Prefrontal Cortical Reactivity and Connectivity Markers Distinguish Youth Depression from Healthy Youth.
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ABSTRACT:
SUBMITTER: Dhami P
PROVIDER: S-EPMC7264684 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveBoth bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task.MethodsWe scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs. Our sample consisted of 22 youth with BPSD, 30 youth with ADHD/no BPSD, and 26 HCs. We used generalized psychophysiological interaction (gPPI) to calculate group differences to emerging emotional faces vs. morphing shapes in FxC between bilateral amygdala and ventral prefrontal cortex/anterior cingulate cortex.ResultsFxC between amygdala and left ventrolateral prefrontal cortex (VLPFC) in response to emotions vs. shapes differed by group (p=.05): while BPSD showed positive FxC (emotions>shapes), HC and ADHD showed inverse FxC (emotions<shapes). A group x emotion interaction was found in amygdala-subgenual cingulate FxC (p=.025), explained by differences in FxC in response to negative emotions. While BPSD showed positive FxC, HC showed inverse FxC; ADHD were intermediate. Amygdala-subgenual FxC was also positively associated with depressive symptoms and stimulant medication.LimitationsCo-morbidity and relatively small sample size.ConclusionsYouth with BPSD showed abnormally positive FxC between amygdala and regions in the ventral prefrontal cortex during emotion processing. In particular, the amygdala-VLPFC finding was specific to BPSD, and not influenced by other diagnoses or medications.
| S-EPMC5154789 | biostudies-literature
Project description:Theta burst stimulation (TBS), a specific form of repetitive transcranial magnetic stimulation (TMS), is a promising treatment for youth with Major Depressive Disorder (MDD) who do not respond to conventional therapies. However, given the variable response to TBS, a greater understanding of how baseline features relate to clinical response is needed to identify which patients are most likely to benefit from this treatment. In the current study, we sought to determine if baseline neurophysiology, specifically cortical excitation and/or inhibition, is associated with antidepressant response to TBS. In two independent open-label clinical trials, youth (aged 16-24 years old) with MDD underwent bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment. Clinical trial one and two consisted of 10 and 20 daily sessions of bilateral DLPFC TBS, respectively. At baseline, single-pulse TMS combined with electroencephalography was used to assess the neurophysiology of 4 cortical sites: bilateral DLPFC and inferior parietal lobule. Measures of cortical excitation and inhibition were indexed by TMS-evoked potentials (i.e., P30, N45, P60, N100, and P200). Depression severity was measured before, during and after treatment completion using the Hamilton Rating Scale for Depression-17. In both clinical trials, the baseline left DLPFC N45 and P60, which are believed to reflect inhibitory and excitatory mechanisms respectively, were predictors of clinical response. Specifically, greater (i.e., more negative) N45 and smaller P60 baseline values were associated with greater treatment response to TBS. Accordingly, cortical excitation and inhibition circuitry of the left DLPFC may have value as a TBS treatment response biomarker for youth with MDD.Clinical trial 1 registration number: NCT02472470 (June 15, 2015).Clinical trial 2 registration number: NCT03708172 (October 17, 2018).
| S-EPMC10625527 | biostudies-literature
Project description:The organization of the cerebral cortex into distinct modules may be described along several dimensions, most importantly, structure, connectivity and function. Identification of cortical modules by differences in whole-brain connectivity profiles derived from diffusion tensor imaging or resting state correlations has already been shown. These approaches, however, carry no task-related information. Hence, inference on the functional relevance of the ensuing parcellation remains tentative. Here, we demonstrate, that Meta-Analytic Connectivity Modeling (MACM) allows the delineation of cortical modules based on their whole-brain co-activation pattern across databased neuroimaging results. Using a model free approach, two regions of the medial pre-motor cortex, SMA and pre-SMA were differentiated solely based on their functional connectivity. Assessing the behavioral domain and paradigm class meta-data of the experiments associated with the clusters derived from the co-activation based parcellation moreover allows the identification of their functional characteristics. The ensuing hypotheses about functional differentiation and distinct functional connectivity between pre-SMA and SMA were then explicitly tested and confirmed in independent datasets using functional and resting state fMRI. Co-activation based parcellation thus provides a new perspective for identifying modules of functional connectivity and linking them to functional properties, hereby generating new and subsequently testable hypotheses about the organization of cortical modules.
