William Gaetz

Post-movement beta rebound is generated in motor cortex: evidence from neuromagnetic recordings.

Voluntary movements are accompanied by amplitude changes in cortical rhythms presumably as a result of functional activation of sensorimotor areas. Recently, the location of the neural generators involved in increasing power within the beta (15-30 Hz) frequency band following movement (post-movement beta rebound, PMBR) has come into question [Parkes, L.M, Bastiaansen, M.C.M, Norris, D.G., 2006. Combining EEG and fMRI to investigate the post-movement beta rebound. NeuroImage 29, 685-696.]. We used the synthetic aperture magnetometry (SAM) spatial filtering method to identify the time course and location of oscillatory changes within the beta and mu (8-14 Hz) frequency bands during the performance of voluntary movements. Neuromagnetic activity was recorded from 10 adult subjects during abduction of the right index finger. Changes in beta and mu source power were calculated for periods during and following movement, relative to pre-movement baseline activity. Decreases in beta band activity (event-related desynchronization, ERD) were observed during movement, with a strong increase (PMBR) beginning 230+/-170 ms following movement, lasting for 680+/-170 ms. Mu band ERD was observed both during and following movement, with little to no post-movement rebound. Beta and mu ERD were localized bilaterally to the hand region of postcentral gyrus whereas PMBR was localized bilaterally to the hand region of precentral gyrus (motor cortex). Both PMBR and beta ERD were strongest contralateral to the side of movement. These results provide further evidence that movement influences independent cortical rhythms in sensorimotor areas, and confirm previous reports of precentral generators of PMBR in the region of motor cortex, with postcentral generators of beta and mu ERD during movement.

Spatiotemporal mapping of cortical activity accompanying voluntary movements using an event-related beamforming approach.

We describe a novel spatial filtering approach to the localization of cortical activity accompanying voluntary movements. The synthetic aperture magnetometry (SAM) minimum‐variance beamformer algorithm was used to compute spatial filters three‐dimensionally over the entire brain from single trial neuromagnetic recordings of subjects performing self‐paced index finger movements. Images of instantaneous source power (“event‐related SAM”) computed at selected latencies revealed activation of multiple cortical motor areas prior to and following left and right index finger movements in individual subjects, even in the presence of low‐frequency noise (e.g., eye movements). A slow premovement motor field (MF) reaching maximal amplitude ∼50 ms prior to movement onset was localized to the hand area of contralateral precentral gyrus, followed by activity in the contralateral postcentral gyrus at 40 ms, corresponding to the first movement‐evoked field (MEFI). A novel finding was a second activation of the precentral gyrus at a latency of ∼150 ms, corresponding to the second movement‐evoked field (MEFII). Group averaging of spatially normalized images indicated additional premovement activity in the ipsilateral precentral gyrus and the left inferior parietal cortex for both left and right finger movements. Weaker activations were also observed in bilateral premotor areas and the supplementary motor area. These results show that event‐related beamforming provides a robust method for studying complex patterns of time‐locked cortical activity accompanying voluntary movements, and offers a new approach for the localization of multiple cortical sources derived from neuromagnetic recordings in single subject and group data. Hum. Brain Mapping 2005.

Relating MEG Measured Motor Cortical Oscillations to resting γ-Aminobutyric acid (GABA) Concentration

The human motor cortex exhibits characteristic beta (15-30 Hz) and gamma oscillations (60-90 Hz), typically observed in the context of transient finger movement tasks. The functional significance of these oscillations, such as post-movement beta rebound (PMBR) and movement-related gamma synchrony (MRGS) remains unclear. Considerable animal and human non-invasive studies, however, suggest that the networks supporting these motor cortex oscillations depend critically on the inhibitory neurotransmitter γ-Aminobutyric acid (GABA). Despite such speculation, a direct relation between MEG measured motor cortex oscillatory power and frequency with resting GABA concentrations has not been demonstrated. In the present study, motor cortical responses were measured from 9 healthy adults while they performed a cued button-press task using their right index finger. In each participant, PMBR and MRGS measures were obtained from time-frequency plots obtained from primary motor (MI) sources, localized using beamformer differential source localization. For each participant, complimentary magnetic resonance spectroscopy (MRS) GABA measures aligned to the motor hand knob of the left central sulcus were also obtained. GABA concentration was estimated as the ratio of the motor cortex GABA integral to a cortical reference NAA resonance at 2 ppm. A significant linear relation was observed between MI GABA concentration and MRGS frequency (R(2)=0.46, p<0.05), with no association observed between GABA concentration and MRGS power. Conversely, a significant linear relation was observed between MI GABA concentration and PMBR power (R(2)=0.34, p<0.05), with no relation observed for GABA concentration and PMBR frequency. Finally, a significant negative linear relation between the participants age and MI gamma frequency was observed, such that older participants had a lower gamma frequency (R(2)=0.40, p<0.05). Present findings support a role for GABA in the generation and modulation of endogenous motor cortex rhythmic beta and gamma activity.

