Magnetoencephalographic Imaging Research Articles

Impaired speaking-induced suppression in schizophrenia predicts auditory verbal hallucinations.

A successful efference copy self-prediction suppresses auditory signals in the primary auditory cortex (A1) is necessary for speakers to successfully compare auditory feedback during speech production with auditory feedback during passive listening, this is called speaker-induced suppression (SIS). The top-rank positive symptom in schizophrenic (SZ) patients, auditory verbal hallucination, for instance, is hypothesized to relate to failure to distinguish the internal voice and external sounds, and this deficit is thought to be associated with impaired self-prediction in comparing external and self-generated contents. In this magnetoencephalographic imaging (MEGI) study, we compared SIS M100 in the primary auditory cortex (A1) between the healthy controls (HC; N = 30) and SZ patients (N = 22). The SZ patients displayed reduced SIS and M100 in the A1, and this impairment is negatively correlated with auditory hallucinations. These outcomes suggest that the SZ patients' hallucinatory symptoms are caused by misattribution between the external and self-generated stimuli. We proposed that the weakened self-agency and neural oscillations may lead to this misattribution.

Clinical markers of HIV predict redox-regulated neural and behavioral function in the sensorimotor system

Even in the modern era of combination antiretroviral therapy, aberrations in motor control remain a predominant symptom contributing to age-related functional dependencies (e.g., neurocognitive impairment) in people with HIV (PWH). While recent evidence implicates aberrant mitochondrial redox environments in the modulation of neural oscillatory activity serving motor control in PWH, the contribution of important clinical and demographic factors on this bioenergetic-neural-behavioral pathway is unknown. Herein, we evaluate the predictive capacity of clinical metrics pertinent to HIV (e.g., CD4 nadir, time with viremia) and age on mitochondrial redox-regulated sensorimotor brain-behavior dynamics in 69 virally-suppressed PWH. We used state-of-the-art systems biology and neuroscience approaches, including Seahorse analyzer of mitochondrial energetics, EPR spectroscopy of intracellular oxidant levels, antioxidant activity assays pertinent to superoxide and hydrogen peroxide (H2O2) redox environments, and magnetoencephalographic (MEG) imaging to quantify sensorimotor oscillatory dynamics. Our results demonstrate differential effects of redox systems on the neural dynamics serving motor function in PWH. In addition, measures of immune stability and duration of compromise due to HIV had dissociable effects on this pathway, above and beyond the effects of age alone. Moreover, peripheral measures of antioxidant activity (i.e., superoxide dismutase) fully mediated the relationship between immune stability and current behavioral performance, indicative of persistent oxidative environments serving motor control in the presence of virologic suppression. Taken together, our data suggest that disease-related factors, in particular, are stronger predictors of current redox, neural and behavioral profiles serving motor function, which may serve as effective targets for alleviating HIV-specific alterations in cognitive-motor function in the future.

Disruption of Sensorimotor Cortical Oscillations by Visual Interference Predicts the Altered Motor Performance of Persons with Cerebral Palsy

Emerging evidence indicates that aberrations in sensorimotor cortical oscillations likely play a key role in uncharacteristic motor actions seen in cerebral palsy. This interpretation is largely centered on the assumption that the aberrant cortical oscillations primarily reflect the motor aspects, with less consideration of possible higher-order cognitive connections. To directly probe this view, we examined the impact of cognitive interference on the sensorimotor cortical oscillations seen in persons with cerebral palsy using magnetoencephalography. Persons with cerebral palsy (N = 26, 9–47 years old) and controls (N = 46, 11–49 years) underwent magnetoencephalographic imaging while completing an arrow-based version of the Eriksen flanker task. Structural equation modeling was used to evaluate the relationship between the extent of interference generated by the flanker task and the strength of the sensorimotor cortical oscillations and motor performance. Our results indicated that the impact of cognitive interference on beta and gamma oscillations moderated the interference effect on reaction times in persons with cerebral palsy, above and beyond that seen in controls. Overall, these findings suggest that alterations in sensorimotor oscillatory activity in those with cerebral palsy at least partly reflects top-down control influences on the motor system. Thus, suppression of distracting stimuli should be a consideration when evaluating altered motor actions in cerebral palsy.

