Cognitive process in high neuroticism: incompatible flexibility in frontal brain region

Objective: This study examines the difference of interference effect in high and low neuroticism. Material and Methods: Low and high groups of neuroticism performed the congruent and incongruent Stroop Colour Word task in the Event Related Potential session. The ERP P300 was extracted and analysed. Results: High neuroticism exhibited larger P300 amplitude than low neuroticism in both congruent and incongruent condition. Conclusion: High neuroticism appraises conflict and non-conflict condition under incompatibility manner driven by prefrontal cortical top–down control. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 129-134

Disrupting inferior frontal cortex activity alters affect decoding efficiency from clear but not from ambiguous affective speech

The evaluation of socio-affective sound information is accomplished by the primate neural auditory cortex in collaboration with limbic and inferior frontal brain nodes. For the latter, activity in inferior frontal cortex (IFC) is often observed during classification of voice sounds, especially if they carry affective information. Partly opposing views have been proposed, with IFC either coding cognitive processing challenges in case of sensory ambiguity or representing categorical object and affect information for clear vocalizations. Here, we presented clear and ambiguous affective speech to two groups of human participants during neuroimaging, while in one group we inhibited right IFC activity with transcranial magnetic stimulation (TMS) prior to brain scanning. Inhibition of IFC activity led to partly faster affective decisions, more accurate choice probabilities and reduced auditory cortical activity for clear affective speech, while fronto-limbic connectivity increased for clear vocalizations. This indicates that IFC inhibition might lead to a more intuitive and efficient processing of affect information in voices. Contrarily, normal IFC activity might represent a more deliberate form of affective sound processing (i.e., enforcing cognitive analysis) that flags categorial sound decisions with precaution (i.e., representation of categorial uncertainty). This would point to an intermediate functional property of the IFC between previously assumed mechanisms.

Cognitive and affective Theory of Mind double dissociation after parietal and temporal lobe tumors

Extensive neuroimaging literature suggests that understanding others' thoughts and emotions engages a wide network encompassing parietal, temporal and medial frontal brain areas. However, the causal role played by these regions in social inferential abilities is still unclear. Moreover very little is known about ToM deficits in brain tumours and whether potential anatomical substrates are comparable to those identified in fMRI literature. This study evaluated the performance of 105 tumour patients, before and immediately after brain surgery, on a cartoon-based non-verbal task evaluating Cognitive (Intention Attribution) and Affective (Emotion Attribution) ToM, as well as a non-social control condition (Causal Inference). Across multiple analyses, we found converging evidence of a double dissociation between patients with right superior parietal damage, selectively impaired in Intention Attribution, and those with right antero-medial temporal lesion, exhibiting deficits only in Emotion attribution. Instead, patients with damage to the frontal cortex were impaired in all kinds of inferential processes, including those from the non-social control conditions. Overall, our data provides novel reliable causal evidence of segregation between different aspects of the ToM network from both the cognitive and also the anatomical point of view.

Neural Correlates of Decisions in Quasi-Realistic, Affective Social Interactions in Individuals With Violence-Related Socialization

Appropriate social behavior in aggressive-provocative interactions is a prerequisite for a peaceful life. In previous research, the dysfunctions of the control of aggression were suggested to be modulated by enhanced bottom-up (sub-cortically driven) and reduced top-down (iso-cortical frontal) processing capability. In the present study, two groups of individuals with enhanced (EG) and normal (NG) experiences of violent acts during their socialization made binary behavioral decisions in quasi-realistic social interactions. These interactions were presented in short video clips taken from a first-person perspective. The video clips showed social interaction scenarios oriented on realistic everyday life situations. The behavioral data supported the distinct affective qualities of three categories of social interactions. These categories were labeled as aggressive–provocative, social–positive, and neutral–social interactions. Functional neuroimaging data showed extended activation patterns and higher signal intensity for the NG compared to the EG in the lateral inferior frontal brain regions for the aggressive provocative interactions. Furthermore, the peri-aqueductal gray (PAG) produced enhanced activations for the affective interaction scenarios (i.e., aggressive-provocative and social-positive) in both groups and as a trend with the medium effect size for the neutral interactions in the EG. As the individuals in the EG did not show open aggression during the functional MRIA (fMRI) investigation, we concluded that they applied individual self-control strategies to regulate their aggressive impulses immediately. These strategies appeared to be top-down regulated through the dorsal frontal brain areas. The predominant recruitment of the heteromodal cortices during the neural processing of complex social interactions pointed to the important role of the learning history of individuals and their socialization with differing levels of violent experiences as crucial modulators in convicts. Our data suggest that building or strengthening the association between prototypical social contexts (e.g., aggressive-provocative interactions) and appropriate behaviors as a response to it provides a promising approach to successfully re-socialize people with a delinquent history.

Region-specific KCC2 rescue by rhIGF-1 and oxytocin in a mouse model of Rett syndrome

Rett syndrome (RTT) is characterized by dysfunction in neuronal excitation/inhibition (E/I) balance, potentially impacting seizure susceptibility via deficits in K+/Cl- cotransporter 2 (KCC2) function. Mice lacking the Methyl-CpG binding protein 2 (MeCP2) recapitulate many symptoms of RTT, and recombinant human insulin-like growth factor-1 (rhIGF-1) restores KCC2 expression and E/I balance in MeCP2 KO mice. However, clinical trial outcomes of rhIGF-1 in RTT have been variable, and increasing its therapeutic efficacy is highly desirable. To this end, the neuropeptide oxytocin (OXT) is promising, as it also critically modulates KCC2 function during early postnatal development. We measured basal KCC2 expression levels in MeCP2 KO mice and identified three key frontal brain regions showing KCC2 alterations in young adult mice but not in postnatal P10 animals. We thus hypothesized that deficits in IGF-1/OXT signaling crosstalk modulating KCC2 may occur in RTT during postnatal development. Consistently, we detected alterations of IGF-1 receptor (IGF-1R) and OXT receptor (OXTR) levels in those brain areas. rhIGF-1 and OXT treatments in KO mice rescued KCC2 expression in a region-specific and complementary manner. These results suggest that region-selective combinatorial pharmacotherapeutic strategies could be the most effective at normalizing E/I balance in key brain regions subtending the RTT pathophysiology.

Mechanisms Underlying Motivational Dysfunction in Schizophrenia

Negative symptoms are a debilitating feature of schizophrenia which are often resistant to pharmacological intervention. The mechanisms underlying them remain poorly understood, and diagnostic methods rely on phenotyping through validated questionnaires. Deeper endo-phenotyping is likely to be necessary in order to improve current understanding. In the last decade, valuable behavioural insights have been gained through the use of effort-based decision making (EBDM) tasks. These have highlighted impairments in reward-related processing in schizophrenia, particularly associated with negative symptom severity. Neuroimaging investigations have related these changes to dysfunction within specific brain networks including the ventral striatum (VS) and frontal brain regions. Here, we review the behavioural and neural evidence associated with negative symptoms, shedding light on potential underlying mechanisms and future therapeutic possibilities. Findings in the literature suggest that schizophrenia is characterised by impaired reward based learning and action selection, despite preserved hedonic responses. Associations between amotivation and reward-processing deficits have not always been clear, and may be mediated by factors including cognitive dysfunction or dysfunctional or self-defeatist beliefs. Successful endo-phenotyping of negative symptoms as a function of objective behavioural and neural measurements is crucial in advancing our understanding of this complex syndrome. Additionally, transdiagnostic research–leveraging findings from other brain disorders, including neurological ones–can shed valuable light on the possible common origins of motivation disorders across diseases and has important implications for future treatment development.