RESUMEN

In severely affected stroke survivors, cortico-muscular control is disturbed and volitional upper limb movements often absent. Mental rehearsal of the impaired movement in conjunction with sensory feedback provision are suggested as promising rehabilitation exercises. Knowledge about the underlying neural processes, however, remains vague. In male and female chronic stroke patients with hand paralysis, a brain-computer interface controlled a robotic orthosis and turned sensorimotor beta-band desynchronization during motor imagery (MI) of finger extension into contingent hand opening. Healthy control subjects performed the same task and received the same proprioceptive feedback with a robotic orthosis or visual feedback only. Only when proprioceptive feedback was provided, cortico-muscular coherence (CMC) increased with a predominant information flow from the sensorimotor cortex to the finger extensors. This effect (i) was specific to the beta frequency-band, (ii) transferred to a motor task, (iii) was proportional to subsequent corticospinal excitability and correlated with behavioral changes in the (iv) healthy and (v) post-stroke condition; notably, MI-related enhancement of beta-band CMC in the ipsilesional premotor cortex correlated with motor improvements after the intervention.In the healthy and injured human nervous system, synchronized activation of motor-related cortical and spinal neural pools facilitates, in accordance with the communication-through-coherence hypothesis, cortico-spinal communication and may, thereby, be therapeutically relevant for functional restoration after stroke, when voluntary movements are no longer possible.Significance statement:This study provides insights into the neural processes that transfer effects of brain-computer interface neurofeedback to subsequent motor behavior. Specifically, volitional control of cortical oscillations and proprioceptive feedback enhances both cortical activity and behaviorally relevant connectivity to the periphery in a topographically circumscribed and frequency-specific way. This enhanced cortico-muscular control can be induced in the healthy and post-stroke brain. Thereby, activating the motor cortex with mental rehearsal of the impaired movement and closing the loop by robot-assisted feedback synchronizes ipsilesional premotor cortex and spinal neural pools in the beta-frequency band. This facilitates, in accordance with the communication-through-coherence hypothesis, cortico-spinal communication and may, thereby, be therapeutically relevant for functional restoration after stroke, when voluntary movements are no longer possible.

RESUMEN

BACKGROUND: Pairing cortical and peripheral input during motor imagery (MI)-related sensorimotor desynchronization (ERD) modulates corticospinal excitability at the cortical representation (hotspot) of the imagined movement. OBJECTIVE: To determine the effects of this associative stimulation protocol on the cortical motor map beyond the hotspot. METHODS: In healthy subjects, peripheral stimulation through passive hand opening by a robotic orthosis and single-pulse transcranial magnetic stimulation to the respective cortical motor representation were applied in a brain-machine interface environment. State-dependency was investigated by concurrent, delayed or non-specific stimulation with respect to ERD in the beta-band (16-22 Hz) during MI of finger extension. RESULTS: Concurrent stimulation led to increased excitability of an extended motor map. Delayed and non-specific stimulation led to heterogeneous changes, i.e., opposite patterns of increased excitability in either the center or the periphery of the motor map. CONCLUSION: These results could be instrumental in closed-loop, state-dependent stimulation in the context of neurorehabilitation.

Asunto(s)

RESUMEN

Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the ß-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during ß-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract.SIGNIFICANCE STATEMENT The activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment. In this study, a brain-machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional ß-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract.

Asunto(s)

RESUMEN

Motor maps acquired with transcranial magnetic stimulation (TMS) are evolving as a biomarker for monitoring disease progression or the effects of therapeutic interventions. High test-retest reliability of this technique for long observation periods is therefore required to differentiate daily or weekly fluctuations from stable plastic reorganization of corticospinal connectivity. In this study, a novel projection, interpolation, and coregistration technique, which considers the individual gyral anatomy, was applied in healthy subjects for biweekly acquired TMS motor maps over a period of twelve weeks. The intraclass correlation coefficient revealed long-term reliability of motor maps with relevant interhemispheric differences. The sensorimotor cortex and nonprimary motor areas of the dominant hemisphere showed more extended and more stable corticospinal connectivity. Long-term correlations of the MEP amplitudes at each stimulation site revealed mosaic-like clusters of consistent corticospinal excitability. The resting motor threshold, centre of gravity, and mean MEPs across all TMS sites, as highly reliable cortical map parameters, could be disentangled from more variable parameters such as MEP area and volume. Cortical TMS motor maps provide high test-retest reliability for long-term monitoring when analyzed with refined techniques. They may guide restorative interventions which target dormant corticospinal connectivity for neurorehabilitation.

