Lesions of primate primary visual cortex (V1) lead to loss of conscious visual perception, and ar... more Lesions of primate primary visual cortex (V1) lead to loss of conscious visual perception, and are often devastating to those affected. Understanding the neural consequences of such damage may aid the development of rehabilitation methods. In this rare case of a Rhesus macaque (monkey S), likely born without V1, we investigated the brain structures underlying residual visual abilities using multimodal magnetic resonance imaging. In-group behaviour was unremarkable. Compared to controls, visual structures outside of monkey S’s lesion appeared normal. Visual stimulation under anaesthesia with checkerboards activated lateral geniculate nucleus of monkey S, but not the pulvinar, while full-field moving dots activated the pulvinar. Functional connectivity analysis revealed a network of bilateral dorsal visual areas temporally correlated with V5/MT, consistent across lesion and control animals. Overall, we found an intact network of visual cortical areas even without V1, but little eviden...
The function of the human mediodorsal thalamic nucleus (MD) has so far eluded a clear definition ... more The function of the human mediodorsal thalamic nucleus (MD) has so far eluded a clear definition in terms of specific cognitive processes and tasks. Although it was at first proposed to play a role in long-term memory, a set of recent studies in animals and humans has revealed a more complex, and broader, role in several cognitive functions. The MD seems to play a multifaceted role in higher cognitive functions together with the prefrontal cortex and other cortical and subcortical brain areas. Specifically, we propose that the MD is involved in the regulation of cortical networks especially when the maintenance and temporal extension of persistent activity patterns in the frontal lobe areas are required. Nevertheless, Euryclea, take his bed outside the bed chamber that he himself built. Odyssey, Book XXIII, verses 177-178. Butler translation. The Mediodorsal Nucleus: A Reappraisal When faced with the prospect of welcoming a stranger as her long-missing husband, and unable to recognize him, Penelope resorted to her 'thalamus' with the words reported abovethe bed had roots in the foundation of the house and could not be moved, a detail her husband would certainly know. Initially entering the scene as something instrumental to recognition, the thalamus (see Glossary) in the Odyssey becomes the center of the scene in the last two books. Likewise, in neuroscience, the investigation of the mediodorsal thalamic nucleus (MD) is gaining momentum. Until recently, the function of the MD has been mapped onto specific cognitive domains, such as memory or executive function. An influential model on a role of the MD in recognition memory for instance suggested it might play a role in familiarity [1]. However, abundant evidence indicates that this view is limited and that the role of the MD in human cognition must be reconsidered. For example, clinicians have known for a long time that the MD and its brain networks are involved in several neurological and psychiatric conditions in which the cognitive deficits are not restricted to memory functions [2]. Neuroimaging and neurophysiology studies of the human MD in vivo further support this view change. This review evaluates the latest evidence in humans and aims at formulating hypotheses to elucidate the cognitive functions of the human MD in future studies. We argue that the MD is involved in regulating activity patterns in the frontal lobe that are key to perform cognitive functions characterized by persistent thalamocortical interactions for long delays, in the face of Highlights
Background: Neuroscience studies with macaque monkeys may require cranial implants to stabilize t... more Background: Neuroscience studies with macaque monkeys may require cranial implants to stabilize the head or gain access to the brain for scientific purposes. Wound management that promotes healing after the cranial implant surgery in non-human primates can be difficult as it is not necessarily possible to cover the wound margins. New method: Here, we developed an easily modifiable head cap that protects the sutured skin margins after cranial implant surgery and contributes to wound healing. The protective head cap was developed in response to monkeys picking at sutured skin margins around an implant, complicating healing. The user-friendly protective cap, made from Klarity-R™ Sheet (3.2 mm thick with 36 % or 42 % perforation) is affixed to the implant postsurgically. Once secured and while the monkey is still anesthetized, the plastic sheeting is molded around the implant. The protective head cap restricts the monkey's finger access to its' wound margins while allowing air to circulate to promote wound healing. Results and comparison with existing methods: Across two UK primate facilities, the protective head cap promoted wound healing. In monkeys that did not wear the head cap, re-suturing was necessary in ~30 % of cases. In contrast, none of the monkeys that wore the head cap required re-suturing. The monkeys wearing the head cap also had reduced numbers of days of prescribed antibiotics and analgesia. Conclusion: This bespoken, easily adaptable, protective head cap supports postoperative wound healing, and enhances the welfare of monkeys involved in neuroscience research.
