Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis.

Mutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-fexpressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkB neurons on energy homeostasis has not been explored. In this study, we show that activation of DMHTrkB neurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMHTrkB neurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMHTrkB neurons that regulate food intake or thermogenesis. Activation of DMHTrkB neurons projecting to the raphe pallidus (RPa) stimulates thermogenesis and increased energy expenditure, whereas DMHTrkB neurons that send collaterals to the paraventricular hypothalamus (PVH) and preoptic area (POA) inhibit feeding. Together, our findings provide evidence that DMHTrkB neuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMHTrkB neuronal activity on food intake and thermogenesis.

Understanding the habenula: A major node in circuits regulating emotion and motivation.

Over the last decade, the understanding of the habenula has rapidly advanced from being an understudied brain area with the Latin name 'habena" meaning "little rein", to being considered a "major rein" in the control of key monoaminergic brain centers. This ancient brain structure is a strategic node in the information flow from fronto-limbic brain areas to brainstem nuclei. As such, it plays a crucial role in regulating emotional, motivational, and cognitive behaviors and has been implicated in several neuropsychiatric disorders, including depression and addiction. This review will summarize recent findings on the medial (MHb) and lateral (LHb) habenula, their topographical projections, cell types, and functions. Additionally, we will discuss contemporary efforts that have uncovered novel molecular pathways and synaptic mechanisms with a focus on MHb-Interpeduncular nucleus (IPN) synapses. Finally, we will explore the potential interplay between the habenula's cholinergic and non-cholinergic components in coordinating related emotional and motivational behaviors, raising the possibility that these two pathways work together to provide balanced roles in reward prediction and aversion, rather than functioning independently.

Optogenetic and chemogenetic insights into the neurocircuitry of depression-like behaviour: A systematic review.

Major depressive disorder (MDD) and its treatment are challenges for global health. Optogenetics and chemogenetics are driving MDD research forward by unveiling causal relations between cell-type-specific control of neurons and depressive-like behaviour in rodents. Using a systematic search process, in this review, a set of 43 original studies applying optogenetic or chemogenetic techniques in rodent models of depression was identified. Our aim was to provide an examination of all available studies elucidating central neuronal mechanisms leading to depressive-like behaviour in rodents and thereby unveiling the most promising routes for future research. A complex interacting network of relevant structures, in which central circuitries causally related to depressive-like behaviour are implicated, has been identified. As most relevant structures emerge: medial prefrontal cortex, anterior cingulate cortex, amygdala, nucleus accumbens, ventral tegmental area, hippocampus and raphe nuclei. Further evidence, though examined by only few studies, emerges for structures like the lateral habenula, or medial dorsal thalamus. Most of the identified brain areas have previously been associated with MDD neuropathology, but now evidence can be provided for causal pathological mechanisms within a complex cortico-limbic reward circuitry. However, the studies also show conflicting results concerning the mechanisms underlying the causal involvement of specific circuitries. Comparability of studies is partly limited since even small deviations in methodological approaches lead to different outcomes. Factors influencing study outcomes were identified and need to be considered in future studies (e.g. frequency used for stimulation, time and duration of stimulation, limitations of applied animal models of MDD).

Toward a transdiagnostic neurocircuitry-based biomarker model for pro-cognitive effects: challenges, opportunities, and next steps.

Cognitive impairment has emerged as a key treatment priority in neuropsychiatric disorders. However, there is a lack of treatments with solid and lasting efficacy on cognition. A neurocircuitry-based biomarker model of pro-cognitive effects is critically needed to select among new candidate treatments. In a recent review of functional magnetic resonance imaging (fMRI) studies in mood disorders, we found that cognitive impairments are consistently accompanied by aberrant (hypo- and hyper-) activity in the dorsal prefrontal cortex (PFC) and the default mode network (DMN), and that activity change in these regions commonly occurs with cognitive improvements. Here, we (i) review the putative model from our recent review article, which explains the discrepant findings regarding the direction of aberrant dorsal PFC activity and treatment-related activity change in mood disorders. Inspired by the Research Domain Criteria project, we do this in order to (ii) examine whether a similar pattern of activity change occurs across distinct neuropsychiatric disorders and thereby provides a common biomarker for pro-cognitive effects. Lastly, we (iii) discuss whether dorsal PFC and DMN target engagement is a putative transdiagnostic neurocircuitry-based biomarker model for pro-cognitive effects, and (iv) outline the necessary next steps to address this question.

