Summary of SPD Scientific Work Group

  Roianne Ahn PhD. and Lucy Jane Miller Ph.D., OTR, The KID Foundation Research Institute

  The Wallace Foundation granted a fund to be used for the development and implementation of a master strategy plan for DSM-V inclusion. Dr. Roianne Ahn was hired in September 2005 to coordinate a DSM-V inclusion plan for KID Foundation. A strategic plan has been completed, and the first priority of the is to submit a written proposal to DSM by January 2007 requesting inclusion of SPD in the upcoming revision of DSM. The first of five major sections of the proposal is currently being drafted.

  To support this aim, a critical secondary priority is to create a national communication network that organizes researchers and authors to advocate for professional and public SPD acceptance. Communication with OT's, researchers, other professionals, and parents has been initiated addressing the impact of the new SPD diagnosis on clinicians and families, and pilot opinion data have been collected using parent surveys and focus groups. Data analysis of the pilot data is in process.

  Although strategically critical, a long-term SPD Advocacy project has not yet been funded. While the DSM proposal project terminates at the end of this year, the communication and networking tasks of the DSM-V inclusion project will need to be continued to meet the goals of long-term SPD advocacy (campaign with insurance companies; acceptance by the ICD) is to be successful. Additional, full-time resources will be required to manage, organize, and administer a broad successful SPD advocacy and awareness campaign.

  Margaret Bauman MD Harvard University Medical School

  Dr. Bauman and colleagues are completing histoanatomic observations of the brain in nicotine treated rats. Previous studies have shown that nicotine improves auditory sensory gating as measured by pre-pulse inhibition in animals. Additional studies suggest that GABA agonists may attenuate symptoms of sensory defensiveness. This study is neuroanatomically surveying the brains of nicotine treated Sprague-Dawley rats in comparison to age and sex-matched controls using histoanatomic and immunocytochemical techniques. She suspects that in the nicotine treated rats, microscopic structural abnormalities will be found in specific brain regions and will co-exist with cholinergic and GABAergic systems differences compared to controls. Identification of specific brain regions and neurotransmitter systems associated with auditory sensory gating will localize these areas and expand our understanding of the neurobiological mechanisms of processing of sensory information.

  Barbara Brett-Green, Lucy Jane Miller and Sarah Schoen

  Drs. Brett-Green, Miller and Schoen have a long term program of research studying electrodermal activity and vagal tone in children with SPD compared to those with ADHD and Autistic Spectrum Disorder. In addition, Dr Brett-Green is undertaking EEG (event related potential) research evaluating the effect of multi-sensory stimulation at the cortical level on typically developing children and adults compared to those with SPD and autism. (See also research by Miller and Team for more detailed explanations.)

 

  Alice Carter Ph.D. and Margaret Briggs-Gowen Ph.D. University of MA and Yale University Lucy Jane Miller PhD OTR and Sarah Schoen, PhD OTR

  The study by Carter and Briggs-Cowen is examining the prevalence of SOR in a representative longitudinal birth cohort of children in the Greater New Haven area who have been followed from either 1- or 2-years of age and assessed with the Sensory Over-Responsivity Scale in Second Grade. Data about early emerging social-emotional problems and competencies, including a measure of sensory sensitivities at ages 1, 2, and 3 years of age and psychiatric diagnostic status in Kindergarten and Second Grade is already available in the larger longitudinal study.

  This project is providing data on the prevalence and correlates of SOR in a representative community sample. It is also examining associations between infant/toddler and concurrent social-emotional and behavior problem correlates of SOR in school-aged children.

  Patti Davies Ph.D. OTR and William Gavin PhD. CO State University

  Drs. Davies and Gavin are using electroencephalography (EEG) and event-related potentials (ERPs) to examine the brain activity of children with sensory processing disorders. Recently they compared the brain activity of 28 children with sensory processing disorders to 25 typically developing children using two ERP paradigms, sensory gating (P50) and sensory registration (N100 and P200).

  The sensory gating or P50 paradigm measures an individualÍs ability to suppress irrelevant or repeated stimuli. Drs. Davies and GavinÍs results illustrate that children with sensory processing disorders display significantly less auditory sensory gating; that is, they do not demonstrate suppressed brain activity to a second click sound presented a half second after the first click sound when compared to the brain activity of typically developing children. In their analyses for developmental trends, typically developing children showed that sensory gating improves as children mature. In contrast, children with SPD did not demonstrate a relationship between sensory gating and age, suggesting that their gating abilities do not change as a function of either biologically driven maturity (e.g., physical growth) or the accumulation of experiences across time (e.g., learning).