| S-EPMC3129435 | biostudies-literature
Project description:Treatment-resistant depression presents a serious challenge to both patients and clinicians. The anterior and midlateral prefrontal cortices play complementary roles in integrating emotional and cognitive experiences and in modulating subcortical regions. Both regions offer a distinct opportunity for targeted antidepressant treatments. We chose to pilot the safety and therapeutic benefits of chronic and intermittent epidural prefrontal cortical stimulation (EpCS) in patients with treatment-resistant depression.We enrolled five adults with an average of 5.8 failed antidepressant treatments in their current depressive episode. All subjects underwent comprehensive clinical assessments, detailed neuropsychological testing, and presurgical magnetic resonance imaging. Four cortical stimulation paddle leads were stereotactically placed bilaterally over the anterior frontal poles and midlateral prefrontal cortex. We also acquired a postsurgical computed tomography scan and repeatedly assessed clinical outcomes over time of EpCS as an adjunctive treatment to constant medications.All patients tolerated the therapy. At 7-month follow-up, the average improvement from preimplant baseline on the Hamilton Rating Scale for Depression and the Inventory of Depressive Symptoms-Self-Report were 54.9% (+/- 37.7) and 60.1% (+/- 34.1), respectively. Three implanted subjects reached remission. One patient's left hemisphere leads were explanted 12 weeks postsurgery because of a scalp infection.Bilateral EpCS over anterior and midlateral frontal cortex is a promising new technology for treatment-resistant depression. Future double-blind studies are warranted.
| S-EPMC2863140 | biostudies-literature
Project description:BackgroundPatients with bipolar depression are characterized by dysregulation across the full spectrum of mood, differentiating them from patients with unipolar depression. The ability to switch neural resources among the default mode network, salience network, and executive control network (ECN) has been proposed as a key mechanism for adaptive mood regulation. The anterior insula is implicated in the modulation of functional network switching. Differential connectivity between anterior insula and functional networks may provide insights into pathophysiological differences between bipolar and unipolar mood disorders, with implications for diagnosis and treatment.MethodsResting-state functional magnetic resonance imaging data were collected from 98 subjects (35 unipolar, 24 bipolar, and 39 healthy control subjects). Pearson correlations were computed between bilateral insula seed regions and a priori defined target regions from the default mode network, salience network, and ECN. After r-to-z transformation, a one-way multivariate analysis of covariance was conducted to identify significant differences in connectivity between groups. Post hoc pairwise comparisons were conducted and Bonferroni corrections were applied. Receiver-operating characteristics were computed to assess diagnostic sensitivity.ResultsPatients with bipolar depression evidenced significantly altered right anterior insula functional connectivity with the inferior parietal lobule of the ECN relative to patients with unipolar depression and control subjects. Right anterior insula-inferior parietal lobule connectivity significantly discriminated patients with bipolar depression.ConclusionsImpaired functional connectivity between the anterior insula and the inferior parietal lobule of the ECN distinguishes patients with bipolar depression from those with unipolar depression and healthy control subjects. This finding highlights a pathophysiological mechanism with potential as a therapeutic target and a clinical biomarker for bipolar disorder, exhibiting reasonable sensitivity and specificity.
| S-EPMC6467478 | biostudies-literature
Project description:BackgroundBy adolescence, foundational cognitive and affective neurobehavioral processes specialize based on environmental demands, such as stress, to determine the basis of adult trajectories. The ongoing COVID-19 pandemic has increased stress for everyone, particularly adolescents who face unique stressors such as restrictions in socialization and education. However, variability in brain processes supporting stress reactivity is not well understood. Here, we leverage pre-pandemic brain development studies to identify how maturity of prefrontal connectivity with the amygdala and hippocampus (HPC) is associated with response to COVID-19. We hypothesized that age-related changes in connectivity of affective and cognitive brain systems may underlie the emotional response of adolescents during the pandemic.MethodsIn this study, 10- to 31-year-old participants (n = 111) completed resting-state functional magnetic resonance imaging scans prior to the pandemic and then completed a questionnaire 9 months into the pandemic measuring worry, COVID-related stress, sadness, perceived stress, and positive affect. Associations between pairwise functional connectivity of HPC/amygdala subregions with prefrontal cortex subdivisions and affective reactivity during the pandemic were examined.ResultsRegression analyses indicated that both worry and COVID-19-related stress increased with age (false discovery rate-corrected p < .05). Furthermore, greater connectivity between the anterior ventromedial prefrontal cortex and posterior HPC was associated with greater worry and COVID-19-related stress (p < .05 corrected), which was primarily driven by individuals younger than 18 years.ConclusionsTaken together, our results indicate that increases in stress reactivity to the COVID-19 pandemic across the transition to adulthood are driven by maturation of posterior HPC-ventromedial prefrontal cortex coupling, which integrates stress response and emotional memory processing.
