Corticolimbic Neural System Research Articles

Gender differences of amplitude of low-frequency fluctuations in bipolar disorder: A resting state fMRI study

Background: The clinical and epidemiological features of bipolar disorder (BD) between females and males have many differences. The association between brain function and gender in BD is unknown. This research aimed to investigate the association between brain function and gender in BD by using amplitude of low-frequency fluctuations (ALFFs). Methods: Ninety-eight patients (49 females and 49 males) with BD and 171 matched healthy controls (HCs, 89 females and 82 males) were recruited for resting-state functional magnetic resonance imaging. ALFF was used to estimate brain function. Results: A main effect of diagnosis in ALFF was observed in the dorsal lateral prefrontal cortex (DLPFC), ventral prefrontal cortex (VPFC), caudate and occipital lobe. A main effect of gender in ALFF was found in the right VPFC, DLPFC, thalamus, and occipital lobe. A main effect of diagnosis gender interaction in ALFF was observed in the left DLPFC. Analyses of two-sample t-test indicated that male patients with BD had increased ALFF in the right hippocampus, right amygdala, left caudate, and left DLPFC, and decreased ALFF in the occipital lobe compared with male HC. Female patients with BD demonstrated increased ALFF in the right VPFC and right DLPFC compared with female HC. Male patients with BD exhibited increased ALFF in the right VPFC and left DLPFC and decreased ALFF in the occipital lobe compared with female patients with BD. Limitations: This study did not consider the effect of medications and emotional states on brain activity. Conclusions: Results suggested gender differences in the dysfunctions of the cortico-limbic neural system in BD.

Structural and functional alterations in untreated patients with major depressive disorder and bipolar disorder experiencing first depressive episode: A magnetic resonance imaging study combined with follow-up

BackgroundMagnetic resonance imaging (MRI) could assist in identifying objective biomarkers and follow-up study could effectively improve subjective diagnostic accuracy. By combining MRI with follow-up, this study aims to determine the shared and distinct alterations between major depressive disorder (MDD) and bipolar disorder (BD). MethodsUntreated patients with MDD experiencing the first episode were subjected to MRI and subsequent follow-up. Fifteen patients with mania or hypomania were regrouped into BD group. Twenty patients were still grouped as MDD after an average of 37.95 months follow-up. Thirty healthy controls (HCs) were recruited to match the patients. Gray matter volume (GMV) and amygdala-seed functional connectivity (FC) in the whole brain were detected and compared among the three groups. ResultsGMV analysis revealed that the MDD and BD groups presented reduced GMV predominantly in the parietal, occipital, and frontal regions in the bilateral cerebrum compared with the HCs. The BD group had reduced GMV predominantly in the parietal, temporal, insular regions and the Rolandic operculum in the right-side cerebrum compared with MDD and HC groups. FC analysis revealed that the MDD and BD patients displayed increased FC values mainly in the bilateral parietal, and left occipital regions. Only the BD group displayed increased FC values in the temporal, occipital, parietal and limbic regions in the right-side cerebrum relative to HCs. LimitationsThe main limitation is the relatively small sample size. ConclusionsAlterations in the cortical regions and cortico-limbic neural system may provide the scientific basis for differential diagnosis in affective disorders.

Maladaptive emotion regulation traits predict altered corticolimbic recovery from psychosocial stress

BackgroundAdaptive recovery from stress promotes healthy cognitive affective functioning, whereas maladaptive recovery is linked to poor psychological outcomes. Neural regions, like the anterior cingulate and hippocampus, play critical roles in psychosocial stress responding and serve as hubs in the corticolimbic neural system. To date, however, it is unknown how cognitive emotion regulation traits (cER), adaptive and maladaptive, influence corticolimbic stress recovery. Here, we examined acute psychosocial stress neural recovery, accounting for cER. MethodsFunctional neuroimaging data were collected while forty-seven healthy participants performed blocks of challenging, time-sensitive, mental calculations. Participants immediately received performance feedback (positive/negative/neutral) and their ranking, relative to fictitious peers. Participants rested for 90 seconds after each feedback, allowing for a neural stress recovery period. Collected before scanning, cER scores were correlated with neural activity during each recovery condition. ResultsNegative feedback recovery yielded increased activity within the dorsomedial prefrontal cortex and amygdala, but this effect was ultimately explained by maladaptive cER (M-cER), like rumination. Isolating positive after-effects (i.e. positive > negative recovery) yielded a significant positive correlation between M-cER and the anterior cingulate, anterior insula, hippocampus, and striatum. ConclusionsWe provide first evidence of M-cER to predict altered neural recovery from positive stress within corticolimbic regions. Positive feedback may be potentially threatening to individuals with poor stress regulation. Identifying positive stress-induced activation patterns in corticolimbic neural networks linked to M-cER creates the possibility to identify these neural responses as risk factors for social-emotional dysregulation subsequent to rewarding social information, often witnessed in affective disorders, like depression.

Corticolimbic functional connectivity in adolescents with bipolar disorder.

