A multisensory perspective onto primate pulvinar functions Mathilda Froesel, Céline Cappe, Suliann Ben Hamed

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Mathilda Froesel, Céline Cappe, Suliann Ben Hamed. A multisensory perspective onto primate pulv- inar functions. Neuroscience & Biobehavioral Reviews, Oxford: Elsevier Ltd., 2021, 125, pp.231-243. ￿10.1016/j.neubiorev.2021.02.043￿. ￿hal-03219659￿

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A multisensory perspective onto primate pulvinar functions

Mathilda Froesel a,*, C´eline Cappe b, Suliann Ben Hamed a,* a Institut des Sciences Cognitives Marc Jeannerod, CNRS UMR 5229, Universit´e Claude Bernard Lyon I, 67 Boulevard Pinel, 69675, Bron Cedex, France b Centre de Recherche Cerveau et Cognition, Universit´e Paul Sabatier, Universit´e de Toulouse, 31062, Toulouse Cedex 9, France

ARTICLE INFO ABSTRACT

Keywords: Perception in ambiguous environments relies on the combination of sensory information from various sources. Pulvinar Most associative and primary sensory cortical areas are involved in this multisensory active integration process. Cortex As a result, the entire cortex appears as heavily multisensory. In this review, we focus on the contribution of the Multisensory pulvinar to multisensory integration. This subcortical thalamic nucleus plays a central role in visual detection Visual and selection at a fast time scale, as well as in the regulation of visual processes, at a much slower time scale. Auditory Somatosensory However, the pulvinar is also densely connected to cortical areas involved in multisensory integration. In spite of Anatomy this, little is known about its multisensory properties and its contribution to multisensory perception. Here, we fMRI review the anatomical and functional organization of multisensory input to the pulvinar. We describe how visual, auditory, somatosensory, pain, proprioceptive and olfactory projections are differentially organized across the main subdivisions of the pulvinar and we show that topography is central to the organization of this complex nucleus. We propose that the pulvinar combines multiple sources of sensory information to enhance fast re­ sponses to the environment, while also playing the role of a general regulation hub for adaptive and flexible cognition.

1. Introduction Though the activity of these sensory areas are dominated by one sensory modality, there is now ample evidence that they are modulated Vision is the dominant sensory modality in both humans and by other sensory modalities, including at the earliest processing levels nonhuman primates. Up to 50 % of identified non-human primate (Brosch et al., 2005; Calvert et al., 1999; Cl´ery et al., 2015a; Foxe et al., functional areas are involved in visual processing (20–30 % in the 2000; Ghazanfar et al., 2005; Giard and Peronnet, 1999; Guipponi et al., humans, (Van Essen and Drury, 1997; Van Essen, 2003)). As a result, 2015; Kayser et al., 2008; von Kriegstein et al., 2005; Lakatos et al., vision is still to date the most studied sensory system. This contrasts with 2007; Molholm et al., 2002). For example, neuronal activity in the pri­ the rising view that perception and brain functions are intrinsically mary visual cortex is modulated by auditory (Wang et al., 2008) as well multisensory (Schroeder and Foxe, 2005). For example, audition, touch as by tactile stimulations (Guipponi et al., 2015). At the anatomical and proprioception play a crucial role in the sensory-motor exploration level, direct projections between early sensory areas have been of the world. Likewise, audition, olfaction and touch are essential to described, between the somatosensory and visual cortex (Cappe et al., social interactions and communication. These different sensory modal­ 2012, 2009a; Cappe and Barone, 2005). At higher cortical levels, in the ities have very similar anatomical organizational principles in the brain: associative cortices, multisensory convergence and integration is the incoming sensory information from the distal sensory receptors are rule (Noesselt et al., 2007; Werner and Noppeney, 2010; Calvert, 2001; transduced into a neuronal code and reach the cortex through special­ Bremmer et al., 2001; Miller and D’Esposito, 2005; Avillac et al., 2007; ized primary sensory cortical areas (Fig. 1, colored cortex, Van Essen Guipponi et al., 2013), to the degree that the entire brain is often et al., 1990; Carmichael et al., 1994; Camalier et al., 2012). From there, considered as of multisensory nature (Cl´ery et al., 2018a, 2015a; Clery´ this sensory information runs through a sequence of reciprocally con­ and Ben Hamed, 2018; Driver and Noesselt, 2008; Ghazanfar and nected cortical regions, organized along a hierarchical pattern, pro­ Schroeder, 2006; Schroeder and Foxe, 2005). Most of these associative gressively describing the incoming sensory information at higher levels multisensory areas have direct projections to and from early sensory of complexity (Fig. 1, associative cortices). areas. For example, superior temporal polysensory area (STP), activated

* Corresponding authors. E-mail addresses: [email protected] (M. Froesel), [email protected] (S. Ben Hamed). https://doi.org/10.1016/j.neubiorev.2021.02.043 Received 6 March 2020; Received in revised form 18 February 2021; Accepted 25 February 2021 Available online 1 March 2021 0149-7634/© 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license

(http://creativecommons.org/licenses/by-nc-nd/4.0/). M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243

projections (Rouiller and Welker, 2000; Sherman, 2007). Based on these highly complex cortico-pulvino-cortical connectivity patterns, the pulvinar is proposed to play a key role as a mediator/modulator between cortical areas (Benarroch, 2015; Saalmann and Kastner, 2011). In the following, we specifically focus onto the primate pulvinar, which is classically divided in three large distinct regions, based on their specific cytoarchitectonic properties: the lateral, the medial and the inferior pulvinar (Fig. 2, Walker, 1938; Olszewski, 1952; Gutierrez et al., 1995; Stepniewska and Kaas, 1997). The organization of the primate pulvinar complex and its connectivity with the cortex has undergone substantial changes during primate evolution (Kaas and Baldwin, 2020). Specifically,while the visual inferior and ventro-lateral pulvinar nuclei are well preserved across primates, the medial pulvinar is considered as fully identifiableonly in the haplorhini primate suborder (Baldwin et al., 2017; Homman-Ludiye and Bourne, 2019), but not in the non-haplorhini primates such as the galagos or the lemurs. The rodent and carnivore Fig. 1. Organization of main sensory input to the primate brain,visual in homologues of the pulvinar can be defined based on the observed pink, somatosensory in purple and auditory in green. These cortices are pattern of projections of the superficial layers of the superior colliculus dominated by responses to one sensory modality and are reciprocally connected or optic tectum to the primate pulvinar (Zhou et al., 2017). In spite of the to the rest of the cortex in so called-associative areas, i.e. areas associating or integrating together multiple sensory inputs. fact that pulvinar lesions in these latter mammalian phylogenetic orders do not exhibit the same visual deficitsas in primates, a certain functional and cortical connectivity pattern homology can be noted between the by both auditory and somatosensory information, has direct projections lateral-posterior pulvinar complex of rodents and carnivores and the to primary visual area V1 (Clavagnier et al., 2004). In addition, they are primate inferior and ventro-lateral pulvinar nuclei (Kaas and Baldwin, characterized by specific laminar and connectional patterns with 2020). No homologue for the medial primate pulvinar can be identified cortical and subcortical structures (Foxworthy et al., 2013). in rodents and carnivores as is the case for non-haplorhini primates (Kaas Overall, multisensory integration thus involves complex patterns of and Baldwin, 2020). multisensory interactions i) within associative areas, ii) between distant While the contribution of the pulvinar to visual cognition has been associative areas, iii) between associative areas and early sensory extensively studied including during development (Benarroch, 2015; cortices, iv) within early sensory cortices and v) between distant early Bourne and Morrone, 2017; Bridge et al., 2016), we will here focus onto sensory cortices. All sensory information reaches the neocortex through its contribution to multisensory processes and its interactions with the the thalamus and the superior colliculus. In turn, both these subcortical multisensory cortex (Cappe et al., 2009b; Tyll et al., 2011). Indeed, and structures receive sensory input from the cortex and from each other. quite surprisingly, in spite of its reciprocal connections with both uni­ The pulvinar, the largest and most posterior thalamic nucleus, also has, sensory and multisensory cortical regions, the primate multisensory as detailed below, strong feedforward and feedback connections with pulvinar functions are still by and large unknown. Here, we provide an the cortex as well as with the superior colliculus (Benevento and exhaustive review of the contribution of the primate pulvinar to the Standage, 1983; Lin and Kaas, 1979; Meredith et al., 1987; Meredith and processing of multisensory information, we identify the current knowl­ Stein, 1986; Stein and Meredith, 1993; Wallace et al., 1998, 1993). The edge gaps and we propose a novel ecologically anchored perspective pulvinar is thus expected to play a key role in multisensory integration. onto primate pulvinar functions. We will first review the anatomical However, and quite surprisingly, very little is known about the multi­ organization of the multisensory pulvinar and its connectivity pattern sensory organization and properties of this subcortical structure. In the with the cortex. We will then revisit lesion studies beyond the commonly following, we review current knowledge about the contribution of the described visual deficits to include evidence for other categories of pulvinar to multisensory processes and multisensory cortico-subcortical sensory deficits. We will next review the multisensory functions of the interactions, and identify current knowledge gaps thereof. pulvinar, highlighting the challenge of matching these functional The pulvinar is a subcortical thalamic nucleus that has first been multisensory properties with the current anatomical knowledge of the described as an early sensory relay between incoming sensory infor­ multisensory pulvinar. We will review the sparse evidence for multi­ mation and the cortex (to the exception of olfactory stimuli). It is the sensory integration in the pulvinar. We will then describe the role of the largest thalamic nucleus, located medial and dorsal to the lateral pulvinar in sensory detection and selection and as a behavioral and geniculate nucleus (LGN), in the most posterior aspect of the thalamus. processing regulator, i.e. in two distinct functions operating at very Most relevant to the present review, most cortical regions have recip­ different time scales, an ultra-fast and a slow time scale respectively. We rocal connections with the pulvinar, including early visual, somatosen­ will conclude, proposing to generalize the role of the pulvinar in sory and auditory processing areas as well as higher order parietal, detection and selection on the one hand and emotional and attention temporal, premotor and prefrontal associative areas that are known to regulation on the other hand, from the visual domain to the multisen­ be highly multisensory (Asanuma et al., 1985; Cappe et al., 2009a,b; Leh sory context thus shifting from a view of the pulvinar as a modulator of et al., 2008). It is actually proposed that for each direct cortico-cortical the visual system, to the view of the pulvinar as a general regulation hub pathway (e.g. between the parietal and the prefrontal cortex), there for adaptive, flexible cognition and survival. exists an indirect cortico-pulvino-cortical pathway (e.g. parieto-pulvino-prefrontal pathway). This hypothesis, called the repli­ 2. Anatomical evidence for multiple parallel cortico-pulvinar cation principal, thus proposes a topographical organization of the con­ sensory pathways nections of the pulvinar with the cortex matching cortical organization (Shipp, 2003). The pulvinar is described as a high order thalamic nu­ Seminal and more recent studies have sought to characterize the cleus due to the multiple reciprocal pulvino-cortical pathways it is connectivity patterns of the pulvinar with the neocortex. These con­ involved in (Sherman and Guillery, 2006) and its characteristic synaptic nectivity patterns are summarized below. All connections are reciprocal, organization. Specifically, small synaptic terminals (<1 μm) are typical unless mentioned otherwise. Pulvino-cortical connections are discussed of (feedback) cortico-thalamic projections, while giant synaptic termi­ in relation with the major nuclei, and when possible in relation to their nals, fewer in number, are typical of (feedforward) thalamo-cortical anatomical subdivisions. Indeed, these major pulvinar nuclei can be

