Reproducibility of Rolandic beta rhythm modulation in MEG and EEG.

The Rolandic beta rhythm, at ∼20 Hz, is generated in the somatosensory and motor cortices and is modulated by motor activity and sensory stimuli, causing a short lasting suppression that is followed by a rebound of the beta rhythm. The rebound reflects inhibitory changes in the primary sensorimotor (SMI) cortex, and thus it has been used as a biomarker to follow the recovery of patients with acute stroke. The longitudinal stability of beta rhythm modulation is a prerequisite for its use in long-term follow-ups. We quantified the reproducibility of beta rhythm modulation in healthy subjects in a 1-year-longitudinal study both for MEG and EEG at T0, 1 month (T1-month, n = 8) and 1 year (T1-year, n = 19). The beta rhythm (13-25 Hz) was modulated by fixed tactile and proprioceptive stimulations of the index fingers. The relative peak strengths of beta suppression and rebound did not differ significantly between the sessions, and intersession reproducibility was good or excellent according to intraclass correlation-coefficient values (0.70-0.96) both in MEG and EEG. Our results indicate that the beta rhythm modulation to tactile and proprioceptive stimulation is well reproducible within 1 year. These results support the use of beta modulation as a biomarker in long-term follow-up studies, e.g., to quantify the functional state of the SMI cortex during rehabilitation and drug interventions in various neurological impairments.NEW & NOTEWORTHY The present study demonstrates that beta rhythm modulation is highly reproducible in a group of healthy subjects within a year. Hence, it can be reliably used as a biomarker in longitudinal follow-up studies in different neurological patient groups to reflect changes in the functional state of the sensorimotor cortex.

Biomarkers of plasticity for stroke recovery.

Stroke is the commonest cause of physical disability in the world. Our understanding of the biologic mechanisms involved in recovery and repair has advanced to the point that therapeutic opportunities to promote recovery through manipulation of post-stroke plasticity have never been greater. This work has almost exclusively been carried out in rodent models of stroke with little translation into human studies. The challenge ahead is to develop a mechanistic understanding of recovery from stroke in humans. Advances in neuroimaging techniques can now provide the appropriate intermediate level of description to bridge the gap between a molecular and cellular account of recovery and a behavioral one. Clinical trials can then be designed in a stratified manner taking into account when an intervention should be delivered and who is most likely to benefit. This approach is most likely to lead to the step-change in how restorative therapeutic strategies are delivered in human stroke patients.

The effect of alertness and attention on the modulation of the beta rhythm to tactile stimulation.

Beta rhythm modulation has been used as a biomarker to reflect the functional state of the sensorimotor cortex in both healthy subjects and patients. Here, the effect of reduced alertness and active attention to the stimulus on beta rhythm modulation was investigated. Beta rhythm modulation to tactile stimulation of the index finger was recorded simultaneously with MEG and EEG in 23 healthy subjects (mean 23, range 19-35 years). The temporal spectral evolution method was used to obtain the peak amplitudes of beta suppression and rebound in three different conditions (neutral, snooze, and attention). Neither snooze nor attention to the stimulus affected significantly the strength of beta suppression nor rebound, although a decrease in suppression and rebound strength was observed in some subjects with a more pronounced decrease of alertness. The reduction of alertness correlated with the decrease of suppression strength both in MEG (left hemisphere r = 0.49; right hemisphere r = 0.49, *p < 0.05) and EEG (left hemisphere r = 0.43; right hemisphere r = 0.72, **p < 0.01). The results indicate that primary sensorimotor cortex beta suppression and rebound are not sensitive to slightly reduced alertness nor active attention to the stimulus at a group level. Hence, tactile stimulus-induced beta modulation is a suitable tool for assessing the sensorimotor cortex function at a group level. However, subjects' alertness should be maintained high during recordings to minimize individual variability.

Comparing MEG and EEG in detecting the ~20-Hz rhythm modulation to tactile and proprioceptive stimulation.