Convergent evidence supports regional dysfunction within a corticolimbic neural system that subserves emotional processing and regulation in adolescents and adults with bipolar disorder (BD), with abnormalities prominent within the amygdala and its major anterior paralimbic cortical connection sites including ventral anterior cingulate, orbitofrontal, insular and temporopolar cortices. Recent studies of adults with BD demonstrate abnormalities in the functional connectivity between the amygdala and anterior paralimbic regions suggesting an important role for the connections between these regions in the development of the disorder. This study tests the hypothesis that these functional connectivity abnormalities are present in adolescents with BD. Fifty-seven adolescents, twenty-one with BD and thirty-six healthy comparison (HC) adolescents, participated in functional magnetic resonance imaging while processing emotional face stimuli. The BD and HC groups were compared in the strength of functional connectivity from amygdala to the anterior paralimbic cortical regions, and explored in remaining brain regions. Functional connectivity was decreased in the BD group, compared to the HC group, during processing of emotional faces in ventral anterior cingulate (VACC), orbitofrontal, insular and temporopolar cortices (p<0.005). Orbitofrontal and VACC findings for the happy condition, and additionally right insula for the neutral condition, survived multiple comparison correction. Exploratory analyses did not reveal additional regions of group differences. This study provides evidence for decreased functional connectivity between the amygdala and anterior paralimbic cortices in adolescents with BD. This suggests that amygdala-anterior paralimbic connectivity abnormalities are early features of BD that emerge at least by adolescence in the disorder.

Stress Reactivity and Corticolimbic Response to Emotional Faces in Adolescents

Adolescence is a critical period in the development of lifelong patterns of responding to stress. Understanding underpinnings of variations in stress reactivity in adolescents is important, as adolescents with altered stress reactivity are vulnerable to negative risk-taking behaviors including substance use, and have increased lifelong risk for psychopathology. Although both endocrinological and corticolimbic neural system mechanisms are implicated in the development of stress reactivity patterns, the roles of these systems and interactions between the systems in reactivity to social stimuli in adolescents are not clear. We investigated the relationship between cortisol response to a laboratory-based social stressor and regional brain responses to emotional face stimuli in adolescents. Changes in cortisol levels following the Trier Social Stress Test-Child version (TSST-C) were measured in 23 disadvantaged and chronically stressed adolescents who also participated in functional magnetic resonance imaging during processing of emotional faces and structural magnetic resonance imaging. The relationships between changes in cortisol following the TSST-C with regional brain activation during face processing, as well as with regional brain morphology, were assessed. Cortisol change on the TSST-C showed a significant inverse relationship with left hippocampus response to fearful faces (p < .05, corrected); significant associations with volume were not observed. Increased cortisol response to the Trier social stressor was associated with diminished response of the left hippocampus to faces depicting fear. This suggests that HPA-corticolimbic system mechanisms may underlie vulnerability to maladaptive responses to stress in adolescents that may contribute to development of stress-related disorders.

Role of Variation in the Serotonin Transporter Protein Gene (SLC6A4) in Trait Disturbances in the Ventral Anterior Cingulate in Bipolar Disorder

Bipolar disorder (BD) is associated with abnormalities of the ventral anterior cingulate cortex (vACC) and its connection sites, including the amygdala, which are key components of a corticolimbic neural system that subserves emotional regulation. Decreased functional connectivity from the vACC to the amygdala in healthy individuals is associated with the short 's' allele--as opposed to the long 'l' allele--of a well-known serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4), as are features of BD. This study tests the hypothesis that the s allele influences dysfunction in the vACC-amygdala neural system in BD. A total of 30 euthymic individuals with BD (20 s carriers, 10 ll) and 48 healthy comparison (HC) participants (34 s, 14 ll) participated in an event-related functional magnetic resonance imaging scan while processing fearful, happy, or neutral faces. During fear and happy face processing, vACC activation was significantly lower in the BD compared to the HC group, and in s carriers compared to ll individuals within both the HC and BD groups, such that BD s carriers exhibited the greatest magnitude of vACC dysfunction. No significant differences were detected in amygdala activation. The findings suggest that the 5-HTTLPR s allele may contribute to a trait-related, genetically derived, neurobiological subgroup within BD characterized by prominent vACC dysfunction. Future treatment may be optimized for this BD subgroup by targeting the serotonergic system and the vACC.

Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging

Convergent evidence implicates white matter abnormalities in bipolar disorder. The cingulum is an important candidate structure for study in bipolar disorder as it provides substantial white matter connections within the corticolimbic neural system that subserves emotional regulation involved in the disorder. To test the hypothesis that bipolar disorder is associated with abnormal white matter integrity in the cingulum. Fractional anisotropy in the anterior and posterior cingulum was compared between 42 participants with bipolar disorder and 42 healthy participants using diffusion tensor imaging. Fractional anisotropy was significantly decreased in the anterior cingulum in the bipolar disorder group compared with the healthy group (P=0.003); however, fractional anisotropy in the posterior cingulum did not differ significantly between groups. Our findings demonstrate abnormalities in the structural integrity of the anterior cingulum in bipolar disorder. They extend evidence that supports involvement of the neural system comprising the anterior cingulate cortex and its corticolimbic gray matter connection sites in bipolar disorder to implicate abnormalities in the white matter connections within the system provided by the cingulum.