are general enough that they are likely to apply to humans.

The Dorsal (Posterior) Column System The extremely large dorsal column afferent pathway in humans occupies over a third of the spinal cord at high cervical levels (Wall, 1970). The two major divisions are the more medial gracile tract subserving the trunk and lower limb and the cuneate tract for the upper limb and associated trunk and neck. Inputs from the FIGURE 30.5 A section of the cervical spinal cord in a macaque face and head via the trigeminal system form an analo- monkey (A). The rapidly conducting cutaneous afferents of peripheral gous tract in the brainstem (see Chapter 31). The axons nerves terminate in a somatotopic pattern in the dorsal horn of the spinal cord (B). Tracers were injected into the glabrous skin of digits 1, in the dorsal columns are large, myelinated dorsal root 3, and 5 (D1, D3, D5). Although afferents from each digit typically fibers that branch to ascend to the dorsal column nuclei, enter the spinal cord over more than one cervical dorsal root (C5, 6, 7, send descending collaterals for several segments in the and 8), the inputs terminate in an orderly pattern. Inputs from D1, D2, dorsal columns, and emit a number of local collaterals and D5 terminate in a rostrocaudal pattern (white) in the medial to terminate on neurons in the dorsal horn. Other axons dorsal horn (black) with other digit inputs in between. The dorsal hand and palm are represented more laterally, and the forearm, in originate from spinal cord neurons and ascend over rostral and caudal bands. Based on Florence et al. (1988, 1989). The box several segments to terminate in the spinal cord on local in (A) indicates the plane illustrated in (B). circuit neurons or on neurons that project to the

VI. SYSTEMS RECEPTOR TYPES AND AFFERENT PATHWAYS 1083 brainstem. Some of these secondary sensory neurons The dorsal columns apparently carry all of the inputs project via the dorsal columns to the dorsal column from the body that activate anterior parietal cortex. After nuclei. Thus, both first- and higher-order axons are found complete lesions of the dorsal columns at a high cervical in the dorsal column pathway (Rustioni et al., 1979; level in monkeys, neurons throughout the forelimb and Cliffer and Willis, 1994; Al-Chaer et al., 1999). A few adjacent trunk representations in areas 3a, 3b, l, and 2 descending fibers may also travel in the dorsal columns. totally fail to respond to somatosensory stimuli (Jain Entering fibers from each dorsal root form a narrow et al., 1997, 2008). Given the distribution of information layer at the lateral margin of fibers from lower levels, from anterior parietal cortex to areas of posterior pari- but some mixing of levels occurs as the axons ascend. etal and lateral parietal cortex (Figure 30.4), the impact Most of what is known about the types of information on somatosensory processing at the cortical level is conveyed by the dorsal columns comes from microelec- major. However, the effects of dorsal column lesions trode recordings in monkeys (Whitsel et al., 1969), on behavior have been difficult to study because the although limited recordings in humans revealed nerve somatosensory system of adult primates has a great fibers activated by pressure and limb movement (Puletti capacity for plasticity, and the survival of only a few and Blomquist, 1967). The gracile and cuneate tracts dorsal column axons can have a substantial impact on differ at high spinal cord levels in the classes of axons cortical neurons (Jain et al., 1997, 2008). As expected, they contain. The gracile tract at lower levels contains humans (Nathan et al., 1986) and monkeys (e.g., Vierck a mixture of cutaneous afferents, largely rapidly adapt- and Cooper, 1998) with dorsal column lesions at the ing afferents (probably RA-I), and muscle afferents level of the cervical spinal cord are greatly impaired in that leave to terminate in Clarke’s nucleus, which forelimb and hand use compared to leg and foot use, projects in turn to the cerebellum and other structures because some of the proprioceptive afferents from the via the dorsal . At higher levels, leg travel outside the dorsal columns. The somatosen- the remaining axons that travel to nucleus gracilis are sory abilities that remain demonstrate the importance almost completely RA cutaneous afferents. The cuneate of the spinal cord connections and other ascending path- tract contains a mixture of RA cutaneous and muscle ways, especially the spinothalamic pathway, although afferents, but the cutaneous inputs terminate in the the role of the spinothalamic pathway in touch seems cuneate nucleus, and the muscle afferents separate to limited (Bjo¨rnsdotter et al., 2009). innervate the external cuneate nucleus. Thus, lesions of Primary afferents from oral and facial structures the dorsal columns deactivate RA neurons, regardless of travel in the trigeminal (fifth) nerve and enter the brain- the level of the lesion, but muscle afferents from the stem to branch and terminate in the principal trigeminal lower body terminate on neurons that project outside nucleus and subdivisions of the spinal trigeminal of the gracile tract. Presumably, the dorsal columns of complex (May and Porter, 1998; see Chapter 31). The monkeys and humans also contain SA-I, SA-II, and PC axon branches terminating in the principal nucleus are afferents, as in other mammals (see Willis and Cogge- largely of the low-threshold SA and RA classes, and shall, 1991). they constitute the equivalent of the dorsal column Lesions of the dorsal columns in humans have little pathway. Terminations in the subdivisions of the spinal effect on many simple tactile abilities, but major defects trigeminal complex correspond to those from the body occur in the abilities to detect the speed and direction of that terminate in the dorsal horn of the spinal cord. moving stimuli and to identify figures drawn on the skin (Nathan et al., 1986; see Mountcastle, 1975, and Wall and Second-Order Axons of the Dorsolateral Spinal Noordenhos, 1977, for reviews). These changes obvi- Cord (The Spinomedullothalamic System) ously can be attributed to the loss of inputs from RA cutaneous afferents. Other defects in the control of fore- In monkeys, all the muscle afferents for the lower limb movements (Beck, 1976) may relate to disruption of body apparently leave the gracile column and synapse proprioceptive afferents. The sensory changes following on neurons that send axons in the dorsolateral (postero- dorsal column lesions in monkeys are similar, where lateral) spinal cord to the dorsal column nuclear they have been extensively studied (see Vierck and complex (Whitsel et al., 1972). In humans, lesions of Cooper, 1998; Mountcastle, 2005, for review). Disrup- both the dorsal columns and the dorsolateral spinal tions occur in the ability to discriminate the frequency cord result in severe defects in proprioception, but it is of stimulation, the spatiotemporal sequence of tactile not certain that all proprioceptive axons from the lower stimuli, the directions of moving stimuli and changes limbs are in the dorsolateral pathway rather than the in texture. The results of such lesion studies should be dorsal column pathway (Nathan et al., 1986). interpreted with caution as a small number of afferents Many or all mammals have other inputs to the dorso- surviving a lesion can mediate the recovery of lost abil- lateral pathway, including a spinocervical pathway from ities (Darian-Smith and Ciferri, 2005). second-order neurons in the dorsal horn that project

VI. SYSTEMS 1084 30. SOMATOSENSORY SYSTEM ipsilaterally to the lateral cervical nucleus. A compara- ventroposterior complex of the thalamus (Figure 30.4). tively reduced lateral cervical nucleus has been The part of the system originating in dorsal root ganglia described for humans (Truex et al., 1970), but the types and coursing in the dorsal columns terminates in the of inputs activating this nucleus are known only from gracile nucleus for the lower body and the cuneate studies on other mammals, particularly cats (see Willis nucleus for the upper body. The trigeminal complex and Coggeshall, 1991, for review). Neurons projecting receives inputs from cutaneous mechanoreceptors in into the spinocervical tract have receptive fields on the face and mouth. The gracile, cuneate, and trigeminal both the hairy and glabrous skin in monkeys (Bryan “nuclei” form a somatotopic map from hindlimb to head et al., 1974). Peripheral inputs activating these neurons in a mediolateral sequence in the lower medulla (Xu and are cutaneous rapidly adapting afferents, and there is Wall, 1996, 1999). The gracile and cuneate nuclei are an apparent lack of slowly adapting cutaneous and elongated in the rostrocaudal dimension (Figure 30.4). deep receptor influences. The overall appearance of the nuclei in humans (see Chapter 8) is quite similar to that observed in macaque monkeys and other primates (Florence et al., 1988, 1989; The Spinothalamic Pathways Strata et al., 2003; Qi and Kaas, 2006). In both, the middle Many second-order somatosensory neurons in the regions contain discrete clusters of neurons outlined by dorsal horn of the spinal cord have axons that cross in myelinated fibers. Stains for the mitochondrial enzyme the spinal cord to ascend in the ventrolateral or dorsolat- cytochrome oxidase (CO) show that the cell clusters eral white matter. Many axons in these pathways termi- have more of the enzyme and, presumably, higher meta- nate before reaching the thalamus, but others branch to bolic activity than the surrounding fiber regions. The reach several thalamic nuclei. In Old World monkeys, details of the parcellation pattern of these nuclei in a dorsolateral consists of locally humans and monkeys are quite comparable (Florence crossing axons of lamina I cells of the dorsal horn, while et al., 1989), suggesting the significance of the parcella- the ventrolateral spinothalamic tract contains locally tion is the same. Afferents from individual digits and crossing axons of laminae I-X cells (Apkarian and other body parts terminate in specific cell clusters, and Hodge, 1989a). In monkeys, spinothalamic tract neurons thus, the parcellation reflects the somatotopic organiza- have been found to respond to tactile stimuli and move- tion of the gracile and cuneate nuclei. The rostral and ment of hairs, stimuli ranging from tactile to noxious caudal poles of the cuneate nucleus have more conver- (wide dynamic range neurons), noxious stimuli, and gent terminations from afferents of the digits. Thus, temperature (see Willis and Coggeshall, 1991; Craig, the nucleus appears to segregate inputs into a discrete 2003). In humans, some capacity for mechanoreceptive somatotopic map in the central part of the nucleus and sensibility remains after large lesions of other ascending into less precise maps in the rostral and the caudal poles pathways (Bjo¨rnsdotter et al., 2009). Electrical stimula- of the nucleus in monkeys, and probably in humans. tion of the ventral quadrants of the spinal cord has The projection neurons of the dorsal column nuclei produced sensations of pain and temperature (Sweet send axons into the contralateral medial lemniscus, et al., 1950; Tasker et al., 1976). where they course to the ventroposterior complex (see Kaas, 2008). In humans, as in other mammals, some axons probably send collaterals to the inferior olive, RELAY NUCLEI OF THE MEDULLA AND which projects to the cerebellum (see Schroeder and UPPER SPINAL CORD Jane, 1976; Molinari et al., 1996). In monkeys and other mammals, the dorsal column nuclei, especially the Several groups of neurons in the spinal cord and rostral poles, receive inputs from the contralateral medulla are important in relaying information to higher somatosensory and motor cortex (areas 4, 3a, 3b, l, brain centers. These include the dorsal column nuclear and 2) that may modulate the relay of sensory informa- complex, the dorsal nucleus of the spinal cord (Clarke’s tion (e.g., Cheema et al., 1985; Bentivoglio and Rustioni, nucleus or column), and the lateral cervical nucleus. The 1986; see Marino et al., 1999, for a review). trigeminal nuclear complex adds analogous pathways The trigeminal complex includes the principal (Pr 5) for information from the head. or main sensory nucleus and three spinal trigeminal sub-nuclei (Chapter 31). The principal nucleus is Dorsal Column–Trigeminal Nuclear Complex thought to be analogous to the cuneate and gracile nuclei, and the three together form a systematic repre- The dorsal column–trigeminal nuclear complex sentation of cutaneous receptors of the body (Noriega consists of groups of cells in the lower brainstem and and Wall, 1991; Xu and Wall, 1996). The principal upper spinal cord that receive inputs from ipsilateral nucleus projects via the medial lemniscus to the low-threshold mechanoreceptors and project to the medial subnucleus of the contralateral ventroposterior

