Overreactive brain responses to sensory stimuli in youth with autism spectrum disorders.

OBJECTIVES: Sensory over-responsivity (SOR), defined as a negative response to or avoidance of sensory stimuli, is both highly prevalent and extremely impairing in youth with autism spectrum disorders (ASD), yet little is known about the neurological bases of SOR. This study aimed to examine the functional neural correlates of SOR by comparing brain responses to sensory stimuli in youth with and without ASD. METHOD: A total of 25 high-functioning youth with ASD and 25 age- and IQ-equivalent typically developing (TD) youth were presented with mildly aversive auditory and visual stimuli during a functional magnetic resonance imaging (fMRI) scan. Parents provided ratings of children's SOR and anxiety symptom severity. RESULTS: Compared to TD participants, ASD participants displayed greater activation in primary sensory cortical areas as well as amygdala, hippocampus, and orbital-frontal cortex. In both groups, the level of activity in these areas was positively correlated with level of SOR severity as rated by parents, over and above behavioral ratings of anxiety. CONCLUSIONS: This study demonstrates that youth with ASD show neural hyper-responsivity to sensory stimuli, and that behavioral symptoms of SOR may be related to both heightened responsivity in primary sensory regions as well as areas related to emotion processing and regulation.

Attachment figures activate a safety signal-related neural region and reduce pain experience.

Although it has long been hypothesized that attachment figures provide individuals with a sense of safety and security, the neural mechanisms underlying attachment-induced safety have not been explored. Here, we investigated whether an attachment figure acts as a safety signal by exploring whether viewing an attachment figure during a threatening experience (physical pain) led to increased activity in a neural region associated with safety signaling, the ventromedial prefrontal cortex (VMPFC), and corresponding reductions in pain. Female participants in long-term romantic relationships were scanned as they received painful stimuli while viewing pictures of their partner and control images (stranger, object). Consistent with the idea that the attachment figure may signal safety, results revealed that viewing partner pictures while receiving painful stimulation led to reductions in self-reported pain ratings, reductions in pain-related neural activity (dorsal anterior cingulate cortex, anterior insula), and increased activity in the VMPFC. Moreover, greater VMPFC activity in response to partner pictures was associated with longer relationship lengths and greater perceived partner support, further highlighting a role for the VMPFC in responding to the safety value of the partner. Last, greater VMPFC activity while viewing partner pictures was associated with reduced pain ratings and reduced pain-related neural activity. An implication of these findings is that, in the same way that stimuli that historically have threatened survival (e.g., snakes, spiders) are considered to be prepared fear stimuli, attachment figures, who have historically benefited survival, may serve as prepared safety stimuli, reducing threat- or distress-related responding in their presence.

Remember and know judgments during recognition in chronic schizophrenia.

Deficits in learning and memory are among the most robust correlates of schizophrenia. It has been hypothesized that these deficits are in part due to reduced conscious recollection and increased reliance on familiarity assessment as a basis for retrieval. The Remember-Know (R-K) paradigm was administered to 35 patients with chronic schizophrenia and 35 healthy controls. In addition to making "remember" and "know" judgments, the participants were asked to make forced-choice recognition judgments with regard to details about the learning episode. Analyses comparing response types showed a significant reduction in "remember" responses and a significant increase in "know" responses in schizophrenia patients relative to controls. Both patients and controls recalled more details of the learning episode for "remember" compared to "know" responses, although, in particular for "remember" responses, patients recalled fewer details compared with controls. Notably, patients recognized fewer inter-item but not intra-item stimulus features compared with controls. These findings suggest deficits in organizing and integrating relational information during the learning episode and/or using relational information for retrieval. A Dual-Process Signal Detection interpretation of these findings suggests that recollection in chronic schizophrenia is significantly reduced, while familiarity is not. Additionally, a unidimensional Signal Detection Theory interpretation suggests that chronic schizophrenia patients show a reduction in memory strength, and an altered criterion on the memory strength distribution for detecting new compared with old stimuli but not for detecting stimuli that are remembered versus familiar. Taken together, these findings are consistent with a deficit in recollection and increased reliance on familiarity in making recognition memory judgments in chronic schizophrenia.