232 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243

Fig. 2. Organization of main pulvino-cortical identified anatomical connections.A/ Left panel identifies connections between the cortex and the inferior pulvinar, middle panel identifies connections between the cortex and the lateral pulvinar, and right panel identifies connections between the cortex and the medial pulvinar. Visual inputs are in shades of red, auditory inputs in green, somatosensory inputs in blue and multisensory inputs in purple. Smaller brain insets represent the general pulvino-cortical connectivity gradients for each of the main pulvinar nuclei. B/ Left panel identifies connections between subcortical structures and the inferior pulvinar, middle panel identifies connections between subcortical structures and the lateral pulvinar visual, and right panel identifies connections between subcortical structures and the medial pulvinar. Connections with superior colliculus (SC), lateral geniculate nuclei (LGN) and retina are in black. Connections with the amygdala in gray. C/ Global representation of pulvinar connectivity gradient with the cortex. Red indicates dominant PI and PLvl connectivity, orange, dominant PM and PLdm connectivity and yellow, dominant PM connectivity. Note that this structural general connectivity gradient matches the reported functional gradient. divided in smaller anatomical units, based on their cytoarchitectonic connected with extrastriate dorsal visual stream areas such as MT (V5) organization. It is important to note that no direct connections between (Adams et al., 2000; Mundinano et al., 2019; O’Brien et al., 2001; the left and right pulvinar are reported. Relevant to human pulvinar Warner et al., 2010) and MST (Baleydier and Morel, 1992; Kaas and functions, a certain degree of lateralization is described. Lyon, 2007). It is worth noting that these projections to MT are topo­ graphically organized (Mundinano et al., 2019). PI, and specifically its 2.1. The inferior pulvinar (PI, Fig. 2A and B, left panel) subparts PIp and PIcm, also has dense connections with extrastriate ventral visual stream areas such as V4 (Adams et al., 2000; O’Brien et al., From a cytoarchitectonic, myeloarchitectonic and chemo­ 2001; Warner et al., 2010), FST (Baleydier and Morel, 1992; Kaas and architectonic point of view, PI is non-homogenous and can be sub­ Lyon, 2007) and TEO (Baizer et al., 1993; Webster et al., 1993; Weller divided into three further distinct regions, PIc (central, 70 % of PI), PIm and Steele, 1992). The connectivity between PI and FST is worth high­ (medial, 20 %) and PIp (posterior, 10 %) that are encapsulated by fibers lighting. Indeed, FST neurons are responsive to all of visual, auditory (Lin and Kaas, 1979) and characterized thanks to Nissl, myelin, cyto­ and somatosensory stimulations and is thus massively multisensory. PI is chrome oxidase (CO), acetylcholinesterase (AChE), calbindin-D28 K also connected with primary auditory cortex A1 (Kaas and Lyon, 2007) (Cb) and monoclonal antibody Cat-301 staining. PIp is dark in Cd and as well as to higher order caudal STG and to the rostral belts of the expresses AChE and CO. There is a strong expression of AChE and CO auditory cortex cAC and rAC (Gutierrez et al., 2000). To our knowledge, and to a lesser extent Cb in PIm. Based on these staining protocols, PIc there is no evidence for a functional connectivity between this cortical shows a complex cellular organization that leads to its further subdivi­ region and primary somatosensory, proprioceptive or olfactory cortices. sion as follows: PIcm, characterized by a strong Cb but light CO and AChe staining; and PIcl, characterized by a strong CO and AChE staining 2.2. The lateral pulvinar (PL, Fig. 2A and B, middle panel) and only few Cb responsive neurons (Gray et al., 1999; Gutierrez et al., 2000, 1995; Stepniewska and Kaas, 1997). In terms of cortical connec­ From a cytoarchitectonic point of view, PL can be distinguished by its tivity, PIm and PIc are densely connected with the visual system. In dense fiberbundles as well as by its cellular non-homogeneity. It can be particular, PIcm receives direct inputs from the retina through the subdivided into two further distinct regions, PLdm (dorso-medial) and thalamic lateral geniculate body (Adams et al., 2000; O’Brien et al., PLvl (ventral) characterized respectively by Cb-dark large neurons and 2001; Warner et al., 2010). PIp is densely connected with the superior PIcl-like Cb patterns (Gutierrez et al., 1995; Stepniewska and Kaas, colliculus (SC) as well as PIcm (Elorette et al., 2018; Huerta and Harting, 1997). Similarly to PI, PLvl is connected with the primary and secondary 1983; Lin and Kaas, 1979; Stepniewska et al., 2000). PI has reciprocal visual areas V1 and V2 (Benevento and Davis, 1977; Adams et al., 2000), connections with the primary visual area V1 and the secondary visual as well as with the superior colliculus (SC) (Benevento and Standage, area V2 (Benevento and Davis, 1977). PI and more so PIm, is also 1983; Lin and Kaas, 1979). PLdm is also connected with SC (Benevento

233 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243 and Fallon, 1975; Elorette et al., 2018; Huerta and Harting, 1983). PL is 1980). These SC projection pulvinar neurons project back to the lateral further connected with several visual ventral stream areas. Specifically, amygdala (Elorette et al., 2018) and predominantly originate from the PLvl is connected with V4 and TEO (Benevento and Rezak, 1976) while deep/intermediate SC layers (Benevento and Standage, 1983; Elorette PLdm is connected with temporal areas TEO and TE (Adams et al., 2000; et al., 2018). It is to be noted that this connectivity of SC with PM is Shipp, 2003; Webster et al., 1993). This connectivity pattern is very debated (Baldwin et al., 2017; Zhou et al., 2017). However, the similar to the one described for PI. PL is also specificallyconnected with discrepancy in the experimental observations may come from the dorsal visual stream. These connections are specific of PLdm which inter-species differences (Baldwin et al., 2013). Globally speaking, PM is has dense connections with the posterior parietal and temporo-parietal the thalamic nucleus that presents the densest thalamocortical pro­ cortex, including with areas MT, MST, LIP, VIP, MIP and AIP (Adams jections to auditory and premotor cortex (Cappe et al., 2009a). et al., 2000; Shipp, 2003; Webster et al., 1993). While these cortical Thus, overall, although the pulvinar has globally dense connections regions have strong visual functions, they also play a key role in with the striate and extrastriate visual cortex, a general multisensory visuo-oculomotor coordination (LIP), reaching (MIP), grasping (AIP), or pattern can be identified. Namely, the inferior pulvinar can be seen as self-movement perception (VIP), as well as in somatosensation (VIP) and being mainly interconnected to early visual areas and auditory circuitry, proprioception (MIP, AIP). PLdm is also densely connected with superior the lateral pulvinar as being mainly interconnected to extrastriate visual parietal areas PE and PEa which are involved in all of visual, somato­ areas and somatosensory circuitry, and the dorsal, medial pulvinar as sensory and proprioceptive functions. This cortical region is also densely being interconnected to all cortical areas, in particular the fronto- connected to the dorsolateral prefrontal cortex, as well as to the dorsal parietal circuitry (hence its role in sensory-motor transformation and (PMd) and ventral (PMv) premotor cortices (Asanuma et al., 1985; eye-hand coordination) –insets in Fig. 2A. This thus defines a ventro- Baizer et al., 1993; Clower et al., 2001; Gutierrez et al., 2000; Hardy and dorsal/postero-anterior projection gradient from PI, to PL to PM Lynch, 1992) thus defining a (or multiple) pulvino-parieto-prefrontal (Fig. 2C) coarsely matching the functional pulvinar gradients discussed functional network(s). These strong parietal and prefrontal connec­ below. However, at closer inspection, more complex pulvino-cortical tions suggest that PLdm is functionally distinct from PLvl, but quite connectivity patterns can be identified (as described above and in similar to the medial pulvinar (PM) discussed next. This is further dis­ Fig. 2A). This matches the complexity of the contribution of the pulvinar cussed in the section entitled dorso-ventral functional gradient in the to multisensory cognition, as described in the lesional and functional pulvinar below. studies described next.

2.3. The medial pulvinar (PM, Fig. 2A and B, right panel) 3. Clinical evidence for non-visual sensory pulvinar functions

From a structural point of view, PM lacks the fiberbundles seen in PL, In spite of these neuro-anatomical evidence for a multisensory role of and has a higher density of cells that are characterized by a rounder the pulvinar, from a functional point of view, primate pulvinar is clas­ shape than in PL. It is also non-homogenous and can be subdivided into sically considered as a highly visual and attentional structure. This is due two further distinct regions, PMl (lateral) and PMm (medial) charac­ to the fact that subcortical lesions including the pulvinar often lead to terized by a difference in AChE staining (Gutierrez et al., 2000; Step­ hemineglect symptoms, that is to say an absence of conscious processing niewska and Kaas, 1997). PMl is strongly interconnected with the of the contralateral visual hemifield, as well as a disruption of spatial ventrolateral part of the LGN, the retina (Itaya and Van Hoesen, 1983), and temporal visual attention (Rafal and Posner, 1987; Ward and Arend, as well as the primary and secondary visual cortices V1 and V2 2007; Zihl and von Cramon, 1979). More recent studies confirm this (Benevento and Davis, 1977). This region also has connections with the role. Indeed, pulvinar lesions are associated with contra-lesional visual ipsilateral superior collicullus (SC) (Benevento and Fallon, 1975; deficitsranging from visual extinction and response competition deficits Benevento and Standage, 1983; Elorette et al., 2018; Huerta and Hart­ during visual attentional tasks (Danziger et al., 2004) to feature ing, 1983). PMl is also reciprocally connected with ventral visual stream discrimination deficitsin the presence of salient distracters (Snow et al., areas V4 and TEO as well as with intraparietal area LIP, with a topo­ 2009). However, lesion studies in human patients often include patients graphical organization of its cortical projecting fibers (Romanski et al., with heterogeneous pulvinar lesion topographies (Snow et al., 2009). 1997; Shipp, 2003). In contrast, PMm has reciprocal connections with These lesions sometimes extend beyond the pulvinar. In addition, they the caudal and the rostral belts of the auditory cortex (cAC and rAC) often do not allow a precise investigation of the distinctive functions of (Cappe et al., 2009a; Hackett et al., 1998; de la Mothe et al., 2006, 2012; the different pulvinar subdivisions. Monkey studies can be very infor­ Kaas and Hackett, 1998; Hackett et al., 2007), the entire extent of the mative in this respect, as they allow for focal and reproducible pertur­ superior temporal gyrus (STG) (Gutierrez et al., 2000; Jones and Burton, bations of the pulvinar and its subdivisions. For example, localized 1976; Kosmal et al., 1997) as well as with the superior temporal sulcus inactivations or stimulations in the dorsal pulvinar in monkeys lead to (STS), all of which are involved in auditory processing (Romanski et al., similar deficits as described above (Desimone et al., 1990; Domi­ 1997). PMm is also interconnected with somatosensory and proprio­ nguez-Vargas et al., 2017; Petersen et al., 1987; Wilke et al., 2013) and ceptive posterior parietal areas PE and PEa, as well as with the dorsal confirmthe idea of a strong functional homology between macaque and premotor cortex (Acuna˜ et al., 1990; Cappe et al., 2009a; Impieri et al., human pulvinar functional organization. 2018; Morel et al., 2005; Romanski et al., 1997; Schmahmann and While most evaluations of pulvinar functions in lesioned patients rely Pandya, 1990). Last but not least, PMm is characterized by strong con­ on the visual modality, pulvinar lesions have also been associated with nections with the parietal, temporal and prefrontal cortex (Asanuma other very diverse clinical symptoms not necessarily involving visual et al., 1985; Bos and Benevento, 1975; Cappe et al., 2007; Cappe et al., processes. For example, lesions that cover the mediodorsal thalamus, the 2009a; Clower et al., 2001; Hardy and Lynch, 1992). It has connections pulvinar and the lateral compartment, are described to lead to deficitsin with TE, MST, LIP, VIP, and more generally with both the superior pa­ the detection, identification and hedonic rating of odors (Sela et al., rietal and the inferior parietal cortices (Baizer et al., 1993; Baleydier and 2009). While only the mediodorsal thalamus appears to connect to an Morel, 1992; Webster et al., 1993). It also projects to the frontal eye field olfactory piriform-orbitofrontal functional circuit (Price and Slotnick, (FEF) (Trojanowski and Jacobson, 1974) and receives widespread inputs 1983), sparse functional evidence suggests that the pulvinar may play a topographically organized with the dorsolateral and ventrolateral pre­ modulator role through its connectivity with layer 6 of the orbitofrontal frontal cortex, as well as reciprocal connections with the orbito-frontal cortex. Lesions of the pulvinar, including the anterior superior and the cortex (Romanski et al., 1997; Bos and Benevento, 1975). Subcorti­ lateral nuclei are also described to lead to disruption in speech recog­ cally, PMm receives projections from the SC (Bender and Butter, 1987; nition and production, up to total aphasia (Van and Borke, 1969). In Benevento and Standage, 1983; Elorette et al., 2018; Harting et al., contrast, dorsal damage of the pulvinar leads to a slower initiation of

234 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243 grasping movements while specificmedio-dorsal pulvinar lesions lead to snakes, monkey faces and hands (Maior et al., 2010; Nguyen et al., 2013; major postural deficits, thus possibly associating this region with pro­ Van Le et al., 2013). Apart from the visual modality, PL neurons are also prioception (Wilke et al., 2018). A systematic multisensory evaluation of responsive to pressure and tactile stimulations (Acuna˜ et al., 1990; patients with pulvinar lesions is thus lacking. This systematic multi­ Gattass et al., 1979, 1978; Mathers and Rapisardi, 1973; Yirmiya and sensory evaluation of pulvinar patients could be instructed by the Hocherman, 1987).The ventral part of PL is involved in auditory functional multisensory properties of the pulvinar as described next. perception (Gattass et al., 1978; Magarinos-Ascone˜ et al., 1988; Yirmiya and Hocherman, 1987). Specifically, complex sounds such as vocaliza­ 4. Functional sensory maps in the pulvinar tions and alarm screams are shown to activate the ventrolateral part of PL (Gattass et al., 1979). Last, one study reports neuronal responses in PL A marked challenge in understanding the physiology of the pulvinar to olfactory stimuli (Gattass et al., 1978). In addition to these multi­ is the observation that its sensory functional gradients are not neces­ sensory properties, PL, as has been described for PI, is involved in eye sarily defined by the above described anatomical parcellation. movements and saccades (Perryman et al., 1980; Robinson et al., 1991). It is also involved in reaching and grasping movements (Acuna˜ et al., 4.1. Dorso-ventral functional gradient in the pulvinar 1990; Gattass et al., 1979, 1978; Mathers and Rapisardi, 1973; Yirmiya and Hocherman, 1987). All of these functional observations nicely While the pulvinar is anatomically divided into the three main nuclei correlate with the anatomical studies described above. described above (PI, PL and PM), functionally, a dorso-ventral gradient is often described (Arcaro et al., 2018, 2015; Dominguez-Vargas et al., 2017; Kaas and Lyon, 2007; Kinoshita et al., 2019; Komura et al., 2013; 4.4. The medial pulvinar Wilke et al., 2010). The functional ventral pulvinar includes the anatomically defined inferior pulvinar as well as the lateral ventral Based on the available experimental evidence, the medial pulvinar is pulvinar (PLvl). It is considered as the "visual pulvinar" (Bridge et al., the most multisensory subdivision of the pulvinar. The activity of its 2016). The functional dorsal pulvinar corresponds to the anatomically neurons correlates with the orientation, direction and velocity of visual ˜ defined medial pulvinar and dorsal lateral pulvinar (PLdm). This stimuli (Magarinos-Ascone et al., 1988; Mathers and Rapisardi, 1973). dorso-ventral functional gradient is thus coherent with the global Like has been reported for the dorsal part of PL, the medial part of PM anatomical pulvino-cortical connectivity organization described above responds to complex visual stimuli such as faces, geometrical forms, eye (Fig. 2C). In addition, it is worth noting that, at least for the visual like patterns and snakes (Almeida et al., 2015; Maior et al., 2010; modality, in both the human and the non-human primate pulvinar, two Nguyen et al., 2013). PM neurons also respond to auditory stimuli, both independent visual field maps are described along a dorsolateral visual simple and more complex like whistles and handclaps (Gattass et al., ˜ gradient that doesn’t coincide with neither the described anatomical 1978; Magarinos-Ascone et al., 1988; Mathers and Rapisardi, 1973; subdivisions nor the dorso-medial functional gradient described above Yirmiya and Hocherman, 1987). Last, PM neurons are also active during ˜ (Arcaro et al., 2015). Whether this functional gradient exists also for the somatosensory perception (Acuna et al., 1986; Gattass et al., 1978; other sensory modalities and how it maps onto our current knowledge of Perryman et al., 1980) and display olfactory responses (Gattass et al., the pulvino-cortical connectivity and the well-established topographi­ 1978). From the motor perspective, PM is responsive to both hand and ˜ cally organized dorso-ventral gradient (Baizer et al., 1993; Shipp, 2003) eye movements (Acuna et al., 1986; Gattass et al., 1978; Perryman et al., remains to be explored. On top of these general gradients, specific 1980). These highly multisensory functional properties of the pulvinar functional responses have been mapped onto the anatomically defined are summarized in Fig. 3. pulvinar subdivisions. This is discussed next. Touch, proprioception and pain correspond to very distinct percep­ tual modalities. While touch is dominated by exteroception and the ’ 4.2. The inferior pulvinar monitoring of the interaction of the outside world with the body s margin (Cl´ery and Ben Hamed, 2018), proprioception and pain are more The neurons of inferior pulvinar respond to visual stimuli, expressing interoceptive senses respectively processing postural body-related in­ a strong orientation and movement selectivity (Mathers and Rapisardi, formation and emotion-based body-related experience. The contribution 1973). They also respond to eye movements in the light and in the dark of the pulvinar to these two latter modalities, namely proprioception (Perryman et al., 1980; Petersen et al., 1985). This is in agreement with and pain, is still hardly explored. We have thus decided to discuss these the high connectivity of this region with the visual system including the two sensory modalities independently of touch. Likewise, there are for retina. This is also in agreement with the specific connectivity pattern observed between PIm and the magnocellular pathway connecting SC to cortical area MT which has been associated with visually guided actions (Mundinano et al., 2018). PI neurons also respond to auditory stimuli during auditory discrimination (Yirmiya and Hocherman, 1987). They additionally respond to hand movement (Yirmiya and Hocherman, 1987) as well as to eye movements and saccades (Perryman et al., 1980; Robinson et al., 1991). Importantly, most neuronal responses are enhanced during active as compared to passive tasks (Yirmiya and Hocherman, 1987).

