Family Conflict Associated With Intrinsic Hippocampal-OFC Connectivity in Adolescent Depressive Disorder

BackgroundFamily environment and life events have long been suggested to be associated with adolescent depression. The hippocampus plays a crucial role in the neural mechanism of major depressive disorder (MDD) through memory during stressful events. However, few studies have explored the exact neural mechanisms underlying these associations. Thus, the current study aimed to explore alterations in hippocampal functional connectivity (FC) in adolescent MDD based on resting-state functional magnetic resonance imaging and further investigate the relationship between hippocampal FC, environmental factors, and clinical symptom severity.MethodsHippocampal FC was calculated using the seed-based approach with the bilateral hippocampus as the seed for 111 adolescents with and without MDD; comparisons were made between participants with MDD and controls. We applied the Chinese version of the Family Environment Scale (FES-CV) and Adolescents Self-Rating Life Events Checklist (ASLEC) to evaluate family environment and life stress. Their relationship with hippocampal FC alterations was also investigated.ResultsWe found that compared to controls, adolescents with MDD showed decreased connectivity between the left hippocampus and bilateral orbital frontal cortex (OFC) and right inferior temporal gyrus. In addition, the hippocampal-OFC connectivity was negatively correlated with conflict scores of the FES-CV in the MDD group and mediated the association between family conflict and depressive and anxiety symptoms.ConclusionOur findings are novel in the field and demonstrate how family conflict contributes to MDD symptomatology through hippocampal-OFC connectivity; these findings may provide potential targets for personalized treatment strategies.

Neural mechanisms of credit assignment for inferred relationships in a structured world

Animals have been proposed to abstract compact representations of a task's structure that could, in principle, support accelerated learning and flexible behavior. Whether and how such abstracted representations may be used to assign credit for inferred, but unobserved, relationships in structured environments are unknown. Here, we develop a novel hierarchical reversal-learning task and Bayesian learning model to assess the computational and neural mechanisms underlying how humans infer specific choice-outcome associations via structured knowledge. We find that the medial prefrontal cortex (mPFC) efficiently represents hierarchically related choice-outcome associations governed by the same latent cause, using a generalized code to assign credit for both experienced and inferred outcomes. Furthermore, mPFC and lateral orbital frontal cortex track the inferred current "position" within a latent association space that generalizes over stimuli. Collectively, these findings demonstrate the importance both of tracking the current position in an abstracted task space and efficient, generalizable representations in prefrontal cortex for supporting flexible learning and inference in structured environments.

Functional Network Connectivity Imprint In Febrile Seizures

Complex febrile seizures (CFS), a subset of paediatric febrile seizures (FS), have been studied for their prognosis, epileptogenic potential and neurocognitive outcome. We evaluated their functional connectivity differences with simple febrile seizures (SFS) in children with recent-onset FS. Resting-state fMRI (rsfMRI) datasets of 24 children with recently diagnosed FS (SFS n=11; CFS n=13) were analysed. Functional connectivity (FC) was estimated using time series correlation of seed region to whole brain voxels and network topology was assessed using graph theory measures. Regional connectivity differences were correlated with clinical characteristics (FDR corrected p < 0.05). CFS patients demonstrated increased FC of the bilateral middle temporal pole (MTP), and bilateral thalami when compared to SFS. Network topology study revealed increased clustering coefficient and decreased participation coefficient in basal ganglia and thalamus suggesting an inefficient-unbalanced network topology in patients with CFS. The number of seizure recurrences negatively correlated with the integration of Left Thalamus ( r= -0.58 ) and FC measures of Left MTP to 'Right Supplementary Motor and left Precentral' connectivity (r=-0.53). The FC of Right MTP to Left Amygdala, Putamen, Parahippocampal, and Orbital Frontal Cortex ( r=0.61 ) and FC of Left Thalamus to left Putamen, Pallidum, Caudate, Thalamus Hippocampus and Insula (r 0.55) showed a positive correlation to the duration of the longest seizure. The findings of the current study report altered connectivity in children with CFS proportional to the seizure recurrence and duration. Regardless of the causal/consequential nature, such observations demonstrate the imprint of these disease-defining variables of febrile seizures on the developing brain.

The Effect of Olfactory Training on Olfaction, Cognition, and Brain Function in Patients with Mild Cognitive Impairment

Background: The olfactory system is affected very early in Alzheimer’s disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI), an early stage of AD. Objective: The aim of this randomized, prospective, controlled, blinded study was to evaluate whether olfactory training (OT) may have an effect on olfactory function, cognitive impairment, and brain activation in MCI patients after a 4-month period of frequent short-term exposure to various odors. Methods: A total of 38 MCI outpatients were randomly assigned to OT or a control training condition, which were performed twice a day for 4 months. Olfactory testing, comprehensive neuropsychological assessment, and magnetic resonance imaging were performed before and after training. Results: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. However, OT exhibited a positive effect on frontal lobe activation (left middle frontal gyrus and orbital-frontal cortex) but exhibited no effect on grey matter volume. Moreover, the change of olfactory scores was positively associated with the change of frontal activation. Conclusion: OT was found to have a limited effect on olfaction and cognition in patients with MCI compared to a non-OT condition but increased their functional response to odors in frontal area.

