Motor Cortex Excitability Research Articles

Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. The pathophysiology of FP is not known, but imaging studies have identified changes in structural and functional connectivity in multiple brain networks. It has been proposed that noninvasive brain stimulation techniques may be used to understand the pathophysiology of FP and may represent a possible therapeutic option. In this paper, we reviewed transcranial magnetic stimulation studies on functional paralysis, focusing on their pathophysiological and therapeutical implications. Overall, there is general agreement on the integrity of corticospinal pathways in FP, while conflicting results have been found about the net excitability of the primary motor cortex and its excitatory/inhibitory circuitry in resting conditions. The possible involvement of spinal cord circuits remains an under-investigated area. Repetitive transcranial magnetic stimulation appears to have a potential role as a safe and viable option for the treatment of functional paralysis, but more studies are needed to investigate optimal stimulation parameters and clarify its role in the context of other therapeutical options.

Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization

Background After stroke, increases in contralesional primary motor cortex (M1CL) activity and excitability have been reported. In pre-clinical studies, M1CL reorganization is related to the extent of ipsilesional M1 (M1IL) injury, but this has yet to be tested clinically. Objectives We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1CL reorganization and its relationship to affected hand function in humans recovering from stroke. Methods Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1IL was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP−)). M1CL reorganization was determined by TMS applied to M1CL at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. Results The extent of M1CL reorganization was related to greater lesion volume in the MEP− group, but not in the MEP+ group. Greater M1CL reorganization was associated with more impaired hand function in MEP− but not MEP+ participants. Absence of an MEP (MEP−), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function. Conclusions In the subacute post-stroke period, stroke volume and M1IL output determine the extent of M1CL reorganization and its relationship to affected hand function, consistent with pre-clinical evidence. ClinicalTrials.gov Identifier: NCT02544503

Sensory and motor cortical excitability changes induced by rTMS and sensory stimulation in stroke: A randomized clinical trial.

The ability to produce coordinated movement is dependent on dynamic interactions through transcallosal fibers between the two cerebral hemispheres of the brain. Although typically unilateral, stroke induces changes in functional and effective connectivity across hemispheres, which are related to sensorimotor impairment and stroke recovery. Previous studies have focused almost exclusively on interhemispheric interactions in the primary motor cortex (M1). To identify the presence of interhemispheric asymmetry (ASY) of somatosensory cortex (S1) excitability and to investigate whether S1 repetitive transcranial magnetic stimulation (rTMS) combined with sensory stimulation (SS) changes excitability in S1 and M1, as well as S1 ASY, in individuals with subacute stroke. A randomized clinical trial. Participants with a single episode of stroke, in the subacute phase, between 35 and 75 years old, were allocated, randomly and equally balanced, to four groups: rTMS/sham SS, sham rTMS/SS, rTMS/SS, and sham rTMS/Sham SS. Participants underwent 10 sessions of S1 rTMS of the lesioned hemisphere (10 Hz, 1,500 pulses) followed by SS. SS was applied to the paretic upper limb (UL) (active SS) or non-paretic UL (sham SS). TMS-induced motor evoked potentials (MEPs) of the paretic UL and somatosensory evoked potential (SSEP) of both ULs assessed M1 and S1 cortical excitability, respectively. The S1 ASY index was measured before and after intervention. Evaluator, participants and the statistician were blinded. Thirty-six participants divided equally into groups (nine participants per group). Seven patients were excluded from MEP analysis because of failure to produce consistent MEP. One participant was excluded in the SSEP analysis because no SSEP was detected. All somatosensory stimulation groups had decreased S1 ASY except for the sham rTMS/Sham SS group. When compared with baseline, M1 excitability increased only in the rTMS/SS group. S1 rTMS and SS alone or in combination changed S1 excitability and decreased ASY, but it was only their combination that increased M1 excitability. clinicaltrials.gov, identifier (NCT03329807).

Language-related motor facilitation in Italian Sign Language signers.

Linguistic tasks facilitate corticospinal excitability as revealed by increased motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in the dominant hand. This modulation of the primary motor cortex (M1) excitability may reflect the relationship between speech and gestures. It is conceivable that in healthy individuals who use a sign language this cortical excitability modulation could be rearranged. The aim of this study was to evaluate the effect of spoken language tasks on M1 excitability in a group of hearing signers. Ten hearing Italian Sign Language (LIS) signers and 16 non-signer healthy controls participated. Single-pulse TMS was applied to either M1 hand area at the baseline and during different tasks: (i) reading aloud, (ii) silent reading, (iii) oral movements, (iv) syllabic phonation and (v) looking at meaningless non-letter strings. Overall, M1 excitability during the linguistic and non-linguistic tasks was higher in LIS group compared to the control group. In LIS group, MEPs were significantly larger during reading aloud, silent reading and non-verbal oral movements, regardless the hemisphere. These results suggest that in hearing signers there is a different modulation of the functional connectivity between the speech-related brain network and the motor system.