| S-EPMC8612769 | biostudies-literature
Project description:BackgroundThe purpose of this study was to investigate prefrontal cortex (PFC) volumes in youth with posttraumatic stress symptoms (PTSS) and explore the relationship between cortisol secretion and PFC volumes.MethodsTotal brain tissue volumes, segmented areas of the PFC, and diurnal cortisol secretion were examined in a sample of 33 youth aged 10 to 16 years. Cerebral volumes were available for 45 subjects (30 PTSS and 15 control subjects).ResultsYouth with PTSS had significantly decreased total brain tissue and total cerebral gray volumes in comparison with healthy control subjects. While controlling for total cerebral gray volume, the PTSS group demonstrated decreased left ventral and left inferior prefrontal gray volumes. A significant negative association was found between prebedtime cortisol levels and left ventral PFC gray volumes for the full sample.ConclusionsFindings suggest associations between posttraumatic stress and PFC neurodevelopment. Findings also suggest a link between PFC development and cortisol secretion.
| S-EPMC2921458 | biostudies-literature
Project description:Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes.
| S-EPMC7296844 | biostudies-literature
Project description:The association between depressive disorders and measures reflecting myelin content is underexplored, despite growing evidence of associations with white matter tract integrity. We characterized the T1w/T2w ratio using the Glasser atlas in 39 UD and 47 HC participants (ages = 19-44, 75% female). A logistic elastic net regularized regression with nested cross-validation and a subsequent linear discriminant analysis conducted on held-out samples were used to select brain regions and classify patients vs. healthy controls (HC). True-label model performance was compared against permuted-label model performance. The T1w/T2w ratio distinguished patients from HC with 68% accuracy (p < 0.001; sensitivity = 63.8%, specificity = 71.5%). Brain regions contributing to this classification performance were located in the orbitofrontal cortex, anterior cingulate, extended visual, and auditory cortices, and showed statistically significant differences in the T1w/T2w ratio for patients vs. HC. As the T1w/T2w ratio is thought to characterize cortical myelin, patterns of cortical myelin in these regions may be a biomarker distinguishing individuals with depressive disorders from HC.
| S-EPMC8406024 | biostudies-literature
Project description:BackgroundDepression is a common comorbid condition in Parkinson's disease and a major contributor to poor quality of life. Despite this, depression in PD is under-diagnosed due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired old patients.ObjectivesThis study is to explore functional connectivity markers of depression in PD patients using resting-state fMRI and help diagnose whether patients have depression or not.MethodsWe reviewed 156 advanced PD patients (duration > 5 years; 59 depressed ones) and 45 healthy control subjects who underwent a resting-state fMRI scanning. Functional connectivity analysis was employed to characterize intrinsic connectivity networks using group independent component analysis and extract connectivity features. Features were put into an all-relevant feature selection procedure within cross-validation loops, to identify features with significant discriminative power for classification. Random forest classifiers were built for depression diagnosis, on the basis of identified features.Results42 intrinsic connectivity networks were identified and arranged into subcortical, auditory, somatomotor, visual, cognitive control, default-mode and cerebellar networks. Six features were significantly relevant to classification. They were connectivity within posterior cingulate cortex, within insula, between posterior cingulate cortex and insula/hippocampus+amygdala, between insula and precuneus, and between superior parietal lobule and medial prefrontal cortex. The mean accuracy achieved with classifiers to discriminate depressed patients from the non-depressed was 82.4%.ConclusionsOur findings provide preliminary evidence that resting-state functional connectivity can characterize depressed PD patients and help distinguish them from non-depressed ones.
| S-EPMC6931212 | biostudies-literature