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.
•Rapid auditory processing was associated with performance on tasks assessing basic components of language.•Direct associations between rapid processing and overall language performance were not ...identified; rather, phonological processing mediated this relationship.•M100 latency was not associated with any measures of verbal communication.
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.
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.
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.
Rapid auditory processing of speech sounds was significantly associated with speech articulation bilaterally (
= 0.463,
= 0.001 for left hemisphere and
= 0.328,
= 0.020 for right hemisphere). In addition, rapid auditory processing in the left hemisphere was significantly associated with overall expressive language abilities (
= 0.354,
= 0.013); expressive (
= 0.384,
= 0.005) vocabulary; and phonological memory (
= 0.325,
= 0.024). Phonological memory was found to mediate the relationship between rapid cortical processing and receptive language.
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.
Summary
The surgical management of neocortical epilepsy is challenging because many patients are without obvious structural lesions, or lesions are small and easily overlooked during routine clinical ...interpretation of magnetic resonance imaging (MRI) data. Even when functional imaging data suggest focal epileptiform pathology, in the absence of a concordant structural lesion, invasive monitoring is often required to confirm that an appropriate surgical target has been identified. This study sought to determine the extent to which knowledge of magnetoencephalography (MEG) data can augment the MRI‐based detection of structural brain lesions. MRI and whole‐head MEG data were obtained from 40 patients with neocortical epilepsy. As a result of MEG data, 29 cases were sent for MRI reevaluation. In seven of these cases, MEG‐guided review led to specification of now clear, but previously unidentified, lesions. There were two additional cases for which follow‐up high‐resolution imaging did not confirm structural abnormalities. In patients with neocortical epilepsy, MEG is a useful adjunct to MRI for the identification of structural lesions.
Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are leading causes of sustained physical, cognitive, emotional, and behavioral deficits in the general population, ...active-duty military personnel, and veterans. However, the underlying pathophysiology of mTBI/PTSD and the mechanisms that support functional recovery for some, but not all individuals is not fully understood. Conventional MR imaging and computed tomography are generally negative in mTBI and PTSD, so there is interest in the development of alternative evaluative strategies. Of particular note are magnetoencephalography (MEG) -based methods, with mounting evidence that MEG can provide sensitive biomarkers for abnormalities in mTBI and PTSD.
Functional MRI studies have identified a distributed set of brain activations to be associated with auditory verbal hallucinations (AVH). However, very little is known about how activated brain ...regions may be linked together into AVH-generating networks. Fifteen volunteers with schizophrenia or schizoaffective disorder pressed buttons to indicate onset and offset of AVH during fMRI scanning. When a general linear model was used to compare blood oxygenation level dependence signals during periods in which subjects indicated that they were versus were not experiencing AVH ("AVH-on" versus "AVH-off"), it revealed AVH-related activity in bilateral inferior frontal and superior temporal regions; the right middle temporal gyrus; and the left insula, supramarginal gyrus, inferior parietal lobule, and extranuclear white matter. In an effort to identify AVH-related networks, the raw data were also processed using independent component analyses (ICAs). Four ICA components were spatially consistent with an a priori network framework based upon published meta-analyses of imaging correlates of AVH. Of these four components, only a network involving bilateral auditory cortices and posterior receptive language areas was significantly and positively correlated to the pattern of AVH-on versus AVH-off. The ICA also identified two additional networks (occipital-temporal and medial prefrontal), not fully matching the meta-analysis framework, but nevertheless containing nodes reported as active in some studies of AVH. Both networks showed significant AVH-related profiles, but both were most active during AVH-off periods. Overall, the data suggest that AVH generation requires specific and selective activation of auditory cortical and posterior language regions, perhaps coupled to a release of indirect influence by occipital and medial frontal structures.
