Penalized model-based clustering of fMRI data.

Functional magnetic resonance imaging (fMRI) data have become increasingly available and are useful for describing functional connectivity (FC), the relatedness of neuronal activity in regions of the brain. This FC of the brain provides insight into certain neurodegenerative diseases and psychiatric disorders, and thus is of clinical importance. To help inform physicians regarding patient diagnoses, unsupervised clustering of subjects based on FC is desired, allowing the data to inform us of groupings of patients based on shared features of connectivity. Since heterogeneity in FC is present even between patients within the same group, it is important to allow subject-level differences in connectivity, while still pooling information across patients within each group to describe group-level FC. To this end, we propose a random covariance clustering model (RCCM) to concurrently cluster subjects based on their FC networks, estimate the unique FC networks of each subject, and to infer shared network features. Although current methods exist for estimating FC or clustering subjects using fMRI data, our novel contribution is to cluster or group subjects based on similar FC of the brain while simultaneously providing group- and subject-level FC network estimates. The competitive performance of RCCM relative to other methods is demonstrated through simulations in various settings, achieving both improved clustering of subjects and estimation of FC networks. Utility of the proposed method is demonstrated with application to a resting-state fMRI data set collected on 43 healthy controls and 61 participants diagnosed with schizophrenia.

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.

A random covariance model for bi-level graphical modeling with application to resting-state fMRI data.

We consider a novel problem, bi-level graphical modeling, in which multiple individual graphical models can be considered as variants of a common group-level graphical model and inference of both the group- and individual-level graphical models is of interest. Such a problem arises from many applications, including multi-subject neuro-imaging and genomics data analysis. We propose a novel and efficient statistical method, the random covariance model, to learn the group- and individual-level graphical models simultaneously. The proposed method can be nicely interpreted as a random covariance model that mimics the random effects model for mean structures in linear regression. It accounts for similarity between individual graphical models, identifies group-level connections that are shared by individuals, and simultaneously infers multiple individual-level networks. Compared to existing multiple graphical modeling methods that only focus on individual-level graphical modeling, our model learns the group-level structure underlying the multiple individual graphical models and enjoys computational efficiency that is particularly attractive for practical use. We further define a measure of degrees-of-freedom for the complexity of the model useful for model selection. We demonstrate the asymptotic properties of our method and show its finite-sample performance through simulation studies. Finally, we apply the method to our motivating clinical data, a multi-subject resting-state functional magnetic resonance imaging dataset collected from participants diagnosed with schizophrenia, identifying both individual- and group-level graphical models of functional connectivity.

The neurobiology of self-processing in abused depressed adolescents.

Maltreatment is associated with chronic depression, high negative self-attributions, and lifetime psychopathology. Adolescence is a sensitive period for the formation of self-concept. Identifying neurobiomarkers of self-processing in depressed adolescents with and without maltreatment may parse the effects of trauma and depression on self-development and chronic psychopathology. Depressed adolescents (n = 86) maltreated due to omission (DO, n = 13) or commission (DCM, n = 28) or without maltreatment (DC, n = 45), and HCs (HC, n = 37) appraised positive and negative self-descriptors in the scanner. DCM and DO showed hypoactivity in the dorsal anterior cingulate cortex (dACC) while processing positive versus negative self-descriptors compared to DC youth, who in turn showed reduced dACC recruitment versus HC. HC youth showed the highest activation in the dACC and striatum during positive self-descriptors; these regions showed a linear decline in activity across DC, DO, and DCM. Low dACC activity to positive versus negative self-descriptors was linked to inadequate coregulation of children's emotions by parents. Negative self-cognitions prevalent in DCM and DO adolescents may be perpetuated by activity in the dACC and striatum. Reduced activation of the dACC and striatum for positive self-descriptors, coupled with enhanced activity for negative self-descriptors, may heighten the risk for persistent depression.

Brain activity and infant attachment history in young men during loss and reward processing.

