Neurofeedback and Affect Regulation Circuitry in Depressed and Healthy Adolescents.

Neurodevelopmental psychopathology seeks to understand higher-order emotion regulation circuitry to develop new therapies for adolescents with depression. Depressed (N = 34) and healthy youth (N = 19) completed neurofeedback (NF) training and exhibited increased bilateral amygdala and hippocampus activity in the region of interest (ROI) analyses by recalling positive autobiographical memories. We tested factors supportive of the engagement of emotion regulation's neural areas during NF (i.e., parental support, medication, and gender effects upon anterior cingulate cortex (ACC) engagement). Whole-brain analyses yielded effects of NF vs. control condition and effects of diagnosis. Youth showed higher amygdala and hippocampus (AMYHIPPO) activity during the NF vs. control condition, particularly in the left hippocampus. ACC's activity was also higher during NF vs. control. Higher average ACC activity was linked to better parental support, absent depression, female gender, and absent medication. Control youth showed higher average AMYHIPPO and ACC activity throughout the task and a faster decline in activity vs. depressed youths. Whole-brain level analyses showed higher activity in the frontotemporal network during the NF vs. control conditions, suggesting targeting their connectivity in future neurofeedback trials.

Self-compassion and neural activity during self-appraisals in depressed and healthy adolescents.

BACKGROUND: Depression is one of the most concerning mental disorders in youth. Because atypical excessive neural activity during self-referential processing is often implicated in depression, identifying psychological factors that link to lower depression and less excessive neural activity during self-referential processing is critical for treatment development. This study examined the relationship between self-compassion - a protective factor of youth depression - and neural activity during self-appraisals, a well-established experimental paradigm for studying self-referential processing, and their associations with depression severity in depressed and healthy youth. METHODS: The sample consisted of 115 youth (79 met the clinical diagnosis of depression; 36 were matched healthy controls) aged from 11 to 17 years (68 females). Self-compassion and depression severity were measured with self-reported scales. In the scanner, participants were asked to judge whether the phrases they heard described them from four perspectives (self, mother, classmate, and best friend). RESULTS: Higher self-compassion was associated with lower PCC/precuneus activity especially during negatively-valenced self-appraisals and explained its association with reduced depression severity. In depressed youth, higher self-compassion was associated with lower superior temporal gyrus/operculum/postcentral gyrus/insula activity especially during positively-valenced self-appraisals. In healthy youth, higher self-compassion was associated with higher activity in these regions. CONCLUSIONS: Self-compassion was associated with less excessive experiential immersion and/or autobiographical memory retrieval during negative self-appraisals. Neural stimulation interventions targeting PCC/precuneus activity during negative self-appraisals combined with behavioral interventions targeting self-compassion could be a promising approach to youth depression treatment.

Neural Activity Associated with Symptoms Change in Depressed Adolescents following Self-Processing Neurofeedback.

Adolescent depression is prevalent, debilitating, and associated with chronic lifetime mental health disorders. Understanding the neurobiology of depression is critical to developing novel treatments. We tested a neurofeedback protocol targeting emotional regulation and self-processing circuitry and examined brain activity associated with reduced symptom severity, as measured through self-report questionnaires, four hours after neurofeedback. Depressed (n = 34) and healthy (n = 19) adolescents participated in (i) a brief neurofeedback task that involves simultaneously viewing their own happy face, recalling a positive autobiographical memory, and increasing amygdala-hippocampal activity; (ii) a self- vs. other- face recognition task with happy, neutral, and sad facial expressions before and after the neurofeedback. In depressed youth, reduced depression after neurofeedback was associated with increased self-referential and visual areas' activity during neurofeedback, specifically, increased activity in the cuneus, precuneus and parietal lobe. Reduced depression was also associated with increased activation of emotional regulation and cross-modal areas during a self-recognition task. These areas included the cerebellum, middle temporal gyrus, superior temporal gyrus, and supramarginal gyrus. However, decreased rumination was linked to decreased precuneus, angular and temporal gyri activity during neurofeedback. These results tentatively suggest that neurofeedback may induce short-term neurobiological changes in the self-referential and emotional regulation networks associated with reduced symptom severity among depressed adolescents.

Neural substrates of rewarding and punishing self representations in depressed suicide-attempting adolescents.

