Anna S. Mitchell

Diffusion-Weighted Imaging Tractography-Based Parcellation of the Human Parietal Cortex and Comparison with Human and Macaque Resting-State Functional Connectivity

Despite the prominence of parietal activity in human neuroimaging investigations of sensorimotor and cognitive processes, there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species, but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI)-based tractography, and functional interactions were assessed by correlations in activity measured with functional MRI at rest. Resting-state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment, and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into 10 component clusters. The resting-state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex.

Dissociable memory effects after medial thalamus lesions in the rat

Variable neuropathology in cases of diencephalic amnesia has led to uncertainty in identifying key thalamic nuclei and their potential role in learning and memory. Based on the principal neural connections of the medial thalamus, the current study tested the hypothesis that different aggregates of thalamic nuclei contribute to separate memory systems. Lesions of the anterior thalamic aggregate (AT), which comprises the anterodorsal, anteromedial and anteroventral nuclei produced substantial deficits in both working and reference spatial memory in a radial arm maze task in rats, supporting the view that the AT is an integral part of a hippocampal memory system. Lesions to the lateral thalamic aggregate (LT), which comprises the intralaminar nuclei (centrolateral, paracentral and rostral central medial nuclei) and lateral mediodorsal thalamic nuclei (lateral and paralamellar nuclei) produced a mild working memory impairment only, while lesions to the posteromedial thalamic aggregate (MT), which comprises the central and medial mediodorsal thalamic nuclei and the intermediodorsal nucleus had no effect on radial arm maze performance. In contrast, only MT lesions impaired learning associated with memory for reward value, consistent with the idea that the MT contributes to an amygdala memory system. Compared with chance discrimination, the control and AT groups, but not MT or LT groups, showed evidence for temporal order memory for two recently presented objects; all groups showed intact object recognition for novel vs. familiar objects. These new dissociations show that different medial thalamic aggregates participate in multiple memory systems and reinforce the idea that memory deficits in diencephalic amnesics may vary as a function of the relative involvement of different thalamic regions.

Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.

What does the mediodorsal thalamus do

Dense amnesia can result from damage to the medial diencephalon in humans and in animals. In humans this damage is diffuse and can include the mediodorsal nuclei of the thalamus. In animal models, lesion studies have confirmed the mediodorsal thalamus (MD) has a role in memory and other cognitive tasks, although the extent of deficits is mixed. Anatomical tracing studies confirm at least three different subgroupings of the MD: medial, central, and lateral, each differentially interconnected to the prefrontal cortex (PFC). Moreover, these subgroupings of the MD also receive differing inputs from other brain structures, including the basal ganglia thus the MD subgroupings form key nodes in interconnected frontal-striatal-thalamic neural circuits, integrating critical information within the PFC. We will provide a review of data collected from non-human primates and rodents after selective brain injury to the whole of the MD as well as these subgroupings to highlight the extent of deficits in various cognitive tasks. This research highlights the neural basis of memory and cognitive deficits associated with the subgroupings of the MD and their interconnected neural networks. The evidence shows that the MD plays a critical role in many varied cognitive processes. In addition, the MD is actively processing information and integrating it across these neural circuits for successful cognition. Having established that the MD is critical for memory and cognition, further research is required to understand how the MD specifically influences these cognitive processing carried out by the brain.

Neurotoxic Lesions of the Medial Mediodorsal Nucleus of the Thalamus Disrupt Reinforcer Devaluation Effects in Rhesus Monkeys

The mediodorsal thalamus is a major input to the prefrontal cortex and is thought to modulate cognitive functions of the prefrontal cortex. Damage to the medial, magnocellular part of the mediodorsal thalamus (MDmc) impairs cognitive functions dependent on prefrontal cortex, including memory. The contribution of MDmc to other aspects of cognition dependent on prefrontal cortex has not been determined. The ability of monkeys to adjust their choice behavior in response to changes in reinforcer value, a capacity impaired by lesions of orbital prefrontal cortex, can be tested in a reinforcer devaluation paradigm. In the present study, rhesus monkeys with bilateral neurotoxic MDmc lesions were tested in the devaluation procedure. Monkeys learned visual discrimination problems in which each rewarded object is reliably paired with one of two different food rewards and then were given choices between pairs of rewarded objects, one associated with each food. Selective satiation of one of the food rewards reduces choices of objects associated with that food in normal monkeys. Monkeys with bilateral neurotoxic lesions of MDmc learned concurrently presented visual discrimination problems as quickly as unoperated control monkeys but showed impaired reinforcer devaluation effects. This finding suggests that the neural circuitry for control of behavioral choice by changes in reinforcer value includes MDmc.

Advances in understanding mechanisms of thalamic relays in cognition and behavior.

