Auditory entrainment of motor responses in older adults with and without Parkinson's disease: An MEG study.

Medical therapies applied to Parkinson's disease (PD) have advanced tremendously since the 1960's based on advances in our understanding of the underlying neurophysiology. Behavioral therapies, such as rhythmic auditory stimulation (RAS), have been developed more recently and demonstrated efficacy. However, the neural mechanisms of RAS are only vaguely understood. In this study, we examined the neurophysiology of RAS using magnetoencephalography (MEG) in a sample of older adults with (21 people) and without PD (23 participants). All participants underwent high-density MEG during a beat-based cued tapping task with rhythmic and non-rhythmic patterns, and the resulting data were analyzed using a Bayesian image reconstruction method. Complex wavelet based time-frequency decomposition was used to compute inter-trial phase locking factor (PLF) to auditory stimuli for left and right signal space projection vectors. Tapping with a rhythm compared to a non-rhythmic sequence resulted in differential brain activity in each group: (i) a greater activation of temporal, motor and parietal areas was found in healthy adults; (ii) a greater reliance on parietal and frontal gyri was found in PD participants. During rhythmic tapping, older adults without PD had significantly stronger neural activity in bilateral frontal, supplementary and primary motor areas compared to those with PD. Conversely, older adults with PD exhibited significantly stronger activity in the bilateral parietal regions, as well as the rolandic operculum and bilateral supramarginal gyri, relative to their healthy peers. These data suggest that RAS mobilizes diverse oscillatory networks; Healthy controls may shift to frontal areas mobilization whereas PD patients rely on parietal areas to a greater extent, which may reflect frontal network dysfunction with compensation in PD, and could serve as specific regions of interest for further RAS studies.

Schizoaffective disorder - a possible MEG auditory evoked field biomarker.

We recorded magnetoencephalographic auditory steady state responses (SSR) from eight schizoaffective (SAD) subjects and compared the resulting data with previously published findings in persons with schizophrenia (SZ) and controls. SAD subjects exhibited SSR responses similar to controls in the left hemisphere and greater than controls in the right hemisphere, whereas SZ subjects exhibited deficits in both amplitude and phase control in both hemispheres. Our findings suggest preservation of GABAergic inhibitory interneuronal control of layer 3 pyramidal cell activity in primary auditory cortex in SAD.

Fluctuation of gamma-band phase synchronization within the auditory cortex in schizophrenia.

OBJECTIVE: To study the phase stability of the 40Hz auditory steady-state response (ASSR) in Sz, and in addition, to investigate inter-hemispheric phase synchronization using ipsilateral and contralateral hemisphere gamma band ASSRs. METHODS: Whole head magnetoencephalography (MEG) was used to detect ASSR from both hemispheres in Sz patients and their control counterparts. Source localization, spatial and temporal filtering were performed to infer gamma band activity from the neural generators of the ASSR. The response gamma band phase stability relative to a reference signal was quantified using the phase synchronization index (PSI). RESULTS: Results indicated reduced phase synchronization of the ASSR and the stimulus reference signal in Sz patients compared to control subjects, in addition to reduced inter-hemispheric phase synchronization between contralateral and ipsilateral hemispheric responses in Sz patients. CONCLUSIONS: Greater intra and inter hemispheric fluctuations of ASSR gamma band phase synchronization in Sz add to previous studies suggesting timing deficiencies within neural populations, possibly caused by impairments of neural network parameters. SIGNIFICANCE: This study provides experimental support that may aid in understanding the dynamics of neural phase synchrony caused by modifications of underlying neurotransmitter systems, as reflected in disease states such as schizophrenia.

MEG auditory evoked fields suggest altered structural/functional asymmetry in primary but not secondary auditory cortex in bipolar disorder.

OBJECTIVES: Objective physiological indices independently characterizing affective and schizophreniform psychoses would contribute to our understanding of the nature of their relationships. Magnetoencephalography (MEG)-based metrics of altered structural/functional asymmetry in the superior temporal gyrus have previously been found to characterize schizophrenia at the level of both the primary auditory (AI) and the secondary auditory (AII) cortex. This study examines these markers in patients with bipolar disorder, with the goal of improved understanding of the patterns of brain asymmetry that may independently characterize affective and schizophreniform psychosis. METHODS: We studied 17 euthymic bipolar subjects and 17 matched controls. Auditory evoked fields were generated by both 40 Hz auditory stimuli eliciting steady state gamma band (SSR), activating the AI cortex, and discrete 1 kHz tone pips, activating the AII cortex. MEG was recorded from the hemisphere contralateral to the ear stimulated using a 37-channel MEG system. Source location estimates were calculated in both left and right hemispheres. Neuroanatomical location estimates for medial Heschl's gyri were determined from magnetic resonance images for correlation with MEG source locations. RESULTS: Bipolar subjects failed to demonstrate normal laterality of SSR AI responses, indicating altered patterns of asymmetry at the level of AI cortex, but demonstrated normal asymmetry of AII responses (right anterior to left). Medial Heschl's gyri centroids were similarly lateralized in both groups, however (right anterior to left), dissociating function from structure in the AI cortex in the bipolar group. CONCLUSIONS: The findings are compatible with altered functional/structural relationships, including diminished left-right hemisphere asymmetry of the AI, but not the AII cortex in bipolar disorder. In schizophrenia, both the AI and AII cortices exhibit such derangements; thus, the findings support both shared and nonshared features of auditory cortical disruption between the two disorders. This functional disorganization may help explain previously reported decreases in amplitude and phase synchrony of SSR gamma band responses in bipolar subjects, suggesting impaired neocortical synchrony in AI, possibly at a cortico-thalamic level, but perhaps not extending to heteromodal association cortex, and may relate to the cognitive impairments found in bipolar disorder.