  The sensory registration paradigm measures the brain activity to auditory tones presented at different frequencies and intensities. Two ERP components, N100 and P200, are used to measure changes of brain activity to different stimuli intensities and frequencies. Outcomes of these measures along with age were found to predict sensory gating abilities in typically developing children but not for children with SPD. However, differences between actual sensory gating measures and predicted sensory gating based on the prediction equation of the typical children could be used to classify children with SPD and distinguish them from a group of typically developing children with 86% accuracy. Furthermore, the children with SPD were shown to be either hyper-responsive or hypo-responsive in their sensory gating relative to the gating of the typical children.

  These results provide empirical evidence that children seen by occupational therapists for intervention of sensory processing disorders display unique brain processing mechanisms that can be distinguished from typically developing children. The qualitative differences in underlying brain processing demonstrated by children with SPD may explain the abnormal behaviors to sensory stimuli shown these children. Collectively, these findings contribute to the validity of the diagnostic category of sensory processing disorders which previous to this study has been defined primarily through behavioral measures.

  Final Hill Goldsmith Ph.D., University of Wisconsin Madison

  Goldsmith and colleagues are studying genetic influences on tactile and auditory over-responsiveness using twin methodology. They have conducted three studies to d ate:

  The first study was a toddler study and evaluated 1394 twin pairs (mean age 27 months) using a parental report measure that included a five item scale of auditory and tactile over-responsivity. The second study was a preschool study and evaluated 282 twin pairs (age 3-6 years) and was a follow-up of extreme and matched control twins from the toddler study and was based on parental report using 54 parent-rated items of sensory over-responsivity and 78 home visits for observational assessment of twin SD and other symptoms. The third study is an ongoing first grade study of 460 twin pairs, with160 including in-home assessment (age 7-8 years).

  The auditory and tactile symptoms were reasonably normally distributed in the toddler sample, with a small percent of over-responders clearly observed in the tail of the distributions. In a subsample followed up two years later, the scores were moderately stable, with 48% of extreme tactile group remaining extreme and 50% of the extreme auditory group remaining extreme (in the absence of intervention). The association of sensory over-responsiveness with other social, emotional and psychological factors was examined. Auditory and tactile over-responsiveness was significantly correlated with anxiety (.20-.24) but appeared be a relatively independent dimension in the larger population (all other correlations < .20).

  In the first grade study (n=150) significant correlations were observed between auditory and tactile overresponsvity with items on the Diagnostic Interview Schedule for Children (e.g. for anxiety symptoms including agoraphobia, separation anxiety, specific phobia and social phobia, correlations ranged from .18 to .27).

  Lastly, Goldsmith and colleagues examined genetic effects for the full range of trait scores, for extreme scores and for tactile and auditory scores by examining twin similarity and parent-offspring similarity. If genetic effects are present, classic assumptions of twin studies imply that identical (MZ) twins, who share 100% of their genes, should be more similar than fraternal (DX) twins, who share only 50% of segregating genes, on the average. Findings in the toddler study were that, for auditory over-responsiveness, 65% of MZ twin pairs as compared with 50% of DZ twin pairs were concordant. For tactile over-responsiveness, 83% of MZ pairs, compared with 32% of DZ pairs were concordant for tactile symptoms. These findings suggest genetic effects, especially for the tactile domain.

  Michael Kisley PhD. University of CO in CO Springs

  Dr. Kisley is examining the relation between symptoms of auditory defensiveness and underlying neural mechanisms which might account for these symptoms. To this end his research group employs a number of event-related potential (ERP) paradigms including sensory gating and mismatch negativity. They have found that sensory gating was correlated with sensory over-responsivity in an otherwise healthy adult sample (Kisley et al., 2004). Specifically, sensory gating of ERP component P1 (i.e., ñP50î) was correlated with the ability to modulate auditory stimuli (e.g., decrease loudness of stimuli) whereas gating of component N1 (ñN100î) was correlated with the ability to screen out irrelevant stimuli (e.g., ignore background sounds). A follow-up study (Kisley et al, in preparation) with a sample of adults screened for clinical diagnoses other than sensory modulation disorder included comparison of self-reported observations of sensory over-responding to electrophysiological measures of sensory gating in both auditory (P50, N100) and somatosensory (P50/85, N120) domains. In this case ñsensory sensitivityî and ñsensation avoidanceî were both significantly correlated to ERP measures of auditory sensory gating (component N100).

