Global MEG Resting State Functional Connectivity in Children with Autism and Sensory Processing Dysfunction.

Sensory processing dysfunction not only affects most individuals with autism spectrum disorder (ASD), but at least 5% of children without ASD also experience dysfunctional sensory processing. Our understanding of the relationship between sensory dysfunction and resting state brain activity is still emerging. This study compared long-range resting state functional connectivity of neural oscillatory behavior in children aged 8-12 years with autism spectrum disorder (ASD; N=18), those with sensory processing dysfunction (SPD; N=18) who do not meet ASD criteria, and typically developing control participants (TDC; N=24) using magnetoencephalography (MEG). Functional connectivity analyses were performed in the alpha and beta frequency bands, which are known to be implicated in sensory information processing. Group differences in functional connectivity and associations between sensory abilities and functional connectivity were examined. Distinct patterns of functional connectivity differences between ASD and SPD groups were found only in the beta band, but not in the alpha band. In both alpha and beta bands, ASD and SPD cohorts differed from the TDC cohort. Somatosensory cortical beta-band functional connectivity was associated with tactile processing abilities, while higher-order auditory cortical alpha-band functional connectivity was associated with auditory processing abilities. These findings demonstrate distinct long-range neural synchrony alterations in SPD and ASD that are associated with sensory processing abilities. Neural synchrony measures could serve as potential sensitive biomarkers for ASD and SPD.

Associations between rapid auditory processing of speech sounds and specific verbal communication skills in autism.

Introduction: The ability to rapidly process speech sounds is integral not only for processing other's speech, but also for auditory processing of one's own speech, which allows for maintenance of speech accuracy. Deficits in rapid auditory processing have been demonstrated in autistic individuals, particularly those with language impairment. We examined rapid auditory processing for speech sounds in relation to performance on a battery of verbal communication measures to determine which aspects of verbal communication were associated with cortical auditory processing in a sample of individuals with autism. Methods: Participants were 57 children and adolescents (40 male and 17 female) ages 5-18 who were diagnosed with an Autism Spectrum Disorder (ASD). Rapid auditory processing of speech sounds was measured via a magnetoencephalographic (MEG) index of the quality of the auditory evoked response to the second of two differing speech sounds ("Ga" / "Da") presented in rapid succession. Verbal communication abilities were assessed on standardized clinical measures of overall expressive and receptive language, vocabulary, articulation, and phonological processing. Associations between cortical measures of left- and right-hemisphere rapid auditory processing and verbal communication measures were examined. Results: Rapid auditory processing of speech sounds was significantly associated with speech articulation bilaterally (r = 0.463, p = 0.001 for left hemisphere and r = 0.328, p = 0.020 for right hemisphere). In addition, rapid auditory processing in the left hemisphere was significantly associated with overall expressive language abilities (r = 0.354, p = 0.013); expressive (r = 0.384, p = 0.005) vocabulary; and phonological memory (r = 0.325, p = 0.024). Phonological memory was found to mediate the relationship between rapid cortical processing and receptive language. Discussion: These results demonstrate that impaired rapid auditory processing for speech sounds is associated with dysfunction in verbal communication in ASD. The data also indicate that intact rapid auditory processing may be necessary for even basic communication skills that support speech production, such as phonological memory and articulatory control.

Language Abilities are Associated with Both Verbal and Nonverbal Intelligence in Children on the Autism Spectrum.

Intellectual abilities factor into levels of functioning used to characterize autism. Language difficulties are highly prevalent in autism and may impact performance on measures of intellectual abilities. As such, nonverbal tests are often prioritized in classifying intelligence in those with language difficulties and autism. However, the relationship between language abilities and intellectual performance is not well characterized, and the superiority of tests with nonverbal instructions is not well established. The current study evaluates verbal and nonverbal intellectual abilities in the context of language abilities in autism and the potential benefit of tests with nonverbal instructions. Participants were 55 children and adolescents on the autism spectrum who underwent a neuropsychological evaluation as part of a study examining language functioning in autism. Correlation analyses were performed to examine relations between expressive and receptive language abilities. Language abilities (CELF-4) were significantly correlated with all measures of both verbal (WISC-IV VCI) and nonverbal intelligence scores (WISC-IV PRI and Leiter-R). There were no significant differences between nonverbal intelligence measures with verbal or nonverbal instructions. We further discuss the role of assessment of language abilities in interpreting results of intelligence testing in populations with higher prevalence of language difficulties.

