Unravelling the Modulation of Intracortical Inhibition During Motor Imagery: An Adaptive Threshold-Hunting Study.

Motor imagery (MI) is the mental simulation of an action without any apparent muscular contraction. By means of transcranial magnetic stimulation (TMS), few studies revealed a decrease of short-interval intracortical inhibition (SICI) within the primary motor cortex. However, this decrease is ambiguous, as one would expect greater inhibition during MI to prevent overt motor output. The current study investigated the extent of SICI modulation during MI through a methodological and a conceptual reconsideration of (i) the importance of parameters to assess SICI (Exp.1) and (ii) the inhibitory process within the primary motor cortex as an inherent feature of MI (Exp.2). Participants performed two tasks: (1) rest and (2) imagery of isometric abduction of the right index finger. Using TMS, motor evoked potentials were elicited in the right first dorsal interosseous (FDI) muscle. An adaptive threshold-hunting paradigm was used, where the stimulus intensity required to maintain a fixed motor evoked potential amplitude was quantified. To test SICI, we conditioned the test stimulus with a conditioning stimulus (CS) of different intensities. Results revealed an Intensity by Task interaction showing that SICI decreased during MI as compared to rest only for the higher CS intensity (Exp.1). At the lowest CS intensities, a Task main effect revealed that SICI increased during MI (Exp.2). SICI modulation during MI depends critically on the CS intensity. By optimising CS intensity, we have shown that SICI circuits may increase during MI, revealing a potential mechanism to prevent the production of a movement while the motor system is activated.

Neurochemical balance and inhibition at the subacute stage after stroke.

Stroke is a leading cause of death and disability worldwide with many people left with impaired motor function. Evidence from experimental animal models of stroke indicates that reducing motor cortex inhibition may facilitate neural plasticity and motor recovery. This study compared primary motor cortex (M1) inhibition measures over the first 12 wk after stroke with a cohort of age-similar healthy controls. The excitation-inhibition ratio and gamma-aminobutyric acid (GABA) neurotransmission within M1 were assessed using magnetic resonance spectroscopy and threshold hunting paired-pulse transcranial magnetic stimulation respectively. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Patients with a functional corticospinal pathway had motor-evoked potentials on the paretic side and exhibited better recovery from upper limb impairment and recovery of function than patients without a functional corticospinal pathway. Compared with age-similar controls, the neurochemical balance in terms of the excitation-inhibition ratio was greater within contralesional M1 in patients with a functional corticospinal pathway. There was evidence for elevated long-interval inhibition in both ipsilesional and contralesional M1 compared with controls. Short-interval inhibition measures differed between the first and second phases, with evidence for elevation of the former only in ipsilesional M1 and no evidence of disinhibition for the latter. Overall, findings from transcranial magnetic stimulation indicate an upregulation of GABA-mediated tonic inhibition in M1 early after stroke. Therapeutic approaches that aim to normalize inhibitory tone during the subacute period warrant further investigation.NEW & NOTEWORTHY Magnetic resonance spectroscopy indicated higher excitation-inhibition ratios within motor cortex during subacute recovery than age-similar healthy controls. Measures obtained from adaptive threshold hunting paired-pulse transcranial magnetic stimulation indicated greater tonic inhibition in patients compared with controls. Therapeutic approaches that aim to normalize motor cortex inhibition during the subacute stage of recovery should be explored.

The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study.

BACKGROUND: Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. OBJECTIVE: To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke. METHODS: Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration. RESULTS: Short-interval intracortical inhibition was similar between patients and controls ( P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls ( P < .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function ( P = .002 and P = .017). GABA concentration was lower within ipsilesional ( P = .009) and contralesional ( P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients. CONCLUSION: These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.

GABA and primary motor cortex inhibition in young and older adults: a multimodal reliability study.