The main impetus for a mini-symposium on corticothalamic interrelationships was the recent number of studies highlighting the role of the thalamus in aspects of cognition beyond sensory processing. The thalamus contributes to a range of basic cognitive behaviors that include learning and memory, inhibitory control, decision-making, and the control of visual orienting responses. Its functions are deeply intertwined with those of the better studied cortex, although the principles governing its coordination with the cortex remain opaque, particularly in higher-level aspects of cognition. How should the thalamus be viewed in the context of the rest of the brain? Although its role extends well beyond relaying of sensory information from the periphery, the main function of many of its subdivisions does appear to be that of a relay station, transmitting neural signals primarily to the cerebral cortex from a number of brain areas. In cognition, its main contribution may thus be to coordinate signals between diverse regions of the telencephalon, including the neocortex, hippocampus, amygdala, and striatum. This central coordination is further subject to considerable extrinsic control, for example, inhibition from the basal ganglia, zona incerta, and pretectal regions, and chemical modulation from ascending neurotransmitter systems. What follows is a brief review on the role of the thalamus in aspects of cognition and behavior, focusing on a summary of the topics covered in a mini-symposium held at the Society for Neuroscience meeting, 2014.

A neural circuit covarying with social hierarchy in macaques.

A neural circuit that covaries with social hierarchy A neuroimaging study reveals that individual variation in brain circuits in structures below the cerebral cortex of macaques is associated with experience at different ends of the social hierarchy.

The Magnocellular Mediodorsal Thalamus is Necessary for Memory Acquisition, But Not Retrieval

Damage to the magnocellular mediodorsal thalamic nucleus (MDmc) in the human brain is associated with both retrograde and anterograde amnesia. In the present study we made selective neurotoxic MDmc lesions in rhesus monkeys and compared the effects of these lesions on memory acquisition and retrieval. Monkeys learned 300 unique scene discriminations preoperatively and retention was assessed in a one-trial preoperative retrieval test. Bilateral neurotoxic lesions of the MDmc, produced by 10 × 1 μl injections of a mixture of ibotenate and NMDA did not affect performance in the postoperative one-trial retrieval test. In contrast, new postoperative learning of a further 100 novel scene discriminations was substantially impaired. Thus, MDmc is required for new learning of scene discriminations but not for their retention and retrieval. This finding is the first evidence that MDmc plays a specific role in memory acquisition.

Ventrolateral prefrontal cortex is required for performance of a strategy implementation task but not reinforcer devaluation effects in rhesus monkeys

The ability to apply behavioral strategies to obtain rewards efficiently and make choices based on changes in the value of rewards is fundamental to the adaptive control of behavior. The extent to which different regions of the prefrontal cortex are required for specific kinds of decisions is not well understood. We tested rhesus monkeys with bilateral ablations of the ventrolateral prefrontal cortex on tasks that required the use of behavioral strategies to optimize the rate with which rewards were accumulated, or to modify choice behavior in response to changes in the value of particular rewards. Monkeys with ventrolateral prefrontal lesions were impaired in performing the strategy‐based task, but not on value‐based decision‐making. In contrast, orbital prefrontal ablations produced the opposite impairments in the same tasks. These findings support the conclusion that independent neural systems within the prefrontal cortex are necessary for control of choice behavior based on strategies or on stimulus value.

Dissociable performance on scene learning and strategy implementation after lesions to magnocellular mediodorsal thalamic nucleus.

Monkeys with aspiration lesions of the magnocellular division of the mediodorsal thalamus (MDmc) are impaired in object-in-place scene learning, object recognition, and stimulus-reward association. These data have been interpreted to mean that projections from MDmc to prefrontal cortex are required to sustain normal prefrontal function in a variety of task settings. In the present study, we investigated the extent to which bilateral neurotoxic lesions of the MDmc impair a preoperatively learnt strategy implementation task that is impaired by a crossed lesion technique that disconnects the frontal cortex in one hemisphere from the contralateral inferotemporal cortex. Postoperative memory impairments were also examined using the object-in-place scene memory task. Monkeys learnt both strategy implementation and scene memory tasks separately to a stable level preoperatively. Bilateral neurotoxic lesions of the MDmc, produced by 10 × 1 μl injections of a mixture of ibotenate and NMDA did not affect performance in the strategy implementation task. However, new learning of object-in-place scene memory was substantially impaired. These results provide new evidence about the role of the magnocellular mediodorsal thalamic nucleus in memory processing, indicating that interconnections with the prefrontal cortex are essential during new learning, but are not required when implementing a preoperatively acquired strategy task. Thus, not all functions of the prefrontal cortex require MDmc input. Instead, the involvement of MDmc in prefrontal function may be limited to situations in which new learning must occur.