Cognitive flexibility, attributed to frontal cortex, is vital for navigating the complexities of ... more Cognitive flexibility, attributed to frontal cortex, is vital for navigating the complexities of everyday life. The mediodorsal thalamus (MD), interconnected to frontal cortex, may influence cognitive flexibility. Here male rats performed an attentional set-shifting task measuring intra-dimensional and extra-dimensional shifts in sensory discriminations. MD lesion rats needed more trials to learn the rewarded sensory dimension. However, once the choice response strategy was established, learning further two-choice discriminations in the same sensory dimension, and reversals of the reward contingencies in the same dimension, were unimpaired. Critically though, MD lesion rats were impaired during the extra-dimensional shift, when they must rapidly update the optimal choice response strategy. Behavioral analyses showed MD lesion rats had significantly reduced correct within trial second choice responses. This evidence shows transfer of information via the MD is critical when monitoring...
The mediodorsal thalamus (MD) and anterior thalamic nuclei (ATN) are two adjacent brain nodes tha... more The mediodorsal thalamus (MD) and anterior thalamic nuclei (ATN) are two adjacent brain nodes that support our ability to make decisions, learn, update information, form and retrieve memories, and find our way around. The MD and PFC work in partnerships to support cognitive processes linked to successful learning and decision-making, while the ATN and extended hippocampal system together coordinate the encoding and retrieval of memories and successful spatial navigation. Yet, while these distinctions may appear to be segregated, both the MD and ATN together support our higher cognitive functions as they regulate and are influenced by interconnected fronto-temporal neural networks and subcortical inputs. Our review focuses on recent studies in animal models and in humans. This evidence is re-shaping our understanding of the importance of MD and ATN cortico-thalamocortical pathways in influencing complex cognitive functions. Given the evidence from clinical settings and neuroscience research labs, the MD and ATN should be considered targets for effective treatments in neuropsychiatric diseases and disorders and neurodegeneration.
The frontal cortex and temporal lobes together regulate complex learning and memory capabilities.... more The frontal cortex and temporal lobes together regulate complex learning and memory capabilities. Here, we collected resting-state functional and diffusion-weighted MRI data before and after male rhesus macaque monkeys received extensive training to learn novel visuospatial discriminations (reward-guided learning). We found functional connectivity changes in orbitofrontal, ventromedial prefrontal, inferotemporal, entorhinal, retrosplenial, and anterior cingulate cortices, the subicular complex, and the dorsal, medial thalamus. These corticocortical and thalamocortical changes in functional connectivity were accompanied by related white matter structural alterations in the uncinate fasciculus, fornix, and ventral prefrontal tract: tracts that connect (sub)cortical networks and are implicated in learning and memory processes in monkeys and humans. After the well-trained monkeys received fornix transection, they were impaired in learning new visuospatial discriminations. In addition, the functional connectivity profile that was observed after the training was altered. These changes were accompanied by white matter changes in the ventral prefrontal tract, although the integrity of the uncinate fasciculus remained unchanged. Our experiments highlight the importance of different communication relayed among corticocortical and thalamocortical circuitry for the ability to learn new visuospatial associations (learning-to-learn) and to make reward-guided decisions.
The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions (such as ... more The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making) because of its significant interconnectivity with the prefrontal cortex (PFC). Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move), the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cog...
Retrosplenial cortex (RSC) is a region within the posterior neocortical system, heavily interconn... more Retrosplenial cortex (RSC) is a region within the posterior neocortical system, heavily interconnected with an array of brain networks, both cortical and subcortical, that is engaged by a myriad of cognitive tasks. Although there is no consensus as to its precise function, evidence from both human and animal studies clearly points to a role in spatial cognition. However, the spatial processing impairments that follow RSC damage are not straightforward to characterise, leading to difficulties in defining the exact nature of its role. In the present article we review this literature and classify the types of ideas that have been put forward into three broad, somewhat overlapping classes: (i) Learning of landmark location, stability and permanence; (ii) Integration between spatial reference frames, and (iii) Consolidation and retrieval of spatial knowledge ('schemas'). We evaluate these models and suggest ways to test them, before briefly discussing whether the spatial function...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Aug 17, 2016
In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. P... more In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using f...