Women with more severe premenstrual syndrome have an enhanced anticipatory reward processing: a magnetoencephalography study.

Laboratory studies reveal that young women with premenstrual syndrome (PMS) often exhibit decreased reward processing during the late luteal phase. However, studies based on the self-reports find opposite results (e.g., higher craving for high-sweet-fat food). These differences may lie in the difference between the stimulus used and measuring the different aspects of the reward. The present study was designed to expand previous work by using a classic monetary reward paradigm, simultaneously examining the motivational (i.e., reward anticipation, "wanting") and emotional (i.e., reward outcome, "liking") components of reward processing in women with high premenstrual symptoms (High PMS). College female students in their early twenties with High PMS (n = 20) and low premenstrual symptoms (Low PMS, n = 20) completed a monetary incentive delay task during their late luteal phase when the premenstrual symptoms typically peak. Brain activities in the reward anticipation phase and outcome phase were recorded using the magnetoencephalographic (MEG) imaging technique. No group differences were found in various behavioral measurements. For the MEG results, in the anticipation phase, when High PMS participants were presented with cues that predicted the upcoming monetary gains, they showed higher event-related magnetic fields (ERFs) than when they were presented with neutral non-reward cues. This pattern was reversed in Low PMS participants, as they showed lower reward cue-elicited ERFs than non-reward cue-elicited ones (cluster mass = 2560, cluster size = 891, p = .03, corrected for multiple comparisons), mainly in the right medial orbitofrontal and lateral orbitofrontal cortex (cluster mass = 375, cluster size = 140, p = .03, corrected for multiple comparisons). More importantly, women with High PMS had an overall significantly higher level of ERFs than women with Low PMS (cluster mass = 8039, cluster size = 2937, p = .0009, corrected for multiple comparisons) in the bilateral precentral gyrus, right postcentral gyrus, and left superior temporal gyrus (right: cluster mass = 410, cluster size = 128, p = .03; left: cluster mass = 352, cluster size = 98, p = .05; corrected for multiple comparisons). In the outcome phase, women with High PMS showed significantly lower theta power than the Low PMS ones for the expected non-reward feedback in the bilateral temporal-parietal regions (cluster mass = 47620, cluster size = 18308, p = .01, corrected for multiple comparisons). These findings reveal that the severity of PMS might alter reward anticipation. Specifically, women with High PMS displayed increased brain activities to reward-predicting cues and increased action preparation after the cues appear.

Distinct neurophysiology during nonword repetition in logopenic and non-fluent variants of primary progressive aphasia.

Overlapping clinical presentations in primary progressive aphasia (PPA) variants present challenges for diagnosis and understanding pathophysiology, particularly in the early stages of the disease when behavioral (speech) symptoms are not clearly evident. Divergent atrophy patterns (temporoparietal degeneration in logopenic variant lvPPA, frontal degeneration in nonfluent variant nfvPPA) can partially account for differential speech production errors in the two groups in the later stages of the disease. While the existing dogma states that neurodegeneration is the root cause of compromised behavior and cortical activity in PPA, the extent to which neurophysiological signatures of speech dysfunction manifest independent of their divergent atrophy patterns remain unknown. We test the hypothesis that nonword deficits in lvPPA and nfvPPA arise from distinct patterns of neural oscillations that are unrelated to atrophy. We use a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations during a non-word repetition task with voxel-based morphometry-derived measures of gray matter volume to isolate neural oscillation abnormalities independent of atrophy. We find reduced beta band neural activity in left temporal regions associated with the late stages of auditory encoding unique to patients with lvPPA and reduced high-gamma neural activity over left frontal regions associated with the early stages of motor preparation in patients with nfvPPA. Neither of these patterns of reduced cortical oscillations was explained by cortical atrophy in our statistical model. These findings highlight the importance of structure-function imaging in revealing neurophysiological sequelae in early stages of dementia when neither structural atrophy nor behavioral deficits are clinically distinct.

