Tony W. Wilson

Stride-time variability and sensorimotor cortical activation during walking

The time it takes between consecutive foot contacts from the same leg is referred to as the stride-time interval. Several investigations have shown that the variations that are present in the stride time intervals are linked to walking balance. In this study, functional near infrared spectroscopy (fNIRS) was utilized to evaluate whether activation in the medial sensorimotor cortices reflects the amount of variations seen in the stride-time intervals. Thirteen healthy adults (Age=23.7 ± 1.4 yrs.) walked forwards and backwards on a programmable treadmill. Each walking condition consisted of two sessions, with each being comprised of five alternating blocks of standing still or walking at 0.45 m/s. Activation in the medial sensorimotor cortices was measured using an fNIRS system, which consisted of a 4 × 4 grid of infrared optode emitter/detector pairs. The optodes were positioned on the participants head using the International 10/20 system with Cz located beneath the center of the front two rows of optodes. We evaluated the block-wise changes in the amount of oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) in the channels that were located over the supplementary motor area, pre-central gyrus, post-central gyrus and superior parietal lobule. Throughout the experiment, a footswitch system was used to concurrently measure the amount of variation present in the stride-time intervals. Our results showed that oxyHb was greater in the supplementary motor area, pre-central gyrus, and superior parietal lobule when participants walked backwards rather than forwards, which suggests that backward walking presents more of a challenge to the nervous system as it controls the stepping pattern. Additionally, there was a significant decrease in the amount of deoxyHb present in the supplementary motor area while walking backward. Consistent with previous investigations, we noted that the amount of variability present in the stride-time intervals was greater during backward walking compared to forward walking. In addition, the amount of variation in the stride-time intervals while walking forward was positively correlated with the maximum oxyHb response found in the pre-central gyrus and supplementary motor area, which has not been previously shown. This neurobehavioral relationship supports the notion that the subtle variations found in the stride-time intervals are partly associated with processing demands by the motor cortices for regulating the forward temporal kinematics.

Neuromagnetic Evidence of Abnormal Movement-Related Beta Desynchronization in Parkinson's Disease

Parkinsons disease (PD) is a neurodegenerative disorder associated with debilitating motor, posture, and gait abnormalities. Human studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchronization throughout the cortical–basal ganglia motor network in PD. Suppression of such pathological beta synchronization has been associated with improved motor function, which may explain the effectiveness of deep-brain stimulation. We used magnetoencephalography (MEG) to investigate neural population-level beta responses, and other oscillatory activity, during a motor task in unmedicated patients with PD and a matched group of healthy adults. MEG is a noninvasive neurophysiological technique that permits the recording of oscillatory activity during movement planning, execution, and termination phases. Each of these phases was independently examined using beamforming to distinguish the brain areas and movement phases, where pathological oscillations exist during motor control. Patients with PD exhibited significantly diminished beta desynchronization compared with controls prior to and during movement, which paralleled reduced alpha desynchronization. This study is the first to systematically investigate neural oscillatory responses in PD during distinct stages of motor control (e.g. planning, execution, and termination) and indicates that these patients have significant difficulty suppressing cortical beta synchronization during movement planning, which may contribute to their diminished movement capacities.

Broadband neurophysiological abnormalities in the medial prefrontal region of the default-mode network in adults with ADHD.