Amygdala lesions eliminate viewing preferences for faces in rhesus monkeys.

In free-viewing experiments, primates orient preferentially toward faces and face-like stimuli. To investigate the neural basis of this behavior, we measured the spontaneous viewing preferences of monkeys with selective bilateral amygdala lesions. The results revealed that when faces and nonface objects were presented simultaneously, monkeys with amygdala lesions had no viewing preference for either conspecific faces or illusory facial features in everyday objects. Instead of directing eye movements toward socially relevant features in natural images, we found that, after amygdala loss, monkeys are biased toward features with increased low-level salience. We conclude that the amygdala has a role in our earliest specialized response to faces, a behavior thought to be a precursor for efficient social communication and essential for the development of face-selective cortex.

The Arcuate Nucleus of the Hypothalamus and Metabolic Regulation: An Emerging Role for Renin-Angiotensin Pathways.

Obesity is a chronic state of energy imbalance that represents a major public health problem and greatly increases the risk for developing hypertension, hyperglycemia, and a multitude of related pathologies that encompass the metabolic syndrome. The underlying mechanisms and optimal treatment strategies for obesity, however, are still not fully understood. The control of energy balance involves the actions of circulating hormones on a widely distributed network of brain regions involved in the regulation of food intake and energy expenditure, including the arcuate nucleus of the hypothalamus. While obesity is known to disrupt neurocircuits controlling energy balance, including those in the hypothalamic arcuate nucleus, the pharmacological targeting of these central mechanisms often produces adverse cardiovascular and other off-target effects. This highlights the critical need to identify new anti-obesity drugs that can activate central neurocircuits to induce weight loss without negatively impacting blood pressure control. The renin-angiotensin system may provide this ideal target, as recent studies show this hormonal system can engage neurocircuits originating in the arcuate nucleus to improve energy balance without elevating blood pressure in animal models. This review will summarize the current knowledge of renin-angiotensin system actions within the arcuate nucleus for control of energy balance, with a focus on emerging roles for angiotensin II, prorenin, and angiotensin-(1-7) pathways.

Compartmentalized Devices as Tools for Investigation of Human Brain Network Dynamics.

Neuropsychiatric disorders have traditionally been difficult to study due to the complexity of the human brain and limited availability of human tissue. Induced pluripotent stem (iPS) cells provide a promising avenue to further our understanding of human disease mechanisms, but traditional 2D cell cultures can only provide a limited view of the neural circuits. To better model complex brain neurocircuitry, compartmentalized culturing systems and 3D organoids have been developed. Early compartmentalized devices demonstrated how neuronal cell bodies can be isolated both physically and chemically from neurites. Soft lithographic approaches have advanced this approach and offer the tools to construct novel model platforms, enabling circuit-level studies of disease, which can accelerate mechanistic studies and drug candidate screening. In this review, we describe some of the common technologies used to develop such systems and discuss how these lithographic techniques have been used to advance our understanding of neuropsychiatric disease. Finally, we address other in vitro model platforms such as 3D culture systems and organoids and compare these models with compartmentalized models. We ask important questions regarding how we can further harness iPS cells in these engineered culture systems for the development of improved in vitro models. Developmental Dynamics 248:65-77, 2019. © 2018 Wiley Periodicals, Inc.

The Role of Cholinergic Midbrain Neurons in Startle and Prepulse Inhibition.

