Adolescents' neural reactivity to acute psychosocial stress: dysfunctional regulation habits are linked to temporal gyrus response.

Mid-adolescence is a critical time for the development of stress-related disorders and it is associated with significant social vulnerability. However, little is known about normative neural processes accompanying psychosocial stress at this time. Previous research found that emotion regulation strategies critically influence the relationship between stress and the development of psychiatric symptoms during adolescence. Using functional magnetic resonance imaging (fMRI), we examined neural responses to acute stress and analyzed whether the tendency to use adaptive or maladaptive emotion regulation strategies is related to neural and autonomic stress responses. Results show large linear activation increases from low to medium to high stress levels mainly in medial prefrontal, insulae and temporal areas. Caudate and subgenual anterior cingulate cortex, neural areas related to reward and affective valuations, showed linearly decreasing activation. In line with our hypothesis, the current adolescent neural stress profile resembled social rejection and was characterized by pronounced activation in insula, angular and temporal cortices. Moreover, results point to an intriguing role of the anterior temporal gyrus. Stress-related activity in the anterior temporal gyrus was positively related to maladaptive regulation strategies and stress-induced autonomic activity. Maladaptive coping might increase the social threat and reappraisal load of a stressor, relating to higher stress sensitivity of anterior temporal cortices.

Do Belonging and Social Exclusion at School Affect Structural Brain Development During Adolescence?

Students' sense of belonging presents an essential resource for academic and health outcomes, whereas social exclusion at school negatively impacts students' well-being and academic performance. Aiming to understand how feelings of school-related belonging and exclusion shape the structural brain development, this study applied longitudinal questionnaire-based data and MRI data from 71 adolescent students (37 females, Mage at t1 = 15.0; t2 = 16.1 years). All were white participants from Germany. Voxel-based morphometry revealed only an association of social exclusion (and not of belonging) and gray matter volume in the left anterior insula: From t1 to t2, there was less gray matter decrease, the more social exclusion students perceived. School-related social exclusion and disturbed neurodevelopment are thus significantly associated.

Healthy women with severe early life trauma show altered neural facilitation of emotion inhibition under acute stress.

BACKGROUND: Across psychopathologies, trauma-exposed individuals suffer from difficulties in inhibiting emotions and regulating attention. In trauma-exposed individuals without psychopathology, only subtle alterations of neural activity involved in regulating emotions have been reported. It remains unclear how these neural systems react to demanding environments, when acute (non-traumatic but ordinary) stress serves to perturbate the system. Moreover, associations with subthreshold clinical symptoms are poorly understood. METHODS: The present fMRI study investigated response inhibition of emotional faces before and after psychosocial stress situations. Specifically, it compared 25 women (mean age 31.5 ± 9.7 years) who had suffered severe early life trauma but who did not have a history of or current psychiatric disorder, with 25 age- and education-matched trauma-naïve women. RESULTS: Under stress, response inhibition related to fearful faces was reduced in both groups. Compared to controls, trauma-exposed women showed decreased left inferior frontal gyrus (IFG) activation under stress when inhibiting responses to fearful faces, while activation of the right anterior insula was slightly increased. Also, groups differed in brain-behaviour correlations. Whereas stress-induced false alarm rates on fearful stimuli negatively correlated with stress-induced IFG signal in controls, in trauma-exposed participants, they positively correlated with stress-induced insula activation. CONCLUSION: Neural facilitation of emotion inhibition during stress appears to be altered in trauma-exposed women, even without a history of or current psychopathology. Decreased activation of the IFG in concert with heightened bottom-up salience of fear related cues may increase vulnerability to stress-related diseases.

Loneliness and Adolescents' Neural Processing of Self, Friends, and Teachers: Consequences for the School Self-Concept.

