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.

Self-compassion and dorsolateral prefrontal cortex activity during sad self-face recognition in depressed adolescents.

BACKGROUND: Given the prevalence of adolescent depression and the modest effects of current treatments, research ought to inform development of effective intervention strategies. Self-compassion is inversely associated with depression, and self-compassion interventions have demonstrated promising effects on reducing depression. However, little is known about the neural mechanisms underlying that relationship. Maladaptive self-processing is a characteristic of depression that contributes to the onset and chronicity of depression. Because our own face is an automatic and direct cue for self-processing, this study investigated whether self-compassion was associated with neural responses during sad v. neutral self-face recognition and explore their relationship with depression severity in depressed adolescents and healthy controls (HCs). METHODS: During functional magnetic resonance imaging, 81 depressed youth and 37 HCs were instructed to identify whether morphed self or other faces with sad, happy, or neutral expressions resembled their own. RESULTS: Self-compassion correlated negatively with activity during sad v. neutral self-face recognition in the dorsal anterior cingulate cortex in the total sample, and in the right posterior cingulate cortex/precuneus in HCs, respectively. In depressed adolescents, higher self-compassion correlated with lower activity during sad v. neutral self-face recognition in the right dorsolateral prefrontal cortex (DLPFC), implying that less cognitive effort might be needed to avoid dwelling on sad self-faces and/or regulate negative affect induced by them. Moreover, higher self-compassion mediated the relationship between lower DLPFC activity and reduced depression severity. CONCLUSIONS: Our findings imply that DLPFC activity might be a biological marker of a successful self-compassion intervention as potential treatment for adolescent depression.

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.

Neurofeedback and neuroplasticity of visual self-processing in depressed and healthy adolescents: A preliminary study.

Adolescence is a neuroplastic period for self-processing and emotion regulation transformations, that if derailed, are linked to persistent depression. Neural mechanisms of adolescent self-processing and emotion regulation ought to be targeted via new treatments, given moderate effectiveness of current interventions. Thus, we implemented a novel neurofeedback protocol in adolescents to test the engagement of circuits sub-serving self-processing and emotion regulation. METHODS: Depressed (n = 34) and healthy (n = 19) adolescents underwent neurofeedback training using a novel task. They saw their happy face as a cue to recall positive memories and increased displayed amygdala and hippocampus activity. The control condition was counting-backwards while viewing another happy face. A self vs. other face recognition task was administered before and after neurofeedback training. RESULTS: Adolescents showed higher frontotemporal activity during neurofeedback and higher amygdala and hippocampus and hippocampi activity in time series and region of interest analyses respectively. Before neurofeedback there was higher saliency network engagement for self-face recognition, but that network engagement was lower after neurofeedback. Depressed youth exhibited higher fusiform, inferior parietal lobule and cuneus activity during neurofeedback, but controls appeared to increase amygdala and hippocampus activity faster compared to depressed adolescents. CONCLUSIONS: Neurofeedback recruited frontotemporal cortices that support social cognition and emotion regulation. Amygdala and hippocampus engagement via neurofeedback appears to change limbic-frontotemporal networks during self-face recognition. A placebo group or condition and contrasting amygdala and hippocampus, hippocampi or right amygdala versus frontal loci of neurofeedback, e.g. dorsal anterior cingulate cortex, with longer duration of neurofeedback training will elucidate dosage and loci of neurofeedback in adolescents.

Adolescent suicide attempts and ideation are linked to brain function during peer interactions.

Understanding the neural correlates of social interaction among depressed adolescents with suicidal tendencies might help personalize treatment. We tested whether brain function during social interaction is disrupted for depressed adolescents with (1) high suicide ideation and (2) recent attempts. Depressed adolescents with high suicide ideation, including attempters (n = 45;HS) or low suicide ideation (n = 42;LS), and healthy adolescents (n = 39;HC), completed a version of the Cyberball peer interaction task during an fMRI scan. Groups were compared on brain activity during peer exclusion and inclusion versus a non-social condition. During peer exclusion and inclusion, HS youth showed significantly lower activity in precentral and postcentral gyrus, superior temporal gyrus, medial frontal gyrus, insula, and putamen compared to LS youth; and significantly reduced activity in caudate and anterior cingulate cortex compared to HC youth. In a second analysis, suicide attempters (n = 26;SA) were compared to other groups. SA adolescents showed significantly higher activity in ACC and superior and middle frontal gyrus than all other groups. Brain activity was significantly correlated with negative emotionality, social functioning, and cognitive control. Conclusions: Adolescent suicide ideation and attempts were linked to altered neural function during positive and negative peer interactions. We discuss the implications of these findings for suicide prevention efforts.

Amygdala Functional Connectivity During Self-Face Processing in Depressed Adolescents With Recent Suicide Attempt.

OBJECTIVE: Suicide is the second leading cause of death among adolescents; however, objective biomarkers of suicide risk are lacking. Aberrant self-face amygdala activity is associated with suicide ideation, and its connectivity with neural regions that enable self-processing (eg medial prefrontal cortex) may be a suicide risk factor. METHOD: Adolescents (aged 11-17 years; N = 120) were sorted into four groups: healthy controls (HC), depressed individuals with low suicide ideation (LS), depressed individuals with high suicide ideation (HS), and depressed suicide attempters (SA). Youth completed an emotional (Happy, Sad, Neutral) self-face recognition task in the scanner. Bilateral amygdala task-dependent functional connectivity was determined with psychophysiological interaction analysis. Connectivity was compared across groups and within Self versus Other faces across emotions and hemispheres. Voxelwise results were thresholded (p < .005, uncorrected) and corrected for multiple comparisons (p < .05, familywise error). RESULTS: Both HS and SA displayed greater amygdala connectivity with the dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and precuneus, compared to LS, who, in turn, showed greater connectivity than HC. Greater left amygdala-rostral anterior cingulate cortex (rACC) connectivity was observed in SA compared to all other groups, whereas right amygdala-rACC connectivity was greater in HS versus LS and HC. CONCLUSION: Greater connectivity between amygdala and other regions implicated in self-face processing differentiated suicide ideation and suicide attempt groups. A dose-dependent response showed that greater rACC-left amygdala connectivity during self-face processing was associated with a recent suicide attempt, but that a greater rACC-right amygdala connectivity was associated with suicide ideation.