Marie-Hélène Boudrias

Theta Burst Stimulation in the Rehabilitation of the Upper Limb: A Semirandomized, Placebo-Controlled Trial in Chronic Stroke Patients

Background. Noninvasive cortical stimulation could represent an add-on treatment to enhance motor recovery after stroke. However, its clinical value, including anticipated size and duration of the treatment effects, remains largely unknown. Objective. The authors designed a small semi-randomized clinical trial to explore whether long-lasting clinically important gains can be achieved by adding theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (TMS), to a rehabilitation program for the hand. Methods. A total of 41 chronic stroke patients received excitatory TBS to the ipsilesional hemisphere or inhibitory TBS to the contralesional hemisphere in 2 centers; each active group was compared with a group receiving sham TBS. TBS was followed by physical therapy for 10 working days. Patients and therapists were blinded to the type of TBS. Primary outcome measures (9-hole Peg Test [9HPT], Jebsen Taylor Test [JTT], and grip and pinch-grip dynamometry) were assessed 4, 30, and 90 days post treatment. The clinically important difference was defined as 10% of the maximum score. Results. There were no differences between the active treatment and sham groups in any of the outcome measures. All patients achieved small sustainable improvements—9HPT, 5% of maximum (confidence interval [CI] = 3%-7%); JTT, 5.7% (CI = 3%-8%); and grip strength, 6% (CI = 2%-10%)—all below the defined clinically important level. Conclusions. Cortical stimulation did not augment the gains from a late rehabilitation program. The effect size anticipated by the authors was overestimated. These results can improve the design of future work on therapeutic uses of TMS.

Assessing the Integrity of Corticospinal Pathways From Primary and Secondary Cortical Motor Areas After Stroke

Background and Purpose— Aside from the primary motor cortex, the corticospinal tract (CST) also receives fibers from dorsal and ventral premotor cortices and supplementary motor area, all of which might potentially contribute to motor function after stroke. We sought to quantify the microstructural integrity of CST originating from the hand representations in these 4 motor cortices separately and examined how these values related to hand motor impairment. Methods— Probabilistic tractography from functional MRI-defined cortical sites demonstrated continuous CST originating from hand representations within each motor area in a group of healthy subjects. Microstructural integrity for each tract was calculated using fractional anisotropy at the level of the posterior limb of the internal capsule in a group of patients with chronic stroke. Results— Fractional anisotropy was reduced in all 4 CSTs in the affected hemisphere. Grip strength correlated with the integrity of the CSTs originating from primary motor and dorsal premotor cortices, whereas, in a multiple regression model, the latter improved the ability of primary motor cortex CST to explain variability in grip strength. Conclusion— Handgrip critically depends on the CST originating in primary motor cortex but microstructural integrity of CST originating from premotor cortices appears to play a role in supporting motor function after stroke.

Output Properties and Organization of the Forelimb Representation of Motor Areas on the Lateral Aspect of the Hemisphere in Rhesus Macaques

Motor output capabilities of the forelimb representation of dorsal motor area (PMd) and ventral motor area (PMv) were compared with primary motor cortex (M1) in terms of latency, strength, sign, and distribution of effects. Stimulus-triggered averages (60 microA) of electromyographic activity collected from 24 forelimb muscles were computed at 314 tracks in 2 monkeys trained to perform a reach-to-grasp task. The onset latency and magnitude of facilitation effects from PMd and PMv were significantly longer and 7- to 9-fold weaker than those from M1. Proximal muscles were predominantly represented in PMd and PMv. A joint-dependent flexor or extensor preference was also present. Distal and proximal muscle representations were intermingled in PMd and PMv. A gradual increase in latency and decrease in magnitude of effects were observed in moving from M1 surface sites toward more anterior sites in PMd. For many muscles, segregated areas producing suppression effects were found along the medial portion of PMd and adjacent M1. Although some facilitation effects from PMd and PMv had onset latencies as short as those from M1 in the same muscle, suggesting equal direct linkage, the vast majority had properties consistent with a more indirect linkage to motoneurons either through corticocortical connections with M1 and/or interneuronal linkages in the spinal cord.

Do movement-related beta oscillations change after stroke?

Stroke is the most common cause of physical disability in the world today. While the key element of rehabilitative therapy is training, there is currently much interest in approaches that “prime” the primary motor cortex to be more excitable, thereby increasing the likelihood of experience-dependent plasticity. Cortical oscillations reflect the balance of excitation and inhibition, itself a key determinant of the potential for experience-dependent plasticity. In the motor system, beta-band oscillations are important and are thought to maintain the resting sensorimotor state. Here we examined motor cortex beta oscillations during rest and unimanual movement in a group of stroke patients and healthy control subjects, using magnetoencephalography. Movement-related beta desynchronization (MRBD) in contralateral primary motor cortex was found to be significantly reduced in patients compared with control subjects. Within the patient group, smaller MRBD was seen in those with more motor impairment. We speculate that impaired modulation of beta oscillations during affected hand grip is detrimental to motor control, highlighting this as a potential therapeutic target in neurorehabilitation.