The effect of initiation prediction and non-prediction on muscle relaxation control.

[Purpose] This study aimed to examine the difference in the excitability of the primary motor cortex between initiation-predictive and non-predictive tasks, where the onset of muscle relaxation is predicted and not predicted, respectively. [Participants and Methods] Seventeen participants were asked to perform rapid muscle relaxation either through an initiation-predictive or non-predictive task. The baseline was set at 20 percent of the maximum voluntary contraction. Motor-evoked potentials and H-reflexes elicited by transcranial magnetic stimulation and median nerve electrical stimulation, respectively, were measured. The mean stimulation time from the onset of relaxation was calculated, and the motor-evoked potentials and Hoffmann's reflexes elicited during the first (immediately before relaxation) and second half (long before relaxation) were compared. [Results] The amplitude of the motor-evoked potential significantly increased in both initiation-predictive and non-predictive tasks when compared to the baseline, indicating increased excitability of the primary motor cortex. The motor-evoked potential from the initiation-non-predictive task, but not the initiation-predictive task, was associated with increased excitability of the primary motor cortex immediately before relaxation. [Conclusion] Variations in the predictability of motor movements are associated with changes in muscle relaxation control in the central nervous system.

Investigating the effects of cerebellar transcranial ultrasound stimulation on motor cortex excitability

Investigating the effects of cerebellar transcranial ultrasound stimulation on motor cortex excitability

Startling Acoustic Stimulation Has Task-Specific Effects on Intracortical Facilitation and Inhibition at Rest and During Visually Guided Isometric Elbow Flexion in Healthy Individuals.

Startling acoustic stimulation (SAS) causes a transient effect on the primary motor cortex (M1) nonreflexively. It reduces the cortical excitability at rest, but not during voluntary contraction. However, the effect of SAS on intracortical activity is not clear. The purpose of this study was to investigate the SAS effect on short-interval intracortical inhibition and intracortical facilitation using transcranial magnetic stimulation (TMS). Eleven healthy individuals performed isometric elbow flexion at 10% of maximum voluntary contraction on the dominant side with a real-time visual target (i.e.,M1 preactivation) or at rest. TMS was delivered to the M1 ipsilateral to elbow flexion without or with SAS delivered 90ms prior to TMS. There were three TMS delivery conditions: (a)single pulse, (b)short-interval intracortical inhibition, and (c)intracortical facilitation. TMS-induced motor-evoked potential (MEP) was compared between predetermined TMS and SAS conditions at rest and during ipsilateral voluntary contraction. We confirmed that SAS decreased the MEP amplitude at rest, but not during M1 preactivation. SAS caused task-specific effects on intracortical excitability. Specifically, SAS increased intracortical facilitation at rest and during voluntary contraction. However, SAS decreased short-interval intracortical inhibition only during M1 preactivation. Collectively, our results suggest that SAS transiently influences the motor cortex excitability, possibly via its activation of higher centers, to achieve a visually guided goal-directed task.

Motor cortex excitability modulation after intermittent theta burst stimulation: looking for stability and potential predictors of variability

Motor cortex excitability modulation after intermittent theta burst stimulation: looking for stability and potential predictors of variability

Examining the influence of tactile imagery on primary motor cortex excitability using transcranial magnetic stimulation

Examining the influence of tactile imagery on primary motor cortex excitability using transcranial magnetic stimulation

Exploring the links between gut microbiota and excitatory and inhibitory brain processes in alcohol use disorder: A TMS study