VI. SYSTEMS SOMATOSENSORY THALAMUS 1085 complex (VPM). The spinal trigeminal sub-nuclei (Sp 5) brainstem (Sadjadpour and Brodal, 1968; see Chapter 8), correspond to part of the dorsal horn of the spinal cord. projects to the contralateral ventroposterior complex in As in the spinal cord, a marginal zone receives pain and the thalamus. In monkeys, muscle spindle receptor affer- temperature afferents (Craig et al., 1999) and deeper ents related to the forelimb relay over neurons projecting neurons are activated by cutaneous other afferents within the dorsal columns (Dreyer et al., 1974). This prob- (e.g., Price et al., 1976). Second-order neurons in the ably also occurs in humans, since lesions of the dorsal spinal trigeminal nucleus form a relay that joins the columns impair motor control for the upper limbs contralateral spinothalamic tract to terminate in the (Nathan et al., 1986). A separate nucleus X, not clearly ventroposterior inferior nucleus and other nuclei (see present in humans, forms a second group of neurons Burton and Craig, 1979). The mesencephalic trigeminal receiving mostly second-order muscle spindle afferents nucleus consists of the cell bodies of peripheral nerve related to the lower limbs. afferents subserving proprioception. They relay to Pr5. External Cuneate Nucleus Lateral Cervical Nucleus, Nuclei X and Z, The muscle spindle afferents of the upper limbs and External Cuneate Nucleus, and Clarke’s body course in the cuneate fasciculus to terminate in Column the external cuneate nucleus (Hummelsheim et al., 1985). Like nucleus X, the external cuneate nucleus Second- and third-order relay neurons are found in relays to the contralateral ventroposterior complex of several structures in addition to the dorsal column– the thalamus, and to the cerebellum. trigeminal complex and the dorsal horn of the spinal cord (for the human brainstem, see Paxinos and Huang, Clarke’s Nucleus or Column 1995; Chapter 8). A long column of cells called Clarke’s column is located just dorsolateral to the central canal in the Lateral Cervical Nucleus medial part of the spinal cord of T1–L4 levels. Inputs The lateral cervical nucleus consists of a long are largely from muscle spindles. Clarke’s column column of neurons outside the gray matter proper of projects to nucleus Z and, via the dorsal spinocerebellar the dorsal horn of the spinal cord that extends from tract, to the cerebellum (for reviews, see Mann, 1973; C4 to the caudal part of the medulla. Rapidly adapting Willis and Coggeshall, 1991). afferent fibers serving hairs and other tactile afferents enter the dorsal horn to relay on neurons forming the spinocervical tract in the dorsolateral white matter. SOMATOSENSORY REGIONS OF THE These second-order neurons terminate on neurons in MIDBRAIN the ipsilateral lateral cervical nucleus. A subset of multimodal neurons with a convergence of nociceptive Studies in non-human mammals implicate several afferent inputs has been reported in the lateral cervical midbrain structures in somatosensory functions, but nucleus as well (see Boivie, 1978, for a review). The evidence for similar roles in humans is presently lack- lateral cervical nucleus appears to relay touch, pres- ing. Thus, neurons in the external nucleus of the inferior sure, and vibration information, largely from the hairy colliculus respond to somatosensory stimuli and receive skin, to the contralateral thalamus, inferior olive, and inputs from the dorsal column nuclei. The pericentral midbrain. In humans, the lateral cervical nucleus may nucleus may have spinal cord inputs as well. Schroeder be a rudimentary structure because it is only well and Jane (1976) speculate that auditory and somatosen- defined in some individuals (Truex et al., 1970). In sory systems interrelate in these structures in the detec- such humans, the nucleus contains up to 4000 neurons, tion of low-frequency vibratory stimuli. In addition, the while nearly double that number may exist in cats deeper layers of the superior colliculus contain neurons (Boivie, 1983). activated by somatosensory stimuli via inputs from the spinal trigeminal nucleus, the spinal cord, the lateral Nuclei X and Z cervical nucleus, and the dorsal column nuclei (see Other second-order axons of the dorsolateral fascic- Huerta and Harting, 1984, for a review). The somatosen- ulus, possibly collaterals of spinocerebellar axons, termi- sory inputs form a representation that is matched in nate in two small medullary nuclei, termed X and Z by general spatial location with visual and auditory maps, Pompeiano and Brodal (1957). Muscle spindle afferents and the presumed role of the matched maps is to func- for the hindlimb relay via the dorsolateral fasciculus to tion together in directing and head movements nucleus Z, located just rostral to the gracile nucleus. toward sounds, touches, and images of interest (see Nucleus Z, which has been identified in the human Stein et al., 2004).

VI. SYSTEMS 1086 30. SOMATOSENSORY SYSTEM

SOMATOSENSORY THALAMUS monkeys includes additional parts of the thalamus related to motor cortex within an oral division of VPL Various proposals have been made for how to subdi- (VPLo). This use of terminology is not consistent with vide the human thalamus (see Chapter 19), as thalamic that used in other mammals. structures related to somatosensory abilities have been In the human thalamus, the region identified as the given various names or have not been identified with “ventrocaudalis group” or Vc (see Chapter 19) corre- complete certainty. In macaques and several families of sponds closely to our VP in monkeys. Using the termi- New World monkeys, where considerable experimental nology of Ha¨ssler (1982), VPL is Vce (the external evidence is available (e.g., Krubitzer and Kaas, 1992), we segment) and VPM is Vci (the internal segment of Vc). subdivided the somatosensory thalamus into a large VP is composed of a range of neuron sizes that generally ventroposterior nucleus, a ventroposterior superior stain densely for Nissl substance. The dorsal border of nucleus (VPS), and a ventroposterior inferior nucleus the nucleus is described as indistinct, but medial borders (Figure 30.4; see Kaas, 2008 for review). The VP is the with the anterior pulvinar and ventral borders with the principal relay of information from rapidly adapting VPI are distinct. Recent atlases of the human brain use and slowly adapting cutaneous receptors to anterior the terms VPL and VPM (Mai et al., 1997; Morel et al., parietal cortex, the VPS relays information from deep 1997). receptors in muscle and joints, while the significance The VP contains a systematic representation of cuta- of the VPI with spinothalamic inputs is less certain. neous receptors. Each location on the body surface acti- Just caudal to VPI, a ventromedial posterior nucleus vates a small volume of tissue or cluster of neurons in appears to receive spinothalamic inputs mediating VP, and these clusters of neurons are arranged to form pain and temperature (Craig et al., 1994). In addition, a somatotopic representation. The general form of the related nuclei of the posterior complex (Po) appear to somatotopic organization in mammals has been have somatosensory functions. Other nuclei, notably reviewed by Welker (1974), and described in detail for the medial and anterior divisions of the pulvinar squirrel monkeys by Kaas et al. (1984) (Figure 30.6; see complex and the lateral posterior nucleus, are known Rausell and Jones, 1991; Padberg et al., 2009 for VP of to have connections with parietal cortex and thereby macaque monkeys). In all primates, including humans, are implicated in somatosensory functions. However, we expect the tactile receptors of the tongue, teeth, and these nuclei do not appear to have a role in relaying oral cavity to be represented medial to the and sensory information. The somatosensory nuclei are dis- upper face in VPM. Because some of the inputs from cussed and related to proposed subdivisions of the the principal trigeminal nucleus are ipsilateral as well human thalamus below. as contralateral, both the ipsilateral and contralateral teeth and tongue are represented in each VPM. More Ventroposterior Nucleus (VP) medially, a gustatory nucleus, VPM parvocellular (VPMpc), is part of the system for (see Chapter 33). The VP is a basic subdivision of the mammalian thal- The medial portion of VPL contains a mediolateral amus (Welker, 1974; Jones, 2007; Kaas, 2008)thatischar- sequential representation of the digits of the hand from acterized by (1) densely packed and darkly stained thumb to little finger. The lateral portion of VPL is neurons; (2) a systematic representation of cutaneous devoted to the foot, while dorsal portions of the nucleus receptors; (3) inputs from the dorsal column nuclei, the relate to the proximal leg, the trunk, and the proximal spinothalamic tract, and the trigeminal system; and (4) arm in a lateromedial sequence. This arrangement, projections to “primary” somatosensory cortex. The found in monkeys and in other mammals, is basically nucleus has subnuclei of dense aggregates of neurons the order described for the human VP. Recordings partially separated by cell-poor fiber bands, the most and electrical stimulation with microelectrodes in VP conspicuous of which is the arcuate lamina that separates of the human thalamus (Emmers and Tasker, 1975; the part of VP representing the face, the ventroposterior Lenz et al., 1988; Davis et al., 1996; Patel et al., 2006) medial “nucleus” (VPM), from the portion representing indicate that the mouth and tongue relate to ventrome- the rest of the body, the ventroposterior lateral “nucleus” dial portions of VPM, the hand and foot are in (VPL). Another notable fiber band separates the repre- ventrorostral VPL, and the back and neck are in dorso- sentations of the hand and foot in VPL. caudal VPL. Furthermore, the fingers activate a large In macaque monkeys, the dorsal boundaries of VP are portion of medial VPL and the lips and tongue relate not very distinct from the region we now identify as VPS to a large part of VPM. In addition, often groups of (see Paxinos et al., 2000). The VP of some investigators neurons extending in the parasagittal plane are includes VPS, although this region has also been distin- activated by the same restricted skin surface, indicating guished as the VP “shell” (Jones, 2007). Olszewski’s that lines of isorepresentation are largely in the para- (1952) popular atlas of the thalamus of macaque sagittal direction.

VI. SYSTEMS SOMATOSENSORY THALAMUS 1087

FIGURE 30.6 The somatotopic organization of the ventroposterior (VP) nucleus of squirrel monkeys. A similar organization, except for a lateral representation of the tail, exists in VP of humans (Lenz et al., 1988). VP is subdivided into ventroposterior lateral (VPL) for the body and ventroposterior medial (VPM) for the face. VPL has further subnuclei for the hand and foot. The hand subnucleus is shaded. Digits of the hand and foot are represented in mediolateral sequences with the tips ventral in VP. Neurons in VP are activated by slowly and rapidly adapting afferents. Neurons activated by each class form small clusters with VP. Adapted from Kaas et al. (1984).