Modulation of the ~20-Hz brain rhythm has been used to evaluate the functional state of the sensorimotor cortex both in healthy subjects and patients, such as stroke patients. The ~20-Hz brain rhythm can be detected by both magnetoencephalography (MEG) and electroencephalography (EEG), but the comparability of these methods has not been evaluated. Here, we compare these two methods in the evaluating of ~20-Hz activity modulation to somatosensory stimuli. Rhythmic ~20-Hz activity during separate tactile and proprioceptive stimulation of the right and left index finger was recorded simultaneously with MEG and EEG in twenty-four healthy participants. Both tactile and proprioceptive stimulus produced a clear suppression at 300-350 â€‹ms followed by a subsequent rebound at 700-900 â€‹ms after stimulus onset, detected at similar latencies both with MEG and EEG. The relative amplitudes of suppression and rebound correlated strongly between MEG and EEG recordings. However, the relative strength of suppression and rebound in the contralateral hemisphere (with respect to the stimulated hand) was significantly stronger in MEG than in EEG recordings. Our results indicate that MEG recordings produced signals with higher signal-to-noise ratio than EEG, favoring MEG as an optimal tool for studies evaluating sensorimotor cortical functions. However, the strong correlation between MEG and EEG results encourages the use of EEG when translating studies to clinical practice. The clear advantage of EEG is the availability of the method in hospitals and bed-side measurements at the acute phase.

Reproducibility of corticokinematic coherence.

Corticokinematic coherence (CKC) between limb kinematics and magnetoencephalographic (MEG) signals reflects cortical processing of proprioceptive afference. However, it is unclear whether strength of CKC is reproducible across measurement sessions. We thus examined reproducibility of CKC in a follow-up study. Thirteen healthy right-handed volunteers (7 females, 21.7 ±â€¯4.3 yrs) were measured using MEG in two separate sessions 12.6 ±â€¯1.3 months apart. The participant was seated and relaxed while his/her dominant or non-dominant index finger was continuously moved at 3 Hz (4 min for each hand) using a pneumatic movement actuator. Finger kinematics were recorded with a 3-axis accelerometer. Coherence was computed between finger acceleration and MEG signals. CKC strength was defined as the peak coherence value at 3 Hz form a single sensor among 40 pre-selected Rolandic gradiometers contralateral to the movement. Pneumatic movement actuator provided stable proprioceptive stimuli and significant CKC responses peaking at the contralateral Rolandic sensors. In the group level, CKC strength did not differ between the sessions in dominant (Day-1 0.40 ±â€¯0.19 vs. Day-2 0.41 ±â€¯0.17) or non-dominant (0.35 ±â€¯0.16 vs. 0.36 ±â€¯0.17) hand, nor between the hands. Intraclass-correlation coefficient (ICC) values indicated excellent inter-session reproducibility for CKC strength for both dominant (0.86) and non-dominant (0.97) hand. However, some participants showed pronounced inter-session variability in CKC strength, but only for the dominant hand. CKC is a promising tool to study proprioception in long-term longitudinal studies in the group level to follow, e.g., integrity of cortical proprioceptive processing with motor functions after stroke.

Recovery of the 20 Hz Rebound to Tactile and Proprioceptive Stimulation after Stroke.

Sensorimotor integration is closely linked to changes in motor-cortical excitability, observable in the modulation of the 20 Hz rhythm. After somatosensory stimulation, the rhythm transiently increases as a rebound that reflects motor-cortex inhibition. Stroke-induced alterations in afferent input likely affect motor-cortex excitability and motor recovery. To study the role of somatosensory afferents in motor-cortex excitability after stroke, we employed magnetoencephalographic recordings (MEG) at 1-7 days, one month, and 12 months in 23 patients with stroke in the middle cerebral artery territory and 22 healthy controls. The modulation of the 20 Hz motor-cortical rhythm was evaluated to two different somatosensory stimuli, tactile stimulation, and passive movement of the index fingers. The rebound strengths to both stimuli were diminished in the acute phase compared to the controls and increased significantly during the first month after stroke. However, only the rebound amplitudes to tactile stimuli fully recovered within the follow-up period. The rebound strengths in the affected hemisphere to both stimuli correlated strongly with the clinical scores across the follow-up. The results show that changes in the 20 Hz rebound to both stimuli behave similarly and occur predominantly during the first month. The 20 Hz rebound is a potential marker for predicting motor recovery after stroke.

