Neurocircuitry underlying risk and resilience to social anxiety disorder.

BACKGROUND: Almost half of children with an inhibited temperament will develop social anxiety disorder by late adolescence. Importantly, this means that half of children with an inhibited temperament will not develop social anxiety disorder. Studying adults with an inhibited temperament provides a unique opportunity to identify neural signatures of both risk and resilience to social anxiety disorder. METHODS: Functional magnetic resonance imaging (fMRI) was used to measure brain activation during the anticipation of viewing fear faces in 34 young adults (17 inhibited, 17 uninhibited). To identify neural signatures of risk, we tested for group differences in functional activation and connectivity in regions implicated in social anxiety disorder, including the prefrontal cortex, amygdala, and insula. To identify neural signatures of resilience, we tested for correlations between brain activation and both emotion regulation and social anxiety scores. RESULTS: Inhibited subjects had greater activation of a prefrontal network when anticipating viewing fear faces, relative to uninhibited subjects. No group differences were identified in the amygdala. Inhibited subjects had more negative connectivity between the rostral anterior cingulate cortex (ACC) and the bilateral amygdala. Within the inhibited group, those with fewer social anxiety symptoms and better emotion regulation skills had greater ACC activation and greater functional connectivity between the ACC and amygdala. CONCLUSIONS: These findings suggest that engaging regulatory prefrontal regions during anticipation may be a protective factor, or putative neural marker of resilience, in high-risk individuals. Cognitive training targeting prefrontal cortex function may provide protection against anxiety, especially in high-risk individuals, such as those with inhibited temperament.

Discrete neural substrates underlie complementary audiovisual speech integration processes.

The ability to combine information from multiple sensory modalities into a single, unified percept is a key element in an organism's ability to interact with the external world. This process of perceptual fusion, the binding of multiple sensory inputs into a perceptual gestalt, is highly dependent on the temporal synchrony of the sensory inputs. Using fMRI, we identified two anatomically distinct brain regions in the superior temporal cortex, one involved with processing temporal-synchrony, and one with processing perceptual fusion of audiovisual speech. This dissociation suggests that the superior temporal cortex should be considered a "neuronal hub" composed of multiple discrete subregions that underlie an array of complementary low- and high-level multisensory integration processes. In this role, abnormalities in the structure and function of superior temporal cortex provide a possible common etiology for temporal-processing and perceptual-fusion deficits seen in a number of clinical populations, including individuals with autism spectrum disorder, dyslexia, and schizophrenia.

Impaired face recognition is associated with social inhibition.

Face recognition is fundamental to successful social interaction. Individuals with deficits in face recognition are likely to have social functioning impairments that may lead to heightened risk for social anxiety. A critical component of social interaction is how quickly a face is learned during initial exposure to a new individual. Here, we used a novel Repeated Faces task to assess how quickly memory for faces is established. Face recognition was measured over multiple exposures in 52 young adults ranging from low to high in social inhibition, a core dimension of social anxiety. High social inhibition was associated with a smaller slope of change in recognition memory over repeated face exposure, indicating participants with higher social inhibition showed smaller improvements in recognition memory after seeing faces multiple times. We propose that impaired face learning is an important mechanism underlying social inhibition and may contribute to, or maintain, social anxiety.

Amygdala-cingulate intrinsic connectivity is associated with degree of social inhibition.

The tendency to approach or avoid novel people is a fundamental human behavior and is a core dimension of social anxiety. Resting state fMRI was used to test for an association between social inhibition and intrinsic connectivity in 40 young adults ranging from low to high in social inhibition. Higher levels of social inhibition were associated with specific patterns of reduced amygdala-cingulate cortex connectivity. Connectivity was reduced between the superficial amygdala and the rostral cingulate cortex and between the centromedial amygdala and the dorsal anterior cingulate cortex. Social inhibition also modulated connectivity in several well-established intrinsic networks; higher social inhibition correlated with reduced connectivity with default mode and dorsal attention networks and enhanced connectivity in salience and executive control networks. These findings provide important preliminary evidence that social inhibition reflects differences in the underlying intrinsic connectivity of the brain in the absence of social stimuli or stressors.

Structural and functional bases of inhibited temperament.

Children born with an inhibited temperament are at heightened risk for developing anxiety, depression and substance use. Inhibited temperament is believed to have a biological basis; however, little is known about the structural brain basis of this vulnerability trait. Structural MRI scans were obtained from 84 (44 inhibited, 40 uninhibited) young adults. Given previous findings of amygdala hyperactivity in inhibited individuals, groups were compared on three measures of amygdala structure. To identify novel substrates of inhibited temperament, a whole brain analysis was performed. Functional activation and connectivity were examined across both groups. Inhibited adults had larger amygdala and caudate volume and larger volume predicted greater activation to neutral faces. In addition, larger amygdala volume predicted greater connectivity with subcortical and higher order visual structures. Larger caudate volume predicted greater connectivity with the basal ganglia, and less connectivity with primary visual and auditory cortex. We propose that larger volume in these salience detection regions may result in increased activation and enhanced connectivity in response to social stimuli. Given the strong link between inhibited temperament and risk for psychiatric illness, novel therapeutics that target these brain regions and related neural circuits have the potential to reduce rates of illness in vulnerable individuals.

Multisensory perception of action in posterior temporal and parietal cortices.

Environmental events produce many sensory cues for identifying the action that evoked the event, the agent that performed the action, and the object targeted by the action. The cues for identifying environmental events are usually distributed across multiple sensory systems. Thus, to understand how environmental events are recognized requires an understanding of the fundamental cognitive and neural processes involved in multisensory object and action recognition. Here, we investigated the neural substrates involved in auditory and visual recognition of object-directed actions. Consistent with previous work on visual recognition of isolated objects, visual recognition of actions, and recognition of environmental sounds, we found evidence for multisensory audiovisual event-selective activation bilaterally at the junction of the posterior middle temporal gyrus and the lateral occipital cortex, the left superior temporal sulcus, and bilaterally in the intraparietal sulcus. The results suggest that recognition of events through convergence of visual and auditory cues is accomplished through a network of brain regions that was previously implicated only in visual recognition of action.

Shape from sound: evidence for a shape operator in the lateral occipital cortex.

A recent view of cortical functional specialization suggests that the primary organizing principle of the cortex is based on task requirements, rather than sensory modality. Consistent with this view, recent evidence suggests that a region of the lateral occipitotemporal cortex (LO) may process object shape information regardless of the modality of sensory input. There is considerable evidence that area LO is involved in processing visual and haptic shape information. However, sound can also carry acoustic cues to an object's shape, for example, when a sound is produced by an object's impact with a surface. Thus, the current study used auditory stimuli that were created from recordings of objects impacting a hard surface to test the hypothesis that area LO is also involved in auditory shape processing. The objects were of two shapes, rods and balls, and of two materials, metal and wood. Subjects were required to categorize the impact sounds in one of three tasks, (1) by the shape of the object while ignoring material, (2) by the material of the object while ignoring shape, or (3) by using all the information available. Area LO was more strongly recruited when subjects discriminated impact sounds based on the shape of the object that made them, compared to when subjects discriminated those same sounds based on material. The current findings suggest that activation in area LO is shape selective regardless of sensory input modality, and are consistent with an emerging theory of perceptual functional specialization of the brain that is task-based rather than sensory modality-based.