As in monkeys (e.g., Dykes et al., 1981), most neurons sensory trigeminal nucleus via the trigeminal lemniscus. in VP of humans are activated by RA-I or SA inputs, Less-dense, unevenly distributed inputs are from the with local clusters of cells related to one or the other spinothalamic tract and the lateral cervical nucleus class of inputs (Lenz et al., 1988). Thus, there are two (Berkley, 1980; Apkarian and Hodge, 1989b; Craig, fragmented, intermixed representations of the skin in 2006). The spinothalamic inputs appear to relate to VP, one fragmented representation of RA-I afferents small-cell regions of VP that express calbindin (possibly and one fragmented representation of SA afferents. extensions of VPI) that project to superficial layers of The SA inputs could be SA-I or both SA-I and SA-II. areas 3b and 1 (Rausell and Jones, 1991). Thus, this relay There is little evidence for Pacinian (RA-II) inputs, but likely has a modulatory role in somatosensory cortex. In they likely add to the complexity of the nucleus. A few humans, degenerating spinothalamic terminations have neurons respond with an increasing frequency as light been reported in VP after spinal cord damage (Mehler, tactile stimuli become more intense and extend into 1966; see Bowsher, 1957, for a review of classical reports) the painful range (the wide-dynamic-range neurons); and, evoked potentials have been recorded in VP after these neurons may have a role in pain perception (see electrical stimulation of the dorsal columns (Gildenberg Kenshalo et al., 1980) or in signaling the intensity of and Murthy, 1980). stimuli. In humans, electrical stimulation of peripheral The outputs of the ventroposterior nucleus have been nerves results in evoked potentials in the contralateral studied extensively in primates and other mammals (see VP with a latency of 14–17 ms (Fukushima et al., 1976; Kaas and Pons, 1988; Darian-Smith et al., 1990; Krubitzer Celesia, 1979). Electrical stimulation at sites in VP or of and Kaas, 1992; Kaas, 2008; Padberg et al., 2009). In all input fibers in the medial lemniscus generally results mammals studied, VP projects to area 3b or its non- in sharply localized sensations of numbness or tingling homolog S1. In most mammals, other projec- () rather than light touch (Tasker et al., tions are to the second somatosensory area (S2) and 1972; Emmers and Tasker, 1975; Davis et al., 1996; Lenz possibly other fields, but in monkeys, and probably et al., 1998, 1988; Patel et al., 2006). However, sensations humans, projections to S2 are a trivial component of of touch and vibration are also reported (Ohara et al., the output. In monkeys, VP also projects over thinner 2004). Localized lesions of VP are followed by a persis- axons and in a less-dense manner to area 1, and, in tent numbness in a restricted skin region corresponding macaque monkeys, a sparse input exists to part of area to the body surface map in VP (Garcin and LaPresle, 2 related to the hand and even a specialized part of 1960; Domino et al., 1965; Van Buren et al., 1976). area 5 (Pons and Kaas, 1986; Padberg et al., 2009). In The sources of ascending inputs to VP (Figure 30.4) humans, lesions of anterior parietal cortex including have been studied in many mammals, including areas 3b and 1 cause retrograde degeneration and cell macaque monkeys. The dense inputs are from the dorsal loss in VP (Van Buren and Borke, 1972), supporting the column nuclei via the medial lemniscus and the main conclusion that the output patterns in humans and

VI. SYSTEMS 1088 30. SOMATOSENSORY SYSTEM monkeys are similar. Furthermore, recordings from the Ventroposterior Inferior Nucleus surface of somatosensory cortex indicate that potentials evoked by median nerve stimulation are reduced or In all primates, including humans (e.g., Morel et al., abolished by lesions of VP (Domino et al., 1965). 1997), VPI is recognized as a narrow region just ventral to VP that is composed of small, pale-staining neurons. VPI is densely myelinated and reacts lightly to cyto- Ventroposterior Superior Nucleus chrome oxidase. Narrow parts of VPI appear to extend There has been long-standing recognition that inputs dorsally into the cell-poor regions that separate face, from receptors in deep tissues are at least partially segre- hand, and foot subnuclei of VP (Krubitzer and Kaas, gated from inputs from cutaneous receptors in the 1992). Because of this dorsal finger-like extension of ventroposterior thalamus of primates (see Poggio and parts of VPI, and its caudal extension into thalamic Mountcastle, 1963) and perhaps other mammals. The regions of similar appearance and perhaps function zone of activation by deep receptors is dorsal to that (see following discussion), some of the boundaries of related to cutaneous receptors in monkeys, and the VPI have been uncertain. As a result, the major inputs deep receptor zone is further distinguished by its to VPI from the spinothalamic and caudal trigeminotha- pattern of cortical connections and architecture. We lamic afferents have been variously described as have termed the deep receptor zone the ventroposterior including not only VPI but also VP as well as more superior nucleus (VPS; see Kaas and Pons, 1988; Kaas, caudal nuclei (see Apkarian and Hodge, 1989b). Never- 2008). Early investigators included the zone of activation theless, VPI “proper” receives a mixture of inputs from by deep receptors in VP, and several recent researchers lamina I nociceptive neurons and lamina V wide- simply designate the deep receptor zone as the VP dynamic-range neurons of the contralateral spinal cord “shell.” Others conclude that the deep receptor zone (Craig, 2006b). The inputs to VPI reveal a somatotopic includes two nuclei, a VPS and a “ventroposterior pattern with the hindlimb inputs most lateral and the oral” nucleus (see Dykes, 1983), but the evidence for forelimb and face inputs more medial (Gingold et al., such a subdivision in primates is inconclusive. Some 1991). Outputs to cortex also reflect this overall somato- term the VPS region VPO (see Chapter 19) as it is as topic pattern of organization (Cusick and Gould, 1990). much oral (anterior) as superior in some primates. Neurons in the VPI region of both monkeys (Apkarian Finally, the medial posterior nucleus of some investiga- and Shi, 1994) and humans (Lenz et al., 1993) are respon- tors (see Krubitzer and Kaas, 1987, for a review) may sive to noxious stimulation. In monkeys, VPI projects be a non-primate homolog of VPS. densely to areas S2 and PV of lateral parietal cortex In monkeys, VPS contains a representation of deep and less densely and more superficially to areas of ante- receptors for proprioception, principally muscle spindle rior parietal cortex (Friedman and Murray, 1986; Cusick receptors (see Wiesendanger and Miles, 1982; Kaas and and Gould, 1990; Krubitzer and Kaas, 1992). Although Pons, 1988). The representation parallels that in VP so VPI relays spinothalamic tract information, and VPI that the face, hand, and foot activate the medial, middle, includes neurons responsive to noxious stimuli, it seems and lateral portions of VPS in sequence (Kaas et al., likely that the role of VPI projections to cortex are largely 1984). The major input appears to be from the external modulatory. They may have a role in experience-related cuneate nucleus (Boivie and Boman, 1981), and the plasticity of somatosensory cortex (see Kaas and output is largely to area 3a, area 2, and part of area 5 Florence, 2000), or in signaling stimulus intensity (Padberg et al., 2009). Many of the same neurons in without the emotional component of pain (e.g., Brooks VPS appear to project to both area 3a and area 2 via and Tracey, 2005). collaterals (Cusick et al., 1985). Evidence is less complete for VPS of humans. Deep The Posterior Group and the Posterior receptors are represented in an orderly manner in part Ventromedial Nucleus of the thalamus just rostrodorsal to the cutaneous repre- sentation in VP (Lenz et al., 1990; Ohye et al., 1993; Seike, A poorly defined group of nuclei with somatosensory, 1993). The mediolateral progression in the representa- auditory, and multimodal functions, located just caudal tion corresponds to that in VPS with the jaw medial to to the ventroposterior complex, has been referred to as fingers, followed by wrist, elbow, shoulder, and leg. the posterior group or complex (Jones, 2007). The VPS is probably within VP or a VL-VP “transition” complex is commonly divided into separate limitans, zone identified as Vcae or Vim by Ha¨ssler (1959) and suprageniculate, and posterior nuclei. The posterior VPLa in more recent studies (Hirai and Jones, 1989; “nucleus” is often subdivided into medial, lateral, and Morel et al., 1997). Microstimulation of neurons in the even intermediate nuclei. The medial posterior nucleus VPS region of humans can elicit sensations of movement (Pom) is composed of small cells that seem to merge and deep pressure (Ohara et al., 2004). with caudal VPI. There is some evidence that neurons

