Neural Mechanisms of Subclinical Depressive Symptoms in Women: a Pilot Functional Brain Imaging Study

Background Studies of individuals who do not meet criteria for major depressive disorder (MDD) but with subclinical levels of depressive symptoms may aid in the identification of neurofunctional abnormalities that possibly precede and predict the development of MDD. The purpose of this study was to evaluate relations between subclinical levels of depressive symptoms and neural activation patterns during tasks previously shown to differentiate individuals with and without MDD. Methods Functional magnetic resonance imaging (fMRI) was used to assess neural activations during active emotion regulation, a resting state scan, and reward processing. Participants were twelve females with a range of depressive symptoms who did not meet criteria for MDD. Results Increased depressive symptom severity predicted (1) decreased left midfrontal gyrus activation during reappraisal of sad stimuli; (2) increased right midfrontal gyrus activation during distraction from sad stimuli; (3) increased functional connectivity between a precuneus seed region and left orbitofrontal cortex during a resting state scan; and (4) increased paracingulate activation during non-win outcomes during a reward-processing task. Conclusions These pilot data shed light on relations between subclinical levels of depressive symptoms in the absence of a formal MDD diagnosis and neural activation patterns. Future studies will be needed to test the utility of these activation patterns for predicting MDD onset in at-risk samples

Differences in subcortical structures in young adolescents at familial risk for schizophrenia: A preliminary study

Schizophrenia has been associated with reduced volumes of subcortical structures on MRI, but the relation of these reductions to familial risk for the disorder is unclear. We investigated the effect of familial risk for schizophrenia on regional subcortical volumes during adolescence, a period marked by steep maturational changes in brain structure and the emergence of psychotic symptoms. A group of 26 non-help-seeking, first-degree relatives of patients with schizophrenia and 43 matched healthy comparisons, between 9 and 18 years of age, underwent MRI scanning and were rated for the presence of prodromal symptoms. Five subcortical regions-of-interest were tested for group differences and group by age interactions, as well as correlations with low-level prodromal symptoms in the familial risk group. Relative to comparisons, familial risk subjects demonstrated greater positive volume-age relationships in hippocampus, putamen, and globus pallidus. These results suggest that relatives of individuals with schizophrenia exhibit structural abnormalities in the subcortex as early as pre-adolescence, which may reflect altered neurodevelopment of these regions

The Effects of Psychotherapy on Neural Responses to Rewards in Major Depression

Unipolar major depressive disorder (MDD) is characterized by anomalous neurobiological responses to pleasant stimuli, a pattern that may be linked to symptoms of anhedonia. However, the potential for psychotherapy to normalize neurobiological responses to pleasant stimuli has not been evaluated

Altered fronto–limbic activity in children and adolescents with familial high risk for schizophrenia

Early symptoms of schizophrenia tend to emerge during adolescence, which is a critical period for development of executive and emotional processing. While individuals with familial high risk (FHR) for schizophrenia may show cognitive and emotional changes, the neural mechanisms underlying the development of these changes remain unclear. The goal of this study was to identify functional differences in fronto-striato-limbic regions in children with FHR. Functional MRI data was collected from 21 children with a first-degree family member with schizophrenia and 21 controls without FHR. Participants performed an emotional oddball task requiring both selective attention and suppression of task-irrelevant emotional information. During selective attention, the group with FHR showed enhanced activation in inferior frontal gyrus and caudate, with decreases in middle frontal gyrus and insular activation. The FHR group also showed greater age-related recruitment of anterior cingulate, temporal and occipital cortical areas during selective attention. During emotional processing, the FHR group showed decreased anterior cingulate activation, with decreased age-related recruitment of inferior frontal, parietal and occipital areas. The results suggest that FHR for schizophrenia may be associated with abnormal hyperactivation and hypoactivation of the neural circuitry engaged during executive and emotional processing and with age-related changes in neural recruitment during adolescence

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with schizophrenia who are at familial high risk (FHR) may show similar cognitive and emotional changes. However, the neurological changes underlying the emergence of these symptoms remain unclear. This study sought to identify differences in frontal, striatal, and limbic regions in children and adolescents with FHR using functional magnetic resonance imaging. Groups of 21 children and adolescents at FHR and 21 healthy controls completed an emotional oddball task that relied on selective attention and the suppression of task-irrelevant emotional information. The standard oddball task was modified to include aversive and neutral distractors in order to examine potential group differences in both emotional and executive processing. This task was designed specifically to allow for children and adolescents to complete by keeping the difficulty and emotional image content age-appropriate. Furthermore, we demonstrate a technique for suitable fMRI registration for children and adolescent participants. This paradigm may also be applied in future studies to measure changes in neural activity in other populations with hypothesized developmental changes in executive and emotional processing

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders

Abstract Background Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. Methods The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). Results We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. Conclusions These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population

Neural Mechanisms of Reward Prediction Error in Autism Spectrum Disorder.

Few studies have explored neural mechanisms of reward learning in ASD despite evidence of behavioral impairments of predictive abilities in ASD. To investigate the neural correlates of reward prediction errors in ASD, 16 adults with ASD and 14 typically developing controls performed a prediction error task during fMRI scanning. Results revealed greater activation in the ASD group in the left paracingulate gyrus during signed prediction errors and the left insula and right frontal pole during thresholded unsigned prediction errors. Findings support atypical neural processing of reward prediction errors in ASD in frontostriatal regions critical for prediction coding and reward learning. Results provide a neural basis for impairments in reward learning that may contribute to traits common in ASD (e.g., intolerance of unpredictability).</p

Neural mechanisms of subclinical depressive symptoms in women: a pilot functional brain imaging study

Abstract Background Studies of individuals who do not meet criteria for major depressive disorder (MDD) but with subclinical levels of depressive symptoms may aid in the identification of neurofunctional abnormalities that possibly precede and predict the development of MDD. The purpose of this study was to evaluate relations between subclinical levels of depressive symptoms and neural activation patterns during tasks previously shown to differentiate individuals with and without MDD. Methods Functional magnetic resonance imaging (fMRI) was used to assess neural activations during active emotion regulation, a resting state scan, and reward processing. Participants were twelve females with a range of depressive symptoms who did not meet criteria for MDD. Results Increased depressive symptom severity predicted (1) decreased left midfrontal gyrus activation during reappraisal of sad stimuli; (2) increased right midfrontal gyrus activation during distraction from sad stimuli; (3) increased functional connectivity between a precuneus seed region and left orbitofrontal cortex during a resting state scan; and (4) increased paracingulate activation during non-win outcomes during a reward-processing task. Conclusions These pilot data shed light on relations between subclinical levels of depressive symptoms in the absence of a formal MDD diagnosis and neural activation patterns. Future studies will be needed to test the utility of these activation patterns for predicting MDD onset in at-risk samples.</p

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with schizophrenia who are at familial high risk (FHR) may show similar cognitive and emotional changes. However, the neurological changes underlying the emergence of these symptoms remain unclear. This study sought to identify differences in frontal, striatal, and limbic regions in children and adolescents with FHR using functional magnetic resonance imaging. Groups of 21 children and adolescents at FHR and 21 healthy controls completed an emotional oddball task that relied on selective attention and the suppression of task-irrelevant emotional information. The standard oddball task was modified to include aversive and neutral distractors in order to examine potential group differences in both emotional and executive processing. This task was designed specifically to allow for children and adolescents to complete by keeping the difficulty and emotional image content age-appropriate. Furthermore, we demonstrate a technique for suitable fMRI registration for children and adolescent participants. This paradigm may also be applied in future studies to measure changes in neural activity in other populations with hypothesized developmental changes in executive and emotional processing