Mitochondrial redox environments predict sensorimotor brain-behavior dynamics in adults with HIV

Despite virologic suppression, people living with HIV (PLWH) remain at risk for developing cognitive impairment, with aberrations in motor control being a predominant symptom leading to functional dependencies in later life. While the neuroanatomical bases of motor dysfunction have recently been illuminated, the underlying molecular processes remain poorly understood. Herein, we evaluate the predictive capacity of the mitochondrial redox environment on sensorimotor brain-behavior dynamics in 40 virally-suppressed PLWH and 40 demographically-matched controls using structural equation modeling. We used state-of-the-art approaches, including Seahorse Analyzer of mitochondrial function, electron paramagnetic resonance spectroscopy to measure superoxide levels, antioxidant activity assays and dynamic magnetoencephalographic imaging to quantify sensorimotor oscillatory dynamics. We observed differential modulation of sensorimotor brain-behavior relationships by superoxide and hydrogen peroxide-sensitive features of the redox environment in PLWH, while only superoxide-sensitive features were related to optimal oscillatory response profiles and better motor performance in controls. Moreover, these divergent pathways may be attributable to immediate, separable mechanisms of action within the redox environment seen in PLWH, as evidenced by mediation analyses. These findings suggest that mitochondrial redox parameters are important modulators of healthy and pathological oscillations in motor systems and behavior, serving as potential targets for remedying HIV-related cognitive-motor dysfunction in the future.

N400 correlate of brand associations

A number of neuromarketing studies employed brain responses called event-related potentials or ERPs as neural markers of brand associations. The use of the N400 component of ERPs in particular appeared to be the promising to study typicality of product-brand associations and their role for brand extension (Wang et al., 2012). The question, however, remains whether the N400 observed in the product-brand associations and brand associations as such can be explained by the same neurobiological mechanisms as the classical N400 response which in the neuroscience of language reflects semantic associations. In this electroencephalographic study, we compared semantic N400 in response to incongruency of sentence endings with the neural response to the degree of incongruency of associations to brands. To test, whether in the same subjects, incongruent brand associations would elicit the N400 brain response resembling semantic N400 we constructed two-word phrases in which brand names were proceeded by congruent or incongruent adjectives that played the role of brand associations. Sentences lacking any marketing context served as control stimuli and evoked classical centro-parietally distributed N400 response. The sensitivity of the brain activity to the incongruent brand associations was manifested in the fronto-centrally distributed N400 response within the same time window as in the non-marketing context. However, the correlation analysis of the N400 amplitudes in the brand and non-brand conditions did not reveal significant association between them suggesting different neuronal networks subserving processing of pure semantic and brand-association incongruences. To conclude, further studies employing multichannel EEG or magnetoencephalographic imaging would be necessary to elucidate the brain origin of brand and marketing associations as compared to pure semantic associations.

Altered spontaneous cortical activity predicts pain perception in individuals with cerebral palsy.