VI. SYSTEMS ANTERIOR PARIETAL CORTEX 1089 with large cutaneous receptive fields and multimodal Early attempts to subdivide anterior parietal cortex responses in the lateral cervical nucleus relay to Pom resulted in the differing conclusions of Campbell (see Metherate et al., 1987, for a review). Cortical projec- (1905), Smith (1907), Brodmann (1909), Vogt and Vogt tions of the posterior complex appear to be to cortex of (1919), and von Economo and Koskinas (1925). The the lateral fissure near S2. subdivisions made by Campbell and Smith fell into Recently, a part of the posterior group has been disuse, but the proposals of Brodmann, Vogt and Vogt, distinguished in monkeys and humans as posterior and von Economo are in use today (see Chapter 23). ventromedial nucleus, VMpo (Craig et al., 1994; Davis In brief, Brodmann distinguished a mediolateral strip et al., 1999; Blomquist et al., 2000). The nucleus receives of cortex in the caudal bank of the central (Rolandic) somatotopically organized nociceptive and thermore- fissure as area 3, an immediately superficial and caudal ceptive spinothalamic inputs from layer I of the contra- strip on the caudal lip of the sulcus as area 1, and a more lateral dorsal horn of the spinal cord via the caudal strip on the surface of the postcentral gyrus as spinothalamic tract (Craig, 2006a). VMpo projects to area 2. Area 3 was described as a field with densely cortex in the lateral fissure in the region of the dorsal packed small granular cells in layer IV, as is character- posterior insula. This pathway appears to be important istic of sensory fields, while areas 1 and 2 had less domi- in mediating sensations of pain and temperature (see nant sensory features. Brodmann further described Perl, 1998). a “transitional” field (deep in the central fissure) in ante- rior area 3 with both prominent sensory (layer IV granule cells) and motor (layer V pyramidal cells) Anterior Pulvinar, Medial Pulvinar, and Lateral features. Vogt and Vogt (1919) added to this proposal Posterior Nucleus by stressing the distinctiveness of anterior area 3, and subdivided area 3 into two fields, area 3a and area 3b Other thalamic structures without direct inputs from (see Jones and Porter, 1980, for a review). These four second-order somatic afferents can be considered part architectonically defined subdivisions of postcentral of the somatosensory system on the basis of connec- somatosensory cortex are in common use for human tions with somatosensory cortex. These include the and other anthropoid primates today (Qi et al., 2008). anterior (oral) pulvinar with widespread projections However, some investigators use the terms of von to anterior parietal cortex, posterior parietal cortex, Economo (1929) for these subdivisions. Rather than and somatosensory cortex of the lateral fissure (Cusick number cortical fields, von Economo used two letters and Gould, 1990; Krubitzer and Kaas, 1992; Padberg to denote fields, with the first letter indicating the et al., 2009); the medial pulvinar with connections lobe of the brain for the field, and the second letter with posterior parietal cortex and the temporal lobe indicating the order in which fields were described in (e.g., Gutierrez et al., 2000) and the lateral posterior the lobe, typically starting with fields of obvious nucleus (LP) with projections to posterior parietal sensory nature. In general, Brodmann (1909) and von cortex (Cappe et al., 2007). In humans, degeneration Economo (1929) divided the human brain in different has been noted in the anterior pulvinar after damage ways, but the proposed subdivisions of anterior pari- to parietal cortex of the lateral fissure, while LP degen- etal cortex are quite similar, the agreement suggesting erates after lesions of posterior parietal cortex (Van the validity of the divisions. Von Economo’s most ante- Buren and Borke, 1972). The roles of these nuclei in rior field, deep in the central sulcus, is area PA, equiv- the processing of somatosensory information are alent to area 3a. The adjacent field, area PB, was noted unknown, but the lack of direct sensory input and the as sensory “koniocortex” as a result of the powder-like widespread cortical connections suggest modulatory appearance of the small granule cells in layer IV of and integrative functions. what clearly corresponds to area 3b. Area PC, charac- terized by a less distinct laminar structure, is equiva- lent to area 1. A more caudal strip of cortex with ANTERIOR PARIETAL CORTEX a more distinct layer IV and layer VI, is area PD, closely corresponds to area 2. The anterior parietal cortex was first considered as several separate fields in early architectonic studies Anterior Parietal Cortex in Monkeys (e.g., Brodmann, 1909), then as a single primary somato- sensory field or S-I on the basis of electrophysiological Over the last few years, research on monkeys has studies in monkeys (see Marshall et al., 1937), and greatly clarified the significance of the four architectonic more recently as several fields again, as the validity of strips. Conclusions based on an extensive number of early subdivisions as functionally distinct areas has anatomical and electrophysiological studies are briefly been experimentally supported (see Qi et al., 2008). summarized next.

VI. SYSTEMS 1090 30. SOMATOSENSORY SYSTEM

few connections (Killackey et al., 1983). Neurons in Area 3b area 3b have small receptive fields with excitatory and We have termed area 3b “S-I proper” because it inhibitory subregions (Sripati et al., 2006). These small appears to be the homolog of the primary somatosen- excitatory receptive fields do not reflect the callosal sory area, S-I, in non-primates (Kaas, 1983). Area 3b connections, which may contribute to surround contains a separate, complete map of the cutaneous suppression or enhancement, but instead are confined receptors of the body (Nelson et al., 1980). The represen- to locations on the contralateral body surface. Yet, tation proceeds from the foot in medial cortex to the face neuron responses are often reduced or increased by and tongue in lateral cortex, with the digits of the foot stimuli on the hand but outside the receptive field, and and hand pointing “rostrally” (or more precisely, deeper even on the other hand (Reed et al., 2008). In monkeys, in the central sulcus), and the pads of the palm and inactivation or lesions of area 3b or area 3b together of the foot caudal in 3b near the area 1 border. Subdivi- with areas 1 and 2, result in impairments in all but the sions of area 3b related to body parts can be seen in brain crudest of tactile discriminations involving texture and sections cut parallel to the surface as myelin-dense ovals shape (Randolph and Semmes, 1974; Hikosaka et al., separated by myelin-light septa (Jain et al., 1998, 2001; 1985; Zanios et al., 1997; Brochier et al., 1999). Small Iyengar et al., 2007). The most conspicuous septum tran- objects might be unrecognized by touch and ignored, sects lateral area 3b where it separates the more medial and coordination during grasping is impaired. hand representation from the more lateral face represen- tation. In the hand representation, a narrow strip of Area 1 cortex for each digit is bounded on each side by septa Like area 3b, area 1 contains a systematic representa- (Qi and Kaas, 2004). The hand representation is tion of the body surface. The representation parallels bordered laterally by a caudorostral series of three and also roughly mirrors that in area 3b. Thus, the foot, myelin-dense ovals, first for the upper face, next for leg, trunk, forelimb, and face are represented in a medio- the upper lip, and then for the lower lip and chin. lateral cortical sequence (as in area 3b), but the digit tips Next, a succession of four ovals represent the contralat- are represented caudally near the area 2 border rather eral teeth, the contralateral tongue, the ipsilateral teeth, than rostrally near the area 3b border. Most neurons in and the ipsilateral tongue. Except for the rostrolateral area 1 are rapidly adapting and respond as if they representations of the ipsilateral tongue and teeth (also were related to RA-I cutaneous receptors. A small see Manger et al., 1996), the area 3b representation, portion of neurons, perhaps 5%, respond as if activated like other representations in anterior parietal cortex, is by RA-II (Pacinian) afferents. The results of optical almost exclusively of the contralateral body surface. imaging experiments suggest that small regions of The septa-distinguishing body parts in area 3b usefully domains of neurons in area 1 are selectively dominated serve as an anatomical guide for other types of experi- by SA, RA-I, and RA-II (PC) inputs (Friedman et al., ments. They have not been described in area 3b of 2004). Neurons in area 1 tend to have larger and more humans, but they may be present (see Mountcastle, complex receptive fields (Iwamura et al., 1993), 2005). including stronger suppressive or inhibitory surrounds, The activation of area 3b neurons is from RA-I and SA than area 3b neurons (Sur, 1980; Sur et al., 1985). Some (I and possibly II) afferents relayed from the ventropos- neurons code for the direction of movement on the terior nucleus. RA-I and SA inputs appear to be segre- skin (Hyvarinen and Poranen, 1978; Bensmaia et al., gated into bands (columns) in layer IV (Sur et al., 2008). More neurons in area 1 than in area 3b are sensi- 1984). Microstimulation of neurons in the RA modules tive to stimulus (Bensmaia et al., 2008). The of area 3b in monkeys provided psychophysical data activity patterns of most area 1 neurons, but not area that suggest that this stimulus can be perceived as flutter 3b neurons, are modified according to what motor on the fingers (Romo et al., 2000). Most of the large relay behavior will follow the stimulus (Nelson, 1984). Area neurons in VP project to layer 4 of area 3b via thick 1 receives strong inputs from both area 3b and the ven- rapidly conducting afferents. Smaller neurons in the troposterior nucleus. The VP inputs are partly from septa of VP and in VPI project to the superficial layers collaterals of neurons projecting to area 3b (Cusick (Rausell and Jones, 1991). Major outputs in area 3b are et al., 1985), and the terminations are largely of thinner to area 1, area 2, and S2 and the parietal ventral area, axons than those of area 3b. As the inputs from area 3b PV, and these fields provide feedback inputs (Krubitzer are to layer 4 and those from VP are to layer 3 (Jones, and Kaas, 1990; Burton et al., 1995; Romo et al., 2000). 1975), the area 3b inputs appear to provide the major Area 3b is callosally interconnected with areas 3b, 1, activation. Thus, lesions of areas 3a and 3b inactivate and 2, and S2 of the opposite hemisphere. The callosal neurons in area 1 (Garraghty et al., 1990a). Feedforward connections are unevenly distributed, with the large cortical outputs are predominantly to area 2, PV, and S2, representations of the glabrous hand in area 3b having and feedback inputs are from these fields. Callosal

VI. SYSTEMS ANTERIOR PARIETAL CORTEX 1091 connections are more evenly distributed than for area 3b, activation is also apparent, especially in the portion but connections in the hand, foot, and parts of the face devoted to the hand. The representation parallels that regions remain sparse (Killackey et al., 1983). The callosal in area 3b (Krubitzer et al., 2004). Neurons in area 3a connections largely modulate neurons with receptive are responsive during movements and are influenced fields on the contralateral body surface, but some by behavioral intentions (“motor-set,” see Nelson, neurons with ipsilateral or bilateral body midline recep- 1984). The major input is from VPS and roughly half tive fields occur (Taoka et al., 1998). In monkeys, lesions of the VPS relay neurons project to both area 3a and of area 1 impair discriminations of texture rather than area 2, thus providing the same information (Cusick shape (Randolph and Semmes, 1974; Carlson, 1981). et al., 1985). Area 3a projects to area 2, motor cortex, S2, and other fields (Huerta and Pons, 1990; Huffman Area 2 and Krubitzer, 2001). Callosal connections are uneven, Area 2 contains a complex representation of both but the hand region has somewhat more dense cutaneous and non-cutaneous receptors. Neurons callosal connections than the hand representation in appear to be influenced by cutaneous receptors, deep area 3b. receptors, or both. The portions of area 2 related to the hand and face are most responsive to cutaneous stimu- Subcortical Projections lation. The representation is in parallel with those in All four fields project to a number of subcortical fields areas 3b and 1 so that the foot, trunk, hand, and face including feedback to the thalamic relay nuclei, the basal form a mediolateral cortical sequence. A mirror reversal ganglia, the anterior pulvinar, the pons, the dorsal organization of that in area 1 is apparent for parts of area column nuclei, and the spinal cord (see Kaas and Pons, 2 near the area 1 border. However, the overall organiza- 1988). These projections presumably function in modi- tion is more complex than in areas 3b and 1, and some fying motor behavior and sensory afferent flow. The body parts are represented more than once in area 2 projections to the pons are to neurons that relay to the (Pons et al., 1985). Receptive fields for neurons in area cerebellum (Vallbo et al., 1999) where they may modify 2 are typically, but not always, larger than those for motor responses. neurons in areas 3b and 1, and receptive field properties appear to be complex (Iwamura et al., 1993). Many Anterior Parietal Cortex in Humans neurons are best activated by stimuli of certain shapes or directions of movement. Some neurons respond Several types of evidence support the conclusion that during both passive and active movements and others the organization and functions of anterior parietal cortex only during active movements (Prud’Homme and in humans are similar to those in monkeys. Kalaska, 1994). The inputs from deep receptors are largely those related to muscle spindles, suggesting Architectonic Fields that area 2 combines information about limb and digit As in monkeys, four architectonic fields can be iden- position with tactile information during active touch. tified in the anterior parietal cortex of humans – areas The major thalamic input to area 2 is from VPS 3a, 3b, 1, and 2 (see Chapter 23). In early studies, the (Figure 30.4), but a sparse input to the hand region of presumed boundaries of these fields varied somewhat, area 2 originates in VP (Pons and Kaas, 1985; Padberg and other terminologies were sometimes used. et al., 2009). Major cortical inputs are from areas 1, 3b, Recently, a number of studies have reconsidered the and 3a (Pons and Kaas, 1986). There also appear to be issue of how anterior parietal cortex is divided into sparse inputs from the motor cortex and to S2. Callosal fields with the benefit of new chemoarchitectonic connections are fairly evenly distributed and include methods (Zilles et al., 1995; White et al., 1997; Geyer the hand representation (Killackey et al., 1983). Neurons, et al., 1999; Qi et al., 2008). Area 3b is the most obvious however, have excitatory receptive fields mainly on the field, and investigators closely agree on boundaries. contralateral body, but bilateral receptive fields are Area 3a is also easily recognized as distinct from 3b common (Iwamura et al., 2001). Lesions of area 2 in andarea4(motorcortex),althougharea3aappears monkeys impair finger coordination (Hikosaka et al., to have rostral and caudal subdivisions. The area 1 1985) and discriminations of shape and size (Carlson, border with area 2 is also reasonably distinct, while 1981). the area 2 border with posterior parietal cortex (area 5) is the least obvious, as in monkeys. Detailed compar- Area 3a ison of the architecture of these fields in monkeys Area 3, in the depth of the central sulcus, forms the (where somatotopy and connections have been fourth systematic representation of the body in anterior studied), chimpanzees, and humans (Qi et al., 2008) parietal cortex. Area 3a is largely activated by muscle perhaps provides the most compelling evidence for spindle and other deep receptors, but some cutaneous functionally significant boundaries. Overall, as in

