Cortical and STN spectral changes during limb movements in PD patients with and without dystonia

Background: Dystonia is a prevalent yet under-studied motor feature of Parkinson disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear. Objectives: To investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in PD patients with versus without dystonia. Methods: We examined the prevalence and somatotopy of dystonia in PD patients undergoing deep brain stimulation (DBS) surgery. We recorded intracranial electrophysiology from sensorimotor cortex and directional DBS electrodes in subthalamic nucleus (STN), during both rest and voluntary contralateral limb movements. We used wavelet transforms and linear mixed models to characterize spectral content in patients with and without dystonia (n=25). Results: Dystonia was highly prevalent at enrollment (61%) and most common in the foot (78%). PD patients with dystonia display greater subthalamic theta and alpha power during movement (p < 0.05) but not at rest. Regardless of dystonia status, cortical recordings display prominent beta desynchronization (13-30 Hz) during movement, whereas STN signals show increases in spectral power at lower frequencies (4-20 Hz), with peaks at 6.0 +/- 3.3 and 4.2 +/- 2.9 Hz during hand and foot movements, respectively (p < 0.03). Conclusions: Whereas cortex was characterized by beta desynchronization during hand and foot movements similarly, STN showed limb-specific low frequency activity which was increased in PD patients with dystonia. These findings may help elucidate why PD-related dystonia is most common in the foot and help guide future closed-loop DBS devices.

Catch the star! Spatial information activates the manual motor system

Previous research demonstrated a close bidirectional relationship between spatial attention and the manual motor system. However, it is unclear whether an explicit hand movement is necessary for this relationship to appear. A novel method with high temporal resolution – bimanual grip force registration – sheds light on this issue. Participants held two grip force sensors while being presented with lateralized stimuli (exogenous attentional shifts, Experiment 1), left- or right-pointing central arrows (endogenous attentional shifts, Experiment 2), or the words "left" or "right" (endogenous attentional shifts, Experiment 3). There was an early interaction between the presentation side or arrow direction and grip force: lateralized objects and central arrows led to an increase of the ipsilateral force and a decrease of the contralateral force. Surprisingly, words led to the opposite pattern: increased force in the contralateral hand and decreased force in the ipsilateral hand. The effect was stronger and appeared earlier for lateralized objects (60 ms after stimulus presentation) than for arrows (100 ms) or words (250 ms). Thus, processing visuospatial information automatically activates the manual motor system, but the timing and direction of this effect vary depending on the type of stimulus.

Relationship between high-frequency activity in the sensory and the motor hand areas, and regional myelin content

BackgroundThe human primary sensory (S1) and primary motor (M1) hand areas feature high-frequency neuronal responses. Electrical nerve stimulation evokes high-frequency oscillations (HFO) at around 650 Hz in the contralateral S1. Likewise, paired-pulse transcranial magnetic stimulation of M1 produces short interval intracortical facilitation (SICF) of motor evoked potentials in contralateral hand muscles. SICF features several peaks of facilitation which are separated by inter-peak intervals resembling HFO rhythmicity.HypothesisIn this study, we tested the hypothesis that the individual expressions of HFO and SICF are tightly related to each other and to the regional myelin content in the sensorimotor cortex.MethodsIn 24 healthy volunteers, we recorded HFO and SICF, and, in a subgroup of 20 participants, we mapped the cortical myelin content using the ratio between the T1- and T2-weighted MRI signal as read-out.ResultsThe individual frequencies and magnitudes of HFO and SICF were tightly correlated: the intervals between the first and second peak of cortical HFO and SICF showed a positive linear relationship (r= 0.703, p< 0.001), while their amplitudes were inversely related (r= −0.613, p= 0.001). The rhythmicity, but not the magnitude of the high-frequency responses, was related to the cortical myelin content: the higher the cortical myelin content, the shorter the inter-peak intervals of HFO and SICF.ConclusionThe results confirm a tight functional relationship between high-frequency responses in S1 (i.e., HFO) and M1 (i.e., SICF). They also establish a link between the degree of regional cortical myelination and the expression of high-frequency responses in the human cortex, giving further the opportunity to infer their possible generators.

Fatigue induces behavioural improvements in the unfatigued hand via altered functional connectivity and neurochemicals in cortical motor areas

In humans, motor learning is underpinned by changes in functional connectivity (FC) across the sensorimotor network. Unilateral exercise-induced fatigue increases FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Unilateral fatiguing exercise is therefore a promising potential approach to augment motor performance in the non-fatigued, contralateral, hand. In a within-participant, controlled, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional MRI and MR Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands, and after scanning, participants performed a serial reaction time task (SRTT) with their left, unfatigued, hand. Nine minutes of 50% MVC contractions resulted in fatigue. This unimanual fatigue improved motor performance, as indexed by decreased RTs, in the contralateral hand. Although fatigue had no significant effects on sequence learning, fatigue led to a significant increase in the transfer of the learned skill to the untrained hand. These behavioural effects were supported by significant neural changes: an increase in SMA-SMA functional connectivity, and increased connectivity between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of fatigue-induced decrease in GABA in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support unilateral fatiguing exercise as a potential therapeutic intervention in a range of neurological and orthopedic conditions.

Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation

Background: Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer. Objective: To develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region. Methods: We designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand. Results: The transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum. Conclusion: The developed mTMS system enables electronically targeted brain stimulation within a cortical region.

