The Perirhinal, Entorhinal, and Parahippocampal Cortices and 1 9 Hippocampus: An Overview of Functional Anatomy and Protocol for Their Segmentation in MR Images Sasa L. Kivisaari, Alphonse Probst, and Kirsten I. Taylor Abbreviations fi Fimbria gA Gyrus ambiens A Anterior gS Gyrus of Schwalbe Ab Angular bundle (PHg white matter) HB Hippocampal body aCf Anterior calcarine fi ssure Hf Hippocampal fi ssure al Alveus HH Hippocampal head Am Amygdala Hs Hippocampal sulcus bG Band of Giacomini HT Hippocampal tail cf Crus of the fornix I Inferior Cs Collateral sulcus ILg Intralimbic gyrus di Hippocampal digitations Is Isthmus ERc Entorhinal cortex ITg Inferotemporal gyrus Fg Fusiform gyrus L Laterial Lg Lingual gyrus li-gm Limen insulae gray matter S. L. Kivisaari , Ph.D. (*) li-wm Limen insulae white matter Department of Geriatrics , M Medial Memory Clinic, University Hospital Basel , Schanzenstrasse 55, CH-4031 , Basel , Switzerland Mb Mammillary body e-mail: [email protected] MTL Medial temporal lobe A. Probst , M.D. OTs Occipitotemporal sulcus Department of Geriatrics , P Posterior Memory Clinic, University Hospital Basel , Pu Pulvinar Schanzenstrasse 55, CH-4031 , Basel , Switzerland PHc Parahippocampal cortex Department of Neuropathology , PHg Parahippocampal gyrus University Hospital Basel , PRc Perirhinal cortex Schönbeinstrasse 40, CH-4031 , Basel , Switzerland e-mail: [email protected] qgc Quadrigeminal cistern Rs Rhinal sulcus K. I. Taylor , Ph.D. Department of Geriatrics , S Superior Memory Clinic, University Hospital Basel , SAs Semiannular sulcus Schanzenstrasse 55, CH-4031 , Basel , Switzerland SLg Semilunar gyrus Department of Experimental Psychology , Sp Splenium Centre for Speech Language and the Brain, su Subiculum University of Cambridge , TLV Temporal horn of lateral ventricle Downing Street, Cambridge , CB2 3EB , UK e-mail: [email protected] TP Temporal pole S. Ulmer, O. Jansen (eds.), fMRI – Basics and Clinical Applications, 239 DOI 10.1007/978-3-642-34342-1_19, © Springer-Verlag Berlin Heidelberg 2013 240 S.L. Kivisaari et al. TR Transentorhinal cortex identi fi cation of these regions on structural brain U Uncus imaging scans. Indeed, many of the controversies Ug Uncinate gyrus in current human neuropsychological research un Uncal notch may stem from inadequate control of lesion extent and location, as noted by Squire and Wixted: “The importance of thorough neuroanatomical 19.1 Introduction measurement in neuropsychological studies of memory cannot be overstated. Many current dis- Medial temporal lobe (MTL) damage severely agreements about the facts and ideas emerging disrupts our ability to form new memories from neuropsychological research on human (Scoville and Milner 1957 ) . Indeed, memory memory can be traced to concerns about the locus dysfunction is the hallmark of Alzheimer’s dis- and extent of lesions. […] There is no substitute ease (AD; e.g., Salmon 2011 ) , a progressive neu- for thorough, quantitative descriptions of damage rodegenerative disorder which begins in and most based on magnetic resonance imaging, as well as prominently affects the MTL region (Braak and (where possible) detailed neurohistological Braak 1991 ) . Accordingly, the classical model of description of the postmortem brain” (Squire and memory claims that the MTL functions as a sin- Wixted 2011 , p. 268). The identi fi cation of MTL gle system subserving memory formation, and subregions is challenging because of the uncer- not other kinds of cognitive processes (Squire tainty or obscurity of anatomical landmarks, a and Zola-Morgan 1988 ; Squire and Zola 1998 ; dif fi culty compounded by the fact that some MTL Squire and Wixted 2011 ) . gyri and sulci are interindividually highly vari- Converging evidence from animal and human able. A third section therefore describes the gross cognitive neuroscience research suggests a more anatomy of the MTL and, building upon previous differentiated picture, one of functional diversity seminal work of especially Insausti and colleagues in the MTL subregions (e.g., Lee et al. 2005 ; (Insausti et al. 1998 ) , presents a method for delin- Davachi 2006 ) . Thus, in addition to supporting eating the PRc, ERc, PHc, and the hippocampus the formation of memories, each MTL subregion proper on structural MR images (see also Watson may also perform other speci fi c functions. A fi rst et al. 1992 ; Insausti et al. 1998 ; Pruessner et al. section brie fl y describes the putative specialized 2000 ; Van Hoesen et al. 2000 ; Vogt et al. 2006 ; functional roles of the MTL subregions, namely, Malykhin et al. 2007 ; Taylor and Probst 2008 ; the perirhinal cortex (PRc; Broadmann areas Van Hoesen 1995 ) . [BA] 35/36), entorhinal cortex (ERc; BA 28/34), the posteriorly situated parahippocampal cortex (PHc; BA 