Previous investigations of the default‐mode network (DMN) in persons with attention‐deficit/hyperactivity disorder (ADHD) have shown reduced functional connectivity between the anterior and posterior aspects. This finding was originally demonstrated in adults with ADHD, then in youth with ADHD, and has been tentatively linked to ultra low frequency oscillations within the DMN. The current study evaluates the specificity of DMN abnormalities to neuronal oscillations in the ultra low frequency range, and examines the regional specificity of these DMN aberrations in medicated and unmedicated adults with, and those without ADHD. An individually matched sample of adults with and without ADHD completed 6‐minute sessions of resting‐state magnetoencephalography (MEG). Participants with ADHD were known responders to stimulant medications and completed two sessions (predrug/postdrug). MEG data were coregistered to the participants MRI, corrected for head motion, fitted to a regional‐level source model, and subjected to spectral analyses to extract neuronal population activity in regions of the DMN. The unmedicated adults with ADHD exhibited broadband deficits in medial prefrontal cortices (MPFC), but not other DMN regions compared to adults without ADHD. Unmedicated patients also showed abnormal cross‐frequency coupling in the gamma range between the MPFC and posterior cingulate areas, and disturbed balance within the DMN as activity in posterior regions was stronger than frontal regions at beta and lower frequencies, which dissipated at higher γ‐frequencies. Administration of pharmacotherapy significantly increased prefrontal alpha activity (8–14 Hz) in adults with ADHD, and decreased the cross‐frequency gamma coupling. These results indicate that neurophysiological aberrations in the DMN of patients with ADHD are not limited to ultra slow oscillations, and that they may be primarily attributable to abnormal broadband activity in the MPFC. Hum Brain Mapp, 2013.

Abnormal Gamma and Beta MEG Activity During Finger Movements in Early-Onset Psychosis

Patients with psychosis often exhibit abnormalities in basic motor control, but little is known about the neural basis of these deficits. This study examines the neuro-dynamics of movement using magnetoencephalography (MEG) in adolescents with early-onset psychosis and typically developing controls. MEG data were imaged using beamforming then evaluated for task and group effects before, during, and after movement onsets. Primary findings included weaker activation in patients during movement execution in cerebellar cortices. Such aberrations likely contribute to the decreased motor control exhibited by patients with psychosis, and may reflect GABAergic-based inhibitory deficits comparable to those seen in cellular and system-level studies.

Atypical coupling between posterior regions of the default mode network in attention-deficit/hyperactivity disorder: a pharmaco-magnetoencephalography study.

BACKGROUND Dysfunction in the default mode network (DMN), a group of cortical areas more active during the resting state, has been linked to attentional deficits and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Prior imaging studies have shown decreased functional connectivity between DMN nodes in patients with ADHD, primarily between anterior and posterior regions. Using magnetoencephalography (MEG), we evaluated phase coherence (i.e., functional connectivity) among regions of the DMN in healthy controls and adults with ADHD before and after stimulant therapy. METHODS We obtained a resting-state MEG recording for all participants. Magnetoencephalography data were transformed into a ~30 node regional source model using inverse spatial filtering, including regions corresponding to the DMN. We computed the zero-lag phase coherence between these regions pairwise for 5 distinct frequency bands, and we assessed group and medication effects. RESULTS Twelve adults with and 13 without ADHD participated in our study. Functional connectivity was stronger between particular node pairs and showed frequency-specific effects. Unmedicated patients showed reduced phase locking between posterior cingulate/precuneus regions (PCC) and right inferior parietal cortices (RIPL), and between medial prefrontal regions (MPFC) and the left inferior parietal region (LIPL) and the PCC. Unmedicated patients had increased phase locking between the RIPL and LIPL regions compared with controls. Administration of stimulants improved phase locking abnormalities along the MPFC-PCC and LIPL-RIPL pathways in patients with ADHD. LIMITATIONS Modest sample size and lack of duration of patient treatment history may limit the generalizability of our findings. CONCLUSION Adults with ADHD exhibit hyper- and hypoconnectivity between regions of the DMN during rest, which were suppressed after stimulant medication administration.

Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults.

Combination antiretroviral therapy transformed human immunodefiency virus (HIV)‐infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV‐infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high‐resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV‐related cognitive impairments. HIV‐infected adults and individually matched controls completed 3‐Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel‐based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV‐infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV‐infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV‐associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV‐associated cognitive impairment, and may hold promise as a potential disease marker. Hum Brain Mapp 36:897–910, 2015.