Strength of ~20-Hz Rebound and Motor Recovery After Stroke.

BACKGROUND: Stroke is a major cause of disability worldwide, and effective rehabilitation is crucial to regain skills for independent living. Recently, novel therapeutic approaches manipulating the excitatory-inhibitory balance of the motor cortex have been introduced to boost recovery after stroke. However, stroke-induced neurophysiological changes of the motor cortex may vary despite of similar clinical symptoms. Therefore, better understanding of excitability changes after stroke is essential when developing and targeting novel therapeutic approaches. OBJECTIVE AND METHODS: We identified recovery-related alterations in motor cortex excitability after stroke using magnetoencephalography. Dynamics (suppression and rebound) of the ~20-Hz motor cortex rhythm were monitored during passive movement of the index finger in 23 stroke patients with upper limb paresis at acute phase, 1 month, and 1 year after stroke. RESULTS: After stroke, the strength of the ~20-Hz rebound to stimulation of both impaired and healthy hand was decreased with respect to the controls in the affected (AH) and unaffected (UH) hemispheres, and increased during recovery. Importantly, the rebound strength was lower than that of the controls in the AH and UH also to healthy-hand stimulation despite of intact afferent input. In the AH, the rebound strength to impaired-hand stimulation correlated with hand motor recovery. CONCLUSIONS: Motor cortex excitability is increased bilaterally after stroke and decreases concomitantly with recovery. Motor cortex excitability changes are related to both alterations in local excitatory-inhibitory circuits and changes in afferent input. Fluent sensorimotor integration, which is closely coupled with excitability changes, seems to be a key factor for motor recovery.

Cortical Excitability Measured with nTMS and MEG during Stroke Recovery.

OBJECTIVE: Stroke alters cortical excitability both in the lesioned and in the nonlesioned hemisphere. Stroke recovery has been studied using transcranial magnetic stimulation (TMS). Spontaneous brain oscillations and somatosensory evoked fields (SEFs) measured by magnetoencephalography (MEG) are modified in stroke patients during recovery. METHODS: We recorded SEFs and spontaneous MEG activity and motor threshold (MT) short intracortical inhibition (SICI) and intracortical facilitation (ICF) with navigated TMS (nTMS) at one and three months after first-ever hemispheric ischemic strokes. Changes of MEG and nTMS parameters attributed to gamma-aminobutyrate and glutamate transmission were compared. RESULTS: ICF correlated with the strength and extent of SEF source areas depicted by MEG at three months. The nTMS MT and event-related desynchronization (ERD) of beta-band MEG activity and SICI and the beta-band MEG event-related synchronization (ERS) were correlated, but less strongly. CONCLUSIONS: This first report using sequential nTMS and MEG in stroke recovery found intra- and interhemispheric correlations of nTMS and MEG estimates of cortical excitability. ICF and SEF parameters, MT and the ERD of the lesioned hemisphere, and SICI and ERS of the nonlesioned hemisphere were correlated. Covarying excitability in the lesioned and nonlesioned hemispheres emphasizes the importance of the hemispheric balance of the excitability of the sensorimotor system.

Modulation of the ∽20-Hz motor-cortex rhythm to passive movement and tactile stimulation.

BACKGROUND: Integration of afferent somatosensory input with motor-cortex output is essential for accurate movements. Prior studies have shown that tactile input modulates motor-cortex excitability, which is reflected in the reactivity of the ∽ 20-Hz motor-cortex rhythm. ∽ 20-Hz rebound is connected to inhibition or deactivation of motor cortex whereas suppression has been associated with increased motor cortex activity. Although tactile sense carries important information for controlling voluntary actions, proprioception likely provides the most essential feedback for motor control. METHODS: To clarify how passive movement modulates motor-cortex excitability, we studied with magnetoencephalography (MEG) the amplitudes and peak latencies of suppression and rebound of the ∽ 20-Hz rhythm elicited by tactile stimulation and passive movement of right and left index fingers in 22 healthy volunteers. RESULTS: Passive movement elicited a stronger and more robust ∽ 20-Hz rebound than tactile stimulation. In contrast, the suppression amplitudes did not differ between the two stimulus types. CONCLUSION: Our findings suggest that suppression and rebound represent activity of two functionally distinct neuronal populations. The ∽ 20-Hz rebound to passive movement could be a suitable tool to study the functional state of the motor cortex both in healthy subjects and in patients with motor disorders.