Cerebral palsy is the most common paediatric neurological disorder and results in extensive impairment to the sensorimotor system. However, these individuals also experience increased pain perception, resulting in decreased quality of life. In the present study, we utilized magnetoencephalographic brain imaging to examine whether alterations in spontaneous neural activity predict the level of pain experienced in a cohort of 38 individuals with spastic diplegic cerebral palsy and 67 neurotypical controls. Participants completed 5 min of an eyes closed resting-state paradigm while undergoing a magnetoencephalography recording. The magnetoencephalographic data were then source imaged, and the power within the delta (2–4 Hz), theta (5–7 Hz), alpha (8–12 Hz), beta (15–29 Hz), low gamma (30–59 Hz) and high gamma (60–90 Hz) frequency bands were computed. The resulting power spectral density maps were analysed vertex-wise to identify differences in spontaneous activity between groups. Our findings indicated that spontaneous cortical activity was altered in the participants with cerebral palsy in the delta, alpha, beta, low gamma and high gamma bands across the occipital, frontal and secondary somatosensory cortical areas (all pFWE < 0.05). Furthermore, we also found that the altered beta band spontaneous activity in the secondary somatosensory cortices predicted heightened pain perception in the individuals with cerebral palsy (P = 0.039). Overall, these results demonstrate that spontaneous cortical activity within individuals with cerebral palsy is altered in comparison to their neurotypical peers and may predict increased pain perception in this patient population. Potentially, changes in spontaneous resting-state activity may be utilized to measure the effectiveness of current treatment approaches that are directed at reducing the pain experienced by individuals with cerebral palsy.

Virtual intracranial EEG signals reconstructed from MEG with potential for epilepsy surgery

Modelling the interactions that arise from neural dynamics in seizure genesis is challenging but important in the effort to improve the success of epilepsy surgery. Dynamical network models developed from physiological evidence offer insights into rapidly evolving brain networks in the epileptic seizure. A limitation of previous studies in this field is the dependence on invasive cortical recordings with constrained spatial sampling of brain regions that might be involved in seizure dynamics. Here, we propose virtual intracranial electroencephalography (ViEEG), which combines non-invasive ictal magnetoencephalographic imaging (MEG), dynamical network models and a virtual resection technique. In this proof-of-concept study, we show that ViEEG signals reconstructed from MEG alone preserve critical temporospatial characteristics for dynamical approaches to identify brain areas involved in seizure generation. We show the non-invasive ViEEG approach may have some advantage over intracranial electroencephalography (iEEG). Future work may be designed to test the potential of the virtual iEEG approach for use in surgical management of epilepsy.

Impact of HIV-infection on human somatosensory processing, spontaneous cortical activity, and cortical thickness: A multimodal neuroimaging approach.

HIV‐infection has been associated with widespread alterations in brain structure and function, although few studies have examined whether such aberrations are co‐localized and the degree to which clinical and cognitive metrics are related. We examine this question in the somatosensory system using high‐resolution structural MRI (sMRI) and magnetoencephalographic (MEG) imaging of neural oscillatory activity. Forty‐four participants with HIV (PWH) and 55 demographically‐matched uninfected controls completed a paired‐pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. MEG data were transformed into the time‐frequency domain; significant sensor level responses were imaged using a beamformer. Virtual sensor time series were derived from the peak responses. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. The T1‐weighted sMRI data were processed using morphological methods to derive cortical thickness values across the brain. From these, the cortical thickness of the tissue coinciding with the peak response was estimated. Our findings indicated both PWH and control exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls. Follow‐up analyses indicated that the reduction in cortical thickness was significantly correlated with CD4 nadir and mediated the relationship between HIV and spontaneous cortical activity within the left postcentral gyrus. These data indicate that PWH have abnormally strong spontaneous cortical activity in the left postcentral gyrus and such elevated activity is driven by locally reduced cortical gray matter thickness.

MEG signatures of long-term effects of agreement and disagreement with the majority

People often change their beliefs by succumbing to an opinion of others. Such changes are often referred to as effects of social influence. While some previous studies have focused on the reinforcement learning mechanisms of social influence or on its internalization, others have reported evidence of changes in sensory processing evoked by social influence of peer groups. In this study, we used magnetoencephalographic (MEG) source imaging to further investigate the long-term effects of agreement and disagreement with the peer group. The study was composed of two sessions. During the first session, participants rated the trustworthiness of faces and subsequently learned group rating of each face. In the first session, a neural marker of an immediate mismatch between individual and group opinions was found in the posterior cingulate cortex, an area involved in conflict-monitoring and reinforcement learning. To identify the neural correlates of the long-lasting effect of the group opinion, we analysed MEG activity while participants rated faces during the second session. We found MEG traces of past disagreement or agreement with the peers at the parietal cortices 230 ms after the face onset. The neural activity of the superior parietal lobule, intraparietal sulcus, and precuneus was significantly stronger when the participant’s rating had previously differed from the ratings of the peers. The early MEG correlates of disagreement with the majority were followed by activity in the orbitofrontal cortex 320 ms after the face onset. Altogether, the results reveal the temporal dynamics of the neural mechanism of long-term effects of disagreement with the peer group: early signatures of modified face processing were followed by later markers of long-term social influence on the valuation process at the ventromedial prefrontal cortex.