While the impact of the gut microbiota on brain and behavior is increasingly recognized, human studies examining this question are still scarce. The primary objective of the current study was to explore the potential relationships between the gut microbiota composition, motor cortical excitability at rest and during inhibitory control, as well as behavioral inhibition, in healthy volunteers and in patients suffering from alcohol use disorder. Motor cortical excitability was examined using a range of transcranial magnetic stimulation (TMS) measures probed at rest, including the recruitment curve, short and long intracortical inhibition, and intracortical facilitation within the primary motor cortex. Moreover, TMS was applied during a choice reaction time task to assess changes in motor excitability associated with inhibitory control. Finally, behavioral inhibition was investigated using a neuropsychological task (anti-saccade). Overall, our results highlight several interesting correlations between microbial composition and brain measures. Hence, higher bacterial diversity, as well as higher relative abundances of UGC-002 and Christensenellaceae R-7 group were correlated with stronger changes in motor excitability associated with inhibitory control. Also, higher abundance of Anaerostipes was associated with higher level of corticospinal excitability. Finally, relative abundances of Bifidobacterium and Faecalibacterium were positively related to performance in the neuropsychological task, suggesting that they might have a positive impact on behavioral inhibition. Although correlation is not causation, the present study suggests that excitatory and inhibitory brain processes might be related to gut microbiota composition.This article is part of the Special Issue on ‘Microbiome & the Brain: Mechanisms & Maladies’.

Efeitos das terapias de priming nas disfunções motoras e na excitabilidade cortical em sujeitos com AVC: revisão sistemática

Introduction: Approximately 90% of stroke patients are left with some type of functional limitation. A number of auxiliary techniques have emerged in the rehabilitation field, such as priming, which is an unconscious process associated with learning, in which the previous exposure to a stimulus alters the response to a subsequent stimulus. When used in conjunction with another therapeutic intervention, priming may result in a change in behaviour that appears to coincide with changes in neural networks. Objectives: To review and analyse randomised controlled trials (RCT) that evaluate the effects of priming on motor limitations and cortical excitability in stroke patients. Material and Methods: A bibliographic search was made in 3 databases (Pubmed, PEDro and CENTRAL), using the research methodology - Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies conducted in patients who suffered a stroke, whose intervention explicitly used priming therapy, were included. Results: Fourteen studies were included. Four used transcranial magnetic stimulation, 3 used transcranial direct current stimulation, 2 used imagery and action observation, and 5 used movement-based priming. Due to the clinical and methodological heterogeneity of the studies, meta-analysis was not possible. Of the included studies, 10 showed that priming associated with rehabilitation had significant improvements and 4 showed that there were no significant improvements between groups. Conclusions: Priming therapies, when used in conjunction with another therapeutic intervention, seem to enhance the rehabilitation of motor functions after a stroke. In the future, experimental studies with larger samples should be conducted and the way each priming technique is applied should be standardised.

Face emotional expressions influence interhemispheric inhibition.

The processing of face expressions is a key ability to perform social interactions. Recently, it has been demonstrated that the excitability of the hand primary motor cortex (M1) increases following the view of negative faces expressions. Interhemispheric interactions and sensory-motor integration are cortical processes involving M1, which are known to be modulated by emotional and social behaviors. Whether these processes may mediate the effects of face emotional expressions on M1 excitability is unknown. Therefore, the aim of this study was to investigate the influence of the passive viewing of face emotional expressions on M1 interhemispheric connections and sensory-motor integration using standardized transcranial magnetic stimulation (TMS) protocols. Nineteen healthy subjects participated in the study. Interhemispheric inhibition (IHI) and short-afferent inhibition (SAI) were probed in the right first dorsal interosseous (FDI) muscle 300 ms after the randomized presentation of seven different face expressions (neutral, sadness, fear, disgust, surprise and happiness). Results showed a significantly reduced IHI following the passive viewing of fearful faces compared to neutral (p=.001) and happy (p=.035) faces and following the view of sad faces compared to neutral faces (p=.008). No effect of emotional faces was detected on SAI. Data suggest that sensory-motor integration process does not mediate the increased excitability of M1 induced by the view of negative face expressions. By contrast, it may be underpinned by a depression of IHI, which from a functional point of view may promote symmetrical avoiding movements of the hands in response to aversive stimuli.

Anodal-TDCS over Left-DLPFC Modulates Motor Cortex Excitability in Chronic Lower Back Pain.

Chronic pain is associated with abnormal cortical excitability and increased pain intensity. Research investigating the potential for transcranial direct current stimulation (tDCS) to modulate motor cortex excitability and reduce pain in individuals with chronic lower back pain (CLBP) yield mixed results. The present randomised, placebo-controlled study examined the impact of anodal-tDCS over left-dorsolateral prefrontal cortex (left-DLPFC) on motor cortex excitability and pain in those with CLBP. Nineteen participants with CLBP (Mage = 53.16 years, SDage = 14.80 years) received 20-min of sham or anodal tDCS, twice weekly, for 4 weeks. Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were assessed using paired-pulse Transcranial Magnetic Stimulation prior to and immediately following the tDCS intervention. Linear Mixed Models revealed no significant effect of tDCS group or time, on SICI or ICF. The interactions between tDCS group and time on SICI and ICF only approached significance. Bayesian analyses revealed the anodal-tDCS group demonstrated higher ICF and SICI following the intervention compared to the sham-tDCS group. The anodal-tDCS group also demonstrated a reduction in pain intensity and self-reported disability compared to the sham-tDCS group. These findings provide preliminary support for anodal-tDCS over left-DLPFC to modulate cortical excitability and reduce pain in CLBP.

