Comparative insights into insula structure and function.

New functional insights from the monkey claustrum

ABSTRACT The claustrum is a subcortical nucleus with widespread, reciprocal connections to the cortex and beyond, inspiring many models of its function. Decades of work from rodents provide a foundational understanding of the anatomy and functional organization of the claustrum, which is more recently aided by human functional neuroimaging studies. However, important questions remain with broad functional implications. These center on claustrum anatomical boundaries, functional organization, and the putative expansion of human claustrum connectivity over that predicted by rodent studies alone. Providing new insights by spanning the large rodent-to-human void, a landmark study by Lei and colleagues recently provided thorough molecular and connectivity profiling of the macaque claustrum. Surprising findings of lateralized and expanded claustrum connectivity with cortical and subcortical partners help to explain human functional connectivity data and the discovery of a well-developed organization of the monkey claustrum into overlapping functional sub-domains provides deep insight into claustrum function when considering rodent synaptic connectivity data. Contextualizing these findings, we provide an elaborated model of the function of the claustrum in cognition.

The reins of the midbrain: task-based habenula function in healthy humans.

The habenula is a small epithalamic structure that animal models have characterized as a key node linking value-laden information to midbrain monoaminergic systems. Its involvement in mood disorders has driven growing interest in characterizing its function in humans, yet the healthy baseline of habenula function from task-based fMRI has not been systematically synthesised. Thus, we searched PubMed, Scopus, and PsycINFO and identified 34 task-based fMRI studies (37 cohorts, N = 1,480) examining habenular function in healthy adults. To address the methodological challenges of habenular imaging, we appraised each study through a spatial specificity framework. Findings were synthesised across four functional domains: affective and sensory processing, computational signalling, cognitive-affective regulation, and circadian rhythms. The human habenula emerged as a multifunctional integrative node that pulls back on - or modulates - midbrain function, much like the reins from which it takes its name. It processed primary and secondary aversive stimuli, encoded the predictive value of aversive cues, and signalled negative prediction errors across reinforcer types. Research also linked habenula activity to gating response under conflict and threat, and to higher-order cognitive processes. These responses recruited distributed circuits in which cortical inputs drive habenular modulation of midbrain monoaminergic function. Based on our framework, the most rigorous findings involved action gating under threat, foraging paradigms, and Pavlovian aversive conditioning, whereas foundational findings on primary aversion and reward prediction error encoding are starting to be replicated with more appropriate protocols. We recommend systematic adoption of high-specificity protocols and the integration of laterality and sex as biological variables.

Evolution of the motor cortex microstructure and its lateralization: a comparative study of chimpanzees and humans

Using high-resolution qMRI, motor cortex subdivisions controlling the leg, hand, and face in humans and chimpanzees are compared and consistently higher myelin and iron content in the hand-knob in both species are found, suggesting an evolutionarily conserved role.

Functional Neuroimaging of the Human Lateral Septum: A Systematic Review of Behavioral Correlates and Anatomical Localization.

The lateral septum (LS) is a basal forebrain structure extensively studied in rodents, where it regulates social behavior, stress, and motivation. In humans, its subtle anatomy and poor delineation limit systematic investigation with non-invasive imaging. We present the first systematic review of functional neuroimaging studies reporting LS activation in humans. Following PRISMA guidelines and a preregistered protocol, we found 3,728 records. After screening, 26 studies met inclusion criteria. LS activations were categorized by behavioral domain, and spatial coordinates mapped for convergence. Reported LS/septal area activation was associated with prosocial processes including empathy, caregiving, trust, cooperation, and charitable decisions. LS activation was also associated with affiliative reward, sexual arousal, and affective states like guilt and gratitude, with alterations noted in depression. Coordinate-based mapping (where available) showed a tentative tendency toward left/anterior localization for social cognition-related activations in the left anterior septal area, though localization varied across studies due to anatomical and methodological challenges. Overall, the literature suggests the LS/septal area may contribute to multiple social-affective and motivational processes, but anatomical specificity remains uncertain. . Despite challenges to measure LS function in humans, new neuroimaging techniques may elucidate LS function. This review highlights the LS as an underexplored but potentially critical structure for human socio-emotional and motivational processes, with clinical relevance for psychiatric conditions.

The Anatomical Connections of Nucleus Accumbens with Brainstem and Cerebellum in the Rat and Human Subjects

The role of the anterior cingulate cortex in anxiety control, from circuits to disorders

Anxiety is an adaptive response essential for survival that integrates external stimuli, internal states, memory, and decision making to respond to perceived threats. When dysregulated, it can become excessive and persistent, contributing to psychiatric and neurological disorders. The anterior cingulate cortex (ACC) integrates cognitive, emotional, interoceptive, and autonomic information and serves as a key hub in anxiety-related circuits. However, its subregion- and pathway-specific roles remain incompletely integrated across species. This review examines the cytoarchitectural and cellular organization of ACC subregions and their proposed correspondence in humans, non-human primates, and rodents. We then review ACC connectivity with the amygdala, hippocampus, insula, and bed nucleus of the stria terminalis and propose an integrative model in which ACC effects depend on subregion, projection target, and behavioral context. We also summarize structural, functional, connectivity, and neurochemical alterations of the ACC in anxiety-related disorders and neurodegenerative diseases with prominent anxiety symptoms. Finally, we discuss the strengths and limitations of rodent and non-human-primate models and identify priorities for future mechanistic and translational studies. Together, this review provides a timely and comprehensive view of the ACC’s role in adaptive and pathological anxiety and offers a framework for advancing mechanistic and translational research.