Motor beta cortical oscillations are related with the gait kinematics of youth with cerebral palsy.

ObjectiveIt is widely believed that the perinatal brain injuries seen in youth with cerebral palsy (CP) impact neuronal processing of sensory information and the production of leg motor actions during gait. However, very limited efforts have been made to evaluate the connection between neural activity within sensorimotor networks and the altered spatiotemportal gait biomechanics seen in youth with CP. The objective of this investigation was to use magnetoencephalographic (MEG) brain imaging and biomechanical analysis to probe this connection.MethodsWe examined the cortical beta oscillations serving motor control of the legs in a cohort of youth with CP (N = 20; Age = 15.5 ± 3 years; GMFCS levels I‐III) and healthy controls (N = 15; Age = 14.1 ± 3 years) using MEG brain imaging and a goal‐directed isometric knee target‐matching task. Outside the scanner, a digital mat was used to quantify the spatiotemporal gait biomechanics.ResultsOur MEG imaging results revealed that the participants with CP exhibited stronger sensorimotor beta oscillations during the motor planning and execution stages compared to the controls. Interestingly, we also found that those with the strongest sensorimotor beta oscillations during motor execution also tended to walk slower and have a reduced cadence.InterpretationThese results fuel the impression that the beta sensorimotor cortical oscillations that underlie leg musculature control may play a central role in the altered mobility seen in youth with CP.

Prefrontal gating of sensory input differentiates cognitively impaired and unimpaired aging adults with HIV.

Despite effective therapies that have extended the life expectancy of persons living with HIV, 35–70% of these adults still develop some form of cognitive impairment, and with a growing population of aging adults with HIV, the prevalence of these cognitive deficits is likely to increase. The mechanisms underlying these HIV-associated neurocognitive disorders remain poorly understood but are often accelerated by the aging process and accompanied by disturbances in sensory processing, which may contribute to the observed cognitive decline. The goal of the current study was to identify the impact of aging on HIV-related alterations in inhibitory processing and determine whether such alterations are related to cognitive impairment in neuroHIV. We used magnetoencephalographic imaging, advanced time series analysis methods, and a paired-pulse stimulation paradigm to interrogate inhibitory processing in 87 HIV-infected aging adults and 92 demographically matched uninfected controls (22–72 years old). Whole-brain maps linking age and neural indices were computed for each group and compared via Fisher’s Z transformations. Peak voxel time-series data were also extracted from the resulting images to quantify the dynamics of spontaneous neural activity preceding stimulation onset in each group. Whole-brain analyses using the somatosensory gating index, a metric of inhibitory processing and age distinguished impaired adults with HIV from unimpaired HIV-infected adults and controls. Briefly, younger cognitively impaired adults with HIV strongly utilized the prefrontal cortices to gate somatosensory input, and the role of this region in gating was uniquely and significantly modulated by aging only in impaired adults with HIV. Spontaneous neural activity preceding stimulus onset was also significantly elevated in the prefrontal cortices of those with HIV-associated neurocognitive disorder, and this elevation was significantly related to the CD4 nadir across both HIV-infected groups. This is the first study to examine the impact of aging on inhibitory processing in HIV-infected adults with and without cognitive impairment. Our findings suggest that young adults with HIV-associated neurocognitive disorder utilize the prefrontal cortices to gate (i.e. suppress) redundant somatosensory input, and that this capacity uniquely diminishes with advancing age in impaired adults with HIV.