Localization of sensorimotor cortical rhythms induced by tactile stimulation using spatially filtered MEG.

We applied the synthetic aperture magnetometry (SAM) spatial filtering method to localize sensorimotor mu (8-14 Hz) and beta (15-35 Hz) rhythms following tactile (brush) stimulation. Neuromagnetic activity was recorded from 10 adult subjects. Transient brush stimuli were applied separately to the right index finger, medial right toe and lower right lip. Differential images of mu and beta band source power were created for periods during (event-related desynchronization; ERD) or following (event-related synchronization; ERS) tactile stimulation, relative to prestimulus baseline activity. Mu ERD to finger brushing was localized to the contralateral somatosensory cortex and was organized somatotopically. Mu ERS, however, was not consistently observed for each subject. Beta ERD was consistently localized to sensory cortical areas and organized somatotopically in the post-central gyrus (SI), and beta ERS was observed to be organized motorotopically in the precentral gyrus (MI). Longer duration (2-3 s) stimulation of the index finger also produced beta ERS in the primary motor cortex, and its time course demonstrated that these oscillatory changes are an off-response to the termination of the presented sensory stimulus. Interestingly, lip and toe stimulation also produced post-stimulus increases in beta rhythms in the bilateral motor hand areas for all subjects, suggesting that common neural systems in the primary motor cortex are activated during tactile stimulation of different body regions.

Event-related beamforming: a robust method for presurgical functional mapping using MEG.

OBJECTIVE We describe the application of a new spatial filtering technique--event-related beamforming (ERB)--for presurgical functional mapping of primary sensory areas using MEG. This method provides an alternative to equivalent current dipole (ECD) modeling that potentially eliminates problems of intracranial magnetic artifacts due to movement of ferromagnetic materials (e.g., orthodontic braces) or eye movements. METHODS We compared localization results for ERB and ECD localization of primary somatosensory (M20) and auditory (M100) evoked responses in 12 healthy control subjects and four subjects with metallic dental implants. Data were recorded with a 151-channel CTF MEG system using standard presurgical mapping protocols. RESULTS We found a high level of agreement between the two methods in control subjects (overall localization difference was 5.9+/-2.2 mm for M20 and 10.4+/-5.6 mm for M100). Subjects with dental implants showed severely distorted evoked responses that could not be analyzed using ECD, whereas the ERB method localized sources to expected anatomical locations. CONCLUSIONS MEG functional mapping may be carried out without removal of orthodontic or other metallic implants using event-related beamformer analysis. SIGNIFICANCE Spatial filtering methods can overcome some of the limitations associated with MEG expanding its applicability, particularly in pediatric clinical environments.

Enhanced Synchrony in Epileptiform Activity? Local versus Distant Phase Synchronization in Generalized Seizures

Synchronization is a fundamental characteristic of complex systems and a basic mechanism of self-organization. A traditional, accepted perspective on epileptiform activity holds that hypersynchrony covering large brain regions is a hallmark of generalized seizures. However, a few recent reports have described substantial fluctuations in synchrony before and during ictal events, thus raising questions as to the widespread synchronization notion. In this study, we used magnetoencephalographic recordings from epileptic patients with generalized seizures and normal control subjects to address the extent of the phase synchronization (phase locking) in local (neighboring) and distant cortical areas and to explore the ongoing temporal dynamics for particular ranges of frequencies at which synchrony occurs, during interictal and ictal activity. Synchronization patterns were found to differ somewhat depending on the epileptic syndrome, with primary generalized absence seizures displaying more long-range synchrony in all frequency bands studied (3–55 Hz) than generalized tonic motor seizures of secondary (symptomatic) generalized epilepsy or frontal lobe epilepsy. However, all seizures were characterized by enhanced local synchrony compared with distant synchrony. There were fluctuations in the synchrony between specific cortical areas that varied from seizure to seizure in the same patient, but in most of the seizures studied, regardless of semiology, there was a constant pattern in the dynamics of synchronization, indicating that seizures proceed by a recruitment of neighboring neuronal networks. Together, these data indicate that the concept of widespread “hypersynchronous” activity during generalized seizures may be misleading and valid only for very specific neuronal ensembles and circumstances.

GABA estimation in the Brains of Children on the Autism Spectrum: Measurement precision and regional cortical variation