The present interdisciplinary study explored whether perceived loneliness is associated with ventromedial prefrontal cortex (vMPFC) activation during self- and social judgments (friends and teachers) in adolescents. Moreover, we examined how vMPFC activity is related to the academic self-concept (ASC). Results of manifest path analysis indicated that high perceived loneliness was related to lower neural response to self-judgments. In turn, high neural response to self-judgments was positively associated with the ASC, whereas there was a trendwise negative association between high neural response to teacher-related judgments and ASC. This study reveals associations between perceived loneliness and neural processing of the self, underlining the idea that feeling isolated from others may hinder self-insight and, by extension, the formation of a stable academic self-concept.

Reversal learning strategy in adolescence is associated with prefrontal cortex activation.

Adolescence is a critical maturation period for human cognitive control and executive function. In this study, a large sample of adolescents (n = 85) performed a reversal learning task during functional magnetic resonance imaging. We analyzed behavioral data using a reinforcement learning model to provide individually fitted parameters and imaging data with regard to reward prediction errors (PE). Following a model-based approach, we formed two groups depending on whether individuals tended to update expectations predominantly for the chosen stimulus or also for the unchosen one. These groups significantly differed in their problem behavior score obtained using the child behavior checklist (CBCL) and in a measure of their developmental stage. Imaging results showed that dorsolateral striatal areas covaried with PE. Participants who relied less on learning based on task structure showed less prefrontal activation compared with participants who relied more on task structure. An exploratory analysis revealed that PE-related activity was associated with pubertal development in prefrontal areas, insula and anterior cingulate. These findings support the hypothesis that the prefrontal cortex is implicated in mediating flexible goal-directed behavioral control.

Neural correlates of the self-concept in adolescence-A focus on the significance of friends.

The formation of a coherent and unified self-concept represents a key developmental stage during adolescence. Imaging studies on self-referential processing in adolescents are rare, and it is not clear whether neural structures involved in self-reflection are also involved in reflections of familiar others. In the current study, 41 adolescents were asked to make judgments about trait adjectives during functional magnetic resonance imaging (fMRI): they had to indicate whether the word describes themselves, their friends, their teachers or politicians. Findings indicate a greater overlap in neural networks for responses to self- and friend-related judgments compared to teachers and politicians. In particular, classic self-reference structures such as the ventromedial prefrontal cortex and medial posterior parietal cortex also exhibited higher activation to judgments about friends. In contrast, brain responses towards judgments of teachers (familiar others) compared to politicians (unfamiliar others) did not significantly differ. Results support behavioral findings of a greater relevance of friends for the development of a self-concept during adolescence and indicate underlying functional brain processes. Hum Brain Mapp 38:987-996, 2017. © 2016 Wiley Periodicals, Inc.

Adolescents' Socio-Motivational Relationships With Teachers, Amygdala Response to Teacher's Negative Facial Expressions, and Test Anxiety.

The amygdala is essential for processing emotions, including the processing of aversive faces. The aim of this multimethodological study was to relate the amygdala reactivity of students (N = 88) toward teachers' fearful and angry faces, to students' relationship with their teachers. Furthermore, students' neural responses during the perception of teachers' faces were tested as predictors of test anxiety (controlling for neuroticism as a potential trait anxiety effect). Multiple regression analysis revealed that students reporting high-quality teacher-student relationships showed stronger amygdala activity toward fearful faces, which was related to worry. Furthermore, students with high levels of neuroticism tended to perceive their teachers as motivators and showed higher amygdala activity toward angry faces, which was related to the measures of emotionality.

Negative and positive self-beliefs in social anxiety: The strength of believing mediates the affective response.