Rostral ganglia are required for induction but not expression of crayfish escape reflex habituation: role of higher centers in reprogramming low-level circuits.

It is widely assumed that learning results from alterations in the strength of synapses within the neural pathways that mediate a learned behavioral response and that these alterations are directly caused by training-induced activity of neurons connected by the changing synapses. Initial evidence for this view came from studies of habituation of defensive reflexes in several invertebrate species. However, more recent studies of habituation of the escape reflex in one of these species, the crayfish, have shown that habituation is substantially caused by tonic inhibitory input from cephalic ganglia; this descending inhibition suppresses the activity of neurons within the escape circuit, which reside in caudal ganglia. Such control by descending inhibition indicates that animals with encephalized nervous systems do not entirely abdicate to low-level circuitry the important decision of whether to habituate to stimuli that might warn of danger. Higher centers in fact play a major role in controlling the habituation of this potentially life-saving protective response. Another way for higher centers to control lower ones would be to induce alteration of the lower center's intrinsic properties. Here, we show that, whereas descending input from higher ganglia is needed to induce habituation, once established, habituation persists even after rostral ganglia are disconnected. This provides evidence that lower-level neural circuits can be reprogrammed through transient interaction with higher ganglia to decrease their intrinsic tendency to produce escape.

Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia.

CONTEXT: It remains unclear whether altered regional brain physiological activity in patients with schizophrenia during working memory tasks relates to maintenance-related processes, manipulation-related (ie, executive) processes, or both. OBJECTIVE: To examine regional functional activations of the brain during maintenance- and manipulation-related working memory processing in patients with schizophrenia and in healthy comparison subjects. DESIGN: Functional images of the brain were acquired in 11 schizophrenic patients and 12 healthy control subjects (matched for age, sex, handedness, and parental education) during 2 spatial working memory paradigms, one contrasting maintenance-only processing with maintenance and manipulation processing and the other contrasting parametrically varying maintenance demands. RESULTS: Patients and controls showed activation of a large, spatially distributed network of cortical and subcortical regions during spatial working memory processing. When task demands required explicit manipulation of information held in memory, controls recruited right dorsolateral prefrontal cortex (Brodmann areas 45 and 46) to a significantly greater extent than patients. A similar effect was observed for the larger memory set sizes of the memory set size task. No other brain regions showed activation differences between groups for either task. These differences persisted when comparing activation maps for memory set sizes in which the 2 groups were equivalent in behavioral accuracy and when comparing subgroups of patients and controls matched for behavioral accuracy on either task. CONCLUSIONS: Physiological disturbances in the dorsolateral prefrontal cortex contribute differentially to patients' difficulties with maintaining spatial information across a brief delay, as well as with manipulating the maintained representation. These differences persisted when comparing conditions in which the 2 groups were equivalent in behavioral accuracy.

Hippocampal activations during encoding and retrieval in a verbal working memory paradigm.

Though the hippocampus has been associated with encoding and retrieval processes in episodic memory, the precise nature of its involvement in working memory has yet to be determined. This functional magnetic resonance imaging (fMRI) study employed a verbal working memory paradigm that allows for the within-subject comparison of functional activations during encoding, maintenance, and retrieval. In each trial, participants were shown 5 target words and, after an 8 s delay, a series of probe words. Probe words consisted of target matches, phonetically or semantically related foils, or foils unrelated to the target words. Both the left and right hippocampi showed higher mean activation amplitudes during encoding than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC) showed greater activation during maintenance than encoding. Both hippocampal and DLPFC regions were more active during retrieval than maintenance. Furthermore, an analysis of retrieval activation separated by probe type showed a trend toward greater bilateral hippocampal activation for probes related (both semantically and phonetically) to the target than for unrelated probes and still greater activation for target matches. This pattern suggests that there may be roles for the hippocampus and DLPFC in working memory that change as function of information processing stage. Additionally, the trend towards increased involvement of the hippocampus with the increase in relatedness of the probe stimuli to the information maintained is interpreted to be consistent with the role of the hippocampus in recollection-based retrieval in long-term memory and may indicate that this role extends to working memory processes.