4.3. The lateral pulvinar

Neurons in the ventrolateral part of PL are involved in the processing of simple oriented as well as dynamic visual stimuli (Gattass et al., 1979; Mathers and Rapisardi, 1973) and the activity of its neurons correlates with that of temporal area TEO and extrastriate visual area V4 (Saal­ mann et al., 2012). This is further confirmedby functional connectivity Fig. 3. The pulvinar is highly multisensory.Reported sensory modalities to MRI studies (Arcaro et al., 2015). The neurons of dorsolateral PL are which the PI, PL and PM pulvinar subdivisions have been shown to respond to: responsive to more complex visual stimuli such as geometrical figures, visual (red), somatosensory (blue); auditory (green), olfactory (cyan).

235 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243 now, no multisensory functional studies addressing the role of olfaction perception (Roy, 2020). The contribution of this information to the or gustation in primates. We have thus decided to also discuss this over-arching functional role of the pulvinar remains to be explored. sensory modality independently from the other sensory modalities. Thus, multiple sensory modalities coexist in the pulvinar. However, multisensory processes classically imply both a multimodal sensory 4.5. The case of proprioception and pain convergence and a multisensory integration. The following section probes whether such processes exist in the pulvinar. In spite of it spar­ The anterior part of the pulvinar (i.e. the anterior part of the dorsal sity, the available reports confirm that this is the case, thus supporting medial and the lateral pulvinar, also referred to as the oral pulvinar in the contribution of the pulvinar to multisensory processes. the older literature) has been shown to be connected with area 1, area 2 (Padberg et al., 2009), and the lateral parietal cortex (Burton, 1984) as 5. Evidence for multisensory processing in the pulvinar well as area 5 (Yeterian and Pandya, 1985) and area 7b (Friedman and Murray, 1986; Pearson et al., 1978; Weber and Yin, 1984), all these 5.1. Multisensory convergence regions being involved in somatosensory processing and proprioception (Delhaye et al., 2018). This is in agreement with the marked somato­ The involvement of the pulvinar in multisensory processing has been sensory properties of this part of the pulvinar. It coincides with the hypothesised only quite recently (Tyll et al., 2011). Based on the already discussed evidence that medio-dorsal damage to the pulvinar anatomical and functional data presented above, both PL and PM are leads to postural deficits,possibly of proprioceptive origin (Wilke et al., expected to be involved in multisensory processing and integration. 2018) and that the dorsal pulvinar contributes to the maintenance of Indeed, both these pulvinar subdivisions have direct connections with gaze during postural changes (Schneider et al., 2019). more than one primary sensory area, be it primary visual, auditory or Reinforcing the contribution of the pulvinar to somatosensation, somatosensory cortex, as well as direct connections with highly multi­ pulvinar oscillatory power in the alpha band exerts an inhibitory in­ sensory associative cortices (Asanuma et al., 1985; Leh et al., 2008). fluence on the spike timing and firing rate in somatosensory, premotor However, how these different pulvino-thalamic sensory territories and motor areas, as well as on the behavioural performance during organize one with respect to the other is actually unknown and very few visuo-tactile discrimination (Haegens et al., 2011). A similar modulatory studies have directly addressed this question. Cappe et al. (2009b) is one and filteringrole of the pulvinar is also observed during pain processing. of the very few studies that directly tackles this question. Their work For example, a PET-MRI study in humans shows that distraction during demonstrates the existence of overlapping pulvinar territories of pro­ pain involves a specific functional network composed of the orbito­ jection to the rostral and caudal auditory cortex on the one hand and to frontal, perigenual anterior cingulate cortex, the periaqueductal grey the posterior parietal somatosensory cortex on the other hand, in matter and the pulvinar. The interaction between these areas is observed particular in the medial pulvinar. This is direct evidence for multisen­ only during pain stimulation in the presence of distraction but not sory convergence. during pain stimulation alone or (visual) distraction alone (Valet et al., 2004). 5.2. Multisensory integration This role of the pulvinar in proprioception and posture is to be linked to its role in motor and postural control. Grieve et al. (2000) initially However, multisensory processing involves, beyond multisensory propose that the pulvinar plays a central role in the selection and convergence, i.e. the coexistence in a given area of input signals from intention to perform eye and limb movements in peripersonal space multiple senses converging on the same neurons, an active multisensory (Clery´ and Ben Hamed, 2018). Accordingly, pulvinar inactivations integration process that enhances both behavioural performance and disrupt the selection of movement plans (Wilke et al., 2010). Unfortu­ neuronal processing (for review, Cl´ery et al., 2015b). At the behavioural nately, in spite of these compelling evidence, research on the contribu­ level, responses to multisensory stimuli are characterized by faster re­ tion of the pulvinar to proprioception and postural control remains action times (Raab, 1962; Welch et al., 1986), enhanced detection rates sparse. (Grant and Seitz, 2000) as well as enhanced accuracies (Lehmann and Likewise, the role of the pulvinar in proprioception and posture is to Murray, 2005; Murray et al., 2005). At the neuronal level, multisensory be linked to its role in peripersonal space coding and motor planning in processing is characterized by non-linear mechanisms whereby the relation to the body (Grieve et al., 2000). Accordingly, in the marmoset, response of a given neuron to a bimodal input significantlydiffers from the dorsal pulvinar has recently been shown to co-activate during the sum of its responses to each sensory input presented independently looming versus receding visual stimulation with multiple ventral (V4, (Avillac et al., 2007). FST, TE, TPO) and dorsal (MIP) visual pathway areas as well as with Studies directly addressing multisensory integration in the pulvinar prefrontal areas (45b and 47) and subcortical structures (SC, putamen) are scarce. Most of these studies have focussed on visuo-auditory inte­ (Clery´ et al., 2020). Several of these areas are involved in the coding of gration during speech processing. This is based on evidence of a near space (Clery´ et al., 2018b) and visuo tactile impact prediction contribution of the pulvinar to speech production and verbal memory (Clery´ et al., 2017) and are also responsive to touch (Cl´ery et al., 2017, (Hebb and Ojemann, 2013; Hugdahl and Wester, 1997). For example, 2015a). These areas are also expected to play a role in proprioception. the larger the left pulvinar in healthy subjects, the faster they are at As a result, the pulvinar is expected to share these same functionalities understanding degraded speech and the lower are their speech percep­ and be functionally related to this specific cortical network. tion thresholds (Erb et al., 2012). Anterior superior pulvinar lesions lead to aphasia, i.e. a deficit in speech production (Van and Borke, 1969), 4.6. The case of olfaction and gustation while medial dorsal pulvinar lesions lead to anomia, i.e. a deficitin the recall of the names of everyday life objects (Ojemann et al., 1968). This Generally speaking, there is not much evidence of anatomical con­ is confirmedat the neuronal level, whereby medial pulvinar neurons are nections between the pulvinar and gustative or olfactory areas. However shown to respond to the detection of auditory statistical regularities PM has reciprocal connections with the orbitofrontal cortex (Bay and (Barczak et al., 2018). During multisensory audio-visual speech match Çavdar, 2013; Bos and Benevento, 1975; Romanski et al., 1997) which and mismatch tasks, a very early EEG response is observed following the plays a role in the multisensory integration of visual, olfactory, gustatory presentation of audio-visual speech stimuli the source of which has been and intra oral somatosensory stimuli (i.e. food, Kadohisa et al., 2005). proposed to be in the pulvinar (Musacchia et al., 2006). This coincides Accordingly, olfactory related neuronal responses are reported in PL with the description of an early cortical processing network involved in (Gattass et al., 1978) and a very recent study reveals a functional con­ temporal audio-visual integration, composed of the insula, the posterior nectivity between the pulvinar and the amygdala during taste thalamus and including the pulvinar as well as the superior colliculus

236 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243

(Bushara et al., 2001). More recent fMRI and dynamic causal modelling condition is significantly higher than the %SC in the unisensory condi­ studies identify a specific contribution of the pulvinar to speech tion generating the highest %SC. Last, the super-additive criterium im­ perception in blind people. During speech comprehension optimization, plies that the %SC in the multimodal condition is significantly higher the pulvinar of blind people has an enhanced functional connectivity not than the sum of the %SC in the two unisensory conditions. This is the only with the primary auditory cortex A1, but also with primary visual most stringent condition. Four regions of interest (ROIs) can be identi­ cortex V1 (Dietrich et al., 2015, 2013). This mechanism is absent in fied, based on the visuo-tactile predictive stimuli vs. fixation contrast sighted subjects and suggests a recruitment of visual pathways for (p < 0.001, uncorrected). In monkey M1, these ROIs are compatible with auditory processing following sight deprivation. a pulvinar activation. In M2, the identified subcortical ROIs might be While these studies point towards a possible contribution to multi­ somewhat too anterior for a pulvinar activation. Further research is sensory integration, direct functional evidence is missing. In a recent required to support these results. When the integration criteria are study (Cl´ery et al., 2017), macaque monkeys were subjected to visual applied to the %SC observed in these ROIs, comparing the activations to stimuli looming towards the face, presented either alone, or in associ­ pure visual and pure tactile stimulations to their association (i.e. ation with spatially or temporally congruent tactile stimuli to the face, reflecting multisensory integration, Fig. 4, comparing purple %SC while sitting in an MRI scanner for functional MRI acquisitions. The values to red and green %SC values), the left ROI of monkey M1 fulfilled tactile stimuli could either predict the impact of a looming visual all of the multisensory integration criteria, the right ROI of monkey 1 stimulus both spatially and temporally, only spatially or only tempo­ fulfilledone of them, the left ROI of monkey 2 fulfilledone of them, and rally. The fully predictive condition induced maximal pupil dilation, the right ROI of monkey 2 fulfilled the three of them. When the inte­ indicating integrative and anticipatory temporal prediction mecha­ gration criteria are applied to the %SC observed in these ROIs, nisms. These physiological modifications coincided with robust activa­ comparing the activations to visual stimulations spatially, temporally or tions of a large functional network involving the peri-arcuate prefrontal spatio-temporally predictive of the tactile stimulation (i.e. reflecting cortex (PMv), the intraparietal cortex (VIP), the mid temporal cortex spatio-temporal predictive mechanisms, Fig. 4, comparing purple %SC (FST), as well as the occipital visual cortex (Clery´ et al., 2017). In in­ values to orange and blue %SC values), the left ROI of monkey M1 didn’t dependent studies, this network has been described to be involved in fulfil any of the multisensory integration criteria, the right ROI of visuo-tactile convergence (Guipponi et al., 2015) as well as in the pro­ monkey 1 fulfilledtwo of them, the left ROI of monkey 2 fulfilledone of cessing visual near peripersonal space (Cl´ery et al., 2018b). Importantly, them, and the right ROI of monkey 2 fulfilled two of them. This is a this network demonstrates both active integration of visual and tactile strong indicator that the observed activations reflect active integrative information, but also active integration of spatial and temporal predic­ processes rather than mere convergence of information. Quite surpris­ tion information (Cl´ery et al., 2017). Relevant to the present review, the ingly, to our knowledge, very few electrophysiological recordings in the pulvinar (PL and PM) is co-activated together with this cortical network pulvinar have directly addressed this issue. A very recent study by Cappe (Fig. 4). Several criteria for multisensory integration based on fMRI et al. (2020) demonstrates audio-visual multisensory integration in the activations are discussed in the literature. The mean criterium implies local field potential of the medial pulvinar. that the mean percentage of signal change (%SC) in either unisensory Thus, although sparse, converging evidence suggest that the pulvinar conditions is significantly different from the %SC in the multimodal implements multisensory convergence and integration. This raises the condition. The max criterium implies that the %SC in the multimodal question of whether and how these processes contribute to the cognitive

Fig. 4. Temporal and spatial prediction enhances thalamic pulvinar activations in both monkeys. Histograms represent the percent signal change for Visual (Red), Tactile (Green), VT fully predictive (Purple), VT temporally predictive (Orange) and VT spatially predictive (Blue) conditions for monkey 1 and 2, for selected ROIs in the pulvinar. The contrast used to extract percent signal change is the VT predictive versus fixationcontrast (P < 0.001, uncorrected level (unc). For each ROI, block effect is assessed by a repeated measure one-way ANOVA; significance of PSCs difference with respect to baseline and amongst themselves is assessed using ◦ paired t-tests, *P < 0.05; **P < 0.01; ***P < 0.001, 0.05 < P < 0.07). The M1 ROIs are located in the pulvinar. The M2 ROIs are somewhat too anterior for a pulvinar activation. Unpublished research. Companion cortical data published in Clery´ et al. (2017).