BACKGROUND AND OBJECTIVES: Current cognitive models of social anxiety disorder (SAD) propose that individual, situation-specific self-beliefs are central to SAD. However, the role of differences in the degree to which individuals with social anxiety are convinced of self-beliefs, in particular positive ones, is still not fully understood. We compared how much high and low socially anxious individuals agree with their own negative and positive self-beliefs. Furthermore, we investigated whether agreeing with one's self-belief can explain the relation between negative affect in response to self-beliefs and social anxiety. Specifically, we were interested whether social anxiety increases negative affect in response to self-beliefs through an increase in agreement. METHODS: We developed a new experimental self-belief task containing positive and negative semi-idiosyncratic, situation specific self-beliefs typical of high social anxiety and included a direct measure of agreement with these beliefs. Using extreme group sampling, we a-priori selected high (n = 51) and low (n = 50) socially anxious individuals. By multi-level mediation analysis, we analyzed agreement with self-beliefs in both groups and its association with affect. RESULTS: High and low socially anxious individuals chose similar self-beliefs. However, high socially anxious individuals (HSA) agreed more with negative self-beliefs and less with positive self-beliefs compared to low socially anxious individuals (LSA). HSA individuals reported increased negative affect after both, exposition to negative and positive self-beliefs compared to LSA. We found that social anxiety increases affective responses towards negative-self beliefs through an increase in agreeing with these self-beliefs. CONCLUSIONS: These findings suggest that cognitive models of social anxiety can be improved by including not only the content of a self-belief but also the strength of such a belief. In addition, they emphasize the relevance of positive self-beliefs in social anxiety, which has frequently been overlooked.

Childhood trauma and cortical thickness in healthy women, women with post-traumatic stress disorder, and women with borderline personality disorder.

BACKGROUND: Structural brain changes have been associated with childhood trauma (CT) and several trauma-associated mental disorders. It is not known whether specific brain alterations are rather associated with CT as such or with disorders that are common sequelae of CT. In this study, we characterized cortical thickness in three distinct groups with CT: healthy women (HC/CT), women with posttraumatic stress disorder (PTSD/CT) and women with borderline personality disorder (BPD/CT). These three CT-exposed groups were compared with healthy controls not exposed to CT (HC). METHODS: We recruited 129 women (n = 70 HC, n = 25 HC/CT, n = 14 PTSD/CT, and n = 20 BPD/CT) and acquired T1-weighted anatomical images. FreeSurfer was used for conducting whole-brain cortical thickness between-group comparisons, applying separate generalized linear models to compare cortical thickness of each CT-exposed group with HC. RESULTS: The HC/CT group had lower cortical thickness in occipital lobe areas (right lingual gyrus, left lateral occipital lobe) than the HC group. The BPD/CT group showed a broader pattern of reduced cortical thickness compared to the HC group, including the bilateral superior frontal gyrus, and bilateral isthmus, the right posterior, and left caudal anterior of the cingulate cortex as well as the right lingual gyrus of the occipital lobe. We found no differences between PTSD/CT and HC. CONCLUSIONS: Cortical thickness reduction in the right lingual gyrus of the occipital lobe seem to be related to CT but is also present in BPD patients even after adjusting for severity of CT. Possibly, reduced cortical thickness in the lingual gyrus presents a CT-related vulnerability factor for CT-related adult psychopathologies such as BPD. Reduced cortical thickness in the frontal and cingulate cortex may represent unique neuroanatomical markers of BPD possibly related to difficulties in emotion regulation.

The effects of momentary loneliness and COVID-19 stressors on hypothalamic-pituitary adrenal (HPA) axis functioning: A lockdown stage changes the association between loneliness and salivary cortisol.

The COVID-19 pandemic can be characterized as a chronic stressor affecting the hypothalamic-pituitary-adrenal (HPA) axis, indexed by glucocorticoids (e.g., cortisol). We investigated whether salivary cortisol level is increased during a lockdown and whether a lockdown condition affects the association between loneliness, specific COVID-19 related stressors and salivary cortisol level. We conducted a smartphone-based ecological momentary assessment (EMA) study with 280 participants in Germany who experienced at least mild loneliness and distress amid COVID-19 from August 2020 to March 2021. We measured their momentary loneliness and COVID-related stressors including worries, information seeking behaviors and feelings of restriction during "no-lockdown" or "lockdown" stages amid COVID-19. Their salivary cortisol was measured 4 times on the last day of a 7-day EMA study. We found a significant increase in salivary cortisol levels during lockdown compared to no-lockdown. Lockdown stage was found to moderate the relationship between momentary loneliness and salivary cortisol level, i.e., loneliness was positively related to cortisol level specifically during lockdown. Mechanisms explaining the effect of forced social isolation on the association between loneliness and salivary cortisol need to be investigated in future studies.