Difference between the Effects of Peripheral Sensory Nerve Electrical Stimulation on the Excitability of the Primary Motor Cortex: Examination of the Combinations of Stimulus Frequency and Duration.

Peripheral sensory nerve electrical stimulation (PES) excites the primary motor cortex and is expected to improve motor dysfunction post-stroke. However, previous studies have reported a variety of stimulus frequencies and stimulus duration settings, and the effects of these different combinations on primary motor cortex excitability are not clear. We aimed to clarify the effects of different combinations of stimulus frequency and stimulus duration of PES on the excitation of primary motor cortex. Twenty-one healthy individuals (aged > 18 years, right-handed, and without a history of neurological or orthopedic disorders) were included. Each participant experienced three different stimulation frequencies (1, 10 and 50 Hz) and durations (20, 40 and 60 min). Motor-evoked potentials (MEPs) were recorded pre- and post-PES. The outcome measure was the change in primary motor cortex excitability using the MEP ratio. We used a D-optimal design of experiments and response surface analysis to define the optimal combination within nine different settings inducing more satisfying responses. The combination of stimulation frequency and stimulation time that maximized the desirability value was 10 Hz and 40 min, respectively. The results of this study may provide fundamental data for more minimally invasive and effective implementation of PES in patients with stroke.

The effect of tDCS on improving physical performance and attenuating effort perception during maximal dynamic exercise in non-athletes

ObjectivesThis study aimed to test the effects of transcranial direct current stimulation (tDCS), using different electrode positioning and montages, on physical performance in maximum incremental tests of healthy non-athlete subjects. DesignA double-blinded, crossover, sham-controlled study. MethodFifteen subjects (aged 25.8 ± 5 years, nine women) received one of five different tDCS protocols: (i) anodal tDCS on the primary motor cortex (M1) (a-tDCS/M1), (ii) anodal tDCS on the left temporal cortex (T3) (a-tDCS/T3), (iii) cathodal tDCS on M1 (c-tDCS/M1), (iv) cathodal on T3 (c-tDCS/T3), or (v) sham tDCS. The protocols were assigned in a random order in separate sessions. After tDCS, the volunteers performed the maximal incremental exercise test (MIT) on a cycle ergometer in each session. The following measures were used to evaluate physical performance (primary outcome) during MIT: time to exhaustion (TE), maximum power (MAX-P), and Borg Rating of Perceived Exertion (RPE) scale. In addition, as a secondary outcome measure, we assessed the lower-limb corticospinal excitability and electrical muscular activity. ResultstDCS applied over T3 or M1 did not influence electrical muscular activity or increase physical performance during MIT in healthy non-athlete subjects. However, our data confirmed that a-tDCS on the M1 increases lower-limb cortical excitability. ConclusionsOur results suggest that tDCS is not effective in improving performance during maximal dynamic exercise in non-athletes. However, we confirmed that the a-tDCS M1 protocol used in this study might increase cortical excitability in the lower limb motor cortex.

Motor cortex excitability is reduced during freezing of upper limb movement in Parkinson’s disease

Whilst involvement of the motor cortex in the phenomenon of freezing in Parkinson’s disease has been previously suggested, few empiric studies have been conducted to date. We investigated motor cortex (M1) excitability in eleven right-handed Parkinson’s disease patients (aged 69.7 ± 9.6 years, disease duration 11.2 ± 3.9 years, akinesia-rigidity type) with verified gait freezing using a single-pulse transcranial magnetic stimulation (TMS) repetitive finger tapping paradigm. We delivered single TMS pulses at 120% of the active motor threshold at the ‘ascending (contraction)’ and ‘descending (relaxation)’ slope of the tap cycle during i) regular tapping, ii) the transition period of the three taps prior to a freeze and iii) during freezing of upper limb movement. M1 excitability was modulated along the tap cycle with greater motor evoked potentials (MEPs) during ‘ascending’ than ‘descending’. Furthermore, MEPs during the ‘ascending’ phase of regular tapping, but not during the transition period, were greater compared to the MEPs recorded throughout a freeze. Neither force nor EMG activity 10–110 s before the stimulus predicted MEP size. This piloting study suggests that M1 excitability is reduced during freezing and the transition period preceding a freeze. This supports that M1 excitability is critical to freezing in Parkinson’s disease.