Functional specialization within the supplementary motor area: A fNIRS study of bimanual coordination

Bimanual movements can be performed by flexing and extending the target effectors (e.g., hand muscles) in unison, or by flexing units on one side in unison with extension of the same units on the opposite side. The former movement patterns are generally referred to as in-phase or parallel, whereas the latter patterns are often termed anti-phase movements. It is well known that anti-phase patterns are unstable and tend to spontaneously transition to in-phase movements at higher repetition rates, but the mechanisms and brain regions involved are not fully understood. In the current study, we utilized functional near-infrared spectroscopy (fNIRS) to evaluate whether anterior/posterior subdivisions of the supplementary motor complex (SMA) have distinct functional roles in maintaining in-phase and anti-phase movement patterns. Twelve healthy adult participants completed a bimanual coordination task comprised of anti-phase and in-phase trials as 24-channel fNIRS data was recorded from dorsal-medial motor areas. We examined the relative concentrations of oxygenated and deoxygenated hemoglobin in the channels that were located over the anterior SMA (e.g., pre-SMA) and the SMA proper. Our most interesting results indicated that oxygenated hemoglobin responses were greater in the anterior SMA during performance of anti-phase compared to in-phase movements. In the SMA proper, oxygenated hemoglobin responses did not differ between the two movement patterns. These data suggest that the anterior SMA is critical to programming and maintaining the less stable anti-phase movement patterns, and support the conceptual framework of an anterior-directed gradient of progressively more complex functionality in the SMA.

Neurophysiological abnormalities in the sensorimotor cortices during the motor planning and movement execution stages of children with cerebral palsy.

This investigation used magnetoencephalography (MEG) to examine the neural oscillatory responses of the sensorimotor cortices during the motor planning and movement execution stages of children with typical development and children with cerebral palsy (CP).

Is an absolute level of cortical beta suppression required for proper movement? Magnetoencephalographic evidence from healthy aging

Previous research has connected a specific pattern of beta oscillatory activity to proper motor execution, but no study to date has directly examined how resting beta levels affect motor-related beta oscillatory activity in the motor cortex. Understanding this relationship is imperative to determining the basic mechanisms of motor control, as well as the impact of pathological beta oscillations on movement execution. In the current study, we used magnetoencephalography (MEG) and a complex movement paradigm to quantify resting beta activity and movement-related beta oscillations in the context of healthy aging. We chose healthy aging as a model because preliminary evidence suggests that beta activity is elevated in older adults, and thus by examining older and younger adults we were able to naturally vary resting beta levels. To this end, healthy younger and older participants were recorded during motor performance and at rest. Using beamforming, we imaged the peri-movement beta event-related desynchronization (ERD) and extracted virtual sensors from the peak voxels, which enabled absolute and relative beta power to be assessed. Interestingly, absolute beta power during the pre-movement baseline was much stronger in older relative to younger adults, and older adults also exhibited proportionally large beta desynchronization (ERD) responses during motor planning and execution compared to younger adults. Crucially, we found a significant relationship between spontaneous (resting) beta power and beta ERD magnitude in both primary motor cortices, above and beyond the effects of age. A similar link was found between beta ERD magnitude and movement duration. These findings suggest a direct linkage between beta reduction during movement and spontaneous activity in the motor cortex, such that as spontaneous beta power increases, a greater reduction in beta activity is required to execute movement. We propose that, on an individual level, the primary motor cortices have an absolute threshold of beta power that must be reached in order to move, and that an inability to suppress beta power to this threshold results in an increase in movement duration.

Neuromagnetic activity in the somatosensory cortices of children with cerebral palsy

Children with cerebral palsy (CP) have altered tactile, proprioceptive and kinesthetic awareness. These sensory impairments appear to be related to an aberrant organization of the somatosensory cortex. To date, the neuromagnetic responses of somatosensory cortices representing the foot have not been investigated in children with spastic diplegic CP. In this investigation, we used magnetoencephalography (MEG) to evaluate cortical differences in the earliest somatosensory responses elicited by foot stimulation in typically developing children and those with spastic diplegic CP who have a Gross Motor Function Classification Score of III-IV. All participants underwent unilateral tibial nerve stimulation of each foot as whole brain MEG data were acquired. Primary somatosensory cortical responses were modeled using an equivalent current dipole for each foot. The results presented in this study are the first to show that activation of the somatosensory cortices representing the foot in children with spastic diplegic CP is diminished, but not latent.