Optimizing Magnetoencephalographic Imaging Estimation of Language Lateralization for Simpler Language Tasks.

Magnetoencephalographic imaging (MEGI) offers a non-invasive alternative for defining preoperative language lateralization in neurosurgery patients. MEGI indeed can be used for accurate estimation of language lateralization with a complex language task – auditory verb generation. However, since language function may vary considerably in patients with focal lesions, it is important to optimize MEGI for estimation of language function with other simpler language tasks. The goal of this study was to optimize MEGI laterality analyses for two such simpler language tasks that can have compliance from those with impaired language function: a non-word repetition (NWR) task and a picture naming (PN) task. Language lateralization results for these two tasks were compared to the verb-generation (VG) task. MEGI reconstruction parameters (regions and time windows) for NWR and PN were first defined in a presurgical training cohort by benchmarking these against laterality indices for VG. Optimized time windows and regions of interest (ROIs) for NWR and PN were determined by examining oscillations in the beta band (12–30 Hz) a marker of neural activity known to be concordant with the VG laterality index (LI). For NWR, additional ROIs include areas MTG/ITG and for both NWR and PN, the postcentral gyrus was included in analyses. Optimal time windows for NWR were defined as 650–850 ms (stimulus-locked) and −350 to −150 ms (response-locked) and for PN −450 to −250 ms (response-locked). To verify the optimal parameters defined in our training cohort for NWR and PN, we examined an independent validation cohort (n = 30 for NWR, n = 28 for PN) and found high concordance between VG laterality and PN laterality (82%) and between VG laterality and NWR laterality (87%). Finally, in a test cohort (n = 8) that underwent both the intracarotid amobarbital procedure (IAP) test and MEG for VG, NWR, and PN, we identified excellent concordance (100%) with IAP for VG + NWR + PN composite LI, high concordance for PN alone (87.5%), and moderate concordance for NWR alone (66.7%). These findings provide task options for non-invasive language mapping with MEGI that can be calibrated for language abilities of individual patients. Results also demonstrate that more accurate estimates can be obtained by combining laterality estimates obtained from multiple tasks. MEGI

Neurophysiological signatures in Alzheimer's disease are distinctly associated with TAU, amyloid-β accumulation, and cognitive decline.

Neural synchrony is intricately balanced in the normal resting brain but becomes altered in Alzheimer's disease (AD). To determine the neurophysiological manifestations associated with molecular biomarkers of AD neuropathology, in patients with AD, we used magnetoencephalographic imaging (MEGI) and positron emission tomography with amyloid-beta (Aβ) and TAU tracers. We found that alpha oscillations (8 to 12 Hz) were hyposynchronous in occipital and posterior temporoparietal cortices, whereas delta-theta oscillations (2 to 8 Hz) were hypersynchronous in frontal and anterior temporoparietal cortices, in patients with AD compared to age-matched controls. Regional patterns of alpha hyposynchrony were unique in each neurobehavioral phenotype of AD, whereas the regional patterns of delta-theta hypersynchrony were similar across the phenotypes. Alpha hyposynchrony strongly colocalized with TAU deposition and was modulated by the degree of TAU tracer uptake. In contrast, delta-theta hypersynchrony colocalized with both TAU and Aβ depositions and was modulated by both TAU and Aβ tracer uptake. Furthermore, alpha hyposynchrony but not delta-theta hypersynchrony was correlated with the degree of global cognitive dysfunction in patients with AD. The current study demonstrates frequency-specific neurophysiological signatures of AD pathophysiology and suggests that neurophysiological measures from MEGI are sensitive indices of network disruptions mediated by TAU and Aβ and associated cognitive decline. These findings facilitate the pursuit of novel therapeutic approaches toward normalizing network synchrony in AD.