One of the two major cholinergic centers of the mammalian brain is located in the midbrain, i.e., the pedunculopontine tegmentum (PPTg) and the adjacent laterodorsal tegmentum. These cholinergic neurons have been shown to be important for e.g., arousal, reward associations, and sleep. They also have been suggested to mediate sensorimotor gating, measured as prepulse inhibition of startle (PPI). PPI disruptions are a hallmark of schizophrenia and are observed in various other psychiatric disorders, where they are associated with, and often predictive of, other cognitive symptoms. PPI has been proposed to be mediated by a short midbrain circuitry including inhibitory cholinergic projections from PPTg to the startle pathway. Although the data indicating the involvement of the PPTg is very robust, some more recent evidence challenges that there is a cholinergic contribution to PPI. We here use transient optogenetic activation of specifically the cholinergic PPTg neurons in male and female rats to address their role in startle modulation in general, and in PPI specifically. Although we could confirm the crucial role of PPTg cholinergic neurons in associative reward learning, validating our experimental approach, we found that activation of cholinergic PPTg neurons did not inhibit startle responses. In contrast, activation of cholinergic PPTg neurons enhanced startle, which is in accordance with their general role in arousal and indicate a potential involvement in sensitization of startle. We conclude that noncholinergic PPTg neurons mediate PPI in contrast to the longstanding hypothetical view that PPI is mediated by cholinergic PPTg neurons.SIGNIFICANCE STATEMENT Activation of cholinergic neurons in the midbrain has been assumed to mediate prepulse inhibition of startle (PPI), a common measure of sensorimotor gating that is disrupted in schizophrenia and other psychiatric disorders. We here revisit this long-standing hypothesis using optogenetic activation of these specific neurons combined with startle testing in rats. In contrast to the hypothetical role of these neurons in startle modulation, we show that their activation leads to an increase of baseline startle and to prepulse facilitation. This supports recent data by others that have started to cast some doubt on the cholinergic hypothesis of PPI, and calls for a revision of the theoretical construct of PPI mechanisms.

What Does Sex Have to Do with It? The Role of Sex as a Biological Variable in the Development of Posttraumatic Stress Disorder.

PURPOSE OF REVIEW: This review highlights the neurobiological aspects of sex differences in posttraumatic stress disorder (PTSD), specifically focusing on the physiological responses to trauma and presents evidence supporting hormone and neurosteroid/peptide differences from both preclinical and clinical research. RECENT FINDINGS: While others have suggested that trauma type or acute emotional reaction are responsible for women's disproportionate risk to PTSD, neither of these explanations fully accounts for the sex differences in PTSD. Sex differences in brain neurocircuitry, anatomy, and neurobiological processes, such as those involved in learning and memory, are discussed as they have been implicated in risk and resilience for the development of PTSD. Gonadal and stress hormones have been found to modulate sex differences in the neurocircuitry and neurochemistry underlying fear learning and extinction. Preclinical research has not consistently controlled for hormonal and reproductive status of rodents nor have clinical studies consistently examined these factors as potential moderators of risk for PTSD. Sex as a biological variable (SABV) should be considered, in addition to the endocrine and reproductive status of participants, in all stress physiology and PTSD research.

Compromised Neurocircuitry in Chronic Blast-Related Mild Traumatic Brain Injury.

The aim of this study was to apply recently developed automated fiber segmentation and quantification methods using diffusion tensor imaging (DTI) and DTI-based deterministic and probabilistic tractography to access local and global diffusion changes in blast-induced mild traumatic brain injury (bmTBI). Two hundred and two (202) male active US service members who reported persistent post-concussion symptoms for more than 6 months after injury were recruited. An additional forty (40) male military controls were included for comparison. DTI results were examined in relation to post-concussion and post-traumatic stress disorder (PTSD) symptoms. No significant group difference in DTI metrics was found using voxel-wise analysis. However, group comparison using tract profile analysis and tract specific analysis, as well as single subject analysis using tract profile analysis revealed the most prominent white matter microstructural injury in chronic bmTBI patients over the frontal fiber tracts, that is, the front-limbic projection fibers (cingulum bundle, uncinate fasciculus), the fronto-parieto-temporal association fibers (superior longitudinal fasciculus), and the fronto-striatal pathways (anterior thalamic radiation). Effects were noted to be sensitive to the number of previous blast exposures, with a negative association between fractional anisotropy (FA) and time since most severe blast exposure in a subset of the multiple blast-exposed group. However, these patterns were not observed in the subgroups classified using macrostructural changes (T2 white matter hyperintensities). Moreover, post-concussion symptoms and PTSD symptoms, as well as neuropsychological function were associated with low FA in the major nodes of compromised neurocircuitry. Hum Brain Mapp 38:352-369, 2017. © 2016 Wiley Periodicals, Inc.

Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry.

Postconcussional disorder and PTSD symptoms of military-related traumatic brain injury associated with compromised neurocircuitry.

Traumatic brain injury (TBI) is a common combat injury, often through explosive blast, and produces heterogeneous brain changes due to various mechanisms of injury. It is unclear whether the vulnerability of white matter differs between blast and impact injury, and the consequences of microstructural changes on neuropsychological function are poorly understood in military TBI patients. Diffusion tensor imaging (DTI) techniques were used to assess the neurocircuitry in 37 U.S. service members (29 mild, 7 moderate, 1 severe; 17 blast and 20 nonblast), who sustained a TBI while deployed, compared to 14 nondeployed, military controls. High-dimensional deformable registration of MRI diffusion tensor data was followed by fiber tracking and tract-specific analysis along with region-of-interest analysis. DTI results were examined in relation to post-concussion and post-traumatic stress disorder (PTSD) symptoms. The most prominent white matter microstructural injury for both blast and nonblast patients was in the frontal fibers within the fronto-striatal (corona radiata, internal capsule) and fronto-limbic circuits (fornix, cingulum), the fronto-parieto-occipital association fibers, in brainstem fibers, and in callosal fibers. Subcortical superior-inferiorly oriented tracts were more vulnerable to blast injury than nonblast injury, while direct impact force had more detrimental effects on anterior-posteriorly oriented tracts, which tended to cause heterogeneous left and right hemispheric asymmetries of white matter connectivity. The tractography using diffusion anisotropy deficits revealed the cortico-striatal-thalamic-cerebellar-cortical (CSTCC) networks, where increased post-concussion and PTSD symptoms were associated with low fractional anisotropy in the major nodes of compromised CSTCC neurocircuitry, and the consequences on cognitive function were explored as well.

Parental Deprivation- and Threat-Based Factors Associated with Youth Emotion-Based Neurocircuitry and Externalizing Behavior: A Systematic Review.

Parental factors, including negative parenting practices (e.g., family conflict, low monitoring), parental depression, and parental substance use, are associated with externalizing behaviors among youth. However, the ways in which these parental factors are associated with youth brain function and consequent externalizing behavior has been less studied. Both the dimensional and stress acceleration models provide frameworks for understanding how parental factors may be associated with frontolimbic and frontoparietal networks implicated in emotional attention and regulation processes. The current review builds upon this work by examining how deprivation- and threat-based parental factors are associated with youth neurocircuitry involved in emotional functioning and externalizing behaviors. A systematic review using PRISMA guidelines was completed and included five studies assessing parenting behaviors, six studies assessing parental depressive symptoms and/or diagnosis, and 12 studies assessing parental history of substance use. Synthesis of reviewed studies discusses support for the dimensional and stress acceleration models within the context of deprivation and threat. Further, a limited number of studies tested (i.e., six studies) and supported (i.e., three studies) youth neural structure and function as a mediator of the association between parental factors and youth externalizing behavior. Specific recommendations for future work include more deliberate planning related to sample composition, improved clarity related to parental constructs, consistency in methodology, and longitudinal study design in order to better understand associations between contextual parental influences and youth neural and behavioral functioning.

Use of Post-mortem Brain Tissue in Investigations of Obsessive- Compulsive Disorder: A Systematic Review.