The effects of healthy aging on γ-aminobutyric acid (GABA) within primary motor cortex (M1) remain poorly understood. Studies have reported contrasting results, potentially due to limitations with the common assessment technique. The aim of the present study was to investigate the effect of healthy aging on M1 GABA concentration and neurotransmission using a multimodal approach. Fifteen young and sixteen older adults participated in this study. Magnetic resonance spectroscopy (MRS) was used to measure M1 GABA concentration. Single-pulse and threshold-tracking paired-pulse transcranial magnetic stimulation (TMS) protocols were used to examine cortical silent period duration, short- and long-interval intracortical inhibition (SICI and LICI), and late cortical disinhibition (LCD). The reliability of TMS measures was examined with intraclass correlation coefficient analyses. SICI at 1 ms was reduced in older adults (15.13 ± 2.59%) compared with young (25.66 ± 1.44%; P = 0.002). However, there was no age-related effect for cortical silent period duration, SICI at 3 ms, LICI, or LCD (all P > 0.66). The intersession reliability of threshold-tracking measures was good to excellent for both young (range 0.75-0.96) and older adults (range 0.88-0.93). Our findings indicate that extrasynaptic inhibition may be reduced with advancing age, whereas GABA concentration and synaptic inhibition are maintained. Furthermore, MRS and threshold-tracking TMS provide valid and reliable assessment of M1 GABA concentration and neurotransmission, respectively, in young and older adults.NEW & NOTEWORTHY γ-Aminobutyric acid (GABA) in primary motor cortex was assessed in young and older adults using magnetic resonance spectroscopy and threshold-tracking paired-pulse transcranial magnetic stimulation. Older adults exhibited reduced extrasynaptic inhibition (short-interval intracortical inhibition at 1 ms) compared with young, whereas GABA concentration and synaptic inhibition were similar between age groups. We demonstrate that magnetic resonance spectroscopy and threshold-tracking provide valid and reliable assessments of primary motor cortex GABA concentration and neurotransmission, respectively.

Can motor imagery and hypnotic susceptibility explain Conversion Disorder with motor symptoms?

Marked distortions in sense of agency can be induced by hypnosis in susceptible individuals, including alterations in subjective awareness of movement initiation and control. These distortions, with associated disability, are similar to those experienced with Conversion Disorder (CD), an observation that has led to the hypothesis that hypnosis and CD share causal mechanisms. The purpose of this review is to explore the relationships among motor imagery (MI), hypnotic susceptibility, and CD, then to propose how MI ability may contribute to hypnotic responding and CD. Studies employing subjective assessments of mental imagery have found little association between imagery abilities and hypnotic susceptibility. A positive association between imagery abilities and hypnotic susceptibility becomes apparent when objective measures of imagery ability are employed. A candidate mechanism to explain motor responses during hypnosis is kinaesthetic MI, which engages a strategy that involves proprioception or the "feel" of movement when no movement occurs. Motor suppression imagery (MSI), a strategy involving inhibition of movement, may provide an alternate objective measurable phenomenon that underlies both hypnotic susceptibility and CD. Evidence to date supports the idea that there may be a positive association between kinaesthetic MI ability and hypnotic susceptibility. Additional evidence supports a positive association between hypnotic susceptibility and CD. Disturbances in kinaesthetic MI performance in CD patients indicate that MI mechanisms may also underlie CD symptoms. Further investigation of the above relationships is warranted to explain these phenomena, and establish theoretical explanations underlying sense of agency.

Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation.

Impairment or interruption of oxygen supply compromises brain function and plays a role in neurological and neurodegenerative conditions. Creatine is a naturally occurring compound involved in the buffering, transport, and regulation of cellular energy, with the potential to replenish cellular adenosine triphosphate without oxygen. Creatine is also neuroprotective in vitro against anoxic/hypoxic damage. Dietary creatine supplementation has been associated with improved symptoms in neurological disorders defined by impaired neural energy provision. Here we investigate, for the first time in humans, the utility of creatine as a dietary supplement to protect against energetic insult. The aim of this study was to assess the influence of oral creatine supplementation on the neurophysiological and neuropsychological function of healthy young adults during acute oxygen deprivation. Fifteen healthy adults were supplemented with creatine and placebo treatments for 7 d, which increased brain creatine on average by 9.2%. A hypoxic gas mixture (10% oxygen) was administered for 90 min, causing global oxygen deficit and impairing a range of neuropsychological processes. Hypoxia-induced decrements in cognitive performance, specifically attentional capacity, were restored when participants were creatine supplemented, and corticomotor excitability increased. A neuromodulatory effect of creatine via increased energy availability is presumed to be a contributing factor of the restoration, perhaps by supporting the maintenance of appropriate neuronal membrane potentials. Dietary creatine monohydrate supplementation augments neural creatine, increases corticomotor excitability, and prevents the decline in attention that occurs during severe oxygen deficit. This is the first demonstration of creatine's utility as a neuroprotective supplement when cellular energy provision is compromised.