237 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243 role of the pulvinar, that has predominantly been investigated from the and visual selection (Saalmann and Kastner, 2009). Lesions to the pul­ perspective of vision. Indeed, very much like is described in the asso­ vinar in humans result in an impairment in spatial and temporal atten­ ciative cortical areas to which it projects, pulvinar sensory responses are tion (Michael et al., 2001; Ward et al., 2007; Rafal and Posner, 1987; often associated with complex cognitive processes. In a recent meta- Zihl and von Cramon, 1979; Arend et al., 2008). A slowed down visual analysis of human functional neuroimaging studies by Barron et al. search and abnormal prolonged fixationsare also observed (Ungerleider (2015), the authors show that all of pulvinar subdivisions are involved in and Christensen, 1979), as well in most extreme cases a hemineglect the processing of perception, attention, emotions, actions and other syndrome whereby patients do not have awareness of contralesional higher cognitive functions. This has been thoroughly and repeatedly visual stimuli (Karnath et al., 2002). Supporting these lesion observa­ reviewed elsewhere. One of the functions that has been associated with tions, spatial attention enhances visual responses in the pulvinar (Zhou the pulvinar is its role in speeded responses to high saliency external et al., 2016) and the enhanced response of the pulvinar to behaviourally events as well as in emotional regulation. This is discussed next. relevant stimuli precedes that observed in either the parietal and the temporal cortices (Benevento and Port, 1995). This modulation of visual 6. The pulvinar in sensory detection and selection responses by attention is stronger in the presence of distractors, sug­ gesting a contribution of the pulvinar to sensory filtering, i.e. to the 6.1. Ultra-fast emotional processing and the innate alarm system selection of input stimuli of major salience or behavioural relevance, at the expanse of non-relevant stimuli (Fischer and Whitney, 2012; Rob­ A firstemotion processing pathway involving the superior colliculus, inson and Petersen, 1992). This applies to the visual responses of all of the dorsolateral pulvinar and the lateral amygdala has also been PI, PLvl and Pldm. Supporting this point, the reversible inaction of demonstrated with probabilistic tractography in both humans and ma­ ventral PL during spatial attention orientation for object recognition in caques (Rafal et al., 2015). These results have recently been supported the presence of distractors, result in a strong decrease in correct trials to by a tracer study that shows overlapping SC projections and lateral visual items presented in the contralateral field( Zhou et al., 2016). This amygdala projections to the pulvinar. These projections are localized in behavioral effect is less pronounced in the absence of distractors. PM as well as in PI (Elorette et al., 2018). Visual cortex lesions result in Importantly, PL inactivation effects coincide with a reduction of sensory an increase in the strength of the fiber tracts between PL and the evoked responses in extrastriate visual area V4. Last, the reversible amygdala ipsilaterally to the V1 lesion, at the same time that the inactivation of the pulvinar results in depressed visual responses in V1 pulvino-collicular fibers are decreased (Tamietto et al., 2012). The au­ while a stimulation of the pulvinar results in enhanced responses in V1 thors suggest the existence of two different emotion processing path­ at the corresponding visual receptive field sites, together with a sup­ ways, one involved in conscious emotion perception (including the pression of the activity of neurons representing other spatial locations pulvinar, the amygdala and the orbitofrontal cortex) and one involved in (Purushothaman et al., 2012). The contribution of the pulvinar to sen­ unconscious (including the superior colliculus, the pulvinar and the sory selection and filtering is further supported by the clinical obser­ amydgala, see Elorette et al., 2018) emotion perception (Tamietto et al., vation that ventral pulvinar lesions lead to contralesional deficits in 2012; Soares et al., 2017). This hypothesis is supported by an MRI study response competition (Danziger et al., 2004) and in the discrimination of presenting perceived and non-perceived fear-conditioned faces. When target features, specifically in the presence of salient distracters (Snow the faces are processed but not perceived, an increased connectivity is et al., 2009). Importantly, while both the ventral and the dorsal pulvinar observed between the right amygdala, the pulvinar and the superior are associated with distractors filtering, they are not activated by colliculus while the connectivity between the amygdala, the fusiform task-switching (Strumpf et al., 2013). and the orbitofrontal cortices decreases (Morris et al., 1999). It is pro­ posed that this unconscious emotional pathway plays a crucial role in 7. The pulvinar as a processing regulator survival in complex social groups, contributing to a very rapid conscious or unconscious perception of emotion and as fast behavioural reactions 7.1. Emotional regulation as possible. Based on a recent human fMRI study, it is proposed that during the From an anatomic perspective, medial pulvinar PM is densely con­ processing of threatening visual stimuli, information directly reaches the nected with the limbic system. Specifically, PM has reciprocal connec­ superior colliculus, without going through the visual cortex (Liddell tions with the posterior limbic neocortex, the posterior cingulate gyrus et al., 2005), and is then rapidly transmitted to the amygdala and the (Baleydier and Mauguiere, 1985) as well as the paralimbic and para­ locus coeruleus. This results in a noradrenergic cortical neuro­ hippocampal regions (Baleydier and Mauguiere, 1985; Yeterian and modulation, notably in the anterior cingulate cortex (ACC) and in Pandya, 1997). The medial part of PM is reciprocally connected with the fronto-parieto-temporal attentional network. This innate alarm system rostral part of the superior temporal gyrus, the cingulate cortex, the (IAS) is proposed to allow for ultra-fast behavioural responses to posterior insula as well as the lateral amygdala (Mufson and Mesulam, conscious or unconscious threatening stimuli (Lanius et al., 2017). This 1984). The lateral part of PM is reciprocally connected with the insula, IAS is proposed to interact with both the orienting attentional network the posterior cingulate cortex and the superior temporal cortex (Jones (via the inferior parietal cortex, the frontal eye fields, the superior col­ and Burton, 1976; Romanski et al., 1997). Last, orbital frontal, medial liculus, and the pulvinar, and acetylcholine as neuromodulator) and the prefrontal and temporal polar proiscortices project to both dorsal and alerting network (via the locus coeruleus and NA as neuromodulator) for ventral PM whereas the anterior cingulate proisocortex projects only to slower sensory processing (Petersen and Posner, 2012; Posner et al., dorsal PM (Yeterian and Pandya, 1988). From a functional perspective, 1997). cortical evoked responses have been found in the temporal, temporo-parietal junction, the insula, the frontal parietal opercular 6.2. Attention, sensory selection, distractor filtering and perception cortex and in mesial temporal regions following PM stimulations in humans, and vice versa (Rosenberg et al., 2009). All this taken together The pulvinar also contributes to conscious sensory processing. The indicates a strong functional link between the medial pulvinar and the visual response of pulvinar neurons reflectsperceptual awareness (Wilke limbic system. et al., 2009) and confidenceduring visual categorization (Komura et al., Confirming this, during an emotional face processing fMRI task, it 2013) rather than overt behavioural report. The pulvinar functions are has been determined that patient suffering of a general social anxiety proposed to be implemented in interaction with early visual extrastriate disorder (gSAD) have stronger functional interactions within the frontal processing in area V4 (Wilke et al., 2006). In addition to its contribution emotion regulation regions, i.e. between the pulvinar and the middle to conscious perception, the pulvinar is also associated with attention occipital gyrus, the orbitofrontal cortex and the superior frontal gyrus

238 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243

(Tadayonnejad et al., 2016). Independently, the amygdala and PM are induces sedation and interferes with behavioral success in attentional proposed to coordinate cortical networks to evaluate the biological detection task, the introduction of white noise (making the task more significance of affective visual stimuli (Pessoa and Adolphs, 2010), complex perceptually speaking) recovers behavioral performance and amplifying the responses of cortico-pulvino-cortical circuits to weak this effect coincides with an increased activity in the left pulvinar. This emotional visual stimulus (Padmala et al., 2010). argues in favor of a contribution of the pulvinar, beyond the attentional Overall, the pulvinar is thus proposed to act as a modulator of the function, to phasic arousal or alerting process and the noradrenergic limbic system. As a result, the pulvinar is proposed to play a key role in neuromodulation system (Coull et al., 2004). emotional regulation. It is worth noting that sensory detection and selection, as well as emotional and attentional regulation involve a rapid adjustment of 7.2. Attentional regulation behavior to both the environment and the subject’s current covert goals and states. Such flexible behavior is crucial for optimal behavior. This Several recent studies demonstrate that spatial attention orientation includes the ability of rapidly shifting from a state of intense focus on the correlates with enhanced functional LFP coupling between the pulvinar ongoing behavior (e.g. foraging) to a high alertness state (e.g. identi­ and the cortex. PM displays an enhanced functional coupling with both fying a competitor or a predator), or the ability of shifting from peaceful the dorsal visual pathways (LIP, Fiebelkorn et al., 2019), and the pre­ social interactions to a state of high alertness to negative emotions. The frontal cortex (Fiebelkorn et al., 2019). Specifically, Fiebelkorn et al. pulvinar thus appears as a major modulator of behavioral and cognitive (2019) show a significantcoupling between PM spikes and the phase of flexibility. both FEF (8–19 Hz) and LIP (15–20 Hz) alpha/low-beta activity at recording sites with coincident visual response fields.Importantly, they 8. Generalizing the role of the pulvinar in sensory detection, show that this synchronization is unidirectional, the spikes of the pul­ selection and regulation vinar impacting the phase of the LFP in both the FEF and LIP (note that LIP spikes also impacted the pulvinar LFPs, but did so independently Converging evidence thus suggest a very strong contribution of the from the effects of the pulvinar onto LIP). Likewise, PL (mostly PLvl) pulvinar to two independent general cognitive functions operating at displays a marked enhanced coupling with both the ventral (V4, TEO, different time scales, mostly based on studies performed in the visual Saalmann et al., 2018, 2012) and the dorsal visual pathways (LIP, modality: 1) the selection of sensory input based on its emotional Saalmann et al., 2018). Specifically, both Saalmann et al. (2012) and valence, intrinsic salience as well as extrinsic behavioural relevance, a Zhou et al. (2016) show, using Granger causality statistics (a method process requiring fast and flexible adjustments to the environment and that determines whether one time series is useful to predict another one, 2) the regulation of cognitive states and arousal, a much slower process without however inferring causation or causality, in contrast with possibly fluctuating with a variety of internal state modulators ranging inactivation studies), that the pulvinar synchronizes neuronal activity from circadian influences,to emotional and anxiety states, to energetic between interconnected visual areas, in the alpha/low beta range status etc. This suggests that this structure is part of multiple functional (10 20 Hz) during attention orientation. Zhou et al. (2016) additionally loops, transmitting bottom up and top down information to the many show that attention increases the influence of extrastriate visual cortex cortical sensory, and associative areas it is related too, as well as to other (V4) on pulvinar while decreasing the reverse influenceof the pulvinar key subcortical structures such as the amygdala. We will argue that the onto V4 in higher gamma band frequencies. It is thus proposed that PL same two independent general cognitive functions reported in the visual regulates the transmission of information across cortical areas by syn­ domain are at play for such sensory modalities as the auditory and so­ chronizing cortical activity at alpha frequencies (Kastner et al., 2020). matosensory modality, involving the same type of interactions between The reversible inactivation of PL increases alpha frequency power con­ the pulvinar and the cortex, and relying on the same type of neuro­ tent in the visual cortical areas (Zhou et al., 2016). More alpha is often modulator system. That is to say that the pulvinar is proposed to associated with inattention (Bollimunta et al., 2011; Schmid et al., contribute to sensory processing and notably to sensory detection and 2012). Accordingly, this increased visual cortex alpha is concomitant selection at a fast time scale, as well as in sensory regulation, at a much with decreased attentional performance and decreased neuronal re­ slower time scale, along all sensory modalities, including olfaction, sponses in V4. These lesion observations (more visual cortical alpha and proprioception and pain. Whether this is achieved through common or less attention-related spikes) contrast with control observations (pulvi­ multiple functional networks and whether some of the sensory modal­ nar alpha power causally synchronizing attention-related spiking ac­ ities such as pain and olfaction are processed through specific distinct tivity in visual cortical areas). However, if one considers the complex functional networks remains to be explored. This exploration would recurrent cortico-pulvino-cortical connectivity (Lakatos et al., 2016), entail a more systematic multisensory approach to the anatomical, this apparent contradiction actually suggests that the pulvinar might functional and neuropsychological evaluation of the role of the pulvinar. play a crucial role in organizing cortical intra- and inter-areal activity. Overall, the time seems ripe to move from a view of the pulvinar as a Confirming this hypothesis, a recent computational modeling study modulator of the visual system, to the view of the pulvinar as a general (Jaramillo et al., 2019) shows that a pulvino-cortical circuit model, regulation hub for adaptive, flexible cognition and survival. composed of the pulvinar and two cortical areas, reproduces the exact control and lesion behavioral and visual cortex neurophysiological sig­ Fundings natures described above. In this model, effective connections between the two cortical areas are directly gated by the pulvinar. As a result, M.F., C.C. and S.B.H. were funded by the French National Research Jaramillo et al. (2019) suggest that the feedforward and feedback Agency (ANR)ANR-16-CE37-0009-01 grant and the LABEX CORTEX pulvino-cortical pathways modify the relative hierarchical positions of funding (ANR-11-LABX-0042) from the Universite´ de Lyon, within the cortical areas by a direct control over the frequency-dependent inter-­ program Investissements d’Avenir (ANR-11-IDEX-0007) operated by the areal interactions (see also Halassa and Kastner, 2017). This putative French National Research Agency (ANR). role of the pulvinar is expected to generalize beyond the visual function. Supporting this regulatory role of the pulvinar in cognition beyond CRediT authorship contribution statement attentional regulation, functional correlations between the pulvinar and the ipsilateral superior frontal gyrus (SFG), the contralateral tempora­ Mathilda Froesel: Conceptualization, Writing - original draft, l–parietal junction (TPJ) and the visual cortex increase when the per­ Writing - review & editing. Celine´ Cappe: Conceptualization, Writing - formance in a working memory task increase (Rotshtein et al., 2011). In review & editing, Funding acquisition. Suliann Ben Hamed: Concep­ addition, while noradrenergic alpha2 agonist (dexmedotomidine) tualization, Writing - original draft, Writing - review & editing, Funding