BACKGROUND: Post-mortem examination of the brain is a key strategy to increase our understanding of the neurobiology of mental disorders. While extensive post-mortem research has been undertaken on some mental disorders, others appear to have been relatively neglected. OBJECTIVE: The objective of the study was to conduct a systematic review of post-mortem research on obsessive-compulsive disorder (OCD). METHODS: A systematic review was performed in accordance with PRISMA guidelines to provide an overview of quantitative, qualitative, or mixed methods primary research studies on OCD. Search platforms included NCBI Pubmed, SCOPUS, and Web of Science. RESULTS: A total of 52 publications were found, and after the removal of works not meeting the inclusion criteria, six (6) peer-reviewed publications remained. These post-mortem studies have provided data on DNA methylation, cellular and molecular alterations, and gene expression profiling in brain areas associated with OCD. DISCUSSION AND CONCLUSION: Included studies highlight the potential value of post-mortem brains from well-characterized individuals with OCD and suggest the need for additional work in this area.

Corrigendum: Electrical synapses for a pooling layer of the convolutional neural network in retinas.

[This corrects the article DOI: 10.3389/fncel.2023.1281786.].

Subcortico-Cortical Dysconnectivity in ADHD: A Voxel-Wise Mega-Analysis Across Multiple Cohorts.

OBJECTIVE: A large body of functional MRI research has examined a potential role for subcortico-cortical loops in the pathogenesis of attention deficit hyperactivity disorder (ADHD), but has produced inconsistent findings. The authors performed a mega-analysis of six neuroimaging data sets to examine associations between ADHD diagnosis and traits and subcortico-cortical connectivity. METHODS: Group differences were examined in the functional connectivity of four subcortical seeds in 1,696 youths with ADHD diagnoses (66.39% males; mean age, 10.83 years [SD=2.17]) and 6,737 unaffected control subjects (47.05% males; mean age, 10.33 years [SD=1.30]). The authors examined associations between functional connectivity and ADHD traits (total N=9,890; 50.3% males; mean age, 10.77 years [SD=1.96]). Sensitivity analyses were used to examine specificity relative to commonly comorbid internalizing and non-ADHD externalizing problems. The authors further examined results within motion-matched subsamples, and after adjusting for estimated intelligence. RESULTS: In the group comparison, youths with ADHD showed greater connectivity between striatal seeds and temporal, fronto-insular, and supplementary motor regions, as well as between the amygdala and dorsal anterior cingulate cortex, compared with control subjects. Similar findings emerged when ADHD traits were considered and when alternative seed definitions were adopted. Dominant associations centered on the connectivity of the caudate bilaterally. Findings were not driven by in-scanner motion and were not shared with commonly comorbid internalizing and externalizing problems. Effect sizes were small (largest peak d, 0.15). CONCLUSIONS: The findings from this large-scale mega-analysis support established links with subcortico-cortical circuits, which were robust to potential confounders. However, effect sizes were small, and it seems likely that resting-state subcortico-cortical connectivity can capture only a fraction of the complex pathophysiology of ADHD.

Latent-state and model-based learning in PTSD.

Post-traumatic stress disorder (PTSD) is characterized by altered emotional and behavioral responding following a traumatic event. In this article, we review the concepts of latent-state and model-based learning (i.e., learning and inferring abstract task representations) and discuss their relevance for clinical and neuroscience models of PTSD. Recent data demonstrate evidence for brain and behavioral biases in these learning processes in PTSD. These new data potentially recast excessive fear towards trauma cues as a problem in learning and updating abstract task representations, as opposed to traditional conceptualizations focused on stimulus-specific learning. Biases in latent-state and model-based learning may also be a common mechanism targeted in common therapies for PTSD. We highlight key knowledge gaps that need to be addressed to further elaborate how latent-state learning and its associated neurocircuitry mechanisms function in PTSD and how to optimize treatments to target these processes.