Cortical gamma generators suggest abnormal auditory circuitry in early-onset psychosis.

Neurobiological theories of schizophrenia and related psychoses have increasingly emphasized impaired neuronal coordination (i.e., dysfunctional connectivity) as central to the pathophysiology. Although neuroimaging evidence has mostly corroborated these accounts, the basic mechanism(s) of reduced functional connectivity remains elusive. In this study, we examine the developmental trajectory and underlying mechanism(s) of dysfunctional connectivity by using gamma oscillatory power as an index of local and long-range circuit integrity. An early-onset psychosis group and a matched cohort of typically developing adolescents listened to monaurally presented click-trains, as whole-head magnetoencephalography data were acquired. Consistent with previous work, gamma-band power was significantly higher in right auditory cortices across groups and conditions. However, patients exhibited significantly reduced overall gamma power relative to controls, and showed a reduced ear-of-stimulation effect indicating that ipsi- versus contralateral presentation had less impact on hemispheric power. Gamma-frequency oscillations are thought to be dependent on gamma-aminobutyric acidergic interneuronal networks, thus these patients' impairment in generating and/or maintaining such activity may indicate that local circuit integrity is at least partially compromised early in the disease process. In addition, patients also showed abnormality in long-range networks (i.e., ear-of-stimulation effects) potentially suggesting that multiple stages along auditory pathways contribute to connectivity aberrations found in patients with psychosis.

Neuromagnetic evidence of broader auditory cortical tuning in schizophrenia.

Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiological imaging research has documented a structure-function disassociation in the auditory system and altered tonotopic mapping in schizophrenia. The present study examined auditory cortical tuning in patients with schizophrenia. Eighteen patients with schizophrenia and 15 comparison subjects were recorded in a magnetoencephalographic (MEG) experiment of auditory tuning. Auditory cortical tuning at 1 kHz was examined by delivering 1 kHz pure tones in conjunction with pure tones at 5 frequencies surrounding and including 1 kHz. Source reconstruction data were examined for evidence of frequency specificity for the M100 component. There was a significant broadening of tuning in the schizophrenia group evident for the source amplitude of the M100. The frequently reported reduction in anterior-posterior source asymmetry for individuals with schizophrenia was replicated in this experiment. No relationships between symptom severity ratings and MEG measures were observed. This finding suggests that the frequency specificity of the M100 auditory evoked field is disturbed in schizophrenia, and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks.

Children and adolescents with autism exhibit reduced MEG steady-state gamma responses.

BACKGROUND: Recent neuroimaging studies of autism have indicated reduced functional connectivity during both cognitive tasks and rest. These data suggest long-range connectivity may be compromised in this disorder, and current neurological theories of autism contend disrupted inter-regional interactions may be an underlying mechanism explaining behavioral symptomatology. However, it is unclear whether deficient neuronal communication is attributable to fewer long-range tracts or more of a local deficit in neural circuitry. This study examines the integrity of local circuitry by focusing on gamma band activity in auditory cortices of children and adolescents with autism. METHODS: Ten children and adolescents with autism and 10 matched controls participated. Both groups listened to 500 ms duration monaural click trains with a 25 ms inter-click interval, as magnetoencephalography was acquired from the contralateral hemisphere. To estimate 40 Hz spectral power density, we performed time-frequency decomposition of the single-trial magnetic steady-state response data using complex demodulation. RESULTS: Children and adolescents with autism exhibited significantly reduced left hemispheric 40 Hz power from 200-500 ms post-stimulus onset. In contrast, no significant between group differences were observed for right hemispheric cortices. CONCLUSIONS: The production and/or maintenance of left hemispheric gamma oscillations appeared abnormal in participants with autism. We interpret these data as indicating that in autism, particular brain regions may be unable to generate the high-frequency activity likely necessary for binding and other forms of inter-regional interactions. These findings augment connectivity theories of autism with novel evidence that aberrations in local circuitry could underlie putative deficiencies in long-range neural communication.

Development of the 40Hz steady state auditory evoked magnetic field from ages 5 to 52.

OBJECTIVE: Adults exhibit strong auditory 40 Hz magnetic steady state responses (SSR). Although EEG measured SSR has been studied in children, the developmental course of the magnetic SSR is unknown. METHODS: Sixty-nine healthy subjects ranging in age from 5 to 52 years participated in a magnetoencephalographic (MEG) study. Stimuli were monaural 500 ms duration click trains with a 25 ms inter-click interval. Contralateral magnetic responses for both hemispheres were recorded with a 37-channel MEG system. Responses were averaged and examined using wavelet-based time-frequency analysis. Source analyses were also conducted on a subset of the data. RESULTS: Gamma power from 200 to 500 ms post-stimulus onset was computed and was significantly related to subject age in both hemispheres. Hemispheric asymmetry was observed for the anterior-posterior SSR source locations, suggestive of asymmetry similar to that previously described for the SSR and other auditory evoked magnetic field components. CONCLUSIONS: The 40 Hz power findings are generally consistent with previous EEG studies of steady state responses in children showing age-related changes in the 40 Hz SSR. SIGNIFICANCE: Age-related changes in the strength of the magnetic 40 Hz SSR may continue to develop well beyond early childhood, which should be taken into consideration in planning future studies using adolescents and young adults.