Brian W. Haas

More Is Not Always Better: Increased Fractional Anisotropy of Superior Longitudinal Fasciculus Associated with Poor Visuospatial Abilities in Williams Syndrome

We used diffusion tensor imaging to examine white matter integrity in the dorsal and ventral streams among individuals with Williams syndrome (WS) compared with two control groups (typically developing and developmentally delayed) and using three separate analysis methods (whole brain, region of interest, and fiber tractography). All analysis methods consistently showed that fractional anisotropy (FA; a measure of microstructural integrity) was higher in the right superior longitudinal fasciculus (SLF) in WS compared with both control groups. There was a significant association with deficits in visuospatial construction and higher FA in WS individuals. Comparable increases in FA across analytic methods were not observed in the left SLF or the bilateral inferior longitudinal fasciculus in WS subjects. Together, these findings suggest a specific role of right SLF abnormality in visuospatial construction deficits in WS.

Emotional conflict and neuroticism: personality-dependent activation in the amygdala and subgenual anterior cingulate.

The amygdala and subgenual anterior cingulate (AC) have been associated with anxiety and mood disorders, for which trait neuroticism is a risk factor. Prior work has not related individual differences in amygdala or subgenual AC activation with neuroticism. Functional magnetic resonance imaging was used to investigate changes in blood oxygen level-dependent signal within the amygdala and subgenual AC associated with trait neuroticism in a nonclinical sample of 36 volunteers during an emotional conflict task. Neuroticism correlated positively with amygdala and subgenual AC activation during trials of high emotional conflict, compared with trials of low emotional conflict. The subscale of neuroticism that reflected the anxious form of neuroticism (N1) explained a greater proportion of variance within the observed clusters than the subscale of neuroticism that reflected the depressive form of neuroticism (N3). Using a task that is sensitive to individual differences in the detection of emotional conflict, the authors have provided a neural correlate of the link between neuroticism and anxiety and mood disorders. This effect was driven to a greater extent by the anxious relative to the depressive characteristics of neuroticism and may constitute vulnerability markers for anxiety-related disorders.

Genetic influences on sociability: Heightened amygdala reactivity and event-related responses to positive social stimuli in Williams syndrome

Williams syndrome (WS) is a genetic disorder caused by a hemizygous microdeletion on chromosome 7q11.23. WS is associated with a compelling neurocognitive profile characterized by relative deficits in visuospatial function, relative strengths in face and language processing, and enhanced drive toward social engagement. We used a combined functional magnetic resonance imaging (fMRI) and event-related potential (ERP) approach to examine the neural basis of social responsiveness in WS participants to two types of social stimuli, negative (fearful) and positive (happy) emotional facial expressions. Here, we report a double dissociation consistent across both methods such that WS participants exhibited heightened amygdala reactivity to positive (happy) social stimuli and absent or attenuated amygdala reactivity to negative (fearful) social stimuli, compared with controls. The fMRI findings indicate that atypical social processing in WS may be rooted in altered development of disparate amygdalar nuclei that subserve different social functions. The ERP findings suggest that abnormal amygdala reactivity in WS may possibly function to increase attention to and encoding of happy expressions and to decrease arousal to fearful expressions. This study provides the first evidence that the genetic deletion associated with WS influences the function of the amygdala to be particularly responsive to socially appetitive stimuli.

Reduced Hippocampal Activity in Youth with Posttraumatic Stress Symptoms: An fMRI Study

OBJECTIVE Youth who experience interpersonal trauma and have posttraumatic stress symptoms (PTSS) develop cognitive deficits that impact their development. Our goal is to investigate the function of the hippocampus in adolescents with PTSS during a memory processing task. METHODS Twenty-seven adolescents between the ages of 10-17 years (16 with PTSS and 11 healthy controls) encoded and retrieved visually presented nouns (Verbal Declarative Memory Task) while undergoing fMRI scanning. RESULTS The PTSS group demonstrated reduced activation of the right hippocampus during the retrieval component of the task. Further, severity of symptoms of avoidance and numbing correlated with reduced left hippocampal activation during retrieval. CONCLUSIONS Decreased activity of the hippocampus during a verbal memory task may be a neurofunctional marker of PTSS in youth with history of interpersonal trauma. The results of this study may facilitate the development of focused treatments and may be of utility when assessing treatment outcome for PTSS.

Interference produced by emotional conflict associated with anterior cingulate activation

The anterior cingulate cortex (ACC) is involved in cognition and emotion. In the classic Stroop task, presentation of stimuli that are in response conflict with one another produces activation in the caudal ACC. In the emotional Stroop task, presentation of emotionally salient stimuli produces activation in the rostral ACC. Presentation of stimuli that are emotionally conflicting should activate the caudal ACC; stimuli that are emotionally salient should activate the rostral ACC. We tested this prediction using functional magnetic resonance imaging while subjects made emotional valence judgments of words overlaid on emotional faces (word-face Stroop task). Emotionally incongruent pairs were responded to more slowly than emotionally congruent pairs. Emotionally incongruent trials were associated with increased activation within the caudal ACC, whereas no ACC activation was found in response to emotional saliency. These results support the conflict-monitoring model of caudal ACC and extend this function to conflict within the domain of emotional stimuli.