239 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243 acquisition, Supervision. Bollimunta, A., Mo, J., Schroeder, C.E., Ding, M., 2011. Neuronal mechanisms and attentional modulation of corticothalamic alpha oscillations. J. Neurosci. 31, 4935–4943. https://doi.org/10.1523/JNEUROSCI.5580-10.2011. References Bos, J., Benevento, L.A., 1975. Projections of the medial pulvinar to orbital cortex and frontal eye fieldsin the rhesus monkey (Macaca mulatta). Exp. Neurol. 49, 487–496. Acuna,˜ C., Cudeiro, J., Gonzalez, F., 1986. Lateral-posterior (LP) and pulvinar unit https://doi.org/10.1016/0014-4886(75)90103-X. activity related to intentional upper limb movements directed to spatially separated Bourne, J.A., Morrone, M.C., 2017. Plasticity of visual pathways and function in the targets, in behaving Macaca nemestrina monkeys. Rev. Neurol. (Paris) 142, developing brain: is the pulvinar a crucial player? Front. Syst. Neurosci. 11 https:// 354–361. doi.org/10.3389/fnsys.2017.00003. Acuna,˜ C., Cudeiro, J., Gonzalez, F., Alonso, J.M., Perez, R., 1990. Lateral-posterior and Bremmer, F., Schlack, A., Shah, N.J., Zafiris, O., Kubischik, M., Hoffmann, K.-P., pulvinar reaching cells—comparison with parietal area 5a: a study in behaving Zilles, K., Fink, G.R., 2001. Polymodal motion processing in posterior parietal and Macaca nemestrina monkeys. Exp. Brain Res. 82, 158–166. https://doi.org/ premotor cortex: a human fMRI study strongly implies equivalencies between 10.1007/BF00230847. humans and monkeys. Neuron 29, 287–296. https://doi.org/10.1016/S0896-6273 Adams, M.M., Hof, P.R., Gattass, R., Webster, M.J., Ungerleider, L.G., 2000. Visual (01)00198-2. cortical projections and chemoarchitecture of macaque monkey pulvinar. J. Comp. Bridge, H., Leopold, D.A., Bourne, J.A., 2016. Adaptive pulvinar circuitry supports visual Neurol. 419, 377–393. cognition. Trends Cogn. Sci. 20, 146–157. https://doi.org/10.1016/j. Almeida, I., Soares, S.C., Castelo-Branco, M., 2015. The distinct role of the amygdala, tics.2015.10.003. superior colliculus and pulvinar in processing of central and peripheral snakes. PLoS Brosch, M., Selezneva, E., Scheich, H., 2005. Nonauditory events of a behavioral One 10, e0129949. https://doi.org/10.1371/journal.pone.0129949. procedure activate auditory cortex of highly trained monkeys. J. Neurosci. 25, Arcaro, M.J., Pinsk, M.A., Kastner, S., 2015. The anatomical and functional organization 6797–6806. https://doi.org/10.1523/JNEUROSCI.1571-05.2005. of the human visual pulvinar. J. Neurosci. 35, 9848–9871. https://doi.org/10.1523/ Burton, H., 1984. Corticothalamic connections from the second somatosensory area and JNEUROSCI.1575-14.2015. neighboring regions in the lateral sulcus of macaque monkeys. Brain Res. 309, Arcaro, M.J., Pinsk, M.A., Chen, J., Kastner, S., 2018. Organizing principles of pulvino- 368–372. cortical functional coupling in humans. Nat. Commun. 9, 5382. https://doi.org/ Bushara, K.O., Grafman, J., Hallett, M., 2001. Neural correlates of auditory-visual 10.1038/s41467-018-07725-6. stimulus onset asynchrony detection. J. Neurosci. 21, 300–304. Arend, I., Rafal, R., Ward, R., 2008. Spatial and temporal deficits are regionally Calvert, G.A., 2001. Crossmodal processing in the human brain: insights from functional dissociable in patients with pulvinar lesions. Brain J. Neurol. 131, 2140–2152. neuroimaging studies. Cereb. Cortex 11, 1110–1123. https://doi.org/10.1093/ https://doi.org/10.1093/brain/awn135. cercor/11.12.1110. Asanuma, C., Andersen, R.A., Cowan, W.M., 1985. The thalamic relations of the caudal Calvert, G.A., Brammer, M.J., Bullmore, E.T., Campbell, R., Iversen, S.D., David, A.S., inferior parietal lobule and the lateral prefrontal cortex in monkeys: divergent 1999. Response amplificationin sensory-specificcortices during crossmodal binding. cortical projections from cell clusters in the medial pulvinar nucleus. J. Comp. NeuroReport 10, 2619. Neurol. 241, 357–381. https://doi.org/10.1002/cne.902410309. Camalier, C.R., D’Angelo, W.R., Sterbing-D’Angelo, S.J., de la Mothe, L.A., Hackett, T.A., Avillac, M., Ben Hamed, S., Duhamel, J.-R., 2007. Multisensory integration in the ventral 2012. Neural latencies across auditory cortex of macaque support a dorsal stream intraparietal area of the macaque monkey. J. Neurosci. 27, 1922–1932. https://doi. supramodal timing advantage in primates. Proc. Natl. Acad. Sci. U. S. A. 109, org/10.1523/JNEUROSCI.2646-06.2007. 18168–18173. https://doi.org/10.1073/pnas.1206387109. Baizer, J.S., Desimone, R., Ungerleider, L.G., 1993. Comparison of subcortical Cappe, C., Barone, P., 2005. Heteromodal connections supporting multisensory connections of inferior temporal and posterior parietal cortex in monkeys. Vis. integration at low levels of cortical processing in the monkey. Eur. J. Neurosci. 22, Neurosci. 10, 59–72. 2886–2902. https://doi.org/10.1111/j.1460-9568.2005.04462.x. Baldwin, M.K.L., Balaram, P., Kaas, J.H., 2013. Projections of the superior colliculus to Cappe, C., Morel, A., Rouiller, E.M., 2007. Thalamocortical and the dual pattern of the pulvinar in prosimian galagos (Otolemur garnettii) and VGLUT2 staining of the corticothalamic projections of the posterior parietal cortex in macaque monkeys. visual pulvinar. J. Comp. Neurol. 521, 1664–1682. https://doi.org/10.1002/ Neuroscience 146, 1371–1387. https://doi.org/10.1016/j. cne.23252. neuroscience.2007.02.033. Baldwin, M.K.L., Balaram, P., Kaas, J.H., 2017. The evolution and functions of nuclei of Cappe, C., Morel, A., Barone, P., Rouiller, E.M., 2009a. The thalamocortical projection the visual pulvinar in primates. J. Comp. Neurol. 525, 3207–3226. https://doi.org/ systems in primate: an anatomical support for multisensory and sensorimotor 10.1002/cne.24272. interplay. Cereb. Cortex N. Y. N. 1991 (19), 2025–2037. https://doi.org/10.1093/ Baleydier, C., Mauguiere, F., 1985. Anatomical evidence for medial pulvinar connections cercor/bhn228. with the posterior cingulate cortex, the retrosplenial area, and the posterior Cappe, C., Rouiller, E.M., Barone, P., 2009b. Multisensory anatomical pathways. Hear. parahippocampal gyrus in monkeys. J. Comp. Neurol. 232, 219–228. https://doi. Res. 258, 28–36. https://doi.org/10.1016/j.heares.2009.04.017. Multisensory org/10.1002/cne.902320207. integration in auditory and auditory-related areas of cortex. Baleydier, C., Morel, A., 1992. Segregated thalamocortical pathways to inferior parietal Cappe, C., Rouiller, E.M., Barone, P., 2012. Cortical and thalamic pathways for and inferotemporal cortex in macaque monkey. Vis. Neurosci. 8, 391–405. https:// multisensory and sensorimotor interplay. In: Murray, M.M., Wallace, M.T. (Eds.), doi.org/10.1017/S0952523800004922. The Neural Bases of Multisensory Processes, Frontiers in Neuroscience. CRC Press/ Barczak, A., O’Connell, M.N., McGinnis, T., Ross, D., Mowery, T., Falchier, A., Taylor & Francis, Boca Raton (FL). Lakatos, P., 2018. Top-down, contextual entrainment of neuronal oscillations in the Cappe, C., Vittek, A.-L., Anne-Laure; Juan, C., Gaillard, C., Ben Hamed, S., Mercier, M., auditory thalamocortical circuit. Proc. Natl. Acad. Sci. U. S. A. 115, E7605–E7614. Girard, P., 2020. Local Field 817 Potentials Reflect Multisensory Integration in the https://doi.org/10.1073/pnas.1714684115. Medial Pulvinar. IMRF. Barron, D.S., Eickhoff, S.B., Clos, M., Fox, P.T., 2015. Human pulvinar functional Carmichael, S.T., Clugnet, M.-C., Price, J.L., 1994. Central olfactory connections in the organization and connectivity. Hum. Brain Mapp. 36, 2417–2431. https://doi.org/ macaque monkey. J. Comp. Neurol. 346, 403–434. https://doi.org/10.1002/ 10.1002/hbm.22781. cne.903460306. Bay, H.H., Çavdar, S., 2013. Regional connections of the mediodorsal thalamic nucleus in Clavagnier, S., Falchier, A., Kennedy, H., 2004. Long-distance feedback projections to the rat. J. Integr. Neurosci. 12, 201–219. https://doi.org/10.1142/ area V1: implications for multisensory integration, spatial awareness, and visual S021963521350012X. consciousness. Cogn. Affect. Behav. Neurosci. 4, 117–126. https://doi.org/10.3758/ Benarroch, E.E., 2015. Pulvinar: associative role in cortical function and clinical CABN.4.2.117. correlations. Neurology 84, 738–747. https://doi.org/10.1212/ Cl´ery, J., Ben Hamed, S., 2018. Frontier of self and impact prediction. Front. Psychol. 9 WNL.0000000000001276. https://doi.org/10.3389/fpsyg.2018.01073. Bender, D.B., Butter, C.M., 1987. Comparison of the effects of superior colliculus and Cl´ery, J., Guipponi, O., Odouard, S., Wardak, C., Ben Hamed, S., 2015a. Impact pulvinar lesions on visual search and tachistoscopic pattern discrimination in prediction by looming visual stimuli enhances tactile detection. J. Neurosci. 35, monkeys. Exp. Brain Res. 69, 140–154. https://doi.org/10.1007/BF00247037. 4179–4189. https://doi.org/10.1523/JNEUROSCI.3031-14.2015. Benevento, L.A., Davis, B., 1977. Topographical projections of the prestriate cortex to the Cl´ery, J., Guipponi, O., Wardak, C., Ben Hamed, S., 2015b. Neuronal bases of pulvinar nuclei in the macaque monkey: an autoradiographic study. Exp. Brain Res. peripersonal and extrapersonal spaces, their plasticity and their dynamics: knowns 30, 405–424. https://doi.org/10.1007/BF00237265. and unknowns. Neuropsychologia 70, 313–326. https://doi.org/10.1016/j. Benevento, L.A., Fallon, J.H., 1975. The ascending projections of the superior colliculus neuropsychologia.2014.10.022. in the rhesus monkey (Macaca mulatta). J. Comp. Neurol. 160, 339–361. https://doi. Cl´ery, J., Guipponi, O., Odouard, S., Pin`ede, S., Wardak, C., Ben Hamed, S., 2017. The org/10.1002/cne.901600306. prediction of impact of a looming stimulus onto the body is subserved by Benevento, L.A., Port, J.D., 1995. Single neurons with both form/color differential multisensory integration mechanisms. J. Neurosci. 37, 10656–10670. https://doi. responses and saccade-related responses in the nonretinotopic pulvinar of the org/10.1523/JNEUROSCI.0610-17.2017. behaving macaque monkey. Vis. Neurosci. 12, 523–544. Cl´ery, J., Amiez, C., Guipponi, O., Wardak, C., Procyk, E., Ben Hamed, S., 2018a. Reward Benevento, L.A., Rezak, M., 1976. The cortical projections of the inferior pulvinar and activations and face fields in monkey cingulate motor areas. J. Neurophysiol. 119, adjacent lateral pulvinar in the rhesus monkey (macaca mulatta): an 1037–1044. https://doi.org/10.1152/jn.00749.2017. autoradiographic study. Brain Res. 108, 1–24. https://doi.org/10.1016/0006-8993 Cl´ery, J., Guipponi, O., Odouard, S., Wardak, C., Ben Hamed, S., 2018b. Cortical (76)90160-8. networks for encoding near and far space in the non-human primate. NeuroImage Benevento, L.A., Standage, G.P., 1983. The organization of projections of the 176, 164–178. https://doi.org/10.1016/j.neuroimage.2018.04.036. retinorecipient and nonretinorecipient nuclei of the pretectal complex and layers of Cl´ery, J.C., Schaeffer, D.J., Hori, Y., Gilbert, K.M., Hayrynen, L.K., Gati, J.S., Menon, R.S., the superior colliculus to the lateral pulvinar and medial pulvinar in the macaque Everling, S., 2020. Looming and receding visual networks in awake marmosets monkey. J. Comp. Neurol. 217, 307–336. https://doi.org/10.1002/cne.902170307. investigated with fMRI. NeuroImage 215, 116815. https://doi.org/10.1016/j. neuroimage.2020.116815.