Altered functional connectivity between primary and secondary somatosensory areas in panic disorder

Disturbance in the interpretation of bodily sensation has been widely reported in patients with panic disorder (PD). However, it remains substantially unknown whether patients with PD exhibit any defect in cortical somatosensory processing of non-threatening stimuli. Thus, the present study aimed to examine the functional integrity of the cortical somatosensory system in patients with PD using neurophysiological recordings. A total of 20 patients with PD and 20 healthy controls (HC) were recruited to investigate the cortical responses to median nerve stimulation through whole-head magnetoencephalographic (MEG) imaging. To comprehensively investigate all somatosensory functioning, we studied the regional activation of the primary somatosensory cortex (SI), contralateral (SIIc), and ipsilateral (SIIi) secondary somatosensory cortices, as well as functional connectivity among the SI, SIIc, and SIIi in alpha, beta, and gamma frequency bands. We found that patients with PD demonstrated a reduction in SI activity compared with those in the HC group. Furthermore, a significantly weaker gamma-band functional connectivity between SI and SIIc was found in the PD group relative to the HC group. Our data suggest that patients with PD exhibit abnormal responses to non-threatening (i.e., pain-free) stimuli in the cortical somatosensory system.

Sensorimotor Cortical Oscillations during Movement Preparation in 16p11.2 Deletion Carriers.

Sensorimotor deficits are prevalent in many neurodevelopmental disorders like autism, including one of its common genetic etiologies, a 600 kb reciprocal deletion/duplication at 16p11.2. We have previously shown that copy number variations of 16p11.2 impact regional brain volume, white matter integrity, and early sensory responses in auditory cortex. Here, we test the hypothesis that abnormal cortical neurophysiology is present when genes in the 16p11.2 region are haploinsufficient, and in humans that this in turn may account for behavioral deficits specific to deletion carriers. We examine sensorimotor cortical network activity in males and females with 16p11.2 deletions compared with both typically developing individuals, and those with duplications of 16p11.2, using magnetoencephalographic imaging during preparation of overt speech or hand movements in tasks designed to be easy for all participants. In deletion carriers, modulation of beta oscillations (12-30 Hz) were increased during both movement types over effector-specific regions of motor cortices compared with typically developing individuals or duplication carriers, with no task-related performance differences between cohorts, even when corrected for their own cognitive and sensorimotor deficits. Reduced left hemispheric language specialization was observed in deletion carriers but not in duplication carriers. Neural activity over sensorimotor cortices in deletion carriers was linearly related to clinical measures of speech and motor impairment. These findings link insufficient copy number repeats at 16p11.2 to excessive neural activity (e.g., increased beta oscillations) in motor cortical networks for speech and hand motor control. These results have significant implications for understanding the neural basis of autism and related neurodevelopmental disorders.SIGNIFICANCE STATEMENT The recurrent ∼600 kb deletion at 16p11.2 (BP4-BP5) is one of the most common genetic etiologies of ASD and, more generally, of neurodevelopmental disorders. Here, we use high-resolution magnetoencephalographic imaging (MEG-I) to define with millisecond precision the underlying neurophysiological signature of motor impairments for individuals with 16p11.2 deletions. We identify significant increases in beta (12-30 Hz) suppression in sensorimotor cortices related to performance during speech and hand movement tasks. These findings not only provide a neurophysiological phenotype for the clinical presentation of this genetic deletion, but also guide our understanding of how genetic variation encodes for neural oscillatory dynamics.