Rapid auditory processing of puretones is associated with basic components of language in individuals with autism spectrum disorders.

The goal of this study was to identify the specific domains of language that may be affected by deficits in rapid auditory processing in individuals with ASD. Auditory evoked fields were collected from 63 children diagnosed with ASD in order to evaluate processing of puretone sounds presented in rapid succession. Measures of language and its components were assessed via standardized clinical tools to quantify expressive and receptive language, vocabulary, articulation, and phonological processing abilities. Rapid processing was significantly and bilaterally associated with phonological awareness, vocabulary, and articulation. Phonological processing was found to mediate the relationship between rapid processing and language. M100 response latency was not significantly associated with any language measures. Results suggest that rapid processing deficits may impact the basic components of language such as phonological processing, and the downstream effect of this impact may in turn impact overall language development.

Striatal networks for tinnitus treatment targeting.

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross-sectional 2-by-2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high-field 7.0 T resting-state fMRI. The second study was a pilot case-control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting-state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks-dorsal caudate head with Heschl's gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case-series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not.

Global resting-state functional connectivity of neural oscillations in tinnitus with and without hearing loss.

This study examined global resting-state functional connectivity of neural oscillations in individuals with chronic tinnitus and normal and impaired hearing. We tested the hypothesis that distinct neural oscillatory networks are engaged in tinnitus with and without hearing loss. In both tinnitus groups, with and without hearing loss, we identified multiple frequency band-dependent regions of increased and decreased global functional connectivity. We also found that the auditory domain of tinnitus severity, assayed by the Tinnitus Functional Index, was associated with global functional connectivity in both auditory and nonauditory regions. These findings provide candidate biomarkers to target and monitor treatments for tinnitus with and without hearing loss.

Phase I trial of caudate deep brain stimulation for treatment-resistant tinnitus.

OBJECTIVE: The objective of this open-label, nonrandomized trial was to evaluate the efficacy and safety of bilateral caudate nucleus deep brain stimulation (DBS) for treatment-resistant tinnitus. METHODS: Six participants underwent DBS electrode implantation. One participant was removed from the study for suicidality unrelated to brain stimulation. Participants underwent a stimulation optimization period that ranged from 5 to 13 months, during which the most promising stimulation parameters for tinnitus reduction for each individual were determined. These individual optimal stimulation parameters were then used during 24 weeks of continuous caudate stimulation to reach the endpoint. The primary outcome for efficacy was the Tinnitus Functional Index (TFI), and executive function (EF) safety was a composite z-score from multiple neuropsychological tests (EF score). The secondary outcome for efficacy was the Tinnitus Handicap Inventory (THI); for neuropsychiatric safety it was the Frontal Systems Behavior Scale (FrSBe), and for hearing safety it was pure tone audiometry at 0.5, 1, 2, 3, 4, and 6 kHz and word recognition score (WRS). Other monitored outcomes included surgery- and device-related adverse events (AEs). Five participants provided full analyzable data sets. Primary and secondary outcomes were based on differences in measurements between baseline and endpoint. RESULTS: The treatment effect size of caudate DBS for tinnitus was assessed by TFI [mean (SE), 23.3 (12.4)] and THI [30.8 (10.4)] scores, both of which were statistically significant (Wilcoxon signed-rank test, 1-tailed; alpha = 0.05). Based on clinically significant treatment response categorical analysis, there were 3 responders determined by TFI (≥ 13-point decrease) and 4 by THI (≥ 20-point decrease) scores. Safety outcomes according to EF score, FrSBe, audiometric thresholds, and WRS showed no significant change with continuous caudate stimulation. Surgery-related and device-related AEs were expected, transient, and reversible. There was only one serious AE, a suicide attempt unrelated to caudate neuromodulation in a participant in whom stimulation was in the off mode for 2 months prior to the event. CONCLUSIONS: Bilateral caudate nucleus neuromodulation by DBS for severe, refractory tinnitus in this phase I trial showed very encouraging results. Primary and secondary outcomes revealed a highly variable treatment effect size and 60%-80% treatment response rate for clinically significant benefit, and no safety concerns. The design of a phase II trial may benefit from targeting refinement for final DBS lead placement to decrease the duration of the stimulation optimization period and to increase treatment effect size uniformity.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov).