Reactivity of sensorimotor oscillations is altered in children with hemiplegic cerebral palsy: A magnetoencephalographic study.

Cerebral palsy (CP) is characterized by difficulty in control of movement and posture due to brain damage during early development. In addition, tactile discrimination deficits are prevalent in CP. To study the function of somatosensory and motor systems in CP, we compared the reactivity of sensorimotor cortical oscillations to median nerve stimulation in 12 hemiplegic CP children vs. 12 typically developing children using magnetoencephalography. We also determined the primary cortical somatosensory and motor representation areas of the affected hand in the CP children using somatosensory-evoked magnetic fields and navigated transcranial magnetic stimulation, respectively. We hypothesized that the reactivity of the sensorimotor oscillations in alpha (10 Hz) and beta (20 Hz) bands would be altered in CP and that the beta-band reactivity would depend on the individual pattern of motor representation. Accordingly, in children with CP, suppression and rebound of both oscillations after stimulation of the contralateral hand were smaller in the lesioned than intact hemisphere. Furthermore, in two of the three children with CP having ipsilateral motor representation, the beta- but not alpha-band modulations were absent in both hemispheres after affected hand stimulation suggesting abnormal sensorimotor network interactions in these individuals. The results are consistent with widespread alterations in information processing in the sensorimotor system and complement current understanding of sensorimotor network development after early brain insults. Precise knowledge of the functional sensorimotor network organization may be useful in tailoring individual rehabilitation for people with CP.

Alterations in spontaneous brain oscillations during stroke recovery.

Amplitude or frequency alterations of spontaneous brain oscillations may reveal pathological phenomena in the brain or predict recovery from brain lesions, but the temporal evolution and the functional significance of these changes is not well known. We performed follow-up recordings of spontaneous brain oscillations with whole-head MEG in 16 patients with first-ever stroke in the middle cerebral artery territory, affecting upper limb motor function, 1-7 days (T0), 1 month (T1), and 3 months (T2) after stroke, with concomitant clinical examination. Clinical test results improved significantly from T0 to T1 or T2. During recovery (at T1 and T2), the strength of temporo-parietal ≈ 10-Hz oscillations in the affected hemisphere (AH) was increased as compared with the unaffected hemisphere. Abnormal low-frequency magnetic activity (ALFMA) at ≈ 1 Hz in the AH was detected in the perilesional cortex in seven patients at T0. In four of these, ALFMA persisted at T2. In patients with ALFMA, the lesion size was significantly larger than in the rest of the patients, and worse clinical outcome was observed in patients with persisting ALFMA. Our results indicate that temporo-parietal ≈ 10-Hz oscillations are enhanced in the AH during recovery from stroke. Moreover, stroke causes ALFMA, which seems to persist in patients with worse clinical outcome.

Effect of afferent input on motor cortex excitability during stroke recovery.

OBJECTIVE: Afferent input is proposed to mediate its effect on motor functions by modulating the excitability of the motor cortex. We aimed to clarify - in a longitudinal study - how afferent input affects motor cortex excitability after stroke and how it is associated with recovery of hand function. METHODS: The motor cortex excitability was studied by measuring the reactivity of the motor cortex beta rhythm to somatosensory stimulation. We recorded the amplitude of the suppression and subsequent rebound of the beta oscillations during tactile finger stimulation with MEG in 23 first-ever stroke patients within one week and at 1 and 3 months after stroke, with concomitant evaluation of hand function. RESULTS: The strength of the beta rhythm rebound, suggested to reflect decreased motor cortex excitability, was weak in the affected hemisphere after stroke and it was subsequently increased during recovery. The rebound strength correlated with hand function tests in all recordings. CONCLUSION: Motor cortex excitability is modulated by afferent input after stroke. The motor cortex excitability is increased in the AH acutely after stroke and decreases in parallel with recovery of hand function. SIGNIFICANCE: The results implicate the importance of parallel recovery of both sensory and motor systems in functional recovery after stroke.