Association between childhood trauma and brain anatomy in women with post-traumatic stress disorder, women with borderline personality disorder, and healthy women.

Background: Childhood trauma (CT) is associated with altered brain anatomy. These neuroanatomical changes might be more pronounced in individuals with a psychiatric disorder. Post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD) are more prevalent in individuals with a history of CT. Objective: In this study, we examined limbic and total brain volumes in healthy women with and without a history of CT and in females with PTSD or BPD and a history of CT to see whether neuroanatomical changes are a function of psychopathology or CT. Method: In total, 128 women (N = 70 healthy controls without CT, N = 25 healthy controls with CT, N = 14 individuals with PTSD, and N = 19 individuals with BPD) were recruited. A T1-weighted anatomical MRI was acquired from all participants for Freesurfer-based assessment of total brain, hippocampus, and amygdala volumes. Severity of CT was assessed with a clinical interview and the Childhood Trauma Questionnaire. Group differences in hippocampal and amygdala volumes (adjusted for total brain volume) and total brain volume (adjusted for height) were characterized by analysis of covariance. Results: Volume of the total brain, hippocampus, and amygdala did not differ between the four groups (p > .05). CT severity correlated negatively with total brain volume across groups (r = -0.20; p = .029). Conclusions: CT was associated with reduced brain volume but PTSD or BPD was not. The association between CT and reduced brain volume as a global measure of brain integrity suggests a common origin for vulnerability to psychiatric disorders later in life.

Antecedentes: El trauma infantil (TI) se asocia con alteraciones en la anatomía cerebral. Estos cambios neuroanatómicos pueden ser más pronunciados en individuos con trastornos psiquiátricos. El trastorno de estrés postraumático (TEPT) y el trastorno de personalidad limítrofe (TPL) son más prevalentes en individuos con historia de TI.Objetivo: En este estudio, examinamos los volúmenes límbico y cerebral total en mujeres sanas con y sin historia de TI y mujeres con TEPT o TPL e historia de TI para ver si los cambios neuroanatómicos son una función de la psicopatología o del TI.Método: En total, 128 mujeres (N= 70 controles sanas sin TI, N= 25 controles sanas con TI, N= 14 individuos con TEPT y N= 19 individuos con TPL) fueron reclutadas. Se obtuvo una RNM anatómica ponderada en T1 de todas las participantes para la evaluación basada en Freesurfer de los volúmenes totales del cerebro, hipocampo y amígdala. La severidad del TI fue evaluada con una entrevista clínica y con el Cuestionario de Trauma Infantil. Las diferencias grupales en los volúmenes del hipocampo y amígdala (ajustadas por el volumen cerebral total) y el volumen cerebral total (ajustadas por altura) se caracterizaron mediante análisis de covarianza.Resultados: El volumen total del cerebro, hipocampo y amígdala no difirieron entre los cuatro grupos (p > .05). La severidad del TI se correlacionó negativamente con el volumen cerebral total en todos los grupos (r = −0.20; p =.29).Conclusiones: El TI estuvo asociado a un volumen cerebral reducido, pero el TEPT o TPL no se asociaron. La asociación entre TI y volumen cerebral disminuido como una medida global de la integridad cerebral sugiere un origen común de vulnerabilidad a los trastornos psiquiátricos más adelante en la vida.

Adolescents' Personality Development - A Question of Psychosocial Stress.

Following the relational-developmental systems approach, this three-wave study examines whether acute stress (T2) mediates the relationship between the development of personality traits from the beginning of 8th grade (T1, M age = 15.63, SD = 0.59; 22 girls) to the end of 9th grade (T3). Using the Montréal Imaging Stress Task, which is a task that provokes acute social stress by negative social feedback, this study combined the functional magnetic resonance imaging (fMRI), heart rate, and longitudinal survey data of 41 adolescents. Mediation analysis revealed that stress-induced left insula activation partially mediates the longitudinal stability of conscientiousness. These results highlight the impact of negative social feedback during stress on students' personality development.