Functional Brain Basis of Hypnotizability

CONTEXT Focused hypnotic concentration is a model for brain control over sensation and behavior. Pain and anxiety can be effectively alleviated by hypnotic suggestion, which modulates activity in brain regions associated with focused attention, but the specific neural network underlying this phenomenon is not known. OBJECTIVE To investigate the brain basis of hypnotizability. DESIGN Cross-sectional, in vivo neuroimaging study performed from November 2005 through July 2006. SETTING Academic medical center at Stanford University School of Medicine. PATIENTS Twelve adults with high and 12 adults with low hypnotizability. MAIN OUTCOME MEASURES Functional magnetic resonance imaging to measure functional connectivity networks at rest, including default-mode, salience, and executive-control networks; structural T1 magnetic resonance imaging to measure regional gray and white matter volumes; and diffusion tensor imaging to measure white matter microstructural integrity. RESULTS High compared with low hypnotizable individuals had greater functional connectivity between the left dorsolateral prefrontal cortex, an executive-control region of the brain, and the salience network composed of the dorsal anterior cingulate cortex, anterior insula, amygdala, and ventral striatum, involved in detecting, integrating, and filtering relevant somatic, autonomic, and emotional information using independent component analysis. Seed-based analysis confirmed elevated functional coupling between the dorsal anterior cingulate cortex and the dorsolateral prefrontal cortex in high compared with low hypnotizable individuals. These functional differences were not due to any variation in brain structure in these regions, including regional gray and white matter volumes and white matter microstructure. CONCLUSIONS Our results provide novel evidence that altered functional connectivity in the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex may underlie hypnotizability. Future studies focusing on how these functional networks change and interact during hypnosis are warranted.

Stop the sadness: Neuroticism is associated with sustained medial prefrontal cortex response to emotional facial expressions

Neuroticism is a personality trait associated with negative mood states, sensitivity to negative information, negative appraisal and vulnerability to psychopathology. Previous studies have associated the sustained processing of negative information (words) with individual differences such as rumination and depression but not with personality. In the current study, we aimed to investigate the relationship between neuroticism and changes in sustained patterns of activity within a brain region implicated in emotional self-evaluation and appraisal, the Medial Prefrontal Cortex (MedPFC), when responding to emotional facial expressions (happy, fearful, and sad). We tested whether higher scores of neuroticism are associated with greater sustained patterns of brain activity in the MedPFC when responding to blocks of negative facial expressions. We found that higher scores of neuroticism were associated with greater sustained MedPFC activity throughout blocks of sad facial expressions, but not fearful or happy facial expressions. Based on the relationship between neuroticism and sensitivity to negative information, the current finding identifies a sustained temporal mechanism to this relationship.

The Fusiform Face Area is Enlarged in Williams Syndrome

Williams syndrome (WS) is a genetic condition characterized by atypical brain structure, cognitive deficits, and a life-long fascination with faces. Face recognition is relatively spared in WS, despite abnormalities in aspects of face processing and structural alterations in the fusiform gyrus, part of the ventral visual stream. Thus, face recognition in WS may be subserved by abnormal neural substrates in the ventral stream. To test this hypothesis, we used functional magnetic resonance imaging and examined the fusiform face area (FFA), which is implicated in face recognition in typically developed (TD) individuals, but its role in WS is not well understood. We found that the FFA was approximately two times larger among WS than TD participants (both absolutely and relative to the fusiform gyrus), despite apparently normal levels of face recognition performance on a Benton face recognition test. Thus, a larger FFA may play a role in face recognition proficiency among WS.

Early white-matter abnormalities of the ventral frontostriatal pathway in fragile X syndrome.

Aim  Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development.

Individual differences in social behavior predict amygdala response to fearful facial expressions in Williams syndrome

Williams syndrome (WS) is a genetic condition often paired with abnormal social functioning and behavior. In particular, those with WS are characterized as being relatively hypersocial, overly emotional/empathic, and socially uninhibited or fearless. In addition, WS is associated with abnormal amygdala structure and function. Very little is known however about the relationship between specific social behaviors and altered amygdala function in WS. This study was designed to compare three models that relate abnormal social behavior with amygdala function in WS (indiscriminate sociability, emotional and empathic sociability and social fearlessness). We used a social behavior assessment procedure (Salk Institute Sociability Questionnaire), functional magnetic resonance imaging and an implicit emotion face processing task to test these models. Our findings provide support for a model of abnormal social fearlessness by showing that in WS, abnormal amygdala response to fear is paired with an increased tendency to approach strangers. Specifically, individuals with WS that exhibited less amygdala response to fearful facial expressions (compared to neutral) also exhibited an increased tendency to approach strangers. These findings contribute to our understanding of social and emotional functioning in neurodevelopmental conditions and provide evidence that in WS, amygdala response to fear modulates social behavior.