Beta-band activity in medial prefrontal cortex predicts source memory encoding and retrieval accuracy

Reality monitoring is defined as the ability to distinguish internally self-generated information from externally-derived information. The medial prefrontal cortex (mPFC) is a key brain region subserving reality monitoring and has been shown to be activated specifically during the retrieval of self-generated information. However, it is unclear if mPFC is activated during the encoding of self-generated information into memory. If so, it is important to understand whether successful retrieval of self-generated information critically depends on enhanced neural activity within mPFC during initial encoding of this self-generated information. We used magnetoencephalographic imaging (MEGI) to determine the timing and location of cortical activity during a reality-monitoring task involving self generated contextual source memory encoding and retrieval. We found both during encoding and retrieval of self-generated information, when compared to externally-derived information, mPFC showed significant task induced oscillatory power modulation in the beta-band. During initial encoding of self-generated information, greater mPFC beta-band power reductions occurred within a time window of −700 ms to −500 ms prior to vocalization. This increased activity in mPFC was not observed during encoding of externally-derived information. Additionally, increased mPFC activity during encoding of self-generated information predicted subsequent retrieval accuracy of this self-generated information. Beta-band activity in mPFC was also observed during the initial retrieval of self-generated information within a time window of 300 to 500 ms following stimulus onset and correlated with accurate retrieval performance of self-generated information. Together, these results further highlight the importance of mPFC in mediating the initial generation and awareness of participants’ internal thoughts.

Neural correlates of abnormal auditory feedback processing during speech production in Alzheimer\u2019s disease

Accurate integration of sensory inputs and motor commands is essential to achieve successful behavioral goals. A robust model of sensorimotor integration is the pitch perturbation response, in which speakers respond rapidly to shifts of the pitch in their auditory feedback. In a previous study, we demonstrated abnormal sensorimotor integration in patients with Alzheimer’s disease (AD) with an abnormally enhanced behavioral response to pitch perturbation. Here we examine the neural correlates of the abnormal pitch perturbation response in AD patients, using magnetoencephalographic imaging. The participants phonated the vowel /α/ while a real-time signal processor briefly perturbed the pitch (100 cents, 400 ms) of their auditory feedback. We examined the high-gamma band (65–150 Hz) responses during this task. AD patients showed significantly reduced left prefrontal activity during the early phase of perturbation and increased right middle temporal activity during the later phase of perturbation, compared to controls. Activity in these brain regions significantly correlated with the behavioral response. These results demonstrate that impaired prefrontal modulation of speech-motor-control network and additional recruitment of right temporal regions are significant mediators of aberrant sensorimotor integration in patients with AD. The abnormal neural integration mechanisms signify the contribution of cortical network dysfunction to cognitive and behavioral deficits in AD.

Altered motor dynamics in type 1 diabetes modulate behavioral performance.

Type 1 diabetes (T1D) has been linked to alterations in both brain structure and function. However, the neural basis of the most commonly reported neuropsychological deficit in T1D, psychomotor speed, remains severely understudied. To begin to address this, the current study focuses on the neural dynamics underlying motor control using magnetoencephalographic (MEG) imaging. Briefly, 40 young adults with T1D who were clear of common comorbidities (e.g., vascular disease, retinopathy, etc.) and a demographically-matched group of 40 controls without T1D completed an arrow-based flanker movement task during MEG. The resulting signals were examined in the time-frequency domain and imaged using a beamforming approach, and then voxel time series were extracted from peak responses to evaluate the dynamics. The resulting time series were statistically examined for group and conditional effects using a rigorous permutation testing approach. Our primary hypothesis was that participants with T1D would have altered beta and gamma oscillatory dynamics within the primary motor cortex during movement, and that these alterations would reflect compensatory processing to maintain adequate performance. Our results indicated that the group with T1D had a significantly stronger post-movement beta rebound (PMBR) contralateral to movement compared to controls, and a smaller neural flanker effect (i.e., difference in neural activity between conditions). In addition, a significant group-by-condition interaction was observed in the ipsilateral beta event-related desynchronization (bERD) and the ipsilateral PMBR. We also examined the relationship between oscillatory motor response amplitude and reaction time, finding a differential effect of the driving oscillatory responses on behavioral performance by group. Overall, our findings suggest compensatory activity in the motor cortices is detectable early in the disease in a relatively healthy sample of adults with T1D. Future studies are needed to examine how these subtle effects on neural activity in young, otherwise healthy patients affect outcomes in aging.