240 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243

Clower, D.M., West, R.A., Lynch, J.C., Strick, P.L., 2001. The inferior parietal lobule is Guipponi, O., Cl´ery, J., Odouard, S., Wardak, C., Ben Hamed, S., 2015. Whole brain the target of output from the superior colliculus, hippocampus, and cerebellum. mapping of visual and tactile convergence in the macaque monkey. NeuroImage J. Neurosci. 21, 6283–6291. 117, 93–102. https://doi.org/10.1016/j.neuroimage.2015.05.022. Coull, J.T., Jones, M.E.P., Egan, T.D., Frith, C.D., Maze, M., 2004. Attentional effects of Gutierrez, C., Yaun, A., Cusick, C.G., 1995. Neurochemical subdivisions of the inferior noradrenaline vary with arousal level: selective activation of thalamic pulvinar in pulvinar in macaque monkeys. J. Comp. Neurol. 363, 545–562. https://doi.org/ humans. NeuroImage 22, 315–322. https://doi.org/10.1016/j. 10.1002/cne.903630404. neuroimage.2003.12.022. Gutierrez, C., Cola, M.G., Seltzer, B., Cusick, C., 2000. Neurochemical and connectional Danziger, S., Ward, R., Owen, V., Rafal, R., 2004. Contributions of the human pulvinar to organization of the dorsal pulvinar complex in monkeys. J. Comp. Neurol. 419, linking vision and action. Cogn. Affect. Behav. Neurosci. 4, 89–99. 61–86. de la Mothe, L.A., Blumell, S., Kajikawa, Y., Hackett, T.A., 2006. Thalamic connections of Hackett, T.A., Stepniewska, I., Kaas, J.H., 1998. Subdivisions of auditory cortex and auditory cortex in marmoset monkeys: core and medial belt regions. J. Comp. ipsilateral cortical connections of the parabelt auditory cortex in macaque monkeys. Neurol. 496, 72–96. https://doi.org/10.1002/cne.20924. J. Comp. Neurol. 394, 475–495. https://doi.org/10.1002/(SICI)1096-9861 de la Mothe, L.A., Blumell, S., Kajikawa, Y., Hackett, T.A., 2012. Thalamic connections of (19980518)394:4<475::AID-CNE6>3.0.CO;2-Z. auditory cortex in marmoset monkeys: lateral belt and parabelt regions. Anat. Rec. Hackett, T.A., De La Mothe, L.A., Ulbert, I., Karmos, G., Smiley, J., Schroeder, C.E., 2007. 295, 822–836. https://doi.org/10.1002/ar.22454. Multisensory convergence in auditory cortex, II. Thalamocortical connections of the Delhaye, B.P., Long, K.H., Bensmaia, S.J., 2018. Neural basis of touch and proprioception caudal superior temporal plane. J. Comp. Neurol. 502, 924–952. https://doi.org/ in primate cortex. Compr. Physiol. 8, 1575–1602. https://doi.org/10.1002/cphy. 10.1002/cne.21326. c170033. Haegens, S., Nacher,´ V., Luna, R., Romo, R., Jensen, O., 2011. α-Oscillations in the Desimone, R., Wessinger, M., Thomas, L., Schneider, W., 1990. Attentional control of monkey sensorimotor network influence discrimination performance by rhythmical visual perception: cortical and subcortical mechanisms. Cold Spring Harb. Symp. inhibition of neuronal spiking. Proc. Natl. Acad. Sci. U. S. A. 108, 19377–19382. Quant. Biol. 55, 963–971. https://doi.org/10.1073/pnas.1117190108. Dietrich, S., Hertrich, I., Ackermann, H., 2013. Ultra-fast speech comprehension in blind Halassa, M.M., Kastner, S., 2017. Thalamic functions in distributed cognitive control. subjects engages primary visual cortex, fusiform gyrus, and pulvinar - a functional Nat. Neurosci. 20, 1669–1679. https://doi.org/10.1038/s41593-017-0020-1. magnetic resonance imaging (fMRI) study. BMC Neurosci. 14, 74. https://doi.org/ Hardy, S.G., Lynch, J.C., 1992. The spatial distribution of pulvinar neurons that project 10.1186/1471-2202-14-74. to two subregions of the inferior parietal lobule in the macaque. Cereb. Cortex N. Y. Dietrich, S., Hertrich, I., Ackermann, H., 2015. Network modeling for functional N 1991 (2), 217–230. magnetic resonance imaging (fMRI) signals during ultra-fast speech comprehension Harting, J.K., Huerta, M.F., Frankfurter, A.J., Strominger, N.L., Royce, G.J., 1980. in late-blind listeners. PLoS One 10, e0132196. https://doi.org/10.1371/journal. Ascending pathways from the monkey superior colliculus: an autoradiographic pone.0132196. analysis. J. Comp. Neurol. 192, 853–882. https://doi.org/10.1002/cne.901920414. Dominguez-Vargas, A.-U., Schneider, L., Wilke, M., Kagan, I., 2017. Electrical Hebb, A.O., Ojemann, G.A., 2013. The thalamus and language revisited. Brain Lang. 126, microstimulation of the pulvinar biases saccade choices and reaction times in a time- 99–108. https://doi.org/10.1016/j.bandl.2012.06.010. dependent manner. J. Neurosci. 37, 2234–2257. https://doi.org/10.1523/ Homman-Ludiye, J., Bourne, J.A., 2019. The medial pulvinar: function, origin and JNEUROSCI.1984-16.2016. association with neurodevelopmental disorders. J. Anat. 235, 507–520. https://doi. Driver, J., Noesselt, T., 2008. Multisensory interplay reveals crossmodal influences on org/10.1111/joa.12932. ‘sensory-specific’ brain regions, neural responses, and judgments. Neuron 57, 11–23. Huerta, M.F., Harting, J.K., 1983. Sublamination within the superficial gray layer of the https://doi.org/10.1016/j.neuron.2007.12.013. squirrel monkey: an analysis of the tectopulvinar projection using anterograde and Elorette, C., Forcelli, P.A., Saunders, R.C., Malkova, L., 2018. Colocalization of tectal retrograde transport methods. Brain Res. 261, 119–126. https://doi.org/10.1016/ inputs with amygdala-projecting neurons in the macaque pulvinar. Front. Neural 0006-8993(83)91290-8. Circuits 12. https://doi.org/10.3389/fncir.2018.00091. Hugdahl, K., Wester, K., 1997. Lateralized thalamic stimulation: effects on verbal Erb, J., Henry, M.J., Eisner, F., Obleser, J., 2012. Auditory skills and brain morphology memory. Neuropsychiatry Neuropsychol. Behav. Neurol. 10, 155–161. predict individual differences in adaptation to degraded speech. Neuropsychologia Impieri, D., Gamberini, M., Passarelli, L., Rosa, M.G.P., Galletti, C., 2018. Thalamo- 50, 2154–2164. https://doi.org/10.1016/j.neuropsychologia.2012.05.013. cortical projections to the macaque superior parietal lobule areas PEc and PE. Fiebelkorn, I.C., Pinsk, M.A., Kastner, S., 2019. The mediodorsal pulvinar coordinates the J. Comp. Neurol. 526, 1041–1056. https://doi.org/10.1002/cne.24389. macaque fronto-parietal network during rhythmic spatial attention. Nat. Commun. Itaya, S.K., Van Hoesen, G.W., 1983. Retinal projections to the inferior and medial 10, 215. https://doi.org/10.1038/s41467-018-08151-4. pulvinar nuclei in the old-world monkey. Brain Res. 269, 223–230. https://doi.org/ Fischer, J., Whitney, D., 2012. Attention gates visual coding in the human pulvinar. Nat. 10.1016/0006-8993(83)90131-2. Commun. 3, 1051. https://doi.org/10.1038/ncomms2054. Jaramillo, J., Mejias, J.F., Wang, X.-J., 2019. Engagement of pulvino-cortical Foxe, J.J., Morocz, I.A., Murray, M.M., Higgins, B.A., Javitt, D.C., Schroeder, C.E., 2000. feedforward and feedback pathways in cognitive computations. Neuron 101, Multisensory auditory–somatosensory interactions in early cortical processing 321–336. https://doi.org/10.1016/j.neuron.2018.11.023 e9. revealed by high-density electrical mapping. Cogn. Brain Res. 10, 77–83. https:// Jones, E.G., Burton, H., 1976. A projection from the medial pulvinar to the amygdala in doi.org/10.1016/S0926-6410(00)00024-0. primates. Brain Res. 104, 142–147. https://doi.org/10.1016/0006-8993(76)90654- Foxworthy, W.A., Clemo, H.R., Meredith, M.A., 2013. Laminar and connectional 5. organization of a multisensory cortex. J. Comp. Neurol. 521, 1867–1890. https:// Kaas, J.H., Baldwin, M.K.L., 2020. The evolution of the pulvinar complex in primates and doi.org/10.1002/cne.23264. its role in the dorsal and ventral streams of cortical processing. Vision 4, 3. https:// Friedman, D.P., Murray, E.A., 1986. Thalamic connectivity of the second somatosensory doi.org/10.3390/vision4010003. area and neighboring somatosensory fields of the lateral sulcus of the macaque. Kaas, J.H., Hackett, T.A., 1998. Subdivisions of auditory cortex and levels of processing J. Comp. Neurol. 252, 348–373. https://doi.org/10.1002/cne.902520305. in primates. Audiol. Neurootol. 3, 73–85. https://doi.org/10.1159/000013783. Gattass, R., Sousa, A.P.B., Oswaldo-Cruz, E., 1978. Single unit response types in the Kaas, J.H., Lyon, D.C., 2007. Pulvinar contributions to the dorsal and ventral streams of pulvinar of the cebus monkey to multisensory stimulation. Brain Res. 158, 75–87. visual processing in primates. Brain Res. Rev. 55, 285–296. https://doi.org/ https://doi.org/10.1016/0006-8993(78)90007-0. 10.1016/j.brainresrev.2007.02.008. Gattass, R., Oswaldo-Cruz, E., Sousa, A.P.B., 1979. Visual receptive fields of units in the Kadohisa, M., Rolls, E.T., Verhagen, J.V., 2005. Neuronal representations of stimuli in pulvinar of cebus monkey. Brain Res. 160, 413–429. https://doi.org/10.1016/0006- the mouth: the primate insular taste cortex, orbitofrontal cortex and amygdala. 8993(79)91070-9. Chem. Senses 30, 401–419. https://doi.org/10.1093/chemse/bji036. Ghazanfar, A.A., Schroeder, C.E., 2006. Is neocortex essentially multisensory? Trends Karnath, H.O., Himmelbach, M., Rorden, C., 2002. The subcortical anatomy of human Cogn. Sci. 10, 278–285. https://doi.org/10.1016/j.tics.2006.04.008. spatial neglect: putamen, caudate nucleus and pulvinar. Brain J. Neurol. 125, Ghazanfar, A.A., Maier, J.X., Hoffman, K.L., Logothetis, N.K., 2005. Multisensory 350–360. integration of dynamic faces and voices in rhesus monkey auditory cortex. Kastner, S., Fiebelkorn, I.C., Eradath, M.K., 2020. Dynamic pulvino-cortical interactions J. Neurosci. 25, 5004–5012. https://doi.org/10.1523/JNEUROSCI.0799-05.2005. in the primate attention network. Curr. Opin. Neurobiol. 65, 10–19. https://doi.org/ Giard, M.H., Peronnet, F., 1999. Auditory-visual integration during multimodal object 10.1016/j.conb.2020.08.002. recognition in humans: a behavioral and electrophysiological study. J. Cogn. Kayser, C., Petkov, C.I., Logothetis, N.K., 2008. Visual modulation of neurons in auditory Neurosci. 11, 473–490. https://doi.org/10.1162/089892999563544. cortex. Cereb. Cortex 18, 1560–1574. https://doi.org/10.1093/cercor/bhm187. Grant, K.W., Seitz, P.F., 2000. The use of visible speech cues for improving auditory Kinoshita, M., Kato, R., Isa, K., Kobayashi, Kenta, Kobayashi, Kazuto, Onoe, H., Isa, T., detection of spoken sentences. J. Acoust. Soc. Am. 108, 1197–1208. https://doi.org/ 2019. Dissecting the circuit for blindsight to reveal the critical role of pulvinar and 10.1121/1.1288668. superior colliculus. Nat. Commun. 10, 135. https://doi.org/10.1038/s41467-018- Gray, D., Gutierrez, C., Cusick, C.G., 1999. Neurochemical organization of inferior 08058-0. pulvinar complex in squirrel monkeys and macaques revealed by Komura, Y., Nikkuni, A., Hirashima, N., Uetake, T., Miyamoto, A., 2013. Responses of acetylcholinesterase histochemistry, calbindin and Cat-301 immunostaining, and pulvinar neurons reflect a subject’s confidence in visual categorization. Nat. Wisteria floribundaagglutinin binding. J. Comp. Neurol. 409, 452–468. https://doi. Neurosci. 16, 749–755. https://doi.org/10.1038/nn.3393. org/10.1002/(sici)1096-9861(19990705)409:3<452::aid-cne9>3.0.co;2-i. Kosmal, A., Malinowska, M., Kowalska, D.M., 1997. Thalamic and amygdaloid Grieve, K.L., Acuna,˜ C., Cudeiro, J., 2000. The primate pulvinar nuclei: vision and action. connections of the auditory association cortex of the superior temporal gyrus in Trends Neurosci. 23, 35–39. https://doi.org/10.1016/S0166-2236(99)01482-4. rhesus monkey (Macaca mulatta). Acta Neurobiol. Exp. (Warsz.) 57, 165–188. Guipponi, O., Wardak, C., Ibarrola, D., Comte, J.-C., Sappey-Marinier, D., Pin`ede, S., Lakatos, P., Chen, C.-M., O’Connell, M.N., Mills, A., Schroeder, C.E., 2007. Neuronal Hamed, S.B., 2013. Multimodal convergence within the intraparietal sulcus of the oscillations and multisensory interaction in primary auditory cortex. Neuron 53, macaque monkey. J. Neurosci. 33, 4128–4139. https://doi.org/10.1523/ 279–292. https://doi.org/10.1016/j.neuron.2006.12.011. JNEUROSCI.1421-12.2013. Lakatos, P., O’Connell, M.N., Barczak, A., 2016. Pondering the pulvinar. Neuron 89, 5–7. https://doi.org/10.1016/j.neuron.2015.12.022.