  Collectively, these results suggest that individuals with sensory modulation disorder might exhibit a particular deficit in the representation of ñlow salienceî stimuli. Salience is a measure of a stimulusÍ potential importance to an individual, and is affected by the physical properties of a stimulus such as novelty, intensity, and time elapsed since the same stimulus was previously encountered (i.e., ñinter-stimulus intervalî). ERP paradigms like sensory gating involve a systematic variation of stimulus salience. ItÍs expected that, as the salience of a stimulus is decreased (e.g., itÍs novelty is decreased), so too should the brainÍs processing of that stimulus be appropriately decreased. Demonstrated impairments in electrophysiological measures of sensory gating in individuals classified as ñsensory over-respondersî therefore suggests that these individuals specifically over-process stimuli of low salience, as opposed to simply over-responding to all stimuli encountered in their environment.

  Dr. KisleyÍs group is just finishing an investigation into whether sensory over-responsive adults also exhibit impairments in cognitive function, the latter measured through neuropsychological assessment. The rationale for this study comes from the observation that many clinical conditions other than sensory modulation disorder - that yet involve prominent sensory over-responding (e.g., schizophrenia, autism, etc.) - also generally involve neuropsychological impairment including especially deficits in tasks associated with frontal lobe function. For this study, approximately 60 adults have completed self-report measures of sensory over-responding and a number of tests designed to assess executive function (e.g., Wisconsin Card-Sort Test; Tower of London; Rey Auditory Verbal Learning Test, etc.). Preliminarily, the data suggest that sensory over-responding is in fact related to neuropsychological function. Analyses of the full data-set is anticipated to be completed before the end of 2006.

  Ed Levin Ph.D. Duke University

  Levin and colleagues are studying neural mechanisms of normal and impaired sensory modulation was well as potential pharmacological therapeutic approaches using pre-pulse inhibition (PPI) paradigms in a rat model. Sensory processing involves successive stages of discarding extraneous or irrelevant information. By studying inhibition of the startle response, neurotransmitter interactions and basic neurobiology and potential pharmacological therapeutic approaches are evaluated.

  Normally a warning stimulus reduces startle reactions. Both the timing and the intensity of stimulus are relevant to the response which is observed. Levin studied both nicotine effects and the effect of nicotinic glutamate interactions on PPI. He studied both auditory and tactile response modulation. He found that nicotine facilitates prepulse inhibition over various intensities and inter-stimulus intervals. When nicotine and dizocilpine are both administered, there is a decreasing effect on PPI as the dose of dizocilpine increases (65-75 % PPI with no dizocilpine; 60% PPI with 25 mg/kg dizocilpine; 40-50% PPI with 50mg/kg dizocilpine; 0-20%PPI with 100 mg/kg dizocilpine).

  However, when clozapine is added to nicotine and dizocilpine, the % PPI increases significantly in relation to the dose of clozopine administered. With tactile startle there is also a dose effect of dizocilpine on the intensity of response (increasing dizocilpine relates to decreased startle). As the amount of clozopine increases, the effect of the dizocilpline on reducing the %PPI decreases. In other words, clozapine increases sensory gating when gating has been pharmacologically reduced (reduced using dizocilpine.)

 

  Jeffrey Lewine, Ph.D. and Winnie Dunn PhD. OTR, The University of Kansas Medical Center

Lewine and Dunn and colleagues are evaluating the relation of sensory hypersensitivity to the encoding of stimulus intensity in the central nervous system. They hypothesize that sensitivities arise because abnormally broad tuning properties for cortical columns allow ïtoo muchÍ cortex to be activated by moderately intense stimuli. They will test 24 children (6 with AspergerÍs Syndrome with hypersensitivity; 6 with Asperger Syndrome without hypersensitivity; 6 children with Sensory Over-responsivity and no other diagnosis; and 6 typically developing controls) using the Sensory Profile and magnetoencephalographic (MEG). They will using a test paradigm that probes tactile, auditory, and visual domains responses to stimuli of differing intensities.