Adaptive decision-making uses information gained when exploring alternative options to decide whe... more Adaptive decision-making uses information gained when exploring alternative options to decide whether to update the current choice strategy. Magnocellular mediodorsal thalamus (MDmc) supports adaptive decision-making, but its causal contribution is not well understood. Monkeys with excitotoxic MDmc damage were tested on probabilistic three-choice decision-making tasks. They could learn and track the changing values in object-reward associations, but they were severely impaired at updating choices after reversals in reward contingencies or when there were multiple options associated with reward. These deficits were not caused by perseveration or insensitivity to negative feedback though. Instead, monkeys with MDmc lesions exhibited an inability to use reward to promote choice repetition after switching to an alternative option due to a diminished influence of recent past choices and the last outcome to guide future behavior. Together, these data suggest MDmc allows for the rapid disc...
Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. B... more Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesion studies. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state of the art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations fro...
Retrosplenial cortex (RSC) lies at the interface between sensory and cognitive networks in the br... more Retrosplenial cortex (RSC) lies at the interface between sensory and cognitive networks in the brain and mediates between these, although it is not yet known how. It has two distinct subregions, granular (gRSC) and dysgranular (dRSC). The present study investigated how these subregions differ with respect to their electrophysiology and thalamic connectivity, as a step towards understanding their functions. The gRSC is more closely connected to the hippocampal formation, in which theta-band local field potential oscillations are prominent. We, therefore, compared theta-rhythmic single-unit activity between the two RSC subregions and found, mostly in gRSC, a subpopulation of non-directional cells with spiking activity strongly entrained by theta oscillations, suggesting a stronger coupling of gRSC to the hippocampal system. We then used retrograde tracers to test for differential inputs to RSC from the anteroventral thalamus (AV). We found that gRSC and dRSC differ in their afferents from two AV subfields: dorsomedial (AVDM) and ventrolateral (AVVL). Specifically: (1) as a whole AV projects more strongly to gRSC; (2) AVVL targets both gRSC and dRSC, while AVDM provides a selective projection to gRSC, (3) the gRSC projection is layer-specific: AVDM targets specifically gRSC superficial layers. These same AV projections are topographically organized with ventral AV neurons innervating rostral RSC and dorsal AV neurons innervating caudal RSC. These combined results suggest the existence of two distinct but interacting RSC subcircuits: one connecting AVDM to gRSC that may comprise part of the cognitive hippocampal system, and the other connecting AVVL to both RSC regions that may link hippocampal and perceptual regions. We suggest that these subcircuits are distinct to allow for differential weighting during integration of converging sensory and cognitive computations: an integration that may take place in thalamus, RSC, or both.
Our memories are essential in our daily lives. The frontal and cingulate cortices, hippocampal sy... more Our memories are essential in our daily lives. The frontal and cingulate cortices, hippocampal system and medial temporal lobes are key brain regions. In addition, severe amnesia also occurs after damage or dysfunction to the anterior thalamic nuclei; this subcortical thalamic hub is interconnected to these key cortical memory structures. Behavioral, anatomical, and physiological evidence across mammalian species has shown that interactions between the anterior thalamic nuclei, cortex and hippocampal formation are vital for spatial memory processing. Furthermore, the adjacent laterodorsal thalamic nucleus (LD), interconnected to the retrosplenial cortex (RSC) and visual system, also contributes to spatial memory in mammals. However, how these thalamic nuclei contribute to memory still remains largely unknown. Fortunately, our understanding of the importance of the thalamus in cognitive processes is being redefined, as widespread evidence challenges the established view of the thalamus as a passive relay of sensory and subcortical information to the cortex. In this review article, we examine whether the anterior thalamic nuclei and the adjacent LD are suitable candidates for "higher-order" thalamic nuclei, as defined by the Sherman and Guillery model. Rather than simply relaying information to cortex, "higher-order" thalamic nuclei have a prominent role in cognition, as they can regulate how areas of the cortex interact with one another. These considerations along with a review of the latest research will be used to suggest future studies that will clarify the contributions that the anterior and LD have in supporting cortical functions during cognitive processes.