Vagus nerve damage increases alcohol intake and preference in a nonpreferring rat line: Relationship to vagal regulation of the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Clinical and preclinical research indicates that gastric weight loss surgeries, such as Roux-en-Y gastric bypass surgery, can induce alcohol use disorder (AUD). While numerous mechanisms have been proposed for these effects, one relatively unexplored potential mechanism is physical damage to the gastric branch of the vagus nerve, which can occur during bypass surgery. Therefore, we hypothesized that direct damage to the gastric branch of the vagus nerve, without altering other aspects of gastric anatomy, could result in increased alcohol intake. METHODS: To test this hypothesis, we compared alcohol intake and preference in multiple models in male Sprague-Dawley rats that received selective gastric branch vagotomy (VX) with rats who underwent sham surgery. Because the vagus nerve regulates hypothalamic-pituitary-adrenal (HPA) axis function, and alterations to HPA function are critical to the escalation of non-dependent alcohol intake, we also tested the hypothesis that gastric VX increases HPA function. RESULTS: We found that VX increases alcohol intake and preference in the every-other-day, two-bottle choice test and increases preference for 1 g/kg alcohol in the conditioned place preference test. The effects were selective for alcohol, as sucrose intake and preference were not altered by VX. We also found that VX increases corticotropin releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus (PVN), increases putative PVN CRF neuronal action potential firing, and increases corticosterone levels. CONCLUSIONS: Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of PVN CRF mRNA expression and putative PVN CRF neuronal activity. Furthermore, disruptions to vagal regulation of HPA axis function may increase alcohol intake and preference.

Concerning neuromodulation as treatment of neurological and neuropsychiatric disorder: Insights gained from selective targeting of the subthalamic nucleus, para-subthalamic nucleus and zona incerta in rodents.

Neuromodulation such as deep brain stimulation (DBS) is advancing as a clinical intervention in several neurological and neuropsychiatric disorders, including Parkinson's disease, dystonia, tremor, and obsessive-compulsive disorder (OCD) for which DBS is already applied to alleviate severely afflicted individuals of symptoms. Tourette syndrome and drug addiction are two additional disorders for which DBS is in trial or proposed as treatment. However, some major remaining obstacles prevent this intervention from reaching its full therapeutic potential. Side-effects have been reported, and not all DBS-treated individuals are relieved of their symptoms. One major target area for DBS electrodes is the subthalamic nucleus (STN) which plays important roles in motor, affective and associative functions, with impact on for example movement, motivation, impulsivity, compulsivity, as well as both reward and aversion. The multifunctionality of the STN is complex. Decoding the anatomical-functional organization of the STN could enhance strategic targeting in human patients. The STN is located in close proximity to zona incerta (ZI) and the para-subthalamic nucleus (pSTN). Together, the STN, pSTN and ZI form a highly heterogeneous and clinically important brain area. Rodent-based experimental studies, including opto- and chemogenetics as well as viral-genetic tract tracings, provide unique insight into complex neuronal circuitries and their impact on behavior with high spatial and temporal precision. This research field has advanced tremendously over the past few years. Here, we provide an inclusive review of current literature in the pre-clinical research fields centered around STN, pSTN and ZI in laboratory mice and rats; the three highly heterogeneous and enigmatic structures brought together in the context of relevance for treatment strategies. Specific emphasis is placed on methods of manipulation and behavioral impact.

Neurocircuitry of Personality Traits and Intent in Decision-Making.

Even though most personality features are moderately stable throughout life, changes can be observed, which influence one's behavioral patterns. A variety of subjective assessments can be performed to track these changes; however, the subjective characteristic of these assessments may lead to questions about intentions and values. The use of neuroimaging techniques may aid the investigation of personality traits through a more objective lens, overcoming the barriers imposed by confounders. Here, neurocircuits associated with changes in personality domains were investigated to address this issue. Cortical systems involved in traits such as extraversion and neuroticism were found to share multiple components, as did traits of agreeableness and conscientiousness, with these four features revolving around the activation and structural integrity of the medial prefrontal cortex (mPFC). The attribute of openness appears scattered throughout cortical and subcortical regions, being discussed here as a possible reflection of intent, at the same time modulating and being governed by other traits. Insights on how systems operate on personality may increase comprehension on factors acting on the evolution, development, and consolidation of personality traits through life, as in neurocognitive disorders.