Characterizing cognitive and visuomotor control in children with sensory processing dysfunction and autism spectrum disorders.

OBJECTIVE: Children with autism spectrum disorders (ASD) and sensory processing dysfunction (SPD) are reported to show difficulties involving cognitive and visuomotor control. We sought to determine whether performance on computerized, behavioral measures of cognitive control aimed at assessing selective attention, as well as visuomotor abilities differentiated children with ASD (n = 14), SPD (n = 14) and typically developing controls (TDC; n = 28). METHOD: Cognitive control differences were measured by assessing selective attention-based abilities both with and without distracting stimuli, and visuomotor differences were measured by characterizing visuomotor tracking and tracing skills. Performance in cognitive control and visuomotor domains were investigated globally as composite scores, and specifically within each task. RESULTS: Our results indicated that though the ASD group showed the most impaired selective attention performance, the SPD group had intermediate abilities-performing above the ASD group but below the TDC group. Furthermore, both the SPD and ASD groups demonstrated equally impaired visuomotor abilities relative to the TDC group. A correlational analysis between cognitive and visuomotor control suggest a relationship between these overlapping control networks. CONCLUSIONS: This study supports the importance of direct, phenotypic characterizations of control-based abilities in children with ASD and SPD to personalize characterization and treatment interventions for at-risk children. (PsycINFO Database Record

Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions.

Speech and motor deficits are highly prevalent (>70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals.

White Matter Microstructure Associations of Cognitive and Visuomotor Control in Children: A Sensory Processing Perspective.

Objective: Recent evidence suggests that co-occurring deficits in cognitive control and visuomotor control are common to many neurodevelopmental disorders. Specifically, children with sensory processing dysfunction (SPD), a condition characterized by sensory hyper/hypo-sensitivity, show varying degrees of overlapping attention and visuomotor challenges. In this study, we assess associations between cognitive and visuomotor control abilities among children with and without SPD. In this same context, we also examined the common and unique diffusion tensor imaging (DTI) tracts that may support the overlap of cognitive control and visuomotor control. Method: We collected cognitive control and visuomotor control behavioral measures as well as DTI data in 37 children with SPD and 25 typically developing controls (TDCs). We constructed regressions to assess for associations between behavioral performance and mean fractional anisotropy (FA) in selected regions of interest (ROIs). Results: We observed an association between behavioral performance on cognitive control and visuomotor control. Further, our findings indicated that FA in the anterior limb of the internal capsule (ALIC), the anterior thalamic radiation (ATR), and the superior longitudinal fasciculus (SLF) are associated with both cognitive control and visuomotor control, while FA in the superior corona radiata (SCR) uniquely correlate with cognitive control performance and FA in the posterior limb of the internal capsule (PLIC) and the cerebral peduncle (CP) tract uniquely correlate with visuomotor control performance. Conclusions: These findings suggest that children who demonstrate lower cognitive control are also more likely to demonstrate lower visuomotor control, and vice-versa, regardless of clinical cohort assignment. The overlapping neural tracts, which correlate with both cognitive and visuomotor control suggest a possible common neural mechanism supporting both control-based processes.

Magnetoencephalographic Imaging of Auditory and Somatosensory Cortical Responses in Children with Autism and Sensory Processing Dysfunction.