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
•Sarin causes neurobiological abnormalities that persist for at least one month, despite Midazolam standard-of-care (SOC) treatment at 50 min.•When the SOC is augmented by addition of Ketamine, the ...neurobiological burden is markedly reduced as measured by EEG, behavior, and histopathology.•At 30 days post-sarin, most animals treated with the SOC plus Ketamine show near normal memory performance on the Morris Water Maze (MWM).•Addition of Ketamine to the SOC treatment also protects against necrosis, especially in the hippocampus
Rats poisoned with sarin enter into ahyper-cholinergic crisis characterized by excessive salivation, respiratory distress, tremors, seizures, and death. Through the use of rescue medications and an anticonvulsant, death can be avoided in many animals, with the long-term consequences of poisoning partly ameliorated, especially when countermeasures are made available immediately after exposure. However, when anticonvulsant measures are delayed by as little as 30 min, clinical, neurological, cognitive, and psychiatric abnormalities may persist long after the initial exposure. This study sought to determine if the addition of the NMDA receptor antagonist Ketamine to human standard-of-care countermeasures consisting of two rescue medications (2-PAM and atropine) and an anti-convulsant (Midazolam), would afford protection against persistent neurobiological compromise. Rats were exposed to sarin (105 μg/kg via subcutaneous injection), and treated 1 min later with 2-PAM and Atropine Methyl Nitrate (IM) to minimize mortality. One of four anti-convulsant protocols was then initiated at 50 min postsarin:Midazolam alone (MDZ, a single injection (IM) at 0.66 mg/kg); Ketamine alone (KET, a series of five injections (IM) of Ketamine at 7.5 mg/kg, 90 min apart); Midazolam + low dose Ketamine (MDZ + lowKET, a single injection of Midazolam (IM) at 0.66 mg/kg, plus five sequential doses of ketamine (IM) at 2.5 mg/kg, starting at the time of Midazolam dosing and then 90 min apart); Midazolam + high dose Ketamine (MDZ + highKET, a single injection of Midazolam (IM) at 0.66 mg/kg, plus five sequential injections of 7.5 mg/kg Ketamine (IM), starting at the time of Midazolam dosing and then 90 min apart). Animals were preassigned to groups culled at post-exposure Days 1, 7 or 30, for histopathology. For all surviving animals, EEG activity was monitored through skull electrodes for 24-h beginning immediately after sarin exposure. Surviving animals also underwent 24-h EEG monitoring on Days 6, 13, and/or 29, post-sarin. Memory assessment using the Morris Water Maze was performed on Days 1, 4, 7, 14 and 30. Following sarin exposure, 85% of surviving animals demonstrated status epilepticus within 20 min. Each of the anti-convulsant protocols was sufficient to stop convulsions within 1 h of anti-convulsant administration, but all of the animals still showed signs of electrographic status for an additional 2–12 h, without substantial differentiation between treatment groups. However, for post-sarin hours 13–24, the MDZ + highKET group showed significantly less severe EEG abnormalities than the MDZ and KET groups (Mood’s Median Test, p < 0.005). At one month post-exposure, 90% of animals that had received Midazolam alone still showed evidence of some epileptiform activity. In contrast, 90% of animals that had received Midazolam + high dose Ketamine combination therapy had EEG profiles that were within normal limits. This difference in EEG outcomes was highly significant (Mood’s Median Test, p < 0.001). Likewise, on the water maze, the majority of animals that had received Midazolam combined with either high or low dose Ketamine therapy returned to near baseline levels of mnemonic performance within 2 weeks, whereas the majority of the animals that had received midazolam alone or ketamine alone demonstrated persistent and significant memory impairments even at one month postexposure (Mood’s Median Test, p < 0.005). With respect to neuronal necrosis, animals in the MDZ + highKET group showed significantly less overall damage than animals in other treatment groups (Mood’s Median Test, p < 0.001). Of special note were findings in the hippocampus, where only 12% of animals in the MDZ + highKET group showed evidence of necrosis on H&E staining, whereas 100% of animals in the KET group, 70% of animals in the MDZ group, and 40% of animals in the MDZ + lowKET group showed evidence of hippocampal necrosis. Overall, the data demonstrate that Ketamine augmentation of an atropine, 2PAM, and Midazolam standard-ofcare for sarin exposure provides clinically-relevant additional protection against the negative neurobiological consequences of sarin, even when initiation of the anti-convulsant countermeasures is delayed by 50 min.
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.