Different Features of Metabolic Connectivity Map and Granger Causality Method in Revealing Directed Dopamine Pathways: A Pilot Study Based on Integrated PET/MR

Granger causality (GC) analysis and metabolic connectivity map (MCM) are two effective connectivity (EC) methods commonly used in functional brain researches. Although they have a common basis in central neurophysiology, their differences in depicting EC are not clear because of absenting data acquired simultaneously and exactly aligned. Integrated positron emission tomography and magnetic resonance image (PET/MR) technology makes this available. Using the “Monash rs-PET/MR” dataset obtained from the OpenNeuro database, we first conducted GC and MCM analysis of the brain dopamine reward circuit, a well-known system mainly consisting of the bilateral Orbital Frontal Cortex (OFC), Caudate (CAU), Nucleus Accumbens (NAc), Thalamus (THA) and Substantia Nigra (SN). Then, we validated their ability of describing EC to priori knowledge. The significance of each directed pathways within group were tested through one-sample t-test (for MCM) or Wilcoxcon test (for GC), the significance level was set at p<0.05 after FDR correction. Three types of connections were found: the cortico-nucleus (long-range), the nucleus-nucleus (neighborhood) and the symmetrical connections. GC revealed long-range connections including OFC-CAU and OFC-NAc; MCM revealed neighborhood connections including NAc-CAU, SN-THA, and THA-CAU, the symmetrical connections including the bilateral NAc, CAU, THA, as well as OFC-CAU. Thus, different patterns in directional networks of dopamine reward circuit revealed by GC and MCM. GC predominated at aspects of cortico-nucleus bidirected connections, while MCM of directed connections among close regions and symmetrical regions. This study implicates that research involving in effective connections should choose an appropriate analysis method according to the study purpose.

Common and unique structural plasticity after left and right hemisphere stroke

Strokes to the left and right hemisphere lead to distinctive behavioral profiles. Are left and right hemisphere strokes (LHS and RHS) associated with distinct or common poststroke neuroplasticity patterns? Understanding this issue would reveal hemispheric neuroplasticity mechanisms in response to brain damage. To this end, we investigated poststroke structural changes (2 weeks to 3 months post-onset) using longitudinal MRI data from 69 LHS and 55 RHS patients and 31 demographic-matched healthy control participants. Both LHS and RHS groups showed statistically common plasticity independent of the lesioned hemisphere, including 1) gray matter (GM) expansion in the ipsilesional and contralesional precuneus, and contralesional superior frontal gyrus; 2) GM shrinkage in the ipsilesional medial orbital frontal gyrus and middle cingulate cortex. On the other hand, only RHS patients had significant GM expansion in the ipsilesional medial superior and orbital frontal cortex. Importantly, these common and unique GM changes post-stroke largely overlapped with highly-connected cortical hub regions in healthy individuals. Moreover, they correlated with behavioral recovery, indicating that post-stroke GM volumetric changes in cortical hubs reflect compensatory rather than maladaptive mechanisms. These results highlight the importance of structural neuroplasticity in hub regions of the cortex, along with the hemispheric specificity, for stroke recovery.

Selective prefrontal-amygdala circuit interactions underlie social and nonsocial valuation in rhesus macaques

Lesion studies in macaques suggest dissociable functions of the orbitofrontal cortex (OFC) and medial frontal cortex (MFC), with OFC being essential for goal-directed decision making and MFC supporting social cognition. Bilateral amygdala damage results in impairments in both of these domains. There are extensive reciprocal connections between these prefrontal areas and the amygdala; however, it is not known whether the dissociable roles of OFC and MFC depend on functional interactions with the amygdala. To test this possibility, we compared the performance of male rhesus macaques (Macaca mulatta) with crossed surgical disconnection of the amygdala and either MFC (MFC x AMY, n=4) or OFC (OFC x AMY, n=4) to a group of unoperated controls (CON, n=5). All monkeys were assessed for their performance on two tasks to measure: (1) food-retrieval latencies while viewing videos of social and nonsocial stimuli in a test of social interest, and (2) object choices based on current food value using reinforcer devaluation in a test of goal-directed decision making. Compared to the CON group, the MFC x AMY group, but not the OFC x AMY group, showed significantly reduced food-retrieval latencies while viewing videos of conspecifics, indicating reduced social valuation and/or interest. By contrast, on the devaluation task, group OFC x AMY, but not group MFC x AMY, displayed deficits on object choices following changes in food value. These data indicate that the MFC and OFC must functionally interact with the amygdala to support normative social and nonsocial valuation, respectively.Significance StatementAscribing value to conspecifics (social) vs. objects (nonsocial) may be supported by distinct but overlapping brain networks. Here we test whether two nonoverlapping regions of the prefrontal cortex, the medial frontal cortex and the orbitofrontal cortex, must causally interact with the amygdala to sustain social valuation and goal-directed decision making, respectively. We found that these prefrontal-amygdala circuits are functionally dissociable, lending support for the idea that medial frontal and orbital frontal cortex make independent contributions to cognitive appraisals of the environment. These data provide a neural framework for distinct value assignment processes and may enhance our understanding of the cognitive deficits observed following brain injury or in the development of mental health disorders.