This study compared magnetoencephalographic (MEG) imaging-derived indices of auditory and somatosensory cortical processing in children aged 8-12 years with autism spectrum disorder (ASD; N = 18), those with sensory processing dysfunction (SPD; N = 13) who do not meet ASD criteria, and typically developing control (TDC; N = 19) participants. The magnitude of responses to both auditory and tactile stimulation was comparable across all three groups; however, the M200 latency response from the left auditory cortex was significantly delayed in the ASD group relative to both the TDC and SPD groups, whereas the somatosensory response of the ASD group was only delayed relative to TDC participants. The SPD group did not significantly differ from either group in terms of somatosensory latency, suggesting that participants with SPD may have an intermediate phenotype between ASD and TDC with regard to somatosensory processing. For the ASD group, correlation analyses indicated that the left M200 latency delay was significantly associated with performance on the WISC-IV Verbal Comprehension Index as well as the DSTP Acoustic-Linguistic index. Further, these cortical auditory response delays were not associated with somatosensory cortical response delays or cognitive processing speed in the ASD group, suggesting that auditory delays in ASD are domain specific rather than associated with generalized processing delays. The specificity of these auditory delays to the ASD group, in addition to their correlation with verbal abilities, suggests that auditory sensory dysfunction may be implicated in communication symptoms in ASD, motivating further research aimed at understanding the impact of sensory dysfunction on the developing brain.

Audiometric Profiles in Autism Spectrum Disorders: Does Subclinical Hearing Loss Impact Communication?

Rates of hearing impairment in individuals with Autism Spectrum Disorders (ASD) are higher than those reported in the general population. Although ASD is not caused by hearing impairment, it may exacerbate symptomatology. Participants with ASD (N = 60) and typically developing peers (N = 16) aged 5-18 years underwent a comprehensive audiological screening (pure tone audiometry, uncomfortable loudness level, tympanometry, acoustic reflexes, distortion product otoacoustic emissions, and auditory brainstem response) and assessment of communication abilities (expressive/receptive language, articulation, phonological awareness, and vocal affect recognition). Incidence of abnormal findings on at least one measure of audiological functioning was higher for the ASD group (55%) than controls (14.9%) or the general population estimate (6%). The presence of sound sensitivity was also considerably higher for the ASD group (37%) compared with controls (0%) or general population estimates (8-15%). When participants with ASD were dichotomized into groups with and without evidence of clinical audiological abnormality, no significant differences were identified on measures of communication; however, results of correlational analyses indicated that variability in hearing thresholds at middle range frequencies (2000 Hz) was significantly related to performance on all measures of speech articulation and language after correction for multiple comparisons (r = -0.48 to r = -0.53, P < 0.0045). These findings suggest that dichotomized classification of clinical audiology may not be sufficient to understand the role of subclinical hearing loss in ASD symptomatology and that treatment studies for mild/subclinical hearing loss in this population may be worthwhile.

Relations Between Nonverbal and Verbal Social Cognitive Skills and Complex Social Behavior in Children and Adolescents with Autism.

Although there is an extensive literature on domains of social skill deficits in individuals with Autism Spectrum Disorders (ASD), little research has examined the relation between specific social cognitive skills and complex social behaviors in daily functioning. This was the aim of the present study. Participants were 37 (26 male and 11 female) children and adolescents aged 6-18 years diagnosed with ASD. To determine the amount of variance in parent-rated complex social behavior accounted for by the linear combination of five directly-assessed social cognitive variables (i.e., adult and child facial and vocal affect recognition and social judgment) after controlling for general intellectual ability, a hierarchical regression analysis was performed. The linear combination of variables accounted for 35.4 % of the variance in parent-rated complex social behavior. Vocal affect recognition in adult voices showed the strongest association with complex social behavior in ASD. Results suggest that assessment and training in vocal affective comprehension should be an important component of social skills interventions for individuals with ASD.

Shared and Divergent Auditory and Tactile Processing in Children with Autism and Children with Sensory Processing Dysfunction Relative to Typically Developing Peers.