Transcranial direct current stimulation enhances recovery of stereopsis in adults with amblyopia.

Amblyopia is a neurodevelopmental disorder of vision caused by abnormal visual experience during early childhood that is often considered to be untreatable in adulthood. Recently, it has been shown that a novel dichoptic videogame-based treatment for amblyopia can improve visual function in adult patients, at least in part, by reducing inhibition of inputs from the amblyopic eye to the visual cortex. Non-invasive anodal transcranial direct current stimulation has been shown to reduce the activity of inhibitory cortical interneurons when applied to the primary motor or visual cortex. In this double-blind, sham-controlled cross-over study we tested the hypothesis that anodal transcranial direct current stimulation of the visual cortex would enhance the therapeutic effects of dichoptic videogame-based treatment. A homogeneous group of 16 young adults (mean age 22.1 ± 1.1 years) with amblyopia were studied to compare the effect of dichoptic treatment alone and dichoptic treatment combined with visual cortex direct current stimulation on measures of binocular (stereopsis) and monocular (visual acuity) visual function. The combined treatment led to greater improvements in stereoacuity than dichoptic treatment alone, indicating that direct current stimulation of the visual cortex boosts the efficacy of dichoptic videogame-based treatment. This intervention warrants further evaluation as a novel therapeutic approach for adults with amblyopia.

Cutaneous anesthesia of the forearm enhances sensorimotor function of the hand.

Temporary deafferentation of the upper limb, with ischemic or anesthetic nerve block, has rapid effects on sensorimotor cortex. Cutaneous anesthesia of the forearm has recently been found to improve sensory and motor function of the paretic hand in chronic stroke patients. However, the neurophysiological mechanisms are unknown. The aim of this study was to investigate the behavioral and neurophysiological effects of cutaneous forearm anesthesia. Twenty-five healthy right-handed adults participated in this double-blind, randomized study. Participants completed two sessions, with either a topical anesthesia cream (EMLA) or placebo applied to their left forearm in each session. Thresholds for cutaneous sensation and spatial acuity of the left hand were measured before and after the intervention. Transcranial magnetic stimulation was used to measure corticomotor excitability and short-interval intracortical inhibition in the left first dorsal interosseous and abductor digiti minimi muscles before and after the intervention. Manual dexterity was assessed with the grooved pegboard task after the intervention in each session. Left-hand dexterity improved to a greater extent after treatment with EMLA than placebo, and this was related to improved spatial acuity at the fingertips. Corticomotor excitability remained stable, and short-interval intracortical inhibition increased after EMLA treatment. We have confirmed and extended previous reports that cutaneous forearm anesthesia results in improved spatial acuity and manual dexterity of the ipsilateral hand. The neurophysiological mechanisms involve an increase in intracortical inhibition, which may improve the precision of voluntary movement. These results lend support to the therapeutic application of EMLA in movement rehabilitation.

Task-dependent interaction between parietal and contralateral primary motor cortex during explicit versus implicit motor imagery.

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks.

Controversy: Noninvasive and invasive cortical stimulation show efficacy in treating stroke patients.

Stroke is the leading cause of disability in the adult population of western industrialized countries. Despite significant improvements of acute stroke care, two thirds of stroke survivors have to cope with persisting neurologic deficits. Adjuvant brain stimulation is a novel approach to improving the treatment of residual deficits after stroke. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and epidural electrical stimulation have been used in first trials on small cohorts of stroke patients. Effect sizes in the order of 8% to 30% of functional improvement have been reported, but a publication bias toward presenting "promising" but not negative results is likely. Many questions regarding underlying mechanisms, optimal stimulation parameters, combination with other types of interventions, among others, are open. This review addresses six controversies related to the experimental application of brain stimulation techniques to stroke patients. Cortical stimulation after stroke will need to be individually tailored and a thorough patient stratification according to type and extent of clinical deficit, lesion location, lesion size, comorbidities, time in the recovery process, and perhaps also age and gender will be necessary. There is consensus that cortical stimulation in stroke patients is still experimental and should only be applied in the frame of scientific studies.