Asunto(s)

RESUMEN

BACKGROUND: Desynchronization of sensorimotor rhythmic activity increases instantaneous corticospinal excitability, as indexed by amplitudes of motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS). The accumulative effect of cortical stimulation in conjunction with sensorimotor desynchronization is, however, unclear. OBJECTIVE: The aim of this study was to investigate the effects of repetitive pairing event-related desynchronization (ERD) with TMS of the precentral gyrus on corticospinal excitability. METHODS: Closed-loop single-pulse TMS was controlled by beta-band (16-22 Hz) ERD during motor-imagery of finger extension and applied within a brain-computer interface environment in eleven healthy subjects. The same number and pattern of stimuli were applied in a control group of eleven subjects during rest, i.e. independent of ERD. To probe for plasticity resistant to depotentiation, stimulation protocols were followed by a depotentiation task. RESULTS: Brain state-dependent application of approximately 300 TMS pulses during beta-ERD resulted in a significant increase of corticospinal excitability. By contrast, the identical stimulation pattern applied independent of beta-ERD in the control experiment resulted in a decrease of corticospinal excitability. These effects persisted beyond the period of stimulation and the depotentiation task. CONCLUSION: These results could be instrumental in developing new therapeutic approaches such as the application of closed-loop stimulation in the context of neurorehabilitation.

Asunto(s)

RESUMEN

Brain-robot interfaces (BRI) are studied as novel interventions to facilitate functional restoration in patients with severe and persistent motor deficits following stroke. They bridge the impaired connection in the sensorimotor loop by providing brain-state dependent proprioceptive feedback with orthotic devices attached to the hand or arm of the patients. The underlying neurophysiology of this BRI neuromodulation is still largely unknown. We investigated changes of corticospinal excitability with transcranial magnetic stimulation in thirteen right-handed healthy subjects who performed 40min of kinesthetic motor imagery receiving proprioceptive feedback with a robotic orthosis attached to the left hand contingent to event-related desynchronization of the right sensorimotor cortex in the ß-band (16-22Hz). Neural correlates of this BRI intervention were probed by acquiring the stimulus-response curve (SRC) of both motor evoked potential (MEP) peak-to-peak amplitudes and areas under the curve. In addition, a motor mapping was obtained. The specificity of the effects was studied by comparing two neighboring hand muscles, one BRI-trained and one control muscle. Robust changes of MEP amplitude but not MEP area occurred following the BRI intervention, but only in the BRI-trained muscle. The steep part of the SRC showed an MEP increase, while the plateau of the SRC showed an MEP decrease. MEP mapping revealed a distributed pattern with a decrease of excitability in the hand area of the primary motor cortex, which controlled the BRI, but an increase of excitability in the surrounding somatosensory and premotor cortex. In conclusion, the BRI intervention induced a complex pattern of modulated corticospinal excitability, which may boost subsequent motor learning during physiotherapy.

Asunto(s)

RESUMEN

BACKGROUND: Magnetic resonance images are being increasingly deployed in conjunction with navigated transcranial magnetic stimulation (nTMS) to account for inter-individual differences in brain anatomy as well as to reduce the variability of mapping findings. OBJECTIVE: However, despite the fact that the individual gyral anatomy has a significant impact on the TMS-induced electrical field distributions, these approaches still project the TMS coil positions as a plane grid of target points on the brain surface and fail to account for differences in cortex morphology. METHODS: In this study, we have introduced a technique for projecting nTMS sites onto the gyral anatomy to decrease the variability of cortical motor maps between subjects in normalized space. This involved interpolating the discrete map points in the normalized volume space and performing additional surface coregistration. RESULTS: By applying this technique, we increased the spatial overlap between the cortical maps of the extensor digitorum communis muscle between subjects from 80% to 100%. We also managed to significantly reduce the mean Euclidean distance between the average center of gravity and the average hotspots to the respective individual spots from 8 mm to 6.5 mm. CONCLUSION: Our approach facilitates the study of the functional topography of distinct behavioral properties with high spatial resolution, thereby constituting a valuable tool for precise group analysis of cortical TMS maps.

Asunto(s)

RESUMEN

Motor recovery after stroke is an unsolved challenge despite intensive rehabilitation training programs. Brain stimulation techniques have been explored in addition to traditional rehabilitation training to increase the excitability of the stimulated motor cortex. This modulation of cortical excitability augments the response to afferent input during motor exercises, thereby enhancing skilled motor learning by long-term potentiation-like plasticity. Recent approaches examined brain stimulation applied concurrently with voluntary movements to induce more specific use-dependent neural plasticity during motor training for neurorehabilitation. Unfortunately, such approaches are not applicable for the many severely affected stroke patients lacking residual hand function. These patients require novel activity-dependent stimulation paradigms based on intrinsic brain activity. Here, we report on such brain state-dependent stimulation (BSDS) combined with haptic feedback provided by a robotic hand orthosis. Transcranial magnetic stimulation (TMS) of the motor cortex and haptic feedback to the hand were controlled by sensorimotor desynchronization during motor-imagery and applied within a brain-machine interface (BMI) environment in one healthy subject and one patient with severe hand paresis in the chronic phase after stroke. BSDS significantly increased the excitability of the stimulated motor cortex in both healthy and post-stroke conditions, an effect not observed in non-BSDS protocols. This feasibility study suggests that closing the loop between intrinsic brain state, cortical stimulation and haptic feedback provides a novel neurorehabilitation strategy for stroke patients lacking residual hand function, a proposal that warrants further investigation in a larger cohort of stroke patients.