241 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243

Lanius, R.A., Rabellino, D., Boyd, J.E., Harricharan, S., Frewen, P.A., McKinnon, M.C., Padmala, S., Lim, S.-L., Pessoa, L., 2010. Pulvinar and affective significance: responses 2017. The innate alarm system in PTSD: conscious and subconscious processing of track moment-to-moment stimulus visibility. Front. Hum. Neurosci. 4 https://doi. threat. Curr. Opin. Psychol. 14, 109–115. https://doi.org/10.1016/j. org/10.3389/fnhum.2010.00064. copsyc.2016.11.006. Pearson, R.C., Brodal, P., Powell, T.P., 1978. The projection of the thalamus upon the Leh, S.E., Chakravarty, M.M., Ptito, A., 2008. The connectivity of the human pulvinar: a parietal lobe in the monkey. Brain Res. 144, 143–148. diffusion tensor imaging tractography study [WWW document]. Int. J. Biomed. Perryman, K.M., Lindsley, D.F., Lindsley, D.B., 1980. Pulvinar neuron responses to Imaging 2008, 789539. https://doi.org/10.1155/2008/789539. spontaneous and trained eye movements and to light flashes in squirrel monkeys. Lehmann, S., Murray, M.M., 2005. The role of multisensory memories in unisensory Electroencephalogr. Clin. Neurophysiol. 49, 152–161. object discrimination. Cogn. Brain Res. 24, 326–334. https://doi.org/10.1016/j. Pessoa, L., Adolphs, R., 2010. Emotion processing and the amygdala: from a “low road” cogbrainres.2005.02.005. to “many roads” of evaluating biological significance. Nat. Rev. Neurosci. 11, Liddell, B.J., Brown, K.J., Kemp, A.H., Barton, M.J., Das, P., Peduto, A., Gordon, E., 773–783. https://doi.org/10.1038/nrn2920. Williams, L.M., 2005. A direct brainstem-amygdala-cortical “alarm” system for Petersen, S.E., Posner, M.I., 2012. The attention system of the human brain: 20 years subliminal signals of fear. NeuroImage 24, 235–243. https://doi.org/10.1016/j. after. Annu. Rev. Neurosci. 35, 73–89. https://doi.org/10.1146/annurev-neuro- neuroimage.2004.08.016. 062111-150525. Lin, C.S., Kaas, J.H., 1979. The inferior pulvinar complex in owl monkeys: architectonic Petersen, S.E., Robinson, D.L., Keys, W., 1985. Pulvinar nuclei of the behaving rhesus subdivisions and patterns of input from the superior colliculus and subdivisions of monkey: visual responses and their modulation. J. Neurophysiol. 54, 867–886. visual cortex. J. Comp. Neurol. 187, 655–678. https://doi.org/10.1002/ https://doi.org/10.1152/jn.1985.54.4.867. cne.901870403. Petersen, S.E., Robinson, D.L., Morris, J.D., 1987. Contributions of the pulvinar to visual Magarinos-Ascone,˜ C., Buno,˜ W., García-Austt, E., 1988. Monkey pulvinar units related to spatial attention. Neuropsychologia 25, 97–105. motor activity and sensory response. Brain Res. 445, 30–38. https://doi.org/ Posner, M.I., DiGirolamo, G.J., Fernandez-Duque, D., 1997. Brain mechanisms of 10.1016/0006-8993(88)91070-0. cognitive skills. Conscious. Cogn. 6, 267–290. https://doi.org/10.1006/ Maior, R.S., Hori, E., Tomaz, C., Ono, T., Nishijo, H., 2010. The monkey pulvinar neurons ccog.1997.0301. differentially respond to emotional expressions of human faces. Behav. Brain Res. Price, J.L., Slotnick, B.M., 1983. Dual olfactory representation in the rat thalamus: an 215, 129–135. https://doi.org/10.1016/j.bbr.2010.07.009. anatomical and electrophysiological study. J. Comp. Neurol. 215, 63–77. https:// Mathers, L.H., Rapisardi, S.C., 1973. Visual and somatosensory receptive fields of doi.org/10.1002/cne.902150106. neurons in the squirrel monkey pulvinar. Brain Res. 64, 65–83. https://doi.org/ Purushothaman, G., Marion, R., Li, K., Casagrande, V.A., 2012. Gating and control of 10.1016/0006-8993(73)90171-6. primary visual cortex by pulvinar. Nat. Neurosci. 15, 905–912. https://doi.org/ Meredith, M.A., Stein, B.E., 1986. Visual, auditory, and somatosensory convergence on 10.1038/nn.3106. cells in superior colliculus results in multisensory integration. J. Neurophysiol. 56, Raab, D.H., 1962. Division of psychology: statistical facilitation of simple reaction times. 640–662. https://doi.org/10.1152/jn.1986.56.3.640. Trans. N. Y. Acad. Sci. 24, 574–590. https://doi.org/10.1111/j.2164-0947.1962. Meredith, M.A., Nemitz, J.W., Stein, B.E., 1987. Determinants of multisensory tb01433.x. integration in superior colliculus neurons. I. Temporal factors. J. Neurosci. 7, Rafal, R.D., Posner, M.I., 1987. Deficits in human visual spatial attention following 3215–3229. https://doi.org/10.1523/JNEUROSCI.07-10-03215.1987. thalamic lesions. Proc. Natl. Acad. Sci. U. S. A. 84, 7349–7353. Michael, G.A., Boucart, M., Degreef, J.-F., Godefroy, O., 2001. The thalamus interrupts Rafal, R.D., Koller, K., Bultitude, J.H., Mullins, P., Ward, R., Mitchell, A.S., Bell, A.H., top-down attentional control for permitting exploratory shiftings to sensory signals. 2015. Connectivity between the superior colliculus and the amygdala in humans and Neuroreport 12, 2041–2048. macaque monkeys: virtual dissection with probabilistic DTI tractography. Miller, L.M., D’Esposito, M., 2005. Perceptual fusion and stimulus coincidence in the J. Neurophysiol. 114, 1947–1962. https://doi.org/10.1152/jn.01016.2014. cross-modal integration of speech. J. Neurosci. 25, 5884–5893. https://doi.org/ Robinson, D.L., Petersen, S.E., 1992. The pulvinar and visual salience. Trends Neurosci. 10.1523/JNEUROSCI.0896-05.2005. 15, 127–132. Molholm, S., Ritter, W., Murray, M.M., Javitt, D.C., Schroeder, C.E., Foxe, J.J., 2002. Robinson, D.L., McClurkin, J.W., Kertzman, C., Petersen, S.E., 1991. Visual responses of Multisensory auditory–visual interactions during early sensory processing in pulvinar and collicular neurons during eye movements of awake, trained macaques. humans: a high-density electrical mapping study. Cogn. Brain Res. Multisensory J. Neurophysiol. 66, 485–496. https://doi.org/10.1152/jn.1991.66.2.485. Proc. 14, 115–128. https://doi.org/10.1016/S0926-6410(02)00066-6. Romanski, L.M., Giguere, M., Bates, J.F., Goldman-Rakic, P.S., 1997. Topographic Morel, A., Liu, J., Wannier, T., Jeanmonod, D., Rouiller, E.M., 2005. Divergence and organization of medial pulvinar connections with the prefrontal cortex in the rhesus convergence of thalamocortical projections to premotor and supplementary motor monkey. J. Comp. Neurol. 379, 313–332. https://doi.org/10.1002/(SICI)1096-9861 cortex: a multiple tracing study in the macaque monkey. Eur. J. Neurosci. 21, (19970317)379:3<313::AID-CNE1>3.0.CO;2-6. 1007–1029. https://doi.org/10.1111/j.1460-9568.2005.03921.x. Rosenberg, D.S., Maugui`ere, F., Catenoix, H., Faillenot, I., Magnin, M., 2009. Reciprocal Morris, J.S., Ohman, A., Dolan, R.J., 1999. A subcortical pathway to the right amygdala thalamocortical connectivity of the medial pulvinar: a depth stimulation and evoked mediating “unseen” fear. Proc. Natl. Acad. Sci. U. S. A. 96, 1680–1685. potential study in human brain. Cereb. Cortex 19, 1462–1473. https://doi.org/ Mufson, E.J., Mesulam, M.M., 1984. Thalamic connections of the insula in the rhesus 10.1093/cercor/bhn185. monkey and comments on the paralimbic connectivity of the medial pulvinar Rotshtein, P., Soto, D., Grecucci, A., Geng, J.J., Humphreys, G.W., 2011. The role of the nucleus. J. Comp. Neurol. 227, 109–120. https://doi.org/10.1002/cne.902270112. pulvinar in resolving competition between memory and visual selection: a functional Mundinano, I.-C., Fox, D.M., Kwan, W.C., Vidaurre, D., Teo, L., Homman-Ludiye, J., connectivity study. Neuropsychologia 49, 1544–1552. https://doi.org/10.1016/j. Goodale, M.A., Leopold, D.A., Bourne, J.A., 2018. Transient visual pathway critical neuropsychologia.2010.12.002. for normal development of primate grasping behavior. Proc. Natl. Acad. Sci. U. S. A. Rouiller, E.M., Welker, E., 2000. A comparative analysis of the morphology of 115, 1364–1369. https://doi.org/10.1073/pnas.1717016115. corticothalamic projections in mammals. Brain Res. Bull. 53, 727–741. https://doi. Mundinano, I.-C., Kwan, W.C., Bourne, J.A., 2019. Retinotopic specializations of cortical org/10.1016/S0361-9230(00)00364-6. and thalamic inputs to area MT. Proc. Natl. Acad. Sci. U. S. A. 116, 23326–23331. Roy, D.S., 2020. Inhibitory central amygdala outputs to thalamus control the gain of taste https://doi.org/10.1073/pnas.1909799116. perception. J. Neurosci. 40, 9166–9168. https://doi.org/10.1523/ Murray, M.M., Molholm, S., Michel, C.M., Heslenfeld, D.J., Ritter, W., Javitt, D.C., JNEUROSCI.1833-20.2020. Schroeder, C.E., Foxe, J.J., 2005. Grabbing your ear: rapid auditory–somatosensory Saalmann, Y.B., Kastner, S., 2009. Gain control in the visual thalamus during perception multisensory interactions in low-level sensory cortices are not constrained by and cognition. Curr. Opin. Neurobiol. 19, 408–414. https://doi.org/10.1016/j. stimulus alignment. Cereb. Cortex 15, 963–974. https://doi.org/10.1093/cercor/ conb.2009.05.007. bhh197. Saalmann, Y.B., Kastner, S., 2011. Cognitive and perceptual functions of the visual Musacchia, G.A.E., Sams, M., Nicol, T.G., Kraus, N., 2006. Seeing speech affects acoustic thalamus. Neuron 71, 209–223. https://doi.org/10.1016/j.neuron.2011.06.027. information processing in the human brainstem. Exp. Brain Res. Exp. Hirnforsch. Saalmann, Y.B., Pinsk, M.A., Wang, L., Li, X., Kastner, S., 2012. The pulvinar regulates Exp. Cerebrale 168, 1–10. https://doi.org/10.1007/s00221-005-0071-5. information transmission between cortical areas based on attention demands. Nguyen, M.N., Hori, E., Matsumoto, J., Tran, A.H., Ono, T., Nishijo, H., 2013. Neuronal Science 337, 753–756. https://doi.org/10.1126/science.1223082. responses to face-like stimuli in the monkey pulvinar. Eur. J. Neurosci. 37, 35–51. Saalmann, Y.B., Ly, R., Pinsk, M.A., Kastner, S., 2018. Pulvinar InfluencesParietal Delay https://doi.org/10.1111/ejn.12020. Activity and Information Transmission Between Dorsal and Ventral Visual Cortex in Noesselt, T., Rieger, J.W., Schoenfeld, M.A., Kanowski, M., Hinrichs, H., Heinze, H.-J., Macaques. bioRxiv, p. 405381. https://doi.org/10.1101/405381. Driver, J., 2007. Audiovisual temporal correspondence modulates human Schmahmann, J.D., Pandya, D.N., 1990. Anatomical investigation of projections from multisensory superior temporal sulcus plus primary sensory cortices. J. Neurosci. 27, thalamus to posterior parietal cortex in the rhesus monkey: a WGA-HRP and 11431–11441. https://doi.org/10.1523/JNEUROSCI.2252-07.2007. fluorescent tracer study. J. Comp. Neurol. 295, 299–326. https://doi.org/10.1002/ O’Brien, B.J., Abel, P.L., Olavarria, J.F., 2001. The retinal input to calbindin-D28k- cne.902950212. defined subdivisions in macaque inferior pulvinar. Neurosci. Lett. 312, 145–148. Schmid, M.C., Singer, W., Fries, P., 2012. Thalamic coordination of cortical Ojemann, G.A., Fedio, P., Van Buren, J.M., 1968. Anomia from pulvinar and subcortical communication. Neuron 75, 551–552. https://doi.org/10.1016/j. parietal stimulation. Brain J. Neurol. 91, 99–116. neuron.2012.08.009. Olszewski, J., 1952. The Thalamus of the Macaca, Mulatta. An Atlas for use with the Schneider, L., Dominguez-Vargas, A.-U., Gibson, L., Kagan, I., Wilke, M., 2019. Eye Stereotaxic Instrument. Thalamus Macaca Mulatta Atlas Use Ster. Instrum. position signals in the dorsal pulvinar during fixation and goal-directed saccades. Padberg, J., Cerkevich, C., Engle, J., Rajan, A.T., Recanzone, G., Kaas, J., Krubitzer, L., J. Neurophysiol. 123, 367–391. https://doi.org/10.1152/jn.00432.2019. 2009. Thalamocortical connections of parietal somatosensory cortical fields in Schroeder, C.E., Foxe, J., 2005. Multisensory contributions to low-level, ‘unisensory’ macaque monkeys are highly divergent and convergent. Cereb. Cortex N. Y. N 1991 processing. Curr. Opin. Neurobiol. Sens. Syst. 15, 454–458. https://doi.org/ (19), 2038–2064. https://doi.org/10.1093/cercor/bhn229. 10.1016/j.conb.2005.06.008.