Lateralization of motor imagery following stroke.

OBJECTIVE: Motor imagery may activate the primary motor cortex (M1) and promote functional recovery following stroke. We investigated whether the hemisphere affected by stroke affects performance and M1 activity during motor imagery. METHODS: Twelve stroke patients (6 left, 6 right hemisphere) and eight healthy age-matched adults participated. Experiment 1 assessed the speed and ease of actual and imagined motor performance. Experiment 2 measured corticomotor excitability during imagined movement of each hand separately, and both hands together, using transcranial magnetic stimulation. RESULTS: For control participants, imagined movements were performed more slowly than actual movements, and right-hand MEPs were facilitated when they imagined moving their right hand or both hands together. Patients reported being able to imagine movements with either hand, despite no measurable facilitation of MEPs in the stroke-affected hand. In left hemisphere patients, MEPs were facilitated in the left hand during imagery of the right hand and both hands together. In right hemisphere patients, motor imagery did not facilitate MEPs in either hand. CONCLUSIONS: Motor imagery does not appear to facilitate the ipsilesional M1 following stroke. SIGNIFICANCE: Motor imagery may play a role in rehabilitating movement planning, but its role in directly facilitating corticomotor output appears limited.

The effect of coordination mode on use-dependent plasticity.

OBJECTIVE: To evaluate the role of coordination mode on the generation of use-dependent plasticity (UDP) within the primary motor cortex (M1). METHODS: Ten healthy volunteers performed brisk repetitive thumb movements for 30 min in the opposite direction to those evoked by transcranial magnetic stimulation (TMS) prior to training. This practice was synchronized or syncopated with a 1 Hz auditory metronome in two separate sessions. Motor evoked potentials (MEPs) were recorded from 3 intrinsic thumb muscles, to assess changes in corticomotor excitability. RESULTS: Both synchronized and syncopated motor practice induced changes in the direction of TMS-evoked thumb movements, away from the baseline direction toward the trained direction. MEP amplitude increased following synchronized, but not syncopated, motor practice. Changes in movement direction and corticomotor excitability lasted for at least 30 minutes. CONCLUSIONS: UDP can be elicited in the presence or absence of changes in corticomotor excitability. SIGNIFICANCE: Motor practice that is synchronized with external pacing may promote UDP and facilitate corticomotor excitability in patient populations with reduced corticomotor output, such as stroke. Training that is syncopated with external pacing may promote UDP without increasing corticomotor excitability. This could be relevant for individuals with disorders characterized by maladaptive plasticity.

Lateralization of unimanual and bimanual motor imagery.

Most studies of motor imagery have examined motor cortex function during imagery of dominant hand movement. The aim of this study was to examine the modulation of excitability in the dominant and non-dominant corticomotor pathways during kinesthetic motor imagery of unimanual and bimanual movement. Transcranial magnetic stimulation (TMS) was applied over the contralateral motor cortex (M1) to elicit motor-evoked potentials (MEPs) in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles of each hand, in two separate sessions. Transcutaneous electrical stimuli were also delivered to the median nerve at each wrist, to elicit F-waves from APB. Fifteen right-handed volunteers imagined unimanual and bimanual phasic thumb movements, paced with a 1-Hz auditory metronome. Stimuli were delivered at rest, and either 50 ms before (ON phase), or 450 ms after (OFF phase), the metronome beeps. Significant MEP amplitude facilitation occurred only in right APB, during the ON phase of motor imagery of the right hand and both hands. Significant temporal modulation of right APB MEP amplitude was observed during motor imagery of right, left and bimanual performance. F-wave persistence and amplitude were unaffected by imagery. These results demonstrate that the motor imagery is lateralized to the left (dominant) hemisphere, which is engaged by imagery of each hand separately, and bimanual imagery. This finding has implications for the use of motor imagery in rehabilitation.