Visual association cortex links cues with conjunctions of reward and locomotor contexts

Postrhinal cortex (POR) and neighboring lateral visual association areas are necessary for identifying objects and interpreting them in specific contexts, but how POR neurons encode the same object across contexts remains unclear. Here, we imaged excitatory neurons in mouse POR across tens of days throughout initial cue-reward learning and reversal learning. As such, neurons were tracked across sessions/trials where the same cue was rewarded or unrewarded, during both locomotor and stationary contexts. Surprisingly, a large class of POR neurons were minimally cue-driven prior to learning. After learning, distinct clusters within this class responded selectively to a given cue when presented in a specific conjunction of reward and locomotion contexts. In addition, another class involved clusters of neurons whose cue responses were more transient, insensitive to reward learning, and adapted over thousands of presentations. These two classes of POR neurons may support context-dependent interpretation and context-independent identification of sensory cues.

Structural and Functional Changes Are Related to Cognitive Status in Wilson’s Disease

Patients with Wilson’s disease (WD) suffer from prospective memory (PM) impairment, and some of patients develop cognitive impairment. However, very little is known about how brain structure and function changes effect PM in WD. Here, we employed multimodal neuroimaging data acquired from 22 WD patients and 26 healthy controls (HC) who underwent three-dimensional T1-weighted, diffusion tensor imaging (DTI), and resting state functional magnetic resonance imaging (RS-fMRI). We investigated gray matter (GM) volumes with voxel-based morphometry, DTI metrics using the fiber tractography method, and RS-fMRI using the seed-based functional connectivity method. Compared with HC, WD patients showed GM volume reductions in the basal ganglia (BG) and occipital fusiform gyrus, as well as volume increase in the visual association cortex. Moreover, whiter matter (WM) tracks of WD were widely impaired in association and limbic fibers. WM tracks in association fibers are significant related to PM in WD patients. Relative to HC, WD patients showed that the visual association cortex functionally connects to the thalamus and hippocampus, which is associated with global cognitive function in patients with WD. Together, these findings suggested that PM impairment in WD may be modulated by aberrant WM in association fibers, and that GM volume changes in the association cortex has no direct effect on cognitive status, but indirectly affect global cognitive function by its aberrant functional connectivity (FC) in patients with WD. Our findings may provide a new window to further study how WD develops into cognitive impairment, and deepen our understanding of the cognitive status and neuropathology of WD.

Postnatal Development of Glutamate and GABA Transcript Expression in Monkey Visual, Parietal, and Prefrontal Cortices

Visuospatial working memory (vsWM) requires information transfer among multiple cortical regions, from primary visual (V1) to prefrontal (PFC) cortices. This information is conveyed via layer 3 glutamatergic neurons whose activity is regulated by gamma-aminobutyric acid (GABA)ergic interneurons. In layer 3 of adult human neocortex, molecular markers of glutamate neurotransmission were lowest in V1 and highest in PFC, whereas GABA markers had the reverse pattern. Here, we asked if these opposite V1–visual association cortex (V2)–posterior parietal cortex (PPC)–PFC gradients across the vsWM network are present in layer 3 of monkey neocortex, when they are established during postnatal development, and if they are specific to this layer. We quantified transcript levels of glutamate and GABA markers in layers 3 and 6 of four vsWM cortical regions in a postnatal developmental series of 30 macaque monkeys. In adult monkeys, glutamate transcript levels in layer 3 increased across V1–V2–PPC–PFC regions, whereas GABA transcripts showed the opposite V1–V2–PPC–PFC gradient. Glutamate transcripts established adult-like expression patterns earlier during postnatal development than GABA transcripts. These V1–V2–PPC–PFC gradients and developmental patterns were less evident in layer 6. These findings demonstrate that expression of glutamate and GABA transcripts differs across cortical regions and layers during postnatal development, revealing potential molecular substrates for vsWM functional maturation.

Replicability of structural brain alterations associated with general psychopathology: evidence from a population-representative birth cohort

Transdiagnostic research has identified a general psychopathology factor—often called the ‘p’ factor—that accounts for shared variation across internalizing, externalizing, and thought disorders in diverse samples. It has been argued that the p factor may reflect dysfunctional thinking present in serious mental illness. In support of this, we previously used a theory-free, data-driven multimodal neuroimaging approach to find that higher p factor scores are associated with structural alterations within a cerebello-thalamo-cortical circuit (CTCC) and visual association cortex, both of which are important for monitoring and coordinating information processing in the service of executive control. Here we attempt to replicate these associations by conducting region-of-interest analyses using data from 875 members of the Dunedin Longitudinal Study, a five-decade study of a population-representative birth cohort, collected when they were 45 years old. We further sought to replicate a more recent report that p factor scores can be predicted by patterns of distributed cerebellar morphology as estimated through independent component analysis. We successfully replicated associations between higher p factor scores and both reduced gray matter volume of the visual association cortex and fractional anisotropy of pontine white matter pathways within the CTCC. In contrast, we failed to replicate prior associations between cerebellar structure and p factor scores. Collectively, our findings encourage further focus on the CTCC and visual association cortex as core neural substrates and potential biomarkers of general psychopathology.

Replicability of Structural Brain Alterations Associated with General Psychopathology: Evidence from a Population-Representative Birth Cohort

Transdiagnostic research has identified a general psychopathology factor – often called the ‘p’ factor – that accounts for shared variation across internalizing, externalizing, and thought disorders in diverse samples. It has been argued that the p factor may reflect dysfunctional thinking present in serious mental illness. In support of this, we previously used a theory-free, data-driven multimodal neuroimaging approach to find that higher p factor scores are associated with structural alterations within a cerebello-thalamo-cortical circuit (CTCC) and visual association cortex, both of which are important for monitoring and coordinating information processing in the service of executive control. Here we attempt to replicate these associations by conducting region-of-interest analyses of CTCC and visual association cortex using data from 875 members of the Dunedin Longitudinal Study, a five-decade study of a population-representative birth cohort now 45 years old. We further sought to replicate a more recent report that p factor scores can be predicted by patterns of distributed cerebellar morphology as estimated through independent component analysis. We successfully replicated associations between higher p factor scores and both reduced grey matter volume of the visual association cortex and fractional anisotropy of pontine white matter pathways within the CTCC. In contrast, we failed to replicate prior associations between cerebellar structure and p factor scores. Collectively, our findings encourage further focus on the CTCC and visual association cortex as core neural substrates and potential biomarkers of general psychopathology.