36; also known as posterior parahip- 19.2 Functional Neuroanatomy pocampal cortex), and the hippocampus proper, of the MTL highlighting recent fi ndings from animal and human cognitive neuroscience research. The MTL has been irrevocably linked with the The functional neuroanatomy of the MTL, formation of long-term memory traces since including but not limited to the domain of mem- Scoville and Milner’s (Scoville and Milner 1957 ) ory, has implications for the clinical interpreta- description of the patient H.M., who became tion of circumscribed MTL lesions as well as the severely amnesic following an experimental bilat- interpretation of functional impairments in eral MTL resection to treat his intractable epi- patients with neurodegenerative disorders, most lepsy. H.M.’s surgical lesion included the notably AD. A second section therefore describes intraventricular portions of the bilateral hip- the neuropsychology of the early AD syndrome pocampi (see Fig. 19.7 ), the amygdalae, and the including amnestic mild cognitive impairment medial temporal poles and extended laterally to (aMCI; Winblad et al. 2004 ) . the ERc, with relative sparing of the PRc and PHc The prerequisite for advancements in this (Corkin et al. 1997 ) . Following the procedure, important area of research is the valid and reliable H.M. suffered from a persistent and profound 19 The Perirhinal, Entorhinal, and Parahippocampal Cortices and Hippocampus 241 anterograde amnesia , that is, an inability to of the hippocampus, parahippocampal gyrus, and remember events occurring after the operation, amygdala were associated with severe recogni- and a temporally graded retrograde amnesia , that tion memory impairments with otherwise appar- is, dif fi culty remembering events that occurred ently preserved cognitive functions (Mahut et al. within the 11 years preceding the MTL resection. 1982 ; Mishkin 1978 ) . More speci fi c ablation He also suffered from partial anosmia, a lack of studies re fi ned these early results by demonstrat- initiative and emotional bluntness (Corkin 1984 ) . ing that lesions restricted to the hippocampus Strikingly, H.M.’s intellectual functions were rel- (Mahut et al. 1982 ; Zola-Morgan et al. 1989a ; but atively preserved, as were other forms of memory see also Murray and Mishkin 1998 ) or to the such as perceptual and motor skill learning, prim- parahippocampal gyrus (Zola-Morgan et al. ing, habit formation, working memory, and mem- 1989c ; Meunier et al. 1993 ) , but not amygdala ories for facts, events, and verbal semantic (Zola-Morgan et al. 1989b ) or mammillary bod- memories remote from his surgery (Corkin 1984 ) . ies (Aggleton and Mishkin 1985 ) , were suf fi cient These functions enabled him to perform normally to produce a severe recognition memory disorder. in many tasks including his avid crossword puzzle Moreover, the effects of lesions to different sub- hobby (Skotko et al. 2008 ) . regions appeared to be additive, and the most Cases such as H.M. were remarkable on many severe recognition memory impairment was mea- fronts. Most importantly, they demonstrated that sured following PRc lesions (Meunier et al. 1993 ; memory indeed had a circumscribed anatomic Zola-Morgan et al. 1989b ) . Drawing on these basis in the MTL ( cf. Lashley 1929 ) . 1 It became seminal experiments, Squire and colleagues clear that the type of memory typically affected developed the classical, single-process model of in the MTL amnesia syndrome was the acquisi- human memory functioning, which posited that tion of declarative memories, that is, explicit the MTL subregions represent a single memory memories of events from an individual’s autobi- system in which each area is critical for forming ography (episodic memory) and for facts and declarative memories but do not participate in world knowledge (semantic memory), all of other cognitive functions (Zola-Morgan et al. which are available to conscious awareness. The 1986 ; Squire and Zola-Morgan 1988 ; Squire and case of H.M. also sparked intensive work on Zola 1998 ; Squire and Wixted 2011 ) . This classi- rodents and nonhuman primates. The strategy cal, single-process model of MTL function has used in this research was to ablate cytoarchitec- remained highly in fl uential. tonically distinct regions of the MTL and mea- The fi eld of MTL research has since bur- sure ensuing memory performance, research geoned and now uses multimodal imaging meth- which critically relied on the delayed (non) ods with increasingly more detailed cognitive matching-to-sample recognition memory para- paradigms to study multidimensional aspects digm. 2 This work led to the development of an of MTL functioning. This work has led many animal model of amnesia where bilateral lesions authors to reconceptualize the MTL as