Biology subjects

Saunders, R. C.

Publications and source records attributed to Saunders, R. C..

2 recordsLinked to original sources

bioRxiv2023

Paradoxical consequences of early hippocampal damage: greater atrophy is associated with better recall, working memory and visuospatial perception in developmental amnesia

Despite bilateral hippocampal damage dating to perinatal or early-childhood period, and severely-impaired episodic memory that unfolds in later childhood, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganise to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40% while the atrophy of the uncus was moderate (-23%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions, such that the greater the damage, the more likely it is that surrounding cortical areas will be recruited to rescue the putative functions of the damaged subregions. Our findings document for the first time not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

neuroscience↗

bioRxiv2022

Chemogenetic disconnection between the orbitofrontal cortex and the rostromedial caudate nucleus disrupts motivational control of goal-directed action

The orbitofrontal cortex (OFC) and its major downstream target within the basal ganglia--the rostromedial caudate nucleus (rmCD)--are involved in reward-value processing and goal-directed behavior. However, a causal contribution of the pathway linking these two structures to goal-directed behavior has not been established. Using the chemogenetic technology of Designer Receptors Exclusively Activated by Designer Drugs with a crossed inactivation design, we functionally and reversibly disrupted interactions between the OFC and rmCD in two male macaque monkeys. We injected an adeno-associated virus vector expressing an inhibitory designer receptor (hM4Di) into the OFC and contralateral rmCD, the expression of which was visualized in vivo by positron emission tomography (PET) and confirmed by post-mortem immunohistochemistry. Functional disconnection of the OFC and rmCD resulted in a significant and reproducible loss of sensitivity to the cued reward value for goal-directed action. This decreased sensitivity was most prominent when monkeys had accumulated a certain amount of reward. These results provide causal evidence that the interaction between the OFC and the rmCD is needed for motivational control of action on the basis of the relative reward value and internal drive. This finding extends current understanding of the physiological basis of psychiatric disorders in which goal-directed behavior is affected, such as obsessive-compulsive disorder. Significance StatementIn daily life, we routinely adjust the speed and accuracy of our actions on the basis of the value of expected reward. Abnormalities in these kinds of motivational adjustments might be related to behaviors seen in psychiatric disorders such as obsessive-compulsive disorder. In the current study, we show that the connection from the orbitofrontal cortex to the rostromedial caudate nucleus is essential formotivational control of action in monkeys. This finding expands our knowledge about how the primate brain controls motivation and behavior and provides a particular insight into disorders like obsessive-compulsive disorder, in which altered connectivity between the orbitofrontal cortex and the striatum has been implicated.

neuroscience↗