Bimanual coupling effect during a proprioceptive stimulation

Circle-line drawing paradigm is used to study bimanual coupling. In the standard paradigm, subjects are asked to draw circles with one hand and lines with the other hand; the influence of the concomitant tasks results in two “elliptical” figures. Here we tested whether proprioceptive information evoked by muscle vibration inducing a proprioceptive illusion (PI) of movement at central level, was able to affect the contralateral hand drawing circles or lines. A multisite 80 Hz-muscle vibration paradigm was used to induce the illusion of circle- and line-drawing on the right hand of 15 healthy participants. During muscle vibration, subjects had to draw a congruent or an incongruent figure with the left hand. The ovalization induced by PI was compared with Real and Motor Imagery conditions, which already have proved to induce bimanual coupling. We showed that the ovalization of a perceived circle over a line drawing during PI was comparable to that observed in Real and Motor Imagery condition. This finding indicates that PI can induce bimanual coupling, and proprioceptive information can influence the motor programs of the contralateral hand.

An evaluation of contralateral hand involvement in the operation of the Delft Self-Grasping Hand, an adjustable passive prosthesis

The Delft Self-Grasping Hand is an adjustable passive prosthesis operated using the concept of tenodesis (where opening and closing of the hand is mechanically linked to the flexion and extension of the wrist). As a purely mechanical device that does not require harnessing, the Self-Grasping Hand offers a promising alternative to current prostheses. However, the contralateral hand is almost always required to operate the mechanism to release a grasp and is sometimes also used to help form the grasp; hence limiting the time it is available for other purposes. In this study we quantified the amount of time the contralateral hand was occupied with operating the Self-Grasping Hand, classified as either direct or indirect interaction, and investigated how these periods changed with practice. We studied 10 anatomically intact participants learning to use the Self-Grasping Hand fitted to a prosthesis simulator. The learning process involved 10 repeats of a feasible subset of the tasks in the Southampton Hand Assessment Procedure (SHAP). Video footage was analysed, and the time that the contralateral hand was engaged in grasping or releasing was calculated. Functionality scores increased for all participants, plateauing at an Index of Functionality of 33.5 after 5 SHAP attempts. Contralateral hand involvement reduced significantly from 6.47 (first 3 attempts) to 4.68 seconds (last three attempts), but as a proportion of total task time remained relatively steady (increasing from 29% to 32%). For 9/10 participants most of this time was supporting the initiation of grasps rather than releases. The reliance on direct or indirect interactions between the contralateral hand and the prosthesis varied between participants but appeared to remain relatively unchanged with practice. Future studies should consider evaluating the impact of reliance on the contralateral limb in day-to-day life and development of suitable training methods.

Dorsoradial Capsulodesis for Stage I Trapeziometacarpal Joint Arthrosis

Background: Thumb trapeziometacarpal (TM) joint arthrosis is a common cause of thumb pain, which adversely affects hand function. Early arthrosis is characterized by capsular laxity, painful pinch and grip, and physical findings of joint tenderness and laxity. Dorsoradial capsulodesis (DRC) is a surgical technique used to stabilize the TM joint and treat early-stage arthrosis. We aim to evaluate the clinical outcomes of DRC for treating trapeziometacarpal instability in early-stage disease. Methods: Between 2003 and 2019, 23 patients underwent DRC. Patients with stage I TM arthritis and more than 6-month postoperative follow-up were included. Pain and disability scores were calculated along with physical examination and radiographic evaluation at the final follow-up. Results: At mean postoperative follow-up of 43.5 months, 13 patients with a mean age of 39.1 years were examined. The mean Disabilities of the Arm, Shoulder, and Hand score was 5.7, and visual analog pain score was 0.5. Patients had no significant difference in strength or range of motion in the ipsilateral versus contralateral hand. Follow-up radiographs did not demonstrate arthritic changes. Conclusions: Dorsoradial capsulodesis is a technically simple and reasonable option for stabilizing the TM joint in patients with early-stage arthrosis. This intervention showed no midterm progression to advanced arthritis in this cohort.

Visuomotor information drives interference between the hands more than dynamic motor information during bimanual reaching

During complex bimanual movements, interference can occur in the form of one hand influencing the action of the contralateral hand. Interference likely results from conflicting sensorimotor information shared between brain regions controlling hand movements via neural crosstalk. However, how visual and force-related feedback processes interact with each other during bimanual reaching is not well understood. In this study, four groups experienced either a visuomotor perturbation, dynamic perturbation, combined visuomotor and dynamic perturbation, or no perturbation in their right hand during bimanual reaches, with each hand controlling its own cursor. The left hand was examined for interference as a consequence of the right-hand perturbation. The results indicated that the visuomotor and combined perturbations showed greater interference in the left hand than the dynamic perturbation, but that the combined and visuomotor perturbations were equivalent. This suggests that dynamic sensorimotor and visuomotor processes do not interact between hemisphere-hand systems, and that primarily visuomotor processes lead to interference between the hands.

Unconscious Touch Perception After Disruption of the Primary Somatosensory Cortex

Brain damage or disruption to the primary visual cortex sometimes produces blindsight, a striking condition in which patients lose the ability to consciously detect visual information yet retain the ability to discriminate some attributes without awareness. Although there have been few demonstrations of somatosensory equivalents of blindsight, the lesions that produce “numbsense,” in which patients can make accurate guesses about tactile information without awareness, have been rare and localized to different regions of the brain. Despite transient loss of tactile awareness in the contralateral hand after transcranial magnetic stimulation (TMS) of the primary somatosensory cortex but not TMS of a control site, 12 participants (six female) reliably performed at above-chance levels on a localization task. These results demonstrating TMS-induced numbsense implicate a parallel somatosensory pathway that processes the location of touch in the absence of awareness and highlight the importance of primary sensory cortices for conscious perception.