Individualized spectral filters alleviate persistent photophobia, headaches and migraines in active duty military and Veterans following brain trauma.

PURPOSE: Consistent with association between photophobia and headache, growing evidence suggests an underlying causal relationship between light sensitivity and central pain. We investigated whether an intervention to regulate light sensitivity by filtering only wavelengths causing difficulties for the specific individual could alleviate headaches/migraines resulting from traumatic brain injury (TBI). METHODS: Secondary data analysis of a clinical database including N = 392 military personnel (97% men, 3% women), ranging in age from 20 to 51 years, diagnosed with TBI, persistent headaches/migraines, and light sensitivity. The average elapsed time from TBI diagnosis to intervention was 3 years. Headache/migraine severity, frequency, medication use, and difficulties related to daily functioning were assessed pre and 4-12 weeks post-intervention with individualized spectral filters. RESULTS: Monthly migraine frequency decreased significantly from an average of 14.8 to 1.9, with 74% reporting no migraines post-intervention. Prescription and over-the-counter medication use decreased by more than 70%. Individuals also reported significant improvement in light sensitivity, headaches/migraine severity, and physical and perceptual symptoms. CONCLUSIONS: Wearing individualized spectral filters was associated with symptom relief, increased subjective quality of reported health and well-being, and decreased objective medication use for TBI-related persistent headaches/migraines. These results support a suggested relationship between dysregulated light sensitivity and central regulation of pain.

Exploration of the Impact of Brief Noninvasive Vagal Nerve Stimulation on EEG and Event-Related Potentials.

OBJECTIVES: The primary objective of this study was to explore the impact of noninvasive Vagal Nerve Stimulation (nVNS) on brain electrophysiology, as assessed through spontaneous resting-state EEG and stimulus-driven event-related potentials (ERPs). METHODS: A hand-held transcutaneous stimulator was placed on the neck over the main branch of the left vagus (active condition) or more laterally over neck muscles (sham condition), with two 120-sec long bursts of stimulation applied over a five-minute period. For each of eight neurotypical subjects, prior to stimulation, and then again beginning at 15, 120, and 240 min post-stimulation, ten minutes of background EEG data were collected, along with a series of ERPs-N100 auditory sensory-gating; the N1/P2 loudness dependent auditory evoked responses (LDAER); mismatch negativity; P300a; and P300b. Each subject participated in active and sham stimulation sessions. RESULTS: Brief nVNS had a significant (p < 0.05), and in some cases prolonged (>2 hours), impact on the spontaneous EEG (decreased theta and alpha, and increased beta and gamma), and on sensory gating, LDAER, and P300b evoked responses. Based on prior literature, these specific observations may reflect nVNS-induced modulation of particular neurotransmitter systems including those for GABA (gamma power and frequency); acetylcholine (sensory gating); serotonin (LDAER); and noradrenaline (P300b). CONCLUSIONS: Brief nVNS leads to changes in a sub-set of resting-state and event-related electrophysiologic indices of brain activity. These changes are believed to be mediated by vagal afferent projections to the nucleus of the solitary tract, which in turn regulates several neurotransmitter systems through known direct and indirect neuroanatomic pathways.

The effect of days since last concussion and number of concussions on cognitive functioning in Division I athletes.

OBJECTIVE: Cognitive recovery from sports concussion may be incomplete after resolution of other symptoms. It was hypothesized that independent effects of the number of days since last concussion (Days) and total number of concussions (Number) would predict poorer cognitive functioning. METHODS AND PROCEDURES: Cognition was assessed in an NCAA Division I student-athlete population (n = 87) using the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery. In a MANOVA, the five ImPACT Composite scores were dependent variables, with Group (Concussion, Unaffected) as the independent variable and prior number of concussions (Number) and days since last concussion (Days; 68-2495 days) entered as covariates. OUTCOMES AND RESULTS: The hypothesis that Days and Number would each independently affect cognitive functioning (as assessed by ImPACT Composite scores) was only partly supported. A significant, multivariate, main effect of Days (p = 0.01) indicated that more Days predicted better cognitive functioning overall (p = 0.01). Univariate effects emerged such that more Days specifically predicted better visual memory (p = 0.004) and faster reaction times (p = 0.02). A trend toward a Group*Days*Number three-way interaction for reaction time emerged (p = 0.06), such that smaller Number and more Days each predicted slower reaction time. CONCLUSIONS: Cognitive recovery following sports concussion may take far longer than was previously thought, the aetiology of cognitive reductions may be very complex and the ImPACT appears to be sensitive to subtle changes in cognition across time.

Electroconvulsive Therapy Modulates Loudness Dependence of Auditory Evoked Potentials: A Pilot MEG Study.