VI. SYSTEMS 1092 30. SOMATOSENSORY SYSTEM monkeys, areas 3a and 3b have chemoarchitectonic that separate representations with different functions features that are characteristic of , exist in areas 3a, 3b, 1, and 2. The hand representation while areas 1 and 2 resemble secondary areas (see Eske- in area 3b appears to correspond to a bulge in the central nasy and Clarke, 2000), supporting the conclusion that sulcus (Sastre-Janer et al., 1998). areas 3b, 1, and 2 constitute a processing hierarchy in 1. Electrical stimulation of cutaneous afferents in the humans as in monkeys. median nerve of the hand results in a focus of evoked As in macaque monkeys, area 3a of humans occupies potentials after 20–30 ms in area 3b of the caudal bank the depths of the central sulcus, where it extends some- of the central sulcus and a second focus after what from the posterior to the anterior bank. In area 3a, 25–30 ms in area 1 of the dorsolateral surface of layers IV and VI are less pronounced than in area 3b, and postcentral cortex (see Allison et al., 1988; Ploner layer V pyramidal cells are more obvious. Area 3b et al., 2000). The two foci support the view that area occupies roughly the middle half or more of the poste- 3b and area 1 have separate maps of the body surface. rior bank of the central sulcus. The field appears on The area 1 potentials are caudal to the area 3b the surface as the central sulcus ends near the medial potentials, indicating parallel maps, although a slight wall, and the field extends into the medial wall. Area medial shift of the area 1 focus suggests a small 3b is easily distinguished over most of its extent by the displacement of one map relative to the other. As in dense packing of small cells in layer IV, and the rela- monkeys, activity was generated only from tively dense packing of cells in layer VI. The small cells stimulating contralaterally. have led to the terms “koniocellular cortex” and “parvi- 2. Stimulation of muscle afferents from the human hand cellular core” (see Chapter 23). Most investigators show results in a focus of activity that is caudal to that for area 3b as ending with the lateral extent of the central cutaneous afferents (Gandevia et al., 1984). A sulcus, but area 3b extends anteriorly past the end of reasonable interpretation of this result is that the the sulcus in monkeys, where it represents the mouth muscle afferents activate area 2, which is caudal to the and tongue. However, these body parts may be repre- activity produced in areas 1 and 3b by cutaneous sented more medially in humans (see following discus- afferents. More recently, evoked potentials to joint sion). Area 1 occupies the anterior lip of the postcentral movement in the fingers has been attributed to area 2 gyrus where it borders area 3b on the posterior bank of activation (Desmedt and Ozaki, 1991), suggesting the central sulcus and extends over the anterior third of that joint receptor afferents as well as muscle spindle the postcentral gyrus. Layers IV and VI are less densely afferents activate area 2. packed with cells in area 1 than in area 3b, so the overall 3. Another focus of activity produced by deep receptor appearance is of less conspicuous lamination. Area 1 or muscle spindle afferents is deep to foci related to would roughly correspond to the posterior half of the cutaneous stimulation. Using neuromagnetic postcentral area of Campbell (1905), and the full extent recordings, Kaukoranta et al. (1986) found that mixed of area 1 of Brodmann. Area 1 is unlikely to be as wide nerve stimulation resulted in a deeper focus of as area PC of von Economo and Koskinas (1925), area activity in the central sulcus than cutaneous nerve 1 of Sarkossov and co-workers (see Braak, 1980), or the stimulation. The results were interpreted as evidence medial half of the paragranulous belt of Braak (1980). for muscle spindle receptor input to area 3a and Area 2 is characterized by a denser layer IV than is cutaneous receptor input to area 3b. Similar results found in area 1. The caudal border is difficult to delimit have been obtained with fMRI (Moore et al., 2000; in monkeys even with the aid of electrophysiological also see Mima et al., 1996, 1997). data, and the precise location of this border remains 4. More recently, non-invasive imaging techniques have somewhat uncertain in humans (however, see Qi et al., been used to explore the organization of anterior 2008). However, the expected width of area 2 would parietal cortex in awake humans. While positron approximate that of area 1. emission tomography (PET) has been useful for gross localization of sites of induced activity (see Burton Maps in 3a, 3b, 1, and 2: Evidence from Scalp and et al., 1993, 1999), functional magnetic resonance Brain Surface Recordings imaging (fMRI) has provided more resolution. Most As part of efforts to localize abnormal tissue and for notably, vibratory and other stimuli applied to other clinical reasons, recordings have been made from different finger tips provided evidence for separate the scalp, from the surface of anterior parietal cortex, representations in areas 3a, 3b, 1, and 2 (Lin et al., and from depth probes in the cortex of 3b of patients. 1996; Gelnar et al., 1998; Francis et al., 2000; In addition, neuromagnetic recordings and scalp- Blankenburg et al., 2003). Functional magnetic evoked potentials have been recorded from healthy resonance imaging has also demonstrated the volunteers. Such recordings support the conclusion representation of thumb to little finger in

VI. SYSTEMS ANTERIOR PARIETAL CORTEX 1093

a lateromedial sequence in area 3b, area 1, and area 2 6. Extensive observations on the somatotopy of (Kurth et al., 1998, 2000; Francis et al., 2000), and postcentral cortex in humans come from recordings show that the tongue, fingers, and toes are of evoked slow waves from the brain surface during represented in a lateromedial sequence (Sakai et al., neurosurgery (Woolsey et al., 1979). In a sequence of 1995). Hoshiyama et al. (1996) located the recording sites along the posterior lip of the central representation of the lower lip lateral (inferior) to that sulcus, from near the medial wall to over two-thirds of the upper lip, as in monkeys (Jain et al., 2001). of the distance to the lateral (Sylvian) sulcus, Teeth are represented next to the lip followed by the potentials were evoked from foot, leg, thigh, trunk, tongue (Miyamoto et al., 2005), as in monkeys. and hand. In individual patients, there was some 5. Recordings of scalp-recorded evoked potentials in notable variability in organization so that the leg humans also support the conclusion that the maps of representation extended from the medial wall onto receptor surfaces in anterior parietal cortex are the dorsolateral surface in some but not other cases. organized much as they are in monkeys. Thus, By electrically stimulating the dorsal nerve of the electrical stimulation of the little finger activates penis and recording evoked potentials from anterior cortex 1–2 cm medial to that activated by stimulating parietal cortex of humans during surgery, Bradley the thumb (see Hari and Kaukoranta, 1985), and et al. (1998) provided evidence that the penis is activity evoked in cortex by tapping the tongue is represented in cortex near the representation of the lateral to that produced by tapping the finger (Ishiko lower abdomen and lateral to that of the foot (also see et al., 1980). Measurements of magnetic fields, Rothemund et al., 2002). Similar results have now thought to be generated in the depths of the central been obtained with fMRI (Kell et al., 2005). sulcus in area 3b, indicated that the thumb, index 7. More details about the sequence of representation of finger, and ankle are represented at successively more body parts in postcentral cortex have been obtained medial position (Okada et al., 1984). These methods by electrically stimulating the brain in patients. Using have now been used to show that the tongue, lower higher levels of stimulating current than used for lip, upper lip, thumb through little finger, palm, motor cortex, Foerster (1931, 1936a) was able to forearm, elbow, upper arm, chest, thigh, ankle, and produce a postcentral motor map that roughly toes are represented in a lateromedial order matched the precentral motor map in the (Nakamura et al., 1998; Figure 30.7). mediolateral cortical order of leg, hand, and face (Figure 30.8). Penfield and Rasmussen (1950) also reported evoked movements for postcentral stimulation sites, with the postcentral motor map roughly paralleling the precentral motor map in mediolateral organization. More precise information

FIGURE 30.7 The somatotopic organization of the anterior FIGURE 30.8 The order of representation in human postcentral somatosensory cortex according to results obtained from the non- cortex according to Foerster (1931). The summary was based on invasive recording of sensory-evoked magnetic fields (Nakamura sensations reported when the surface of cortex was electrically stim- et al., 1998). The center of activity for the different body parts is shown ulated. Most stimulation sites were in area 1 or area 2, as area 3b is on the lip of the central sulcus, but the regions generating the largely in the central sulcus. No distinctions between the separate magnetic fields were judged to be along the posterior bank of the representations in areas 3a, 3b, 1, and 2 were made. Similar but more central sulcus, most likely reflecting activity in area 3b and part of area detailed maps were later produced by Penfield and Jasper (1954). 1. This map does not address the issue of separate representations in Their maps placed the foot in the cortex of the medial wall and each of area 3a, 3b, 1, and 2. In addition, centers of activity for ankle included the back of the head in center medial to the arm and toes were likely generated from cortex on the medial wall. representation.