Distinct Functional Connectivity Signatures of Impaired Social Cognition in Multiple Sclerosis.

Objective: Multiple sclerosis (MS) is characterized by impairments in basic cognitive functions such as information processing speed as well as in more complex, higher-order domains such as social cognition. However, as these deficits often co-occur, it has remained challenging to determine whether they have a specific pathological basis or are driven by shared biology. Methods: To identify neural signatures of social cognition deficits in MS, data were analyzed from n = 29 patients with relapsing-remitting MS and n = 29 healthy controls matched for age, sex, and education. We used neuropsychological assessments of information processing speed, attention, learning, working memory, and relevant aspects of social cognition (theory of mind, emotion recognition (ER), empathy) and employed neuroimaging of CNS networks using resting-state functional connectivity. Results: MS patients showed significant deficits in verbal learning and memory, as well as implicit ER. Performance in these domains was uncorrelated. Functional connectivity analysis identified a distinct network characterized by significant associations between poorer ER and lower connectivity of the fusiform gyrus (FFG) with the right lateral occipital cortex, which also showed lower connectivity in patients compared to controls. Moreover, while ER was correlated with MS symptoms such as fatigue and motor/sensory functioning on a behavioral level, FFG connectivity signatures of social cognition deficits showed no overlap with these symptoms. Conclusions: Our analyses identify distinct functional connectivity signatures of social cognition deficits in MS, indicating that these alterations may occur independently from those in other neuropsychological functions.

Introduction of a Pathophysiology-Based Diagnostic Decision Support System.

Many current Clinical Decision Support Systems which assist clinical diagnosis, are based on a causal condition-symptom relation. To reach more diagnostic precision Ada's Deep Reasoning is substituting this approach with the use of a model based on pathophysiology.

Introduction of a Pathophysiology-Based Diagnostic Decision Support System and Its Potential Impact on the Use of AI in Healthcare.

Many currently available Diagnostic Decision Support Systems (DDSS) are based on causal condition-symptom relations that exhibit certain shortcomings. Ada's new approach explores the capabilities of DDSS based on pathophysiology, describing a disease as a dynamically evolving process. We generated a pathophysiology model for 8 conditions and 68 findings suitable to assess this approach. Preliminary results meet our expectations while leaving space for further improvement.

Effects of hydrocortisone on autobiographical memory retrieval in patients with posttraumatic stress disorder and borderline personality disorder: the role of childhood trauma.

In a previous study, we found that patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD) showed better autobiographical memory (AM) retrieval after hydrocortisone administration than after placebo administration. Here we investigate the neural correlates of AM retrieval after hydrocortisone administration in patients with PTSD or BPD. We recruited 78 female participants for this placebo-controlled crossover study: 40 healthy controls, 20 patients with PTSD, and 18 patients with BPD (all without medication). All participants received an oral placebo or 10 mg hydrocortisone in a randomized order before performing an AM task. Neural activity was monitored during the task by functional magnetic resonance imaging. Neural activation did not differ between the three groups during AM retrieval, neither in the placebo condition nor after hydrocortisone intake. Multiple regression analysis revealed that Childhood Trauma Questionnaire scores correlated positively with hydrocortisone effects on activation in the anterior medial prefrontal cortex (amPFC), ventrolateral prefrontal cortex (vlPFC), posterior cingulate cortex (PCC), angular gyrus, and cerebellum. These results suggest that hydrocortisone-induced neural activation pattern during AM retrieval is related to childhood trauma. Previously described effects in the hippocampus, which were absent in the current study, might be related to PTSD caused by trauma in adulthood. The effects of hydrocortisone on brain activation and how these effects are influenced by childhood trauma, trauma in adulthood, and PTSD symptoms should be determined in future studies.

Neural correlates of glucocorticoids effects on autobiographical memory retrieval in healthy women.