There is now ample evidence that the quality of early attachment experiences shapes expectations for supportive and responsive care and ultimately serves to scaffold adaptation to the salient tasks of development. Nonetheless, few studies have identified neural mechanisms that might give rise to these associations. Using a moderately large sample of low-income male participants recruited during infancy (N = 171), we studied the predictive significance of attachment insecurity and disorganization at age 18 months (as measured in the Strange Situation Procedure) for patterns of neural activation to reward and loss at age 20 years (assessed during a reward-based task as part of a functional magnetic resonance imaging scan). Results indicated that individuals with a history of insecure attachment showed hyperactivity in (a) reward- and emotion-related (e.g., basal ganglia and amygdala) structures and (b) emotion regulation and self-referential processing (cortical midline structures) in response to positive and negative outcomes (and anticipation of those outcomes). Further, the neural activation of individuals with a history of disorganized attachment suggested that they had greater emotional reactivity in anticipation of reward and employed greater cognitive control when negative outcomes were encountered. Overall, results suggest that the quality of early attachments has lasting impacts on brain function and reward processing.

The impact of early neglect on defensive and appetitive physiology during the pubertal transition: a study of startle and postauricular reflexes.

This study tested the effect of early neglect on defensive and appetitive physiology during puberty. Emotion-modulated reflexes, eye-blink startle (defensive) and postauricular (appetitive), were measured in 12-to-13-year-old internationally adopted youth (from foster care or from institutional settings) and compared to non-adopted US born controls. Startle Reflex: adopted youth displayed lower overall startle amplitude across all valences and startle potentiation to negative images was negatively related to severity of pre-adoption neglect. Postauricular reflex (PAR): adopted youth showed larger PAR magnitude across all valences. Puberty: adopted youth showed diminished PAR potentiation to positive images and startle potentiation during mid/late puberty versus the opposite pattern in not-adopted. Early neglect was associated with blunted fast defensive reflexes and heightened fast appetitive reflexes. After puberty, early neglected youth showed physiological hyporeactivity to threatening and appetitive stimuli versus heightened reactivity in not adopted youth. Behavioral correlates in this sample and possible neurodevelopmental mechanisms of psychophysiological differences are discussed.

Risk-taking and sensation-seeking propensity in postinstitutionalized early adolescents.

BACKGROUND: Youth with histories of institutional/orphanage care are at increased risk for externalizing and internalizing problems during childhood and adolescence. Although these problems have been well described, the related adolescent behaviors of risk-taking and sensation-seeking have not yet been explored in this population. This study examined risk-taking and sensation-seeking propensity, and associations with conduct problems and depressive symptoms, in early adolescents who were adopted as young children from institutional care. METHODS: Risk-taking and sensation-seeking propensities of 12- and 13-year-old postinstitutionalized (PI; n = 54) adolescents were compared with two groups: youth who were internationally adopted early from foster care (PFC; n = 44) and nonadopted youth (NA; n = 58). Participants were recruited to equally represent pre/early- and mid/late-pubertal stages within each group. Participants completed the youth version of the Balloon Analogue Risk Task (Lejuez et al., ) and the Sensation-Seeking Scale for Children (Russo et al., ). Parents completed clinical ratings of participants' conduct problems and depressive symptoms. RESULTS: PI adolescents demonstrated lower risk-taking than PFC and NA peers. Pre/early-pubertal PI youth showed lower sensation-seeking, while mid/late-pubertal PI youth did not differ from other groups. PI adolescents had higher levels of conduct problems but did not differ from the other youth in depressive symptoms. In PI youth only, conduct problems were negatively correlated with risk-taking and positively correlated with sensation-seeking, while depressive symptoms were negatively correlated with both risk-taking and sensation-seeking. CONCLUSIONS: Early institutional care is associated with less risk-taking and sensation-seeking during adolescence. The deprived environment of an institution likely contributes to PI youth having a preference for safe choices, which may only be partially reversed with puberty. Whether this reflects hyporesponsiveness to rewards and how it relates to psychopathology are discussed.

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.

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.

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.

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.

Medial Prefrontal Cortex Activity to Reward Outcome Moderates the Association Between Victimization Due to Sexual Orientation and Depression in Youth.

