Cognitive network interactions through communication subspaces in large-scale models of the neocortex.

Neocortex-wide neural activity is organized into distinct networks of areas engaged in different cognitive processes. To elucidate the underlying mechanism of flexible network reconfiguration, we developed connectivity-constrained macaque and human whole-cortex models. In our model, within-area connectivity consists of a mixture of symmetric, asymmetric, and random motifs that give rise to stable (attractor) or transient (sequential) heterogeneous dynamics.

Multimodal mapping of macaque monkey somatosensory cortex.

The somatosensory cortex is a brain region responsible for receiving and processing sensory information from across the body and is structurally and functionally heterogeneous. Since the chemoarchitectonic segregation of the cerebral cortex can be revealed by transmitter receptor distribution patterns, by using a quantitative multireceptor architectonical analysis, we determined the number and extent of distinct areas of the macaque somatosensory cortex. We identified three architectonically distinct cortical entities within the primary somatosensory cortex (i.

The meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition.

The recent publications of the inter-areal connectomes for mouse, marmoset, and macaque cortex have allowed deeper comparisons across rodent vs. primate cortical organization. In general, these show that the mouse has very widespread, "all-to-all" inter-areal connectivity (i.

Cell type-specific connectome predicts distributed working memory activity in the mouse brain.

Recent advances in connectomics and neurophysiology make it possible to probe whole-brain mechanisms of cognition and behavior. We developed a large-scale model of the multiregional mouse brain for a cardinal cognitive function called working memory, the brain's ability to internally hold and process information without sensory input. The model is built on mesoscopic connectome data for interareal cortical connections and endowed with a macroscopic gradient of measured parvalbumin-expressing interneuron density.

Cytoarchitectonic, receptor distribution and functional connectivity analyses of the macaque frontal lobe.

Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas, including novel subdivisions of Walker's areas 10, 9, 8B, and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Indeed, structural and functional organization of subdivisions encompassing areas 46 and 12 demonstrated significant differences in the interareal levels of α receptors.

Gradients of neurotransmitter receptor expression in the macaque cortex.

Dynamics and functions of neural circuits depend on interactions mediated by receptors. Therefore, a comprehensive map of receptor organization across cortical regions is needed. In this study, we used in vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex.

A polygenic score indexing a DRD2-related co-expression network is associated with striatal dopamine function.

The D2 dopamine receptor (D2R) is the primary site of the therapeutic action of antipsychotics and is involved in essential brain functions relevant to schizophrenia, such as attention, memory, motivation, and emotion processing. Moreover, the gene coding for D2R (DRD2) has been associated with schizophrenia at a genome-wide level. Recent studies have shown that a polygenic co-expression index (PCI) predicting the brain-specific expression of a network of genes co-expressed with DRD2 was associated with response to antipsychotics, brain function during working memory in patients with schizophrenia, and with the modulation of prefrontal cortex activity after pharmacological stimulation of D2 receptors.

The neural basis of delayed gratification.

Balancing instant gratification versus delayed but better gratification is important for optimizing survival and reproductive success. Although delayed gratification has been studied through human psychological and brain activity monitoring and animal research, little is known about its neural basis. We successfully trained mice to perform a waiting-for-water-reward delayed gratification task and used these animals in physiological recording and optical manipulation of neuronal activity during the task to explore its neural basis.

A dopamine gradient controls access to distributed working memory in the large-scale monkey cortex.

Dopamine is required for working memory, but how it modulates the large-scale cortex is unknown. Here, we report that dopamine receptor density per neuron, measured by autoradiography, displays a macroscopic gradient along the macaque cortical hierarchy. This gradient is incorporated in a connectome-based large-scale cortex model endowed with multiple neuron types.

Combining brain perturbation and neuroimaging in non-human primates.

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.

Organization of the macaque monkey inferior parietal lobule based on multimodal receptor architectonics.

The macaque monkey inferior parietal lobe (IPL) is a structurally heterogeneous brain region, although the number of areas it contains and the anatomical/functional relationship of identified subdivisions remains controversial. Neurotransmitter receptor distribution patterns not only reveal the position of the cortical borders, but also segregate areas associated to different functional systems. Thus we carried out a multimodal quantitative analysis of the cyto- and receptor architecture of the macaque IPL to determine the number and extent of distinct areas it encompasses.

Multimodal 3D atlas of the macaque monkey motor and premotor cortex.

In the present study we reevaluated the parcellation scheme of the macaque frontal agranular cortex by implementing quantitative cytoarchitectonic and multireceptor analyses, with the purpose to integrate and reconcile the discrepancies between previously published maps of this region. We applied an observer-independent and statistically testable approach to determine the position of cytoarchitectonic borders. Analysis of the regional and laminar distribution patterns of 13 different transmitter receptors confirmed the position of cytoarchitectonically identified borders.

