Decreased Functional Connectivity of Vermis-Ventral Prefrontal Cortex in Bipolar Disorder

Objectives: To investigate changes in functional connectivity between the vermis and cerebral regions in the resting state among subjects with bipolar disorder (BD).Methods: Thirty participants with BD and 28 healthy controls (HC) underwent the resting state functional magnetic resonance imaging (fMRI). Resting-state functional connectivity (rsFC) of the anterior and posterior vermis was examined. For each participant, rsFC maps of the anterior and posterior vermis were computed and compared across the two groups.Results: rsFC between the whole vermis and ventral prefrontal cortex (VPFC) was significantly lower in the BD groups compared to the HC group, and rsFC between the anterior vermis and the middle cingulate cortex was likewise significantly decreased in the BD group.Limitations: 83.3% of the BD participants were taking medication at the time of the study. Our findings may in part be attributed to treatment differences because we did not examine the effects of medication on rsFC. Further, the mixed BD subtypes in our current study may have confounding effects influencing the results.Conclusions: These rsFC differences of vermis-VPFC between groups may contribute to the BD mood regulation.

Dorsal Prefrontal Cortex

The dorsal prefrontal (PF) cortex generates and plans the goals or targets for foveal search and manual foraging. The goals are conditional on the relative recency of prior events and actions, and the connections of areas 9/46 and 46 explain how these areas can support the ability to generate the next goal. Area 9/46 can generate sequences of eye movements because it has visuospatial inputs from the cortex in the intraparietal sulcus and outputs to the frontal eye field and superior colliculus. Area 46 can generate sequences of hand and arm movements because it has inputs from the inferior parietal areas PFG and SII and outputs to the forelimb regions of the premotor areas and thence to the motor cortex. Both areas get timing and order information indirectly from the parietal cortex and hippocampus, and colour and shape information from the ventral prefrontal cortex. Inputs from the orbital prefrontal cortex enable both areas to integrate generate goals in accordance with current needs.

Ventral Prefrontal Cortex

The ventral prefrontal cortex learns to associate objects, faces, and vocalizations, and its connectional fingerprint explains why it alone can do so. It receives visual inputs from the inferior temporal cortex and auditory ones from the superior temporal cortex. It combines these inputs with those from the orbital prefrontal (PF) cortex so as to specify the goal that is currently desirable. This is then transformed into the target of search via connections with the frontal eye field and the target for manual retrieval via connections with the premotor areas. The ventral PF cortex can also learn to form associations between objects, for example by linking them into categories. These can be retrieved from long-term memory via connections with the hippocampus.

Understanding the Prefrontal Cortex

The primate prefrontal cortex sits at the top of the sensory, motor, and outcome processing hierarchies of the neocortex. It transforms sensory inputs into motor outputs, determining the response that is appropriate given the current context and desired outcome. This transformation involves conditional rules. The dorsal prefrontal cortex supports the learning of behavioural sequences, where the next action is conditional on the previous one. The ventral prefrontal cortex supports associations between objects, where the choice of one object is conditional on the presence of another object. However, because hierarchical processing supports the extraction of abstract representations, the primate prefrontal cortex is able to represent conditional rules that are abstract, meaning that they apply irrespective of the specific inputs. The selective advantage is that by learning these rules, primates can solve new problems rapidly when they have the same conditional logic as prior problems. The human prefrontal cortex has the same fundamental organization as in other primates. The dorsal prefrontal cortex supports the understanding of sequences and the ventral prefrontal cortex supports the ability to learn semantic associations. Thus the human prefrontal cortex has co-opted and elaborated mechanisms that were present in ancestral primates. These mechanisms can be used for new ends. For example, words have been associated with objects so as to communicate with others. This means that to understand human intelligence it is necessary to take into account the fact that the abstract rules are transmitted verbally from one generation to another.

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049–0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.

Gray Matter Correlates of Impulsivity in Psychopathy and in the General Population Differ by Kind, Not by Degree: A Comparison of Systematic Reviews

A fundamental question in neuropsychiatry is whether a neurobiological continuum accompanies the behavioral continuum between subclinical and clinical traits. Impulsivity is a trait that varies in the general population and manifests severely in disorders like psychopathy. Is the neural profile of severe impulsivity in psychopathy an extreme but continuous manifestation of that associated with impulsivity in the general population (different by degree)? Or is it discontinuous and unique (different by kind)? Here, we compare systematic reviews of the relationship between impulsivity and gray matter in psychopathy and in the general population. The findings suggest that the neural profile associated with extreme impulsivity in psychopathy (increased gray matter in rostral and ventral striatum and prefrontal cortex) is distinct from that associated with impulsivity in the general population (decreased gray matter in rostral and ventral prefrontal cortex). Severe impulsivity in psychopathy may therefore arise from a pathophysiological mechanism that is unique to the disorder. The results caution against the use of community samples to examine impulsive psychopathic traits in relation to neurobiology.

Fast recurrent processing via ventral prefrontal cortex is needed by the primate ventral stream for robust core visual object recognition

SummaryDistributed neural population spiking patterns in macaque inferior temporal (IT) cortex that support core visual object recognition require additional time to develop for specific (“late-solved”) images suggesting the necessity of recurrent processing in these computations. Which brain circuit motifs are most responsible for computing and transmitting these putative recurrent signals to IT? To test whether the ventral prefrontal cortex (vPFC) is a critical recurrent circuit node in this system, here we pharmacologically inactivated parts of the vPFC and simultaneously measured IT population activity, while monkeys performed object discrimination tasks. Our results show that vPFC inactivation deteriorated the quality of the late-phase (>150 ms from image onset) IT population code, along with commensurate, specific behavioral deficits for “late-solved” images. Finally, silencing vPFC caused the monkeys’ IT activity patterns and behavior to become more like those produced by feedforward artificial neural network models of the ventral stream. Together with prior work, these results argue that fast recurrent processing through the vPFC is critical to the production of behaviorally-sufficient object representations in IT.