BACKGROUND: Sexual minority youth (SMY) are 3 times more likely to experience depression than heterosexual peers. Minority stress theory posits that this association is explained by sexual orientation victimization, which acts as a stressor to impact depression. For those vulnerable to the effects of stress, victimization may worsen depression by altering activity in neural reward systems. This study examines whether neural reward systems moderate the influence of sexual orientation victimization, a common and distressing experience in SMY, on depression. METHODS: A total of 81 participants ages 15 to 22 years (41% SMY, 52% marginalized race) reported sexual orientation victimization, depression severity, and anhedonia severity, and underwent a monetary reward functional magnetic resonance imaging task. Significant activation to reward > neutral outcome (pfamilywise error < .05) was determined within a meta-analytically derived Neurosynth reward mask. A univariate linear model examined the impact of reward activation and identity on victimization-depression relationships. RESULTS: SMY reported higher depression (p < .001), anhedonia (p = .03), and orientation victimization (p < .001) than heterosexual youth. The bilateral ventral striatum, medial prefrontal cortex (mPFC), anterior cingulate cortex, and right orbitofrontal cortex were significantly active to reward. mPFC activation moderated associations between sexual orientation victimization and depression (p = .03), with higher depression severity observed in those with a combination of higher mPFC activation and greater orientation victimization. CONCLUSIONS: Sexual orientation victimization was related to depression but only in the context of higher mPFC activation, a pattern observed in depressed youth. These novel results provide evidence for neural reward sensitivity as a vulnerability factor for depression in SMY, suggesting mechanisms for disparities, and are a first step toward a clinical neuroscience understanding of minority stress in SMY.

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.

The startle response: developmental effects and a paradigm for children and adults.

A film paradigm was developed to examine baseline and emotion modulated startle across a broad age range from preschool to adulthood. The paradigm was tested in children (3-, 5-, 7-, and 9-year-olds) and adults (total N = 122). The paradigm elicited a similar startle potentiation pattern across age groups; however, baseline startle changed with age: 3- and 5-year-olds showed lower response probability and magnitude of baseline startle than adults. Females exhibited larger baseline startle response probability and overall magnitude than did males; however, no sex by emotion modulated startle interaction was noted. Anxiety measures were obtained for all children. Individual differences in anxiety were associated with baseline startle magnitude among older but not younger children. No association of anxiety with startle potentiation was noted. Overall the film paradigm was applicable across a wide developmental span, revealing potential developmental and gender differences in baseline startle magnitude and response probability.

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.

The onset of puberty: effects on the psychophysiology of defensive and appetitive motivation.

We examined puberty-specific effects on affect-related behavior and on the psychophysiology of defensive and appetitive motivation while controlling for age. Adolescents (N = 94, ages = 12 and 13 years) viewed 75 pictures (International Affective Picture System: pleasant, neutral, and aversive) while listening to auditory probes. Startle response and postauricular (PA) reflex were collected as measures of defensive and appetitive motivation, respectively. Pubertal status and measures of anxiety/stress reaction and sensation/thrill seeking were obtained. Mid-/late pubertal adolescents showed enhanced startle amplitude across all picture valences. A Puberty x Valence interaction revealed that mid-/late pubertal adolescents showed appetitive potentiation of the PA, whereas pre-/early pubertal adolescents showed no modulation of the PA reflex. Mid-/late pubertal adolescents also scored significantly higher on measures of sensation/thrill seeking than did their pre-/early pubertal peers and puberty moderated the association between psychophysiology and behavioral measures, suggesting that it plays a role in reorganizing defensive and appetitive motivational systems.

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.

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.

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.

Early care experiences and HPA axis regulation in children: a mechanism for later trauma vulnerability.

Post-traumatic stress disorder (PTSD) is associated with functional abnormalities of the hypothalamic-pituitary-adrenocortical (HPA) axis. Emerging evidence suggests that failures in social regulation of the HPA axis in young children manifested as neglectful or abusive care may play a role in shaping cortico-limbic circuits involved in processing experiences threatening experiences encountered later in life. Low cortisol levels, particularly near the peak of the diurnal rhythm, have been reported in abused, neglected and deprived children. Thus early imprinting effects of parenting quality on the HPA system regulation may be one of the mechanisms causing heightened risk of PTSD in responses to later trauma. However there is also evidence that the altered patterns of cortisol production seen in the context of early adverse care are not permanent, and remit once the care children receive improves. What awaits study is whether periods of atypical cortisol levels and altered HPA function early in life, even if transient, impact brain development in ways that heighten vulnerability to PTSD in response to traumas experienced later.