Adolescence is a period of plasticity in neural substrates underpinning self-processing. Such substrates are worth studying in depressed youth at risks for suicide because altered neurobiology of self-processing might partially explain differences between suicide attempting youth versus youth who contemplate but do not attempt suicide. Understanding altered substrates of self-processing among depressed adolescents with suicide attempts is critical for developing targeted prevention and treatment. Healthy youth (N = 40), youth with depression and low (N = 33) or high suicide ideation (N = 28), and youth with depression and past suicide attempt (N = 28) heard positive or negative self-descriptors during fMRI and evaluated them from their own, their mother's, classmates', and best friend's perspectives. Lower bilateral caudate activity during positive self-processing distinguished suicide attempting adolescents from all other youth. Higher bilateral caudate activity during negatively valenced self-processing tended to distinguish youth with depression. Blunted reward circuitry during positive vs. negative self-related material tended to distinguish suicide attempting youth, reflecting potentially enhanced behavioral preparedness for punishing vs. rewarding self-relevant cues.

The impact of child abuse on the neurobiology of self-processing in depressed adolescents.

Child abuse is linked to lifetime psychopathology including abnormal self-processing. Given self-processing maturation in adolescence, we tested duration, presence, and abuse accumulation's impact upon self-processing neurobiology among depressed youth with (N = 54) and without an abuse history (N = 40). Youth evaluated positive and negative self-descriptors across four points of view in the scanner. Regression analyses showed that longer abuse duration (in days) was associated with lower activity in inferior temporal (e.g. insula, fusiform & parahippocampus), striatal, cerebellar and midbrain structures when processing negative self-descriptors with the least activity in youth exposed to 6+ abuse years. Abuse presence vs. absence was linked to higher neural activity. However, youth exposed to a single abuse instance to 3 years of abuse might drive that relative neural hyperactivity. Results support: 1) the toxic stress model of blunted overall neuro-reactivity underpinning emotion, sensorimotor gating, and social cognition during negative stimuli as an adaptation to pervasively toxic environments and 2) the differential impact of acute versus chronic stress upon neurophysiological indices. Finally, child abuse duration might impact these ancillary and higher socioemotional processes differently among depressed youth primarily for negative but not positive self-processing.

Amygdala Circuitry During Neurofeedback Training and Symptoms' Change in Adolescents With Varying Depression.

Typical adolescents have increased limbic engagement unchecked by regulatory medial prefrontal cortex (PFC) activity as well as heightened self-focus. The resulting emotion dysregulation and self-focused rumination make adolescents more susceptible to depression and suicide attempts. Heightened self-focus converges with mental illness among depressed adolescents, who deploy exaggerated attention to negative self-relevant stimuli and neglect positive ones as part of depression's phenomenology. This results in rigid negative self-representations during an identity formative period with potential lifetime repercussions. Current empirically supported treatments fail to allay recurrent depression. Evidence-based interventions for illnesses linked to suicide ideation and attempts (e.g., depression) underperform across the lifespan. This could be because current treatments are not successful in altering pervasive negative self-representations and affect dysregulation, which is known to be a risk factor of chronic depression. This study departs from the premise that increasing positive self-processing might be protective against chronic depression particularly during adolescence. The present research is a novel investigation of neurofeedback as a potential treatment alternative for adolescent depression. To enhance positive self-processing, we used the happy self-face as a cue to initiate neurofeedback from the bilateral amygdala and hippocampus and adolescents attempted to upregulate that limbic activity through the recall of positive autobiographical memories. We identified limbic functional circuitry engaged during neurofeedback and links to short-term symptoms' change in depression and rumination. We found that depressed youth showed greater right amygdala to right frontocortical connectivity and lower left amygdala to right frontocortical connectivity compared to healthy controls during neurofeedback vs. control conditions. Depressed youth also showed significant symptom reduction. Connectivity between the right amygdala and frontocortical regions was positively correlated with rumination and depression change, but connectivity between frontocortical regions and the left amygdala was negatively correlated with depression change. The results suggest that depressed youth might engage implicit emotion regulation circuitry while healthy youth recruit explicit emotion regulation circuits during neurofeedback. Our findings support a compensatory approach (i.e., target the right amygdala) during future neurofeedback interventions in depressed youth. Future work ought to include a placebo condition or group.