VI. SYSTEMS 1094 30. SOMATOSENSORY SYSTEM

about the somatotopic organization of postcentral from a focus and spreads to more distant tissue, the cortex has been obtained by noting where sensations order of sensations reflects the order of are located during electrical stimulation of cortical representation. Typical cases are described by sites. As one might expect, sensations evoked from Foerster (1936b) and Penfield and Jasper (1954). The stimulating the cortex match in somatotopic location orders of these sensory marches correspond to the the source of afferents related to the stimulation sites. evoked sensation map (Figure 30.8). For example, Thus, stimulating cortex where evoked responses a sensation of tingling or numbness in the thumb may were obtained to ulnar nerve stimulation resulted in be followed by tingling in the face, or a tingling that sensations largely confined to the ulnar hand (Jasper passes from thumb to fingers, to arm. Sensations are et al., 1960). The extensive report of Penfield and contralateral to the postcentral focus, and they Boldrey (1937) summarizes the results from seldom spread over many body parts (Mauguiere stimulating precentral and postcentral cortex in 163 and Courjon, 1978). patients. Stimulation sites resulting in sensations were scattered over the precentral and postcentral gyri, and even a few more posterior or more anterior Sensory and Perceptual Impairments Following sites were effective. However, the vast majority of Lesions sites were along the posterior lip of the central sulcus Damage to postcentral cortex, if extensive, causes and were probably evoking sensations by activating severe and lasting impairments in pressure sensitivity, neurons in area 1. The evoked sensations were not of two-point discrimination, point localization, and light touch, but were described as a localized discrimination of object shape, size, and texture numbness, tingling, or, infrequently, the of (Head and Holmes, 1911; Semmes et al., 1960; Corkin movement. Sensations were evoked from the cortex et al., 1970; Roland, 1987a; Taylor and Jones, 1997). extending from the medial wall, where the foot is The spatial accuracy of motor movements is also represented, to the lateral fissure, where the mouth is impaired by the reduced sensory control (Aglioti represented. In general, the sensory order et al., 1996). However, the detection and crude locali- corresponds to the detailed maps compiled for zation of tactile stimuli remains intact. Roland monkeys (e.g., Nelson et al., 1980). Cortex devoted to (1987a) reported that lesions of the deep and anterior the foot and toes was most ventral on the medial wall. part of the hand region of postcentral cortex, presum- The back of the head and the neck were in medial ably including much but not all of the area 3b repre- cortex with the trunk representation, while the face sentation and probably the area 1 representation, was in lateral cortex separated from the head by the abolished the ability to discriminate edges from cortex devoted to the arm and hand. The digits were rounded surfaces, while lesions of the surface, appar- represented from little finger to thumb in ently involving areas 1 and 2, left the ability to distin- a mediolateral sequence. As for the area 1 guish edges from rounded surfaces, but removed the representation in macaque monkeys, the orbital skin ability to discriminate shapes and curvatures. This and the nose were represented just lateral to the difference is similar to that reported for monkeys thumb in humans. In monkeys and humans, the where lesions of areas 3b, 1, and 2 permanently abol- tongue and mouth are most lateral in the responsive ished the ability to distinguish the speed of moving cortex. Thus, the mediolateral sequence of tactile stimuli (Zainos et al., 1997), lesions of area 1 representation in the region of anterior area 1 appears impaired texture discriminations, and area 2 lesions to be quite similar in humans (Penfield and Boldrey, altered discrimination of shape (Randolph and 1937; note more detail and some differences in Semmes, 1974; Carlson, 1981;alsoseeLaMotte and summaries in Figures 30.7 and 30.8) and monkeys Mountcastle, 1979). Inactivation of the finger represen- (Nelson et al., 1980). Little can be said about tations in area 2 of monkeys led to a major deficit in sequences of change in the rostrocaudal direction, finger coordination while small food pieces were often however, because only microelectrode maps provide ignored after contact with inactivation of area 3b much detail about this direction in monkeys, and the (Hikosaka et al., 1985). Remarkably, small lesions of surface stimulation and recordings in humans may part of the hand representation result in no obvious involve amounts of tissue that are large relative to the impairment in humans (Evans, 1935; Roland, 1987a, narrow widths of the representations in areas 3b, 1, 1987b). Roland (1987a) estimated that a notable and 2. impairment resulted only after lesions involving 8. Some aspects of somatosensory organization have three-fourths or more of the hand region of anterior long been known from the order of progressions of parietal cortex. Furthermore, the larger the lesion of sensations or movements (“the Jacksonian march”) theregion,thegreatertheimpairment(Roland, during epileptic seizures. Because the seizure starts 1987b). The preservation of abilities after lesions to

VI. SYSTEMS SOMATOSENSORY CORTEX OF THE LATERAL (SYLVIAN) SULCUS INCLUDING INSULA 1095 parts of somatotopically organized representations could be the result of cortical reorganizations that result in the recovery of lost parts of representations. Removing part of a representation or deactivating part of a representation in monkeys can be followed by cortical reorganization, even in adults, so that remaining cortex is activated by skin formerly related to the damaged area, and deactivated cortex becomes responsive to alternative inputs (see Kaas and Florence, 2000,forareview).

SOMATOSENSORY CORTEX OF THE LATERAL (SYLVIAN) SULCUS INCLUDING INSULA

Much of the cortex of the upper bank of the lateral FIGURE 30. 9 A dorsolateral view of the brain showing proposed subdivisions of posterior parietal cortex in macaque monkeys. Areas sulcus and some of the cortex of the insula are somato- 5a, 5b, 7a, and 7b are traditional subdivisions from Brodmann (1909) sensory in function. Because of the general inaccessi- and Vogt and Vogt (1919). The ventral intraparietal region (VIP) and bility of this region in monkeys and humans, there the lateral intraparietal region (LIP) are subdivisions that have been have been relatively few attempts to reveal aspects of distinguished by visual and visuomotor connections (Maunsell and functional organization by stimulation or recording. Van Essen, 1983; Anderson et al., 1985). Other recently proposed fields include the medial (MIP) and the anterior (AIP) intraparietal region. However, there is clear evidence for the existence of The MIP region and adjoining cortex is also known as the parietal several functionally distinct areas from fMRI studies region (PRR). Alternative terms (e.g., PE for 5b) for posterior parietal (Eickhoff et al., 2008) that correspond to separate archi- and frontal motor cortex, based in part on von Economo (1929) are tectonic fields (Eickhoff et al., 2007). The lateral somato- from Rizzolatti and Matelli (2003). Frontal motor fields include the sensory cortex may be part of a critical corticolimbic supplementary motor area (SMA), dorsal (PMd) and ventral (PMv) premotor areas, and primary motor cortex (M1). See text for other pathway for the identification of objects by touch (see areas. Friedman et al., 1986), as monkeys have severe deficits in tactile memory after combined removal of the amyg- dala and hippocampus (Murray and Mishkin, 1984a). et al., 1995; Krubitzer et al., 1995; Disbrow et al., 2000). The pathways for inputs to these limbic structures S2 forms a systematic representation of the contralateral involve convergent inputs from areas 3a, 3b, 1, and 2 body surface on the upper bank of the lateral sulcus to areas of the upper bank of the lateral sulcus (Cusick with the face represented along the outer lip, the hand et al., 1989), and a relay from these areas over more deeper in the sulcus, and the foot near the fundus. A pari- rostral subdivisions of the somatosensory cortex in the etal ventral area (PV) forms a second representation of lateral sulcus (Figure 30.9). Because this lateral pathway the contralateral body surface just rostral to S2 (see Dis- is best understood in macaque monkeys, the organiza- brow et al., 2000, for review). S2 and PV adjoin along tion of lateral somatosensory cortex in these primates representations of the hand, and they form mirror-image is briefly reviewed. representations of each other. PV and S2 are bordered in the fundus of the lateral sulcus by a ventral somatosen- Organization of Cortex of the Lateral Sulcus in sory area (VS), which extends somewhat onto the lower Monkeys bank of the central sulcus and insula to border secondary auditory fields (Cusick et al., 1989; Krubitzer et al., 1995). Much progress has been made in recent years in More recent evidence suggests that VS actually includes understanding the traditional “SII” region (see below) separate rostral, VSr, VSc, and caudal representations, of the lateral somatosensory cortex in monkeys. The large one bordering PV and the other S2 (Qi et al., 2002; Coq “SII” region has now been divided into several areas. One et al., 2004). subdivision that has been repeatedly described is the S2 and PV receive feedforward inputs from all four second somatosensory area (S2), named because it was areas of anterior parietal cortex (Krubitzer and Kaas, the second representation after S1 discovered in cats 1990; Burton et al., 1995; Qi et al., 2002; Disbrow et al., and later in other mammals. S2 appears to border the 2003; Coq et al., 2004). Removing these areas deactivates lateral extension of areas 3b and/or areas 1 and 2 in S2 and PV (Pons et al., 1987; Burton et al., 1990; monkeys, according to species (see Pons et al., 1987; Garraghty et al., 1990b). Major inputs to S2 and PV Cusick et al., 1989; Krubitzer and Kaas, 1990; Burton from the ventroposterior inferior nucleus (Disbrow