(1)H magnetic resonance spectroscopy ((1)H MRS) and spectral editing methods, such as MEGA-PRESS, allow researchers to investigate metabolite and neurotransmitter concentrations in-vivo. Here we address the utilization of (1)H MRS for the investigation of GABA concentrations in the ASD brain, in three locations; motor, visual and auditory areas. An initial repeatability study (5 subjects, 5 repeated measures separated by ~5days on average) indicated no significant effect of reference metabolite choice on GABA quantitation (p>0.6). Coefficients of variation for GABA+/NAA, GABA+/Cr and GABA+/Glx were all of the order of 9-11%. Based on these findings, we investigated creatine-normalized GABA+ ratios (GABA+/Cr) in a group of (N=17) children with autism spectrum disorder (ASD) and (N=17) typically developing children (TD) for Motor, Auditory and Visual regions of interest (ROIs). Linear regression analysis of gray matter (GM) volume changes (known to occur with development) revealed a significant decrease of GM volume with Age for Motor (F(1,30)=17.92; p<0.001) and Visual F(1,16)=14.41; p<0.005 but not the Auditory ROI (p=0.55). Inspection of GABA+/Cr changes with Age revealed a marginally significant change for the Motor ROI only (F(1,30)=4.11; p=0.054). Subsequent analyses were thus conducted for each ROI separately using Age and GM volume as covariates. No group differences in GABA+/Cr were observed for the Visual ROI between TD vs. ASD children. However, the Motor and Auditory ROI showed significantly reduced GABA+/Cr in ASD (Motor p<0.05; Auditory p<0.01). The mean deficiency in GABA+/Cr from the Motor ROI was approximately 11% and Auditory ROI was approximately 22%. Our novel findings support the model of regional differences in GABA+/Cr in the ASD brain, primarily in Auditory and to a lesser extent Motor but not Visual areas.

Neuromagnetic imaging of movement-related cortical oscillations in children and adults: Age predicts post-movement beta rebound

We measured visually-cued motor responses in two developmentally separate groups of children and compared these responses to a group of adults. We hypothesized that if post-movement beta rebound (PMBR) depends on developmentally sensitive processes, PMBR will be greatest in adults and progressively decrease in children performing a basic motor task as a function of age. Twenty children (10 young children 4-6 years; 10 adolescent children 11-13 years) and 10 adults all had MEG recorded during separate recordings of right and left index finger movements. Beta band (15-30 Hz) event-related desynchronization (ERD) of bi-lateral sensorimotor areas was observed to increase significantly from both contralateral and ipsilateral MI with age. Movement-related gamma synchrony (60-90 Hz) was also observed from contralateral MI for each age group. However, PMBR was significantly reduced in the 4-6 year group and, while more prominent, remained significantly diminished in the adolescent (11-13 year) age group as compared to adults. PMBR measures were weak or absent in the youngest children tested and appear maximally from bilateral MI in adults. Thus PMBR may reflect an age-dependent inhibitory process of the primary motor cortex which comes on-line with normal development. Previous studies have shown PMBR may be observed from MI following a variety of movement-related tasks in adult participants - however, the origin and purpose of the PMBR is unclear. The current study shows that the expected PMBR from MI observed from adults is increasingly diminished in adolescent and young children respectively. A reduction in PMBR from children may reflect reduced motor cortical inhibition. Relatively less motor inhibition may facilitate neuronal plasticity and promote motor learning in children.

Cortical Reorganization After Modified Constraint-Induced Movement Therapy in Pediatric Hemiplegic Cerebral Palsy

Constraint-induced movement therapy improves motor function in the affected hand of children with hemiplegic cerebral palsy and results in cortical changes in adults with stroke. This study measured clinical improvement and cortical reorganization in a child with hemiplegia who underwent modified constraint-induced movement therapy for 3 weeks. Clinical, functional magnetic resonance imaging and magnetoencephalography measurements were done at baseline, after therapy, and 6 months after therapy. Modified constraint-induced movement therapy resulted in clinical improvement as measured by the Pediatric Motor Activity Log. Functional magnetic resonance imaging showed bilateral sensorimotor activation before and after therapy and a shift in the laterality index from ipsilateral to contralateral hemisphere after therapy. Magnetoencephalography showed increased cortical activation in the ipsilateral motor field and contralateral movement evoked field after therapy. Cortical reorganization was maintained at the 6-month follow-up. This is the first study to demonstrate cortical reorganization after any version of constraint-induced movement therapy in a child with hemiplegia.

Localization of human somatosensory cortex using spatially filtered magnetoencephalography

A spatial filter algorithm based on minimum-variance beamforming (synthetic aperture magnetometry (SAM)) was applied to single trial neuromagnetic recordings in order to localize primary somatosensory cortex. Magnetoencephalography (MEG) responses to electrical stimulation of the right and left median nerve were recorded using a whole-head MEG system and localized using both SAM spatial filtering and dipole analysis. Spatial filtering was applied to single trial neuromagnetic recordings to produce 3-dimensional difference images of source power between active (0-50 ms) and control states (-50-0 ms) in the range of 15-300 Hz. Average difference between N20m dipole location and location of maximal increase in power in the SAM images was 3.7 mm (1.5 mm SD) and localized to primary somatosensory cortex. Time-frequency analysis of spatially filtered output for the peak SAM locations showed a brief (10 ms) increase in the 60-100 Hz band coincident with the N20m response and a longer duration (approx. 80 ms) increase in power in the 10-40 Hz band following N20m onset. These results indicate that beamformer based spatial filter methods such as SAM can be used to localize temporally discrete cortical activity produced by median nerve stimulation.