242 M. Froesel et al. Neuroscience and Biobehavioral Reviews 125 (2021) 231–243

Sela, L., Sacher, Y., Serfaty, C., Yeshurun, Y., Soroker, N., Sobel, N., 2009. Spared and Wallace, M.T., Meredith, M.A., Stein, B.E., 1993. Converging influences from visual, impaired olfactory abilities after thalamic lesions. J. Neurosci. 29, 12059–12069. auditory, and somatosensory cortices onto output neurons of the superior colliculus. https://doi.org/10.1523/JNEUROSCI.2114-09.2009. J. Neurophysiol. 69, 1797–1809. https://doi.org/10.1152/jn.1993.69.6.1797. Sherman, S.M., 2007. The thalamus is more than just a relay. Curr. Opin. Neurobiol. Wallace, M.T., Meredith, M.A., Stein, B.E., 1998. Multisensory integration in the superior Sens. Syst. 17, 417–422. https://doi.org/10.1016/j.conb.2007.07.003. colliculus of the alert cat. J. Neurophysiol. 80, 1006–1010. https://doi.org/10.1152/ Sherman, S.M., Guillery, R.W., 2006. Exploring the Thalamus and its Role in Cortical jn.1998.80.2.1006. Function, 2nd ed. MIT Press, Cambridge, MA, US. Wang, Y., Celebrini, S., Trotter, Y., Barone, P., 2008. Visuo-auditory interactions in the Shipp, S., 2003. The functional logic of cortico-pulvinar connections. Philos. Trans. R. primary visual cortex of the behaving monkey: electrophysiological evidence. BMC Soc. B Biol. Sci. 358, 1605–1624. https://doi.org/10.1098/rstb.2002.1213. Neurosci. 9, 79. https://doi.org/10.1186/1471-2202-9-79. Snow, J.C., Allen, H.A., Rafal, R.D., Humphreys, G.W., 2009. Impaired attentional Ward, R., Arend, I., 2007. An object-based frame of reference within the human pulvinar. selection following lesions to human pulvinar: evidence for homology between Brain J. Neurol. 130, 2462–2469. https://doi.org/10.1093/brain/awm176. human and monkey. Proc. Natl. Acad. Sci. U. S. A. 106, 4054–4059. https://doi.org/ Ward, R., Calder, A.J., Parker, M., Arend, I., 2007. Emotion recognition following human 10.1073/pnas.0810086106. pulvinar damage. Neuropsychologia 45, 1973–1978. https://doi.org/10.1016/j. Soares, S.C., Maior, R.S., Isbell, L.A., Tomaz, C., Nishijo, H., 2017. Fast detector/first neuropsychologia.2006.09.017. responder: interactions between the superior colliculus-pulvinar pathway and Warner, C.E., Goldshmit, Y., Bourne, J.A., 2010. Retinal afferents synapse with relay cells stimuli relevant to primates. Front. Neurosci. 11, 67. https://doi.org/10.3389/ targeting the middle temporal area in the pulvinar and lateral geniculate nuclei. fnins.2017.00067. Front. Neuroanat. 4 https://doi.org/10.3389/neuro.05.008.2010. Stein, B.E., Meredith, M.A., 1993. The Merging of the Senses, the Merging of the Senses. Weber, J.T., Yin, T.C., 1984. Subcortical projections of the inferior parietal cortex (area The MIT Press, Cambridge, MA, US. 7) in the stump-tailed monkey. J. Comp. Neurol. 224, 206–230. Stepniewska, I., Kaas, J.H., 1997. Architectonic subdivisions of the inferior pulvinar in Webster, M.J., Bachevalier, J., Ungerleider, L.G., 1993. Subcortical connections of New World and Old World monkeys. Vis. Neurosci. 14, 1043–1060. https://doi.org/ inferior temporal areas TE and TEO in macaque monkeys. J. Comp. Neurol. 335, 10.1017/S0952523800011767. 73–91. https://doi.org/10.1002/cne.903350106. Stepniewska, I., Qi, H.-X., Kaas, J.H., 2000. Projections of the superior colliculus to Welch, R.B., DutionHurt, L.D., Warren, D.H., 1986. Contributions of audition and vision subdivisions of the inferior pulvinar in New World and Old World monkeys. Vis. to temporal rate perception. Percept. Psychophys. 39, 294–300. https://doi.org/ Neurosci. 17, 529–549. https://doi.org/10.1017/S0952523800174048. 10.3758/BF03204939. Strumpf, H., Mangun, G.R., Boehler, C.N., Stoppel, C., Schoenfeld, M.A., Heinze, H.-J., Weller, R.E., Steele, G.E., 1992. Cortical connections of subdivisions of inferior temporal Hopf, J.-M., 2013. The role of the pulvinar in distractor processing and visual search. cortex in squirrel monkeys. J. Comp. Neurol. 324, 37–66. https://doi.org/10.1002/ Hum. Brain Mapp. 34, 1115–1132. https://doi.org/10.1002/hbm.21496. cne.903240105. Tadayonnejad, R., Klumpp, H., Ajilore, O., Leow, A., Phan, K.L., 2016. Aberrant pulvinar Werner, S., Noppeney, U., 2010. Superadditive responses in superior temporal sulcus effective connectivity in generalized social anxiety disorder. Medicine (Baltimore) predict audiovisual benefits in object categorization. Cereb. Cortex 20, 1829–1842. 95. https://doi.org/10.1097/MD.0000000000005358. https://doi.org/10.1093/cercor/bhp248. Tamietto, M., Pullens, P., de Gelder, B., Weiskrantz, L., Goebel, R., 2012. Subcortical Wilke, M., Logothetis, N.K., Leopold, D.A., 2006. Local fieldpotential reflectsperceptual connections to human amygdala and changes following destruction of the visual suppression in monkey visual cortex. Proc. Natl. Acad. Sci. U. S. A. 103, cortex. Curr. Biol. CB 22, 1449–1455. https://doi.org/10.1016/j.cub.2012.06.006. 17507–17512. https://doi.org/10.1073/pnas.0604673103. Trojanowski, J.Q., Jacobson, S., 1974. Medial pulvinar afferents to frontal eye fields in Wilke, M., Mueller, K.-M., Leopold, D.A., 2009. Neural activity in the visual thalamus rhesus monkey demonstrated by horseradish peroxidase. Brain Res. 80, 395–411. reflects perceptual suppression. Proc. Natl. Acad. Sci. U. S. A. 106, 9465–9470. https://doi.org/10.1016/0006-8993(74)91025-7. https://doi.org/10.1073/pnas.0900714106. Tyll, S., Budinger, E., Noesselt, T., 2011. Thalamic influences on multisensory Wilke, M., Turchi, J., Smith, K., Mishkin, M., Leopold, D.A., 2010. Pulvinar inactivation integration. Commun. Integr. Biol. 4, 378–381. https://doi.org/10.4161/ disrupts selection of movement plans. J. Neurosci. 30, 8650–8659. https://doi.org/ cib.4.4.15222. 10.1523/JNEUROSCI.0953-10.2010. Ungerleider, L.G., Christensen, C.A., 1979. Pulvinar lesions in monkeys produce Wilke, M., Kagan, I., Andersen, R.A., 2013. Effects of pulvinar inactivation on spatial abnormal scanning of a complex visual array. Neuropsychologia 17, 493–501. decision-making between equal and asymmetric reward options. J. Cogn. Neurosci. Valet, M., Sprenger, T., Boecker, H., Willoch, F., Rummeny, E., Conrad, B., Erhard, P., 25, 1270–1283. https://doi.org/10.1162/jocn_a_00399. Tolle, T.R., 2004. Distraction modulates connectivity of the cingulo-frontal cortex Wilke, M., Schneider, L., Dominguez-Vargas, A.-U., Schmidt-Samoa, C., Miloserdov, K., and the midbrain during pain—an fMRI analysis. Pain 109, 399–408. https://doi. Nazzal, A., Dechent, P., Cabral-Calderin, Y., Scherberger, H., Kagan, I., Bahr,¨ M., org/10.1016/j.pain.2004.02.033. 2018. Reach and grasp deficits following damage to the dorsal pulvinar. Cortex J. Van, J.B., Borke, R.C., 1969. Alterations in speech and the pulvinar. A serial section study Devoted Study Nerv. Syst. Behav. 99, 135–149. https://doi.org/10.1016/j. of cerebrothalamic relationships in cases of acquired speech disorders. Brain J. cortex.2017.10.011. Neurol. 92, 255–284. https://doi.org/10.1093/brain/92.2.255. Yeterian, E.H., Pandya, D.N., 1985. Corticothalamic connections of the posterior parietal Van Essen, D.C., 2003. Organization of visual areas in macaque and human cerebral cortex in the rhesus monkey. J. Comp. Neurol. 237, 408–426. https://doi.org/ cortex. Vis. Neurosci. 1, 507–521. 10.1002/cne.902370309. Van Essen, D.C., Drury, H.A., 1997. Structural and functional analyses of human cerebral Yeterian, E.H., Pandya, D.N., 1988. Corticothalamic connections of paralimbic regions in cortex using a surface-based atlas. J. Neurosci. 17, 7079–7102. https://doi.org/ the rhesus monkey. J. Comp. Neurol. 269, 130–146. https://doi.org/10.1002/ 10.1523/JNEUROSCI.17-18-07079.1997. cne.902690111. Van Essen, D.C., Felleman, D.J., DeYoe, E.A., Olavarria, J., Knierim, J., 1990. Modular Yeterian, E.H., Pandya, D.N., 1997. Corticothalamic connections of extrastriate visual and hierarchical organization of extrastriate visual cortex in the macaque monkey. areas in rhesus monkeys. J. Comp. Neurol. 378, 562–585. https://doi.org/10.1002/ Cold Spring Harb. Symp. Quant. Biol. 55, 679–696. https://doi.org/10.1101/ (SICI)1096-9861(19970224)378:4<562::AID-CNE10>3.0.CO;2-L. SQB.1990.055.01.064. Yirmiya, R., Hocherman, S., 1987. Auditory- and movement-related neural activity Van Le, Q., Isbell, L.A., Matsumoto, J., Nguyen, M., Hori, E., Maior, R.S., Tomaz, C., interact in the pulvinar of the behaving rhesus monkey. Brain Res. 402, 93–102. Tran, A.H., Ono, T., Nishijo, H., 2013. Pulvinar neurons reveal neurobiological https://doi.org/10.1016/0006-8993(87)91051-1. evidence of past selection for rapid detection of snakes. Proc. Natl. Acad. Sci. U. S. A. Zhou, H., Schafer, R.J., Desimone, R., 2016. Pulvinar-cortex interactions in vision and 110, 19000–19005. https://doi.org/10.1073/pnas.1312648110. attention. Neuron 89, 209–220. https://doi.org/10.1016/j.neuron.2015.11.034. von Kriegstein, K., Kleinschmidt, A., Sterzer, P., Giraud, A.-L., 2005. Interaction of face Zhou, N., Maire, P.S., Masterson, S.P., Bickford, M.E., 2017. The mouse pulvinar nucleus: and voice areas during speaker recognition. J. Cogn. Neurosci. 17, 367–376. https:// organization of the tectorecipient zones. Vis. Neurosci. 34 https://doi.org/10.1017/ doi.org/10.1162/0898929053279577. S0952523817000050. Walker, A.E., 1938. The thalamus of the chimpanzee: IV. Thalamic projections to the Zihl, J., von Cramon, D., 1979. The contribution of the “second” visual system to directed cerebral cortex. J. Anat. 73, 37–93. visual attention in man. Brain J. Neurol. 102, 835–856.

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