The aim of this study was to compare sensory processing in typically developing children (TDC), children with Autism Spectrum Disorder (ASD), and those with sensory processing dysfunction (SPD) in the absence of an ASD. Performance-based measures of auditory and tactile processing were compared between male children ages 8-12 years assigned to an ASD (N=20), SPD (N=15), or TDC group (N=19). Both the SPD and ASD groups were impaired relative to the TDC group on a performance-based measure of tactile processing (right-handed graphesthesia). In contrast, only the ASD group showed significant impairment on an auditory processing index assessing dichotic listening, temporal patterning, and auditory discrimination. Furthermore, this impaired auditory processing was associated with parent-rated communication skills for both the ASD group and the combined study sample. No significant group differences were detected on measures of left-handed graphesthesia, tactile sensitivity, or form discrimination; however, more participants in the SPD group demonstrated a higher tactile detection threshold (60%) compared to the TDC (26.7%) and ASD groups (35%). This study provides support for use of performance-based measures in the assessment of children with ASD and SPD and highlights the need to better understand how sensory processing affects the higher order cognitive abilities associated with ASD, such as verbal and non-verbal communication, regardless of diagnostic classification.

Deficits in auditory processing contribute to impairments in vocal affect recognition in autism spectrum disorders: A MEG study.

OBJECTIVE: The primary aim of this study was to examine whether there is an association between magnetoencephalography-based (MEG) indices of basic cortical auditory processing and vocal affect recognition (VAR) ability in individuals with autism spectrum disorder (ASD). METHOD: MEG data were collected from 25 children/adolescents with ASD and 12 control participants using a paired-tone paradigm to measure quality of auditory physiology, sensory gating, and rapid auditory processing. Group differences were examined in auditory processing and vocal affect recognition ability. The relationship between differences in auditory processing and vocal affect recognition deficits was examined in the ASD group. RESULTS: Replicating prior studies, participants with ASD showed longer M1n latencies and impaired rapid processing compared with control participants. These variables were significantly related to VAR, with the linear combination of auditory processing variables accounting for approximately 30% of the variability after controlling for age and language skills in participants with ASD. CONCLUSIONS: VAR deficits in ASD are typically interpreted as part of a core, higher order dysfunction of the "social brain"; however, these results suggest they also may reflect basic deficits in auditory processing that compromise the extraction of socially relevant cues from the auditory environment. As such, they also suggest that therapeutic targeting of sensory dysfunction in ASD may have additional positive implications for other functional deficits.

Individuals with agenesis of the corpus callosum show sensory processing differences as measured by the sensory profile.

OBJECTIVE: Given reports of high pain thresholds and reduced auditory response in individuals with agenesis of the corpus callosum (AgCC), this study investigated whether affected participants report atypical experiences and behaviors on a well-established sensory processing measure. METHODS: Fourteen participants with AgCC (ages 11-59) completed the Adolescent/Adult Sensory Profile (Brown & Dunn, 2001). Sensory profile scales were classified as "Atypical" if they were more than 1 standard deviation from the mean. RESULTS: Fifty-seven percent of participants with AgCC reported reduced sensory registration as compared to an expected 16% of the normative sample. Similarly, 50% of the AgCC participants reported atypically increased auditory processing difficulties. CONCLUSIONS: Using a well-established sensory processing questionnaire, participants with AgCC reported measurable differences in multiple aspects of sensory processing. The most notable difference was in the quadrant of low sensory registration, suggesting that individuals with AgCC may require sensory information to be presented more slowly or at a higher intensity for adequate processing. The sensory modality that was most affected was the auditory system, which is consistent with increased rates of language disorders and autism spectrum disorders in this population. Understanding sensory processing in individuals with AgCC can both elucidate the role of interhemispheric transfer in the development of intact sensory processing as well as contribute to our knowledge of the role of the corpus callosum in a range of disorders in which sensory processes are impacted. (PsycINFO Database Record

A comparison of social cognitive profiles in children with autism spectrum disorders and attention-deficit/hyperactivity disorder: a matter of quantitative but not qualitative difference?

The aim of this study was to compare social cognitive profiles of children and adolescents with Autism Spectrum Disorders (ASD) and ADHD. Participants diagnosed with an ASD (n = 137) were compared to participants with ADHD (n = 436) on tests of facial and vocal affect recognition, social judgment and problem-solving, and parent- and teacher-report of social functioning. Both groups performed significantly worse than the normative sample on all measures. Although the ASD group had more severe deficits, the pattern of deficits was surprisingly similar between groups, suggesting that social cognitive deficit patterns may be more similar in ASD and ADHD than previously thought. Thus, like those with ASDs, individuals with ADHD may also need to be routinely considered for treatments targeting social skills.