VI. SYSTEMS 1096 30. SOMATOSENSORY SYSTEM et al., 2002) do not seem to be capable of independently receives inputs from cutaneous receptors. The anterior activating neurons in these areas. Neurons in both S2 insula includes a gustatory area or areas (Augustine, and PV respond to cutaneous stimulation within recep- 1996; Kaas et al., 2006). Thus, the cortex of the lateral tive fields that are generally larger than those in area sulcus, including the insula, has a number of somatosen- 3b or area 1. Inputs to S2 and PV from areas 3a and 2 sory and multisensory areas. undoubtedly provide some activation from deep recep- tors. Proprioceptive neurons seem to be concentrated Lateral and Insular Parietal Cortex in Humans anteriorly in PV and posteriorly in S2, away from cuta- neous representations of digit tips (Fitzgerald et al., There is increasing evidence that at least some of the 2004). Callosal connections from S2 and PV of the oppo- cortex in the lateral fissure of humans is organized much site hemisphere are particularly dense (Disbrow et al., as in monkeys. An fMRI study using tactile stimuli 2003), and some bilateral receptive fields have been applied to various body parts provides clear evidence reported, although ipsilateral stimuli largely modulate for both S2 and PV in humans. PV and S2 are organized activity based on contralateral receptive fields. Neurons as mirror-reversal images of each other, both proceeding in S2 and PVappear to code for stimulus features such as from face to forelimb to hindlimb from near the lip of the roughness (Pruett et al., 2000) and the orientation of upper bank to the depths of the lateral fissure (Disbrow edges (Fitzgerald et al., 2006). S2 and PV may be et al., 2000). Both S2 and PV demonstrate some increased involved in determinations of the sizes and shapes of activity with ipsilateral stimulation and more activity objects (Fitzgerald et al., 2006). Lesions of the PV-S2 with bilateral stimulation (Disbrow et al., 2001; Eickhoff region greatly impair the abilities of monkeys to make et al., 2008). tactile discriminations and identifications (Murray and Studies of the somatosensory cortex of the lateral Mishkin, 1984b). Ipsilateral cortical projections of PV sulcus in humans traditionally refer to a large “SII” and S2 include PR, , premotor cortex, region that includes S2, PV, and other areas. The term and posterior parietal cortex (Disbrow et al., 2003). S2 is used here to refer to a particular somatosensory Inputs to adjoining areas of lateral somatosensory cortex area with a somatotopy corresponding to that of SII of are relayed to perirhinal and entorhinal cortex early descriptions for a range of mammals. In humans, (Friedman et al., 1986). The processing series from ante- the SII region has been divided into four architectonic rior parietal to lateral parietal to perirhinal cortex and fields, parietal operculum (OP) areas 1, 2, 3, and 4 then to the hippocampus constitutes a proposed lateral (Eickhoff et al., 2006c, 2007). OP4 is thought to be coex- hierarchy of areas involved in the recognition and tensive with PV, OP1 with S2, and OP3 with much of memory of objects by touch (Mishkin, 1979; Murray VS. As VS in monkeys appears to be a composite of and Mishkin, 1984a; Friedman et al., 1986). two somatotopically organized areas, a more rostral Cortex caudal to S2 includes part of 7B that extends area, VSr and a more caudal area VSc (Coq et al., into the lateral sulcus, and the retroinsular area (Ri). 2004). OP3 may correspond to VSr and OP2 to VSc Neurons in both lateral 7B and Ri are responsive to cuta- (see Eickhoff et al., 2006a; Burton et al., 2008). All four neous stimuli (Krubitzer et al., 1995). Cortex caudal to fields are activated by tactile stimulation, and differ- VS on the lower bank of the lateral sulcus has neurons ences in activation occurred with the task (Eickhoff responsive to vision and somatosensory stimuli (Krubit- et al., 2006a; Burton et al., 2008), but differences in the zer et al., 1995). Cortex rostral to PV receives inputs from functional roles of the four areas are not well established PV and S2 and has been called the parietal rostral area, for humans or monkeys. In monkeys and humans, the PR (Krubitzer and Kaas, 1990; Krubitzer et al., 1995). parietal rostroventral area, PR, just anterior to PV, is acti- Cortex along VS on the lower bank of the lateral sulcus vated during body movements (Hinkley et al., 2007), contains primary auditory area and the medial belt of suggesting a role in manual exploration during object secondary auditory areas, including the caudal medial discrimination. Alternatively, cortex in the PR region area, CM, where neurons respond to both auditory may be responsive to visceral stimulation (Eickhoff and somatosensory stimuli, with somatosensory inputs et al., 2006b), and PR is in the region of the proposed coming from retroinsular (Ri) granular insular regions . Cortex caudal to S2 in area 7b is (Smiley et al., 2007). The more posterior portion of the another region responsive in humans to tactile stimula- insula in monkeys is a region of thalamocortical inputs tion of the hand. from VMpo relaying information concerned with pain, The insula of the cortex of the lateral sulcus is a large, temperature, and the well-being of the internal organs multisensory region of the human brain that has long (Craig et al., 2000; Craig, 2002). Part of the posterior been divided into a posterior granular region, with insula and the retrosplenial region (Ri) receives vestib- a well-developed layer 4 of granule cells, a more anterior ular information from the thalamus (Guldin et al., dysgranular region, and an anterior agranular region 1992; Guldin and Gru¨ sser, 1998). Insular cortex also (Augustine, 1996). Each of these regions is likely to

VI. SYSTEMS POSTERIOR PARIETAL CORTEX 1097 contain several functional areas. The posterior insula has (1931, 1936a) was able to produce hand movements been shown to be responsive to painful stimuli, temper- and leg movements on occasion with high levels of ature, auditory, and vestibular stimuli. Painful sensa- stimulating current. Posterior parietal cortex has been tions have been evoked by electrical stimulations from implicated in both somatosensory and visual functions the upper, posterior insula (Ostrowsky et al., 2002; Afif as well as in premotor planning, but lesions do not et al., 2008; also see Chapter 32). The posterior insula produce simple sensory impairments. Rather, large constitutes a multisensory region (Mazzola et al., 2006) lesions produce a variety of complex symptoms, many that possibly codes the magnitudes of sensory inputs included within the general category of contralateral (Baliki et al., 2009). The anterior insula appears to be sensory neglect or inattention. In monkeys, impairments more involved with motor functions via connections are basically the same regardless of the hemisphere of with frontal cortex. One proposed function is to allocate the lesion, but in humans, lesions of the right or “minor” attention and help select appropriate behaviors out of hemisphere produce a much more profound defect. alternatives (Eckert et al., 2009). Major reviews of posterior parietal cortex organization and function in monkeys and humans include those of Mountcastle (1975), Lynch (1980), Hyvarinen (1982), POSTERIOR PARIETAL CORTEX Yin and Medjbeur (1988), Andersen et al. (1997), Colby and Goldberg (1999), Fogassi and Luppino (2005) and Gardner (2008). Also, see Chapter 27 for connections of The posterior parietal region is an arbitrary subdivi- subdivisions of posterior parietal cortex with motor sion of the brain that includes most of the areas of the frontal lobe. caudal to area 2 but excludes the cortex of the lateral (Sylvian) fissure and the supplementary sensory area of the medial wall (Figure 30.10). Current investigators Posterior Parietal Cortex in Monkeys commonly refer to the architectonic subdivisions of Since posterior parietal cortex of all primates is a place Brodmann (1909) or von Economo (1929), and both where somatosensory information is combined with systems are in use. However, research on monkeys visual and auditory inputs in order to guide reaching, suggests that the proposed fields (areas 5a, 5b, 7a, and grasping, looking, and other behaviors via connections 7b or areas PE, PF, and PG) have little validity other with premotor and motor cortex (for review see Cohen than denoting general regions of the lobe. Other subdivi- and Andersen, 2002; Jeannerod and Farne, 2003), and sions have been suggested by patterns of connections posterior parietal cortex in macaque monkeys has and the response characteristics of neuronal popula- many features of functional organization in common tions, but the organization of posterior parietal cortex with posterior parietal cortex in humans, a brief review is not well understood. Electrical stimulation in humans of the results and conclusions from current studies of seldom produces any sensations or motor responses connections, neuron properties, and functional subdivi- (Penfield and Rasmussen, 1950), although Foerster sions in monkeys is useful. One current scheme for subdividing posterior pari- etal cortex in macaque monkeys is shown in Figure 30.9 (also see Preuss and Goldman Rakic, 1991; for an alter- native proposal see Seltzer and Pandya, 1980; Pandya and Seltzer, 1982). The scheme includes the traditional subdivisions of areas 5a, 5b, 7a, and 7b as introduced by Brodmann and the Vogts, with the addition of recently defined intraparietal areas.

Area 5a (PE) Area 5a is not uniform in histological structure, connections, and neuron types, but functional subdivi- sions have not yet been established. Subdivisions of FIGURE 30.10 Posterior parietal and lateral cortex of humans. anterior parietal cortex, especially area 2, provide direct The posterior parietal cortex has been variously subdivided by early somatosensory inputs from both deep and cutaneous investigators (for example, see Campbell, 1905; Smith, 1907; receptors (Pons and Kaas, 1986). Major thalamic inputs Brodmann, 1909; Vogt and Vogt, 1919, 1926; von Economo and are from the anterior pulvinar and the lateral posterior Koskinas, 1925). The subdivisions shown here reflect those of Vogt and Vogt, with the second somatosensory area (S2) and the parietal nucleus (see Yeterian and Pandya, 1985), nuclei without ventral area (PV) of the lateral sulcus added. Much of the region significant sensory inputs from the brainstem or spinal denoted here as 7b would be in Brodmann’s area 40. cord. However, a lateral portion of area 5 receives

VI. SYSTEMS 1098 30. SOMATOSENSORY SYSTEM some input from the ventroposterior nucleus (Pons and the superior temporal sulcus (Cavada and Goldman- Kaas, 1985). Cortical projections include those to area 7, Rakic, 1989; Lewis and Van Essen, 2000a). More recently, S2, motor and premotor cortex, limbic cortex, and parts Gregoriou et al. (2006) provided further architectonic of the superior temporal gyrus; callosal connections evidence for dividing 7b into an anterior half (PF) and are largely between matched regions of area 5 (see a posterior half (PFG), and provided evidence that PF Hyvarinen, 1982). Subcortical projections include projects densely to dorsal premotor cortex while PFG thalamic nuclei, the basal ganglia, the pontine nuclei, also projects to the frontal eye field. Neurons respond and the spinal cord through the pyramidal tract. Neuron to touching the skin, particularly on the head and face properties include those related to both cutaneous and in anterior 7b and the hand and arm in posterior 7b (Lei- deep receptors and to passive and especially active nonen, 1984; Krubitzer et al., 1995). limb movement (Iwamura and Tanaka, 1996). Neurons are preferentially activated during grasping movements. Area 7a (PG) Receptive fields for neurons in area 5a are generally Area 7a is related to visual and visuomotor activities. much larger than those in areas 1 and 2. Specific combi- The visual functions are reflected in both connection nations of positions in several joints may be the most patterns and neuron properties. Visual inputs include effective stimulus for many neurons (Hyvarinen, 1982). those from superior temporal cortex involved in pro- Many neurons in area 5a respond to ipsilateral as well cessing visual motion information (see Maunsell and as contralateral stimulation, with receptive fields that Van Essen, 1983). Other visual inputs are from adjacent include the digits of both , and sometimes extend dorsal portions of the pre-lunate gyrus (May and up onto the arm and even the trunk (Taoka et al., 1998). Andersen, 1986). Connections also include the cortex Some neurons have both somatosensory and visual of the intraparietal sulcus, cortex of the medial wall, receptive fields (Iriki et al., 1996), and visual stimuli prefrontal cortex, multimodal and visual areas of the may modulate proprioceptive activity. Some neurons superior temporal sulcus, cortex of the lateral sulcus in area 5a that were responsive to arm position when and especially dorsal premotor cortex (Cavada and the arm was covered from view responded better to Goldman-Rakic, 1989; Andersen et al., 1990; Gregoriou seeing the arm or even a fake arm in the correct position, et al., 2006). The cortical region just caudal to 7a (PG) but not better to a fake arm in the wrong position is even more involved in , and it (Graziano et al., 2000). Finally, ablation of cortex of the projects to cortex just anterior to dorsal premotor cortex. intraparietal sulcus including area 5a interferes with Other connections are with the medial pulvinar. Several the ability to orient the hand correctly in grasping classes of visual and visuomotor neurons have been (Denny-Brown and Chambers, 1958). Overall, the results described (see Hyvarinen, 1982). Visual tracking suggest that area 5a is involved in providing a mental neurons respond during the visual pursuit of targets. model of what the body is doing, and thereby guiding Another class of neurons is activated during fixation relevant behavior such as reaching for objects. on a moving or stationary visual target. Some neurons seem to be important to the visual guidance of reaching Area 5b (PEc) movements with the hand. Many neurons respond to Area 5b appears to be largely somatosensory in func- visual stimuli, but these neurons respond poorly to tion, despite its position near the . Major visual stimuli when monkeys are not attending and cortical inputs are from area 5a, while outputs include visual responses are suppressed when gaze and atten- adjoining parietal cortex of the medial wall and parts tion are directed to the stimulus (Steinmetz et al., of 7b as well as cortex caudal to S2 in the lateral fissure, 1994). The presence of neurons responding both to and dorsal premotor cortex (Pandya and Seltzer, 1982; visual stimuli and to visuomotor and reaching behavior Marconi et al., 2001). implicates areas 7a in guiding eye and hand movements.