Electroconvulsive therapy (ECT) remains a critical intervention for treatment-resistant depression (MDD), yet its neurobiological underpinnings are not fully understood. This pilot study utilizes high-resolution magnetoencephalography (MEG) in nine depressed patients receiving right unilateral ECT, to investigate the changes in loudness dependence of auditory evoked potentials (LDAEP), a proposed biomarker of serotonergic activity, following ECT. We hypothesized that ECT would reduce the LDAEP slope, reflecting enhanced serotonergic neurotransmission. Contrary to this, our findings indicated a significant increase in LDAEP post-ECT ( t 8 = 3.17, p = .013). The increase in LDAEP was not associated with changes in depression severity or cognitive performance, as assessed by the Hamilton Depression Rating Scale (HAMD-24) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We discussed potential mechanisms for the observed increase, including ECT's impact on serotonergic, dopaminergic, glutamatergic, and GABAergic receptor activity, neuroplasticity involving brain-derived neurotrophic factor (BDNF), and inflammation modulators such as TNF- alpha . Our results suggest a complex interaction between ECT and these neurobiological systems, rather than a direct reflection of serotonergic neurotransmission.

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.

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.

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.

Synchrony 2022: Epilepsy and Seizures in Autism Spectrum Disorder Roundtable.

The BRAIN Foundation (Pleasanton, CA, USA) hosted Synchrony 2022, a translational medicine conference focused on research into treatments for individuals with neurodevelopmental disorders (NDD), including those with autism spectrum disorders (ASD) [...].

The role of magnetoencephalography in "nonlesional" epilepsy.

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.

Magnetoencephalography for Mild Traumatic Brain Injury and Posttraumatic Stress Disorder.

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.

Quantitative EEG Biomarkers for Mild Traumatic Brain Injury.

PURPOSE: The development of objective biomarkers for mild traumatic brain injury (mTBI) in the chronic period is an important clinical and research goal. Head trauma is known to affect the mechanisms that support the electrophysiological processing of information within and between brain regions, so methods like quantitative EEG may provide viable indices of brain dysfunction associated with even mTBI. METHODS: Resting-state, eyes-closed EEG data were obtained from 71 individuals with military-related mTBI and 82 normal comparison subjects without traumatic brain injury. All mTBI subjects were in the chronic period of injury (>5 months since the time of injury). Quantitative metrics included absolute and relative power in delta, theta, alpha, beta, high beta, and gamma bands, plus a measure of interhemispheric coherence in each band. Data were analyzed using univariate and multivariate methods, the latter coupled to machine learning strategies. RESULTS: Analyses revealed significant (P < 0.05) group level differences in global relative theta power (increased for mTBI patients), global relative alpha power (decreased for mTBI patients), and global beta-band interhemispheric coherence (decreased for mTBI patients). Single variables were limited in their ability to predict group membership (e.g., mTBI vs. control) for individual subjects, each with a predictive accuracy that was below 60%. In contrast, the combination of a multivariate approach with machine learning methods yielded a composite metric that provided an overall predictive accuracy of 75% for correct classification of individual subjects as coming from control versus mTBI groups. CONCLUSIONS: This study indicates that quantitative EEG methods may be useful in the identification, classification, and tracking of individual subjects with mTBI.

Spatio-temporal reconstruction of bilateral auditory steady-state responses using MEG beamformers.

A rapidly growing number of neuromagnetic studies focus on the analysis of auditory steady-state responses (ASSR) in relation to a diverse array of factors including age, selective attention, and presence of psychopathology. The objectives of these studies require accurate spatio-temporal estimation of the underlying neural generators, a challenging task due to the relatively low signal strength and high correlation between bilateral auditory cortical sources. This paper evaluates the performance of two beamforming schemes that can potentially overcome such difficulties: 1) the linearly constrained minimum variance beamformer with partial sensor coverage (LCMV-PSC), and 2) the multiple constrained minimum-variance beamformer with coherent source region suppression (MCMV-CSRS). Simulation experiments are conducted to assess the impact of source parameters on the reconstruction accuracy. The results indicate that the LCMV-PSC method is prone to localization errors that essentially occur along medio-lateral directions, increase with source depth, and are associated to amplitude and phase distortions of the estimated time courses of activity. Comparatively, the MCMV-CSRS method exhibits precise localization and minimal amplitude and phase distortion for a broad range of relative interferer's positions within the suppression region. The results from the numerical experiments are validated on real magnetoencephalographic (MEG) data collected from a 40-Hz ASSR paradigm.

Addition of ketamine to standard-of-care countermeasures for acute organophosphate poisoning improves neurobiological outcomes.

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.

Diminished auditory sensory gating during active auditory verbal hallucinations.