Beta oscillations reflect changes in motor cortex inhibition in healthy ageing

Beta oscillations are involved in movement and have previously been linked to levels of the inhibitory neurotransmitter GABA. We examined changes in beta oscillations during rest and movement in primary motor cortex (M1). Amplitude and frequency of beta power at rest and movement-related beta desynchronization (MRBD) were measured during a simple unimanual grip task and their relationship with age was explored in a group of healthy participants. We were able to show that at rest, increasing age was associated with greater baseline beta power in M1 contralateral to the active hand, with a similar (non-significant) trend in ipsilateral M1. During movement, increasing age was associated with increased MRBD amplitude in ipsilateral M1 and reduced frequency (in contralateral and ipsilateral M1). These findings would be consistent with greater GABAergic inhibitory activity within motor cortices of older subjects. These oscillatory parameters have the potential to reveal changes in the excitatory–inhibitory balance in M1 which in turn may be a useful marker of plasticity in the brain, both in healthy ageing and disease.

Age-related changes in causal interactions between cortical motor regions during hand grip

Brain activity during motor performance becomes more widespread and less lateralized with advancing age in response to ongoing degenerative processes. In this study, we were interested in the mechanism by which this change in the pattern of activity supports motor performance with advancing age. We used both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to assess age related changes in motor system connectivity during isometric hand grip. Paired pulse TMS was used to measure the change in interhemispheric inhibition (IHI) from contralateral M1 (cM1) to ipsilateral M1 (iM1) during right hand grip. Dynamic Causal Modelling (DCM) of fMRI data was used to investigate the effect of age on causal interactions throughout the cortical motor network during right hand grip. Bayesian model selection was used to identify the causal model that best explained the data for all subjects. Firstly, we confirmed that the TMS and DCM measures both demonstrated a less inhibitory/more facilitatory influence of cM1 on iM1 during hand grip with advancing age. These values correlated with one another providing face validity for our DCM measures of connectivity. We found increasing reciprocal facilitatory influences with advancing age (i) between all ipsilateral cortical motor areas and (ii) between cortical motor areas of both hemispheres and iM1. There were no differences in the performance of our task with ageing suggesting that the ipsilateral cortical motor areas, in particular iM1, play a central role in maintaining performance levels with ageing through increasingly facilitatory cortico-cortical influences.

Forelimb Muscle Representations and Output Properties of Motor Areas in the Mesial Wall of Rhesus Macaques

In this study, forelimb organizations and output properties of the supplementary motor area (SMA) and the dorsal cingulate motor area (CMAd) were assessed and compared with primary motor cortex (M1). Stimulus-triggered averages of electromyographic activity from 24 muscles of the forelimb were computed from layer V sites of 2 rhesus monkeys performing a reach-to-grasp task. No clear segregation of the forelimb representation of proximal and distal muscles was found in SMA. In CMAd, sites producing poststimulus effects in proximal muscles tended to be located caudal to distal muscle sites, although the number of effects was limited. For both SMA and CMAd, facilitation effects were more prevalent in distal than in proximal muscles. At an intensity of 60 microA, the mean latencies of M1 facilitation effects were 8 and 12.1 ms shorter and the magnitudes approximately 10 times greater than those from SMA and CMAd. Our results show that corticospinal neurons in SMA and CMAd provide relatively weak input to spinal motoneurons compared with the robust effects from M1. However, a small number of facilitation effects from SMA and CMAd had latencies as short as the shortest ones from M1 suggesting a minimum linkage to motoneurons as direct as that from M1.

Changes in the location of cortico-muscular coherence following stroke

Stroke results in reorganization of residual brain networks. The functional role of brain regions within these networks remains unclear, particularly those in the contralesional hemisphere. We studied 25 stroke patients with a range of motor impairment and 23 healthy age-matched controls using magnetoencephalography (MEG) and electromyography (EMG) to measure oscillatory signals from the brain and affected muscles simultaneously during a simple isometric hand grip, from which cortico-muscular coherence (CMC) was calculated. Peaks of cortico-muscular coherence in both the beta and gamma bands were found in the contralateral sensorimotor cortex in all healthy controls, but were more widespread in stroke patients, including some peaks found in the contralesional hemisphere (7 patients for beta coherence and 5 for gamma coherence). Neither the coherence value nor the distance of the coherence peak from the mean of controls correlated with impairment. Peak CMC in the contralesional hemisphere was found not only in some highly impaired patients, but also in some patients with good functional recovery. Our results provide evidence that a wide range of cortical brain regions, including some in the contralesional hemisphere, may have influence over EMG activity in the affected muscles after stroke thereby supporting functional recovery.

Principles of corticospinal system organization and function

Publisher Summary This chapter discusses a set of principles on the current state of knowledge about the organization and function of the corticospinal system in primates. The functional roles of cortical output neurons are (1) movement execution-related, (2) reflex modulation-related, (3) sensory modulation-related, and (4) internal motor program-related. Corticospinal neurons are distributed over broad regions of the fronto-parietal cortex including six premotor areas in the frontal lobe. The map of major body parts within the M1 cortex shows consistent and orderly features as does the intra-areal representation. The chapter discusses the functional properties of the corticospinal system. The secondary cortical motor areas (SMAs) contain a complete motor map of major body parts and corticospinal neurons that terminate largely in the intermediate zone of the spinal cord, produce relatively weak direct output effects on muscle activity, and have been implicated in a number of functions including movement sequence learning, movement programming and execution associated with postural control, coordination of bimanual movements, and execution of internally guided movements. Three cingulate motor areas (CMAs) are located within the cingulate gyrus beneath the SMA. Two lateral premotor areas (PMd and PMv) are located in area 6 anterior to the hand/arm representation of M1. PMd contains a representation of the forelimb, hind limb and face, whereas only forelimb and face representations have been found in the PMv.