Lesions of primate primary visual cortex (V1) lead to loss of conscious visual perception, and ar... more Lesions of primate primary visual cortex (V1) lead to loss of conscious visual perception, and are often devastating to those affected. Understanding the neural consequences of such damage may aid the development of rehabilitation methods. In this rare case of a Rhesus macaque (monkey S), likely born without V1, we investigated the brain structures underlying residual visual abilities using multimodal magnetic resonance imaging. In-group behaviour was unremarkable. Compared to controls, visual structures outside of monkey S’s lesion appeared normal. Visual stimulation under anaesthesia with checkerboards activated lateral geniculate nucleus of monkey S, but not the pulvinar, while full-field moving dots activated the pulvinar. Functional connectivity analysis revealed a network of bilateral dorsal visual areas temporally correlated with V5/MT, consistent across lesion and control animals. Overall, we found an intact network of visual cortical areas even without V1, but little eviden...
The function of the human mediodorsal thalamic nucleus (MD) has so far eluded a clear definition ... more The function of the human mediodorsal thalamic nucleus (MD) has so far eluded a clear definition in terms of specific cognitive processes and tasks. Although it was at first proposed to play a role in long-term memory, a set of recent studies in animals and humans has revealed a more complex, and broader, role in several cognitive functions. The MD seems to play a multifaceted role in higher cognitive functions together with the prefrontal cortex and other cortical and subcortical brain areas. Specifically, we propose that the MD is involved in the regulation of cortical networks especially when the maintenance and temporal extension of persistent activity patterns in the frontal lobe areas are required. Nevertheless, Euryclea, take his bed outside the bed chamber that he himself built. Odyssey, Book XXIII, verses 177-178. Butler translation. The Mediodorsal Nucleus: A Reappraisal When faced with the prospect of welcoming a stranger as her long-missing husband, and unable to recognize him, Penelope resorted to her 'thalamus' with the words reported abovethe bed had roots in the foundation of the house and could not be moved, a detail her husband would certainly know. Initially entering the scene as something instrumental to recognition, the thalamus (see Glossary) in the Odyssey becomes the center of the scene in the last two books. Likewise, in neuroscience, the investigation of the mediodorsal thalamic nucleus (MD) is gaining momentum. Until recently, the function of the MD has been mapped onto specific cognitive domains, such as memory or executive function. An influential model on a role of the MD in recognition memory for instance suggested it might play a role in familiarity [1]. However, abundant evidence indicates that this view is limited and that the role of the MD in human cognition must be reconsidered. For example, clinicians have known for a long time that the MD and its brain networks are involved in several neurological and psychiatric conditions in which the cognitive deficits are not restricted to memory functions [2]. Neuroimaging and neurophysiology studies of the human MD in vivo further support this view change. This review evaluates the latest evidence in humans and aims at formulating hypotheses to elucidate the cognitive functions of the human MD in future studies. We argue that the MD is involved in regulating activity patterns in the frontal lobe that are key to perform cognitive functions characterized by persistent thalamocortical interactions for long delays, in the face of Highlights
Background: Neuroscience studies with macaque monkeys may require cranial implants to stabilize t... more Background: Neuroscience studies with macaque monkeys may require cranial implants to stabilize the head or gain access to the brain for scientific purposes. Wound management that promotes healing after the cranial implant surgery in non-human primates can be difficult as it is not necessarily possible to cover the wound margins. New method: Here, we developed an easily modifiable head cap that protects the sutured skin margins after cranial implant surgery and contributes to wound healing. The protective head cap was developed in response to monkeys picking at sutured skin margins around an implant, complicating healing. The user-friendly protective cap, made from Klarity-R™ Sheet (3.2 mm thick with 36 % or 42 % perforation) is affixed to the implant postsurgically. Once secured and while the monkey is still anesthetized, the plastic sheeting is molded around the implant. The protective head cap restricts the monkey's finger access to its' wound margins while allowing air to circulate to promote wound healing. Results and comparison with existing methods: Across two UK primate facilities, the protective head cap promoted wound healing. In monkeys that did not wear the head cap, re-suturing was necessary in ~30 % of cases. In contrast, none of the monkeys that wore the head cap required re-suturing. The monkeys wearing the head cap also had reduced numbers of days of prescribed antibiotics and analgesia. Conclusion: This bespoken, easily adaptable, protective head cap supports postoperative wound healing, and enhances the welfare of monkeys involved in neuroscience research.