Area 7b (PF and PFG) Areas of the Intraparietal Sulcus: AIP, LIP, CIP, Area 7b also appears to be involved in the higher- VIP, MIP, and PIP order processing of somatosensory information Cortex of the intraparietal sulcus is highly involved in (Andersen et al., 1997). Somatosensory inputs include sensorimotor functions. Specifically, this cortex is those from the anterior parietal cortex (Pons and Kaas, involved in forming of intentions and cognitive plans 1986), secondary somatosensory areas (Disbrow et al., for specific types of movements (Andersen and Buneo, 2003) and other parts of posterior parietal cortex. 2002). Different subregions or areas of the intraparietal Thalamic connections include the ventral lateral nucleus sulcus are involved in the planning of eye movements, and the anterior pulvinar. Cortical projections include grasping movements, reaching, and defensive forelimb pre-motor and prefrontal areas of the frontal lobe, and head movements. Sensory guidance is based on more caudal regions in posterior parietal cortex, and somatosensory, visual, and, to a lesser extent, auditory

VI. SYSTEMS POSTERIOR PARIETAL CORTEX 1099 inputs. Important outputs are to motor and premotor Newsome, 1996). Eye movements are evoked by electri- areas of the frontal lobe. The cortex of the intraparietal cal stimulation of neurons in LIP (Thier and Andersen, sulcus of macaque monkeys has been divided into 1998). Major projections are to the frontal eye fields, a number of areas (Figure 30.9). Along the lateral which are also concerned with eye movements (Huerta (caudal) bank of the sulcus, the anterior intraparietal et al., 1987; Bullier et al., 1996). Somatosensory inputs area, AIP (Sakata and Taira, 1994), the lateral intraparie- to LIP come from other areas of posterior parietal cortex tal area, LIP (Andersen et al., 1985), and the caudal inter- such as AIP. Responses to auditory signals for eye move- parietal area, CIP (Sakata and Taira, 1994) form ments are found in some neurons (Grunewald et al., a rostrocaudal sequence, with more rostral areas more 1999). Visual inputs come from the middle temporal dominated by somatosensory inputs, and more caudal visual area, MT, and other visual areas (Blatt et al., areas by more direct visual inputs (see Stepniewska 1990). Overall, LIP has been implicated in the planning et al., 2005). The fundus of the sulcus contains the of saccadic eye movements, spatial attention, decision ventral intraparietal area, VIP (Maunsel and Van Essen, making, and reward expectation (see Janssen et al., 1983). The medial (rostral) back of the sulcus starts with 2008). part of area 5a anteriorally, followed by the medial intra- VIP, in the depths of the intraparietal sulcus, adjoins parietal area, MIP (Eskandar and Assad, 1999), and the LIP. Most neurons respond to either visual stimuli or posterior parietal area, PIP (Sakata et al., 1998). The light touch (Duhamel et al., 1998). The area seems to MIP and PIP regions have been combined into a poste- contain matched representations of the body surface rior parietal reach region, PPR, by Cohen and Andersen and visual space. Small foveal visual receptive fields (2002). related to neurons with small tactile receptive fields on AIP, the most anterior area of the lateral bank of the the muzzle and larger peripheral visual receptive fields intraparietal sulcus, is important in planning and orga- were determined for neurons with larger receptive fields nizing grasping movements of the hand (Gallese et al., on the side of the head. VIP may have a crude somato- 1994; Rizzolatti et al., 1997). The area is adjacent to topic organization with nearly all of the area devoted part of area 5a on the medial bank of the sulcus that is to the head. Somatosensory inputs arise from areas 1 also involved in grasping (Iwamura and Tanaka, 1996; and 2, 5 and 7b, and S2 and nearby areas of the lateral Padberg et al., 2007). More lateral cortex in area 7b is sulcus (Lewis and Van Essen, 2000b). There also may also involved in grasping (Cohen and Andersen, 2002). be inputs from and auditory areas. A region similar to AIP in relative location, where Visual inputs are from visual areas of the dorsal stream grasping movements of the contralateral hand can be (especially the middle temporal visual area) and LIP. evoked by electrical stimulation with microelectrodes, Outputs include projections to the frontal eye field and has been identified in prosimian primates and New adjoining portions of the frontal lobe, as well as the World monkeys (Stepniewska et al., 2009a). AIP has ventral premotor area. Complex defensive movements, connections with adjoining areas of cortex, including including eye closure, facial grimacing, and movement area 5a, area 2, S2, and PV of the lateral sulcus. Visual of the hand to protect the head, can be evoked by electri- inputs include those from LIP, CIP, dorsal visual cortex, cally stimulating neurons in VIP with microelectrodes and inferior temporal cortex (Nakamura et al., 2001; (Cooke et al., 2003). VIP has been implicated in cross- Borra et al., 2008). Important outputs are to ventral pre- modal (sensory) attention, but a major role appears to motor cortex, a motor area also important in hand move- be in the use of sensory information to form a motor ment control (Luppino et al., 1999). Neurons in AIP plan to avoid harm via defensive movements. appear to code for hand movements that are specific to MIP and PIP function together as a larger posterior the perceived task (Baumann et al., 2009). Grasping parietal reach (PPR) region dedicated to the planning behavior is abnormal after the inactivation of AIP of reaching movements (Andersen and Buneo, 2002). (Gallese et al., 1994). Overall, AIP and adjoining regions This cortex receives inputs from dorsal stream visual of cortex are involved in grasping and manipulating areas and other parts of posterior parietal cortex, objects with the hand, and likely tool use in humans and projects especially to dorsal premotor cortex (Frey, 2008). (Blatt et al., 1990; Caminiti et al., 1998). Recent LIP, just caudal to AIP (Figure 30.9), is an area evidence suggests that neurons in PPR are not only primarily devoted to the planning of eye movements involved in forming plans for reaching, but also in (Andersen and Buneo, 2002), as well as a major source monitoring the course of the movement in order to of visual information about object shape and position correct errors and perform a successful reach to AIP (Janssen et al., 2008). Most neurons in LIP (Mulliken et al., 2008). respond to visual stimuli signaling an eye movement, Finally, CIP, on the caudal part of the lateral bank of and just before spontaneous eye movements to locations the intraparietal sulcus, appears to be largely involved within the neuron’s receptive field (Shandlen and in higher-order visual processing, and not in

VI. SYSTEMS 1100 30. SOMATOSENSORY SYSTEM somatosensory processing (see Tsutsui et al., 2003 for addition, corrections of reach to displaced targets review). CIP receives visual inputs from dorsal and during reach are impaired during posterior parietal ventral stream visual areas, has connections with other cortex inactivation with transcranial magnetic parts of posterior parietal cortex, and with prefrontal stimulation (Desmarget et al., 1999). cortex. Neurons are sensitive to object texture, orienta- 4. Lesions of the right or minor hemisphere may produce tion, and distance, and thus provide information that a defect in drawing even simple objects, such as could guide various motor behaviors via interactions a house, and in constructing simple models. with other areas of posterior parietal cortex. Furthermore, during constructional tasks, blood flow is increased in posterior parietal cortex (Roland et al., 1980). Blood flow also increases in the superior parietal Posterior Parietal Cortex Function in Humans cortex and intraparietal sulcus of humans performing Concepts of posterior parietal cortex function in mental rotations of the hand (Bonda et al., 1995, 1996b). 5. humans are largely derived from the much discussed Lesions, especially those involving the anterior half of behavioral changes that typically follow large lesions posterior parietal cortex, may produce (for reviews, see Critchley, 1949; Denney-Brown and somatosensory deficits. Reported changes include Chambers, 1958; Mesulam, 1981, 1983; DeRenzi, 1982: impairment in length discrimination, weight Hyvarinen, 1982; see Chapter 28 for architecture). In judgment, shape discrimination, and limb position brief, patients with posterior parietal lobe tend sense (see Hyvarinen, 1982). 6. to neglect visual and tactile information coming from Difficulties may exist in performing symbolic visual space or the body surface opposite the lesion gestures and pantomimes. This is attributed to an (see Moscovitch and Behrmann, 1994; Pouget and inability to access or store representations of Driver, 2000). The defect is most severe after lesions of movements adequately. the right hemisphere that is non-dominant for language. The defect may be profound, leading to bizarre symp- Even though posterior parietal cortex is not uniform toms, or it may be quite mild, resulting in little notable in function, much of the region appears to relate to pre- change in spontaneous behavior. Mild defects are typi- motor planning in relation to eye movements and reach. cally revealed by bilateral stimulation. The expected Clearly, the anterior part of posterior parietal cortex is result is that the ipsilateral stimulus is preferentially more related to the somatosensory system, and the attended, either immediately or after a series of trials. posterior part is more related to the . The In more dramatic cases, there is a denial of the existence connections of posterior parietal cortex suggest that of the contralateral (typically left) side of the body and of a motivational component depends on relationships objects in the left side of the visual space. Patients may with limbic cortex of the medial wall and perhaps the fail to shave or dress the neglected side, and food on ventral temporal lobe (see Mesulam, 1981). Connections the contralateral side of the plate may be uneaten. The with the frontal lobe and connections with subcortical defect can be characterized as a change in attention, motor structures such as the superior colliculus and because it is clearly not a result of a sensory impairment. basal ganglia undoubtedly are important in initiating More specifically, a unique aspect of the impairment behavior. More specifically, Mountcastle (1975) hypothe- seems to be a difficulty in the ability to disengage atten- sized that posterior parietal cortex functions as tion from a current focus and move that attention to a “command” center for body movements. Finally, the a new focus in the contralateral world (Posner et al., functional asymmetry of posterior parietal cortex in 1984). Right-hemisphere damage produces a reluctance humans can be explained if the right hemisphere or inability to redirect attention from the right visual contains the neural substrate for attending to both sides field to the left visual field, as well as a reluctance to shift of space, though predominantly contralateral space, attention within the left visual field (Baynes et al., 1986). while the left hemisphere is almost exclusively con- Other defects also occur (see Sirigu et al., 1996). cerned with contralateral space (Mesulam, 1981). Thus, unilateral lesions of the left hemisphere are partially 1. Errors may exist in localizing objects so that accurate compensated by the functions of the right hemisphere, pointing does not occur. Right and left may be but the reverse does not hold. This difference may relate confused, and the patient may have difficulty in to the specialization of the left hemisphere for language. moving from place to place. As posterior parietal cortex is a large region, even in 2. Eye movement patterns are altered, and a reduction proportion to the rest of the brain, in humans, it is in spontaneous eye movements and tracking unlikely that all functional subdivisions found in movements may occur. humans are also present in monkeys. Comparative 3. Errors in reaching into the contralateral hemifield are studies suggest that at least some of the intraparietal common. Targets may be missed by several inches. In areas of monkeys have been retained in humans, likely

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VI. SYSTEMS