Carissa J. Cascio, PhD - US grants

The tactile perception of roughness depends on lateral movement between the skin and the surface, yet studies of the stimulus variables relevant to roughness perception have failed to find substantial evidence for temporal factors. This project asks whether the temporal frequency of a textured stimulus affects roughness perception. The hypothesis that tactile roughness perception depends partially on temporal factors will be investigated using three approaches. First, normal human volunteers will perform either of two psychophysical tasks as temporal frequency is manipulated as an independent variable. Next, the representation of stimulus frequency in somatosensory cortical neurons will be investigated. Finally, numerous studies have linked dyslexia to a mufti- modal sensory deficit specific for high-frequency information. In light of this evidence, volunteers with dyslexia will perform a psychophysical discrimination task using textured stimuli of varying frequencies. This project will contribute not only to the understanding of tactile coding of texture, but also to the understanding of sensory differences in dyslexia.

DESCRIPTION (provided by applicant): Sensory symptoms are among the most commonly reported associated features of autism spectrum disorders (ASD). Sensory abilities develop more rapidly than social and communication skills, and thus if their dysfunction is better understood in ASD, could serve an important role in early identification and intervention. Altered tactile sensitivity is one of the most typical variants of sensory features, but is paradoxically understudied relative to hearing and vision in ASD. The sense of touch in early infancy lays the foundation for the development of communication and social reward throughout development. Thus, a better understanding of tactile dysfunction in ASD is critical. Most experimental work has investigated discriminative touch on the palmar surface of the hand, usually the fingertip. Affiliative or affective touch is believed to be mediated by a unique class of somatosensory afferent (CT fiber) that is absent in the palm. The proposed project undertakes the examination of affective tactile perception in ASD using converging behavioral, neurophysiological, and neuroanatomical techniques. Observational measures of tactile defensiveness will be correlated with diffusion tensor imaging (DTI) data characterizing the strength of thalamocortical circuits, as well as responses from functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) that will elucidate the spatial and temporal characteristics, respectively, of neural response to affective tactile stimuli in ASD. This study of the neurobehavioral basis of affective touch in ASD will add to the existing experimental literature that is primarily focused on discriminative touch, and will complement the existing behavioral literature by exploring neural mechanisms. A better understanding of tactile sensitivity in ASD has significant potential for developing biomarkers for early identification and as a foundation for efficacy studies of sensory-based treatments of ASD.

DESCRIPTION (provided by applicant): Autism spectrum disorders (ASD) are a group of pervasive developmental disorders characterized by deficits in social interaction and communication, and rigid or stereotypical behaviors. These complex behavioral problems arise, in part, from deficits in more basic sensory and motor systems. The thalamus plays a central role in processing sensory information and modulating overall cortical activity. Consequently, dysfunction of the thalamus and its connections with the cortex may account for some of the symptoms of ASD. Indeed, there is growing evidence that the structure and function of the thalamus is abnormal in ASD and contributes to ASD symptoms. Despite emerging evidence of thalamic abnormalities in ASD, several critical gaps in our knowledge about thalamic pathology in ASD remain. First, thalamocortical networks are organized topographically such that separate thalamic nuclei project to specific cortical areas raising the distinct possibility that thalamocortical networks may selectively affected in ASD. Second, we know virtually nothing about the post-natal developmental trajectories of thalamocortical networks in ASD. This is critical given mounting evidence that the developmental trajectories of the brain are altered in ASD. Moreover, the severity of ASD symptoms varies across the lifespan. Consequently, a complete understanding of thalamic circuitry in ASD and the relationship between thalamocortical network disturbances and ASD phenotypes will require systematic mapping of thalamocortical networks across the lifespan. This proposal will begin to address these critical gaps. Using an innovative resting-state fMRI method, we will determine if thalamocortical networks are altered in ASD (Aim 1); examine the developmental trajectories of thalamocortical networks in ASD (Aim 2); and establish the functional relevance of thalamocortical networks to the expression of ASD symptoms (Aim 3). The proposed work will contribute to our understanding of brain-basis of ASD.