Auditory sensory gating, assessed in a paired-click paradigm, indicates the extent to which incoming stimuli are filtered, or "gated", in auditory cortex. Gating is typically computed as the ratio of the peak amplitude of the event related potential (ERP) to a second click (S2) divided by the peak amplitude of the ERP to a first click (S1). Higher gating ratios are purportedly indicative of incomplete suppression of S2 and considered to represent sensory processing dysfunction. In schizophrenia, hallucination severity is positively correlated with gating ratios, and it was hypothesized that a failure of sensory control processes early in auditory sensation (gating) may represent a larger system failure within the auditory data stream; resulting in auditory verbal hallucinations (AVH). EEG data were collected while patients (N=12) with treatment-resistant AVH pressed a button to indicate the beginning (AVH-on) and end (AVH-off) of each AVH during a paired click protocol. For each participant, separate gating ratios were computed for the P50, N100, and P200 components for each of the AVH-off and AVH-on states. AVH trait severity was assessed using the Psychotic Symptoms Rating Scales AVH Total score (PSYRATS). The results of a mixed model ANOVA revealed an overall effect for AVH state, such that gating ratios were significantly higher during the AVH-on state than during AVH-off for all three components. PSYRATS score was significantly and negatively correlated with N100 gating ratio only in the AVH-off state. These findings link onset of AVH with a failure of an empirically-defined auditory inhibition system, auditory sensory gating, and pave the way for a sensory gating model of AVH.

Reduced auditory M100 asymmetry in schizophrenia and dyslexia: applying a developmental instability approach to assess atypical brain asymmetry.

Although atypical structural and functional superior temporal gyrus (STG) asymmetries are frequently observed in patients with schizophrenia and individuals with dyslexia, their significance is unclear. One possibility is that atypical asymmetries reflect a general risk factor that can be seen across multiple neurodevelopmental conditions--a risk factor whose origins are best understood in the context of Developmental Instability (DI) theory. DI measures (minor physical anomalies (MPAs) and fluctuating asymmetries (FAs)) reflect perturbation of the genetic plan. The present study sought to assess whether the presence of peripheral indices of DI predicts anomalous functional auditory cortex asymmetry in schizophrenia patients and dyslexia subjects. The location of the auditory M100 response was used as a measure of functional STG asymmetry, as it has been reported that in controls (but not in subjects with schizophrenia or dyslexia) the M100 source location in the right hemisphere is shifted anterior to that seen for the left hemisphere. Whole-brain auditory evoked magnetic field data were successfully recorded from 14 male schizophrenia patients, 21 male subjects with dyslexia, and 16 normal male control subjects. MPA and FA measures were also obtained. Replicating previous studies, both schizophrenia and dyslexia groups showed less M100 asymmetry than did controls. Schizophrenia and dyslexia subjects also had higher MPA scores than normal controls. Although neither total MPA nor FA measures predicted M100 asymmetry, analyses on individual MPA items revealed a relationship between high palate and M100 asymmetry. Findings suggest that M100 positional asymmetry is not a diagnostically specific feature in several neurodevelopmental conditions. Continued research examining DI and brain asymmetry relationships is warranted.

Reconstruction of fetal cardiac vectors from multichannel fMCG data using recursively applied and projected multiple signal classification.

Previous attempts at unequivocal specification of signal strength in fetal magnetocardiographic (fMCG) recordings have used an equivalent current dipole (ECD) to estimate the cardiac vector at the peak of the averaged QRS complex. However, even though the magnitude of fetal cardiac currents are anticipated to be relatively stable, ECD-based estimates of signal strength show substantial and unrealistic variation when comparing results from different time windows of the same recording session. The present study highlights the limitations of the ECD model, and proposes a new methodology for fetal cardiac source reconstruction. The proposed strategy relies on recursive subspace projections to estimate multiple dipoles that account for the distributed myocardial currents. The dipoles are reconstructed from spatio-temporal fMCG data, and are subsequently used to derive estimators of the cardiac vector over the entire QRS. The new method is evaluated with respect to simulated data derived from a model of ventricular depolarization, which was designed to account for the complexity of the fetal cardiac source configuration on the QRS interval. The results show that the present methodology overcomes the drawbacks of conventional ECD fitting, by providing robust estimators of the cardiac vector. Additional evaluation with real fMCG data show fetal cardiac vectors whose morphology closely resembles that obtained in adult MCG.

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.

Functional MRI Evaluation of Multiple Neural Networks Underlying Auditory Verbal Hallucinations in Schizophrenia Spectrum Disorders.

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.

Distinguishing between moving and stationary sources using EEG/MEG measurements with an application to epilepsy.

Performances of electroencephalography (EEG) and magnetoencephalography (MEG) source estimation methods depend on the validity of the assumed model. In many cases, the model structure is related to physical information. We discuss a number of statistical selection methods to distinguish between two possible models using least-squares estimation and assuming a spherical head model. The first model has a single moving source whereas the second has two stationary sources; these may result in similar EEG/MEG measurements. The need to decide between such models occurs for example in Jacksonian seizures (e.g., epilepsy) or in intralobular activities, where a model with either two stationary dipole sources or a single moving dipole source may be possible. We also show that all of the selection methods discussed choose the correct model with probability one when the number of trials goes to infinity. Finally we present numerical examples and compare the performances of the methods by varying parameters such as the signal-to-noise ratio, source depth, and separation of sources, and also apply the methods to real MEG data for epilepsy.