Altered Cortical Gyrification in Adults Who Were Born Very Preterm and Its Associations With Cognition and Mental Health.

Background: The last trimester of pregnancy is a critical period for the establishment of cortical gyrification, and altered folding patterns have been reported following very preterm birth (< 33 weeks of gestation) in childhood and adolescence. However, research is scant on the persistence of such alterations in adulthood and their associations with cognitive and psychiatric outcomes.

Methods: We studied 79 very preterm and 81 age-matched full-term control adults.

The effect of a genetic variant at the schizophrenia associated AS3MT/BORCS7 locus on striatal dopamine function: A PET imaging study.

One of the most statistically significant loci to result from large-scale GWAS of schizophrenia is 10q24.32. However, it is still unclear how this locus is involved in the pathoaetiology of schizophrenia.

Interindividual Variability of Functional Connectivity in Awake and Anesthetized Rhesus Macaque Monkeys.

Background: Nonhuman primate (NHP) models are commonly used to advance our understanding of brain function and organization. However, to date, they have offered few insights into individual differences among NHPs. In large part, this is due to the logistical challenges of NHP research, which limit most studies to 5 subjects or fewer.

Verbal Fluency Is Affected by Altered Brain Lateralization in Adults Who Were Born Very Preterm.

Language difficulties have been reported in children and adolescents who were born very preterm (<32 weeks' gestation) and associated with an atypical lateralization of language processing, i.e., increased right-hemispheric engagement.

Macro-connectomics and microstructure predict dynamic plasticity patterns in the non-human primate brain.

The brain displays a remarkable ability to adapt following injury by altering its connections through neural plasticity. Many of the biological mechanisms that underlie plasticity are known, but there is little knowledge as to when, or where in the brain plasticity will occur following injury. This knowledge could guide plasticity-promoting interventions and create a more accurate roadmap of the recovery process following injury.

An Open Resource for Non-human Primate Imaging.

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI).

Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis.

While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by social impairment. Leveraging data from the large longitudinal IMAGEN cohort, including 2096 14-year old adolescents that were followed-up to age 18, we tested whether the association between polygenic risk and PEs is mediated by (increasing) impairments in social functioning and social cognitive processes.

The Rhesus Monkey Hippocampus Critically Contributes to Scene Memory Retrieval, But Not New Learning.

Humans can recall a large number of memories years after the initial events. Patients with amnesia often have lesions to the hippocampus, but human lesions are imprecise, making it difficult to identify the anatomy underlying memory impairments. Rodent studies enable great precision in hippocampal manipulations, but not investigation of many interleaved memories.

The effect of the DISC1 Ser704Cys polymorphism on striatal dopamine synthesis capacity: an [18F]-DOPA PET study.

Whilst the role of the Disrupted-in-Schizophrenia 1 (DISC1) gene in the aetiology of major mental illnesses is debated, the characterization of its function lends it credibility as a candidate. A key aspect of this functional characterization is the determination of the role of common non-synonymous polymorphisms on normal variation within these functions. The common allele (A) of the DISC1 single-nucleotide polymorphism (SNP) rs821616 encodes a serine (ser) at the Ser704Cys polymorphism, and has been shown to increase the phosphorylation of extracellular signal-regulated protein Kinases 1 and 2 (ERK1/2) that stimulate the phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme for dopamine biosynthesis.

Reward-Based Learning as a Function of Severity of Substance Abuse Risk in Drug-Naïve Youth with ADHD.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is associated with elevated risk for later development of substance use disorders (SUD), specifically because youth with ADHD, similar to individuals with SUD, exhibit deficits in learning abilities and reward processing. Another known risk factor for SUD is familial history of substance dependence. Youth with familial SUD history show reward processing deficits, higher prevalence of externalizing disorders, and higher impulsivity scores.

A dimensional approach to assessing psychiatric risk in adults born very preterm.

Background: Individuals who were born very preterm have higher rates of psychiatric diagnoses compared with term-born controls; however, it remains unclear whether they also display increased sub-clinical psychiatric symptomatology. Hence, our objective was to utilize a dimensional approach to assess psychiatric symptomatology in adult life following very preterm birth.

Methods: We studied 152 adults who were born very preterm (before 33 weeks' gestation; gestational range 24-32 weeks) and 96 term-born controls.

The effect of perinatal brain injury on dopaminergic function and hippocampal volume in adult life.

Perinatal brain injuries, including hippocampal lesions, cause lasting changes in dopamine function in rodents, but it is not known if this occurs in humans. We compared adults who were born very preterm with perinatal brain injury to those born very preterm without perinatal brain injury, and age-matched controls born at full term using [18F]-DOPA PET and structural MRI. Dopamine synthesis capacity was reduced in the perinatal brain injury group relative to those without brain injury (Cohen's = 1.