 

  Teresa May-Benson ScD. The Spiral Foundation at OTA-Watertown , Watertown MA

Dr. May-Benson and colleagues are studying the reliability of a method of evaluating changes after treatment called goal attainment scaling (GAS). Children with SPD often make life changing functional gains with Occupational Therapy (OT), however, these gains are often not captured by or reflected on standardized assessments traditionally used as outcome measures for intervention effectiveness studies. The ability to reliably and validly measure the effectiveness of interventions is limiting the completion of rigorous randomized controlled trials. GAS has been used in community mental health to evaluate program effectiveness, but has not yet been shown to be a reliable outcome measure for use with OT. Through pre- and post-intervention parent interviews and use of the GAS goal setting process, this study is examining the reliability of GAS in 40 children to evaluate changes in functional performance from before OT to after OT.

  Lucy Jane Miller PhD OTR and Sarah Schoen, PhD OTR

  Dr. Miller and Dr. Schoen and colleagues are focusing on the development of reliable and valid scales that can be used to diagnose each of the six subtypes of Sensory Processing Disorder. Each scale has two components: 1) an Assessment which is an examiner administered performance evaluation and an Inventory which is a caregiver/self-rated symptom checklist.

  The purpose of the Sensory Processing Disorder Scales is to accurately diagnose SPD for clinical purposes and to identify homogeneous populations for research purposes. Existing measures are not based on the theoretical conceptualization of SPD and therefore are inadequate for the diagnosis of subtypes of Sensory Processing Disorder.

  The measure of Sensory Over-Responsivity is most fully developed and has been validated on a sample of 125 participants with and without sensory over-responsivity. Data has been collected on another cohort and is currently being analyzed for internal reliability, test-retest reliability and discriminant validity.

  A caregiver/self-rated symptom checklist exists for all of the other subtypes of SPD. The checklists are currently being piloted at sites across the country in order to determine which items best discriminate each subtype.

  Also in the process of development are items for an examiner administered performance evaluation for the other two subtypes of Sensory Modulation Disorder, Sensory Under-Responsivity and Sensory Seeking. Test items will be administered to typically developing children as well as children with each disorder so as to determine which items best discriminate between groups.

  David Pauls PhD, Harvard University Medical School

Dr. Pauls and colleagues are conducting a prevalence and family study of sensory over responsiveness (SOR) in individuals with Attention Deficit Hyperactivity Disorder, Obsessive Compulsive Disorder or Gilles de la Tourette Syndrome. Despite the high prevalence of SOR symptoms in the general population (estimated to be ~5%), little research has been done to understand better the phenomenology and etiology of SOR and its relation to other conditions. This study is collecting SOR data on a sample of 600 children with ADHD (N=200), OCD (N=200) and GTS (N=200) and their first degree relatives. It will be the first systematic study designed to obtain prevalence data in a sample of children with psychiatric disorders and their families. Since data is being collected from all family members, it will also be possible to examine the familial patterns and test specific genetic hypotheses regarding the transmission of SOR within families. In addition, DNA is being collected from all families participating in this study. Thus future studies can include candidate gene studies once more is known about the underlying etiology of SOR.

  Roseann Schaaf PhD, OTR Thomas Jefferson University

  Schaaf and colleagues are studying the parasympathetic system (PsNS) in children with Sensory Processing Disorder. Specifically, they are recruiting75 children with Sensory Modulation Disorder. These children will participate in the Sensory Challenge Protocol, a physiologic laboratory paradigm that exposes children to a series of approximately 50 sensory stimuli for three seconds each. The protocol will be adapted to include a prolonged administration of auditory stimuli to assess not only reactivity and recovery, but also sustained coping and self-regulation. In addition to the Sensory Challenge Protocol,a number of behavioral assessmentswill be administered including the Short Sensory Profile (Miller, et al 2001) to assess behavioral responses to sensation, the Vineland Adaptive Behavior Scales, Second Edition, to assess adaptive behavior, and the Sensory Challenge Protocol to assess PsNS activity during the administration of sensory stimuli (Miller, et al, 2001). To control for the heterogeneity within the group of SPD, they will be classified into three groups (over-responsive, under-responsive and seeking) using criteria developed by Miller, et al and these groups will be compared to the other two. A 4 (group) X 3 (condition) ANOVA will be conducted to determine any group differences between the groups during each condition. Next, building on work in collaboration with the Miller lab, a series of regression analyses will be used to determine whether VTi is a predictor of adaptive behavior or sensory reactivity. The primary dependent measure is vagal tone, although heart rate and heart period will also be evaluated.