Cognitive flexibility, attributed to frontal cortex, is vital for navigating the complexities of ... more Cognitive flexibility, attributed to frontal cortex, is vital for navigating the complexities of everyday life. The mediodorsal thalamus (MD), interconnected to frontal cortex, may influence cognitive flexibility. Here male rats performed an attentional set-shifting task measuring intra-dimensional and extra-dimensional shifts in sensory discriminations. MD lesion rats needed more trials to learn the rewarded sensory dimension. However, once the choice response strategy was established, learning further two-choice discriminations in the same sensory dimension, and reversals of the reward contingencies in the same dimension, were unimpaired. Critically though, MD lesion rats were impaired during the extra-dimensional shift, when they must rapidly update the optimal choice response strategy. Behavioral analyses showed MD lesion rats had significantly reduced correct within trial second choice responses. This evidence shows transfer of information via the MD is critical when monitoring...
The mediodorsal thalamus (MD) and anterior thalamic nuclei (ATN) are two adjacent brain nodes tha... more The mediodorsal thalamus (MD) and anterior thalamic nuclei (ATN) are two adjacent brain nodes that support our ability to make decisions, learn, update information, form and retrieve memories, and find our way around. The MD and PFC work in partnerships to support cognitive processes linked to successful learning and decision-making, while the ATN and extended hippocampal system together coordinate the encoding and retrieval of memories and successful spatial navigation. Yet, while these distinctions may appear to be segregated, both the MD and ATN together support our higher cognitive functions as they regulate and are influenced by interconnected fronto-temporal neural networks and subcortical inputs. Our review focuses on recent studies in animal models and in humans. This evidence is re-shaping our understanding of the importance of MD and ATN cortico-thalamocortical pathways in influencing complex cognitive functions. Given the evidence from clinical settings and neuroscience research labs, the MD and ATN should be considered targets for effective treatments in neuropsychiatric diseases and disorders and neurodegeneration.
The frontal cortex and temporal lobes together regulate complex learning and memory capabilities.... more The frontal cortex and temporal lobes together regulate complex learning and memory capabilities. Here, we collected resting-state functional and diffusion-weighted MRI data before and after male rhesus macaque monkeys received extensive training to learn novel visuospatial discriminations (reward-guided learning). We found functional connectivity changes in orbitofrontal, ventromedial prefrontal, inferotemporal, entorhinal, retrosplenial, and anterior cingulate cortices, the subicular complex, and the dorsal, medial thalamus. These corticocortical and thalamocortical changes in functional connectivity were accompanied by related white matter structural alterations in the uncinate fasciculus, fornix, and ventral prefrontal tract: tracts that connect (sub)cortical networks and are implicated in learning and memory processes in monkeys and humans. After the well-trained monkeys received fornix transection, they were impaired in learning new visuospatial discriminations. In addition, the functional connectivity profile that was observed after the training was altered. These changes were accompanied by white matter changes in the ventral prefrontal tract, although the integrity of the uncinate fasciculus remained unchanged. Our experiments highlight the importance of different communication relayed among corticocortical and thalamocortical circuitry for the ability to learn new visuospatial associations (learning-to-learn) and to make reward-guided decisions.
The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions (such as ... more The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making) because of its significant interconnectivity with the prefrontal cortex (PFC). Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move), the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cog...
Retrosplenial cortex (RSC) is a region within the posterior neocortical system, heavily interconn... more Retrosplenial cortex (RSC) is a region within the posterior neocortical system, heavily interconnected with an array of brain networks, both cortical and subcortical, that is engaged by a myriad of cognitive tasks. Although there is no consensus as to its precise function, evidence from both human and animal studies clearly points to a role in spatial cognition. However, the spatial processing impairments that follow RSC damage are not straightforward to characterise, leading to difficulties in defining the exact nature of its role. In the present article we review this literature and classify the types of ideas that have been put forward into three broad, somewhat overlapping classes: (i) Learning of landmark location, stability and permanence; (ii) Integration between spatial reference frames, and (iii) Consolidation and retrieval of spatial knowledge ('schemas'). We evaluate these models and suggest ways to test them, before briefly discussing whether the spatial function...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Aug 17, 2016
In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. P... more In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using f...