It is well known that elevated cortisol after stress or after exogenous administration impairs episodic memory retrieval including autobiographical memory (AM) retrieval. This impairment might be mediated by deactivation of a neural network associated with memory retrieval including the prefrontal cortex (PFC) and limbic structures. However, the neural underpinnings of these cortisol effects on AM retrieval have not been investigated yet. In this study, thirty-three healthy women received either placebo or 10 mg hydrocortisone in a double blind cross-over design before completing an AM test during fMRI. In this test, participants are asked to recall specific events from their own past in response to a cue word. In a first step, we analyzed the neural underpinnings of AM retrieval in the placebo condition. We found an activation pattern consistent with core regions involved in autobiographical memory recall, including the ventromedial PFC, anterior medial (am)PFC, inferior frontal gyrus, the posterior cingulate cortex, the tempoparietal junction, the middle temporal gyrus and the hippocampus. Further, we analyzed brain activation during AM retrieval after hydrocortisone compared to placebo. Region of interest (ROI) analyses revealed a hydrocortisone-induced deactivation during AM retrieval in the right amPFC. Results of the ROI analyses were non-significant in the left and right hippocampus, the left and right vmPFC and the left amPFC In sum, during AM retrieval hydrocortisone had the most pronounced effects on the amPFC. This might be explained by the strong involvement of this brain region in self-referential behavior, which is essential for recalling autobiographic information.

Resting-state functional connectivity after hydrocortisone administration in patients with post-traumatic stress disorder and borderline personality disorder.

In a previous study, we found that - in contrast to healthy individuals - patients with borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD) showed better memory retrieval performance after hydrocortisone administration compared to placebo. As these results suggest an altered function of corticosteroid receptors in the brain in PTSD and BPD, we examined the effect of hydrocortisone on brain activation in both disorders. We recruited 40 female healthy controls, 20 female unmedicated patients with PTSD and 18 female unmedicated patients with BPD. We conducted a placebo-controlled cross-over study, in which all participants underwent two resting state MRI measurements after they received either a placebo or 10 mg hydrocortisone orally and in randomized order. There was a time interval of one week between the measurements. We analysed resting state functional connectivity (RSFC) with the hippocampus and the amygdala as seed regions. Compared to healthy controls, both patient groups showed reduced hippocampus RSFC to dorsomedial prefrontal cortex (dmPFC). Positive hippocampus dmPFC RSFC correlated negatively with childhood trauma (r = -0.47) and with severity of clinical symptoms, measured with the Borderline Symptom List (r = -0.44) and the Posttraumatic Stress Diagnostic Scale (r = -0.45). We found neither differences in amygdala RSFC nor an effect of hydrocortisone administration. Childhood trauma might lead to decreased positive hippocampus dmPFC RSFC. This might explain symptoms of PTSD and BPD that are characterized by dysfunctional fear regulation.

Does Feedback-Related Brain Response during Reinforcement Learning Predict Socio-motivational (In-)dependence in Adolescence?

This multi-methodological study applied functional magnetic resonance imaging to investigate neural activation in a group of adolescent students (N = 88) during a probabilistic reinforcement learning task. We related patterns of emerging brain activity and individual learning rates to socio-motivational (in-)dependence manifested in four different motivation types (MTs): (1) peer-dependent MT, (2) teacher-dependent MT, (3) peer-and-teacher-dependent MT, (4) peer-and-teacher-independent MT. A multinomial regression analysis revealed that the individual learning rate predicts students' membership to the independent MT, or the peer-and-teacher-dependent MT. Additionally, the striatum, a brain region associated with behavioral adaptation and flexibility, showed increased learning-related activation in students with motivational independence. Moreover, the prefrontal cortex, which is involved in behavioral control, was more active in students of the peer-and-teacher-dependent MT. Overall, this study offers new insights into the interplay of motivation and learning with (1) a focus on inter-individual differences in the role of peers and teachers as source of students' individual motivation and (2) its potential neurobiological basis.