  Mary Schneider Ph.D., OTR University of Wisconsin - Madison

 
Schneider and colleagues are studying the neurobiological correlates of sensory processing impairments in a primate model including habituation and sensitization to repeated tactile stimuli and dopamine function. A longitudinal study of 49 Rhesus monkeys was undertaken. All monkeys were administered a sensory processing measure which consisted of 18 trials of tactile stimulation and sensory reactivity was rated by blind coders.
As infants, all subjects were tested on a primate neonatal behavioral assessment modeled after the Brazelton infant behavioral scale, measuring muscle tone and consolability. At 6 months of age, plasma ACTH and cortisol obtained from a series of blood draws were assessed before and after a 3-day maternal separation. At 3 years of age, a standard primate cognitive battery was administered.
Findings were that the monkeys with low scores on the sensory processing measure (poor habituation and high responsivity) had significantly poorer neonatal consolability and muscle tone, showed significantly more stress reactivity upon maternal separation, and showed significantly more hyperactivity, impulsivity, irritability, and stereotypical behavior during the cognitive testing. The results showed significantly different scores between primates with hyper-responsive sensory processing scores and those with optimal sensory processing at all three ages and on all three types of outcome measures. Thus over development, sensory processing problems were associated with disruption of neonatal attention, muscle tone development, narrow range for tolerating stress, and compromised learning performance.

  Since there were multiple symptoms of inattention, poor motor control and executive function problems the dopamine system was targeted for further evaluation in young adulthood. The primates underwent neuroimaging (PET scans) at approximately 5-6 years of age to evaluate their dopamine systems. In particular the D-2-like receptors in the striatum were targeted for study because they underlie inhibitory control and attention. A linear relation between the primatesÍ score on the sensory processing measure and D2 receptor binding was found. Thus, sensory processing was found to be associated with striatal dopamine system dysfunction. Reduced habituation to repeated tactile stimuli was associated with increased D2 receptor binding of radiotracer, suggesting up-regulation or super-sensitivity of striatal D2 receptors.

  Sinclair Smith ScD, Drexel University and Temple University

  Smith and colleagues are studying Sensory Processing and Brain metabolism in Sensory Hyper-Responsive Adults. Initial results suggested that adults with sensory over-responsivity have an elevated skin conductance response to stimuli compared to controls.

  Next, brain metabolism using proton magnetic resonance spectroscopy was evaluated. In a small study (4 each group) the thalamus and frontal white matter of each group was compared using proton magnetic resonance spectroscopy. A trend toward significance was found comparing creatine (p= .051), glutamate (p=.053) , lactate (p = .044) and cholinate (p = .08). Preliminary brain MRS results suggest that sensory-defensive persons may have compromised CNS energy metabolism given the reduced levels of total creatine and increased levels of glutamate found in the brain.

  Barry Stein PhD, Wake Forest College

  Dr. Stein and colleagues is studying how multisensory neurons pool intersensory information. To benefitî from this information pooling in the CNS, there must be multisensory integration e.g. the response to cross-modal cues must be significantly different from the responses to the most effective of the cues presented alone.

  Dr. Stein is using a number of animal models to determine w hen in life sensory input is begins to develop. Known is that the neural circuit responsible for the integration of tactile, auditory and visual cues to initiate and control attentive and orientation behavior involves the midbrain superior colliculus and the control exercised over the multisensory processing in this structure by association cortex.

  For this circuit to develop its multisensory integrative capabilities and produce adaptive responses, it must have normal experience with cross-modal cues early in life. Otherwise the multisensory neurons cannot integrate cross-modal cues. If early cross-modal experiences are abnormal, atypical responses to cross-modal cues will result.

  Stein and colleagues are hypothesizing that the sensory anomalies observed in SPD involve miscommunication between cortex and superior colliculus. They propose to render the superior colliculus temporally inactive during that phase of early life when the multisensory capabilities of the superior colliculus are first being formed. They predict will result in the multisensory integrative capabilities of the superior colliculus not developing. They further predict that deficits in the association cortex will also be exhibited.

  This study is relevant to children with SPD if the anomalies in sensory processing exhibited by children with SPD reflect problems cortico-collicular axis. This study will permit insights into the etiology of the symptoms of SPD, will be relevant to the development of intervention strategies to ameliorate SPD during early development, and the development of intervention strategies to enhance compensation once the sensitive period is over.

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