DESCRIPTION (provided by applicant): Altered responsiveness to basic sensory input is an under-studied symptom in autism spectrum disorders (ASD) that likely has far-reaching effects on development, although these effects are not well understood. While the term sensory typically connotes stimuli external to the body, there is copious sensory information within the body as well, including visceral and proprioceptive signals. Hypo-responsiveness to external sensory stimuli shows very strong association with core clinical symptoms, and differentiates ASD from other developmental disorders better than hyper-responsiveness. The experiments described in this project are designed to investigate possible mechanisms for this under-responsiveness, and attempts to reconcile these with growing evidence that individuals with ASD show enhanced reliance on internal sensory signals when they are in competition with external cues. We predict that basic sensory perception of internal (interoceptive) and external sensory cues will not differ in ASD, but expect differences in higher order neural networks that integrate these signals and compare competing signals for salience in order to allocate attention. The project will emphasize the salience network, comprising anterior insular and anterior cingulate cortices, which integrate both internal and external cues with limbic input to determine their relative affective significance. We hypothesize that this system is involved in excessive focus on internal sensory cues, at the expense of external input, in ASD. We further predict that the neural and behavioral correlates of enhanced attention to internal sensory input relative to external will positively relate to social deficits and sensory hypo-responsiveness in ASD. If these predictions are supported, neural differences in the salience network could serve as novel biomarkers for ASD and behavioral differences could be parlayed into improved therapeutic approaches, including mindfulness-based therapies that could capitalize on an existing strength in attending to internal sensory cues.

? DESCRIPTION (provided by applicant): The objective of the proposed project is to compare and contrast multisensory representation of peripersonal space (PPS) in two clinical groups: adults with autism spectrum disorder (ASD) and schizophrenia (SZ). The NIMH has stressed the importance of investigations that cross diagnostic categories and identify neural substrates of symptoms that are both shared and divergent across clinical groups. This project will follow this directive and extend it by focusing on basic sensory processes, which underlie more complex behavioral phenotypes and for which the neural bases are more completely understood. The project will assess the size and gradient of PPS representation in these two groups, within the hypothetical framework that shared social deficits exhibited in both groups may arise from divergent deficits in the multisensory representation of PPS. Individuals with ASD may show smaller representations of PPS and steeper gradients between PPS and extrapersonal space (EPS), reflecting a proximal focus of attention that leads to difficulty with reciprocal social interaction. In contrast, individuals with SZ are expected to show expanded PPS representation and shallower gradients between PPS and EPS, reflecting a distal or external focus that leads to problems distinguishing ownership. Both aberrant representations are predicted to relate to the specific social deficits observed in each group. We will also explor the malleability of these representations following a period of paired visual-tactile stimulation, which has been demonstrated to alter PPS representation in adults. While this exploratory aim is not designed to assess manipulating PPS representation as a treatment, and thus does not constitute an intervention study, we will assess the relationship between changes in PPS representation and social symptoms in each group as a preliminary step in determining whether there are links between these domains in ASD and SZ.

PROJECT SUMMARY Altered sensory experiences are prevalent in autism and have been implicated in not only the core behavioral characteristics of impaired social communication and repetitive behaviors, but in a range of associated comorbidities including sleep disturbances2 and anxiety24. Recent work in the sensory domain strongly suggests that the predictability, or lack thereof, of sensory stimuli heavily influences aberrant reactions and mediates relations between sensory sensitivity, anxiety, and social motivation in autism78-79. Most sensory research thus far has emphasized exteroceptive sensation?sensory signals that originate in the external environment?with less work on interoceptive sensation?sensory signals that arise from the viscera and skin to signal the brain about the physiological condition of the body6. These interoceptive cues are often the precursors of emotional experience, and thus have significant transdiagnostic clinical relevance in psychiatry. Evaluation of the emotional relevance of the external environment?within which social stimuli are embedded?requires a continuous exchange of information between exteroceptive and interoceptive processing streams. In other words, successful navigation of the social world depends on multisensory integration across the body boundary. Critically for autism, many visceral interoceptive signals tend to be very rhythmic (e.g., cardiac signals), and/or are under voluntary control (e.g., respiratory signals) and are thus far more predictable than environmental exteroceptive cues. This predictability is enhanced on average in individuals with autism, who tend to have higher heart rates and lower heart rate variability than controls. In the current project period, we found evidence for profoundly disrupted temporal integration of visceral interoceptive and exteroceptive signals, without clear evidence of disrupted interoception alone. We now propose, in this renewal, to isolate and test potential neural drivers and clinical sequelae of this disrupted integration. The proposed work will provide important new insights into the consequences of sensory processing deficits in autism that go beyond exteroceptive sensation, incorporating a sensory milieu that has high relevance for social-emotional functioning.