Adaptive decision-making uses information gained when exploring alternative options to decide whe... more Adaptive decision-making uses information gained when exploring alternative options to decide whether to update the current choice strategy. Magnocellular mediodorsal thalamus (MDmc) supports adaptive decision-making, but its causal contribution is not well understood. Monkeys with excitotoxic MDmc damage were tested on probabilistic three-choice decision-making tasks. They could learn and track the changing values in object-reward associations, but they were severely impaired at updating choices after reversals in reward contingencies or when there were multiple options associated with reward. These deficits were not caused by perseveration or insensitivity to negative feedback though. Instead, monkeys with MDmc lesions exhibited an inability to use reward to promote choice repetition after switching to an alternative option due to a diminished influence of recent past choices and the last outcome to guide future behavior. Together, these data suggest MDmc allows for the rapid disc...
Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. B... more Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesion studies. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state of the art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations fro...
Retrosplenial cortex (RSC) lies at the interface between sensory and cognitive networks in the br... more Retrosplenial cortex (RSC) lies at the interface between sensory and cognitive networks in the brain and mediates between these, although it is not yet known how. It has two distinct subregions, granular (gRSC) and dysgranular (dRSC). The present study investigated how these subregions differ with respect to their electrophysiology and thalamic connectivity, as a step towards understanding their functions. The gRSC is more closely connected to the hippocampal formation, in which theta-band local field potential oscillations are prominent. We, therefore, compared theta-rhythmic single-unit activity between the two RSC subregions and found, mostly in gRSC, a subpopulation of non-directional cells with spiking activity strongly entrained by theta oscillations, suggesting a stronger coupling of gRSC to the hippocampal system. We then used retrograde tracers to test for differential inputs to RSC from the anteroventral thalamus (AV). We found that gRSC and dRSC differ in their afferents from two AV subfields: dorsomedial (AVDM) and ventrolateral (AVVL). Specifically: (1) as a whole AV projects more strongly to gRSC; (2) AVVL targets both gRSC and dRSC, while AVDM provides a selective projection to gRSC, (3) the gRSC projection is layer-specific: AVDM targets specifically gRSC superficial layers. These same AV projections are topographically organized with ventral AV neurons innervating rostral RSC and dorsal AV neurons innervating caudal RSC. These combined results suggest the existence of two distinct but interacting RSC subcircuits: one connecting AVDM to gRSC that may comprise part of the cognitive hippocampal system, and the other connecting AVVL to both RSC regions that may link hippocampal and perceptual regions. We suggest that these subcircuits are distinct to allow for differential weighting during integration of converging sensory and cognitive computations: an integration that may take place in thalamus, RSC, or both.
Our memories are essential in our daily lives. The frontal and cingulate cortices, hippocampal sy... more Our memories are essential in our daily lives. The frontal and cingulate cortices, hippocampal system and medial temporal lobes are key brain regions. In addition, severe amnesia also occurs after damage or dysfunction to the anterior thalamic nuclei; this subcortical thalamic hub is interconnected to these key cortical memory structures. Behavioral, anatomical, and physiological evidence across mammalian species has shown that interactions between the anterior thalamic nuclei, cortex and hippocampal formation are vital for spatial memory processing. Furthermore, the adjacent laterodorsal thalamic nucleus (LD), interconnected to the retrosplenial cortex (RSC) and visual system, also contributes to spatial memory in mammals. However, how these thalamic nuclei contribute to memory still remains largely unknown. Fortunately, our understanding of the importance of the thalamus in cognitive processes is being redefined, as widespread evidence challenges the established view of the thalamus as a passive relay of sensory and subcortical information to the cortex. In this review article, we examine whether the anterior thalamic nuclei and the adjacent LD are suitable candidates for "higher-order" thalamic nuclei, as defined by the Sherman and Guillery model. Rather than simply relaying information to cortex, "higher-order" thalamic nuclei have a prominent role in cognition, as they can regulate how areas of the cortex interact with one another. These considerations along with a review of the latest research will be used to suggest future studies that will clarify the contributions that the anterior and LD have in supporting cortical functions during cognitive processes.
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Papers by Anna Mitchell