Assessing the interaction between L-dopa and γ-transcranial alternating current stimulation effects on primary motor cortex plasticity in Parkinson's disease.

L-dopa variably influences transcranial magnetic stimulation (TMS) parameters of motor cortex (M1) excitability and plasticity in Parkinson's disease (PD). In patients OFF dopaminergic medication, impaired M1 plasticity and defective GABA-A-ergic inhibition can be restored by boosting gamma (γ) oscillations via transcranial alternating current stimulation (tACS) during intermittent theta-burst stimulation (iTBS). However, it is unknown whether L-dopa modifies the beneficial effects of iTBS-γ-tACS on M1 in PD. In this study, a PD patients group underwent combined iTBS-γ-tACS and iTBS-sham-tACS, each performed both OFF and ON dopaminergic therapy (four sessions in total). Motor evoked potentials (MEPs) elicited by single TMS pulses and short-interval intracortical inhibition (SICI) were assessed before and after iTBS-tACS. We also evaluated possible SICI changes during γ-tACS delivered alone in OFF and ON conditions. The amplitude of MEP elicited by single TMS pulses and the degree of SICI inhibition significantly increased after iTBS-γ-tACS. The amount of change produced by iTBS-γ-tACS was similar in patients OFF and ON therapy. Finally, γ-tACS (delivered alone) modulated SICI during stimulation and this effect did not depend on the dopaminergic condition of patients. In conclusion, boosting cortical γ oscillatory activity via tACS during iTBS improved M1 plasticity and enhanced GABA-A-ergic transmission in PD patients to the same extent regardless of dopaminergic state. These results suggest a lack of interaction between L-dopa and γ-tACS effects at the M1 level. The possible neural substrate underlying iTBS-γ tACS effects, that is, γ-resonant GABA-A-ergic interneurons activity, may explain our findings.

Modulation of Human Motor Cortical Excitability and Plasticity by Opuntia Ficus Indica Fruit Consumption: Evidence from a Preliminary Study through Non-Invasive Brain Stimulation.

Indicaxanthin (IX) from Opuntia Ficus Indica (OFI) has been shown to exert numerous biological effects both in vitro and in vivo, such as antioxidant, anti-inflammatory, neuro-modulatory activity in rodent models. Our goal was to investigate the eventual neuro-active role of orally assumed fruits containing high levels of IX at nutritionally-relevant amounts in healthy subjects, exploring cortical excitability and plasticity in the human motor cortex (M1). To this purpose, we applied paired-pulse transcranial magnetic stimulation and anodal transcranial direct current stimulation (a-tDCS) in basal conditions and followed the consumption of yellow cactus pear fruits containing IX or white cactus pear fruits devoid of IX (placebo). Furthermore, resting state-functional MRI (rs-fMRI) preliminary acquisitions were performed before and after consumption of the same number of yellow fruits. Our data revealed that the consumption of IX-containing fruits could specifically activate intracortical excitatory circuits, differently from the placebo-controlled group. Furthermore, we found that following the ingestion of IX-containing fruits, elevated network activity of glutamatergic intracortical circuits can homeostatically be restored to baseline levels following a-tDCS stimulation. No significant differences were observed through rs-fMRI acquisitions. These outcomes suggest that IX from OFI increases intracortical excitability of M1 and leads to homeostatic cortical plasticity responses.

Effect of electroacupuncture at back-shu points of five zang on fatigue status and cortical excitability in chronic fatigue syndrome

To observe the effect of electroacupuncture (EA) at back-shu points of five zang on fatigue status, quality of life and motor cortical excitability in patients with chronic fatigue syndrome (CFS), so as to explore the possible mechanism of EA for CFS. A total of 72 patients with CFS were randomized into an EA group (36 cases, 4 cases dropped off) and a sham EA group (36 cases, 3 cases dropped off). In the EA group, EA at Ganshu (BL 18), Xinshu (BL 15), Pishu (BL 20), Feishu (BL 13) and Shenshu (BL 23) was adopted, with continuous wave, 2 Hz in frequency. In the sham EA group, sham EA at non-acupoints (1.5-2.0 cm lateral to back-shu points of five zang) was applied, with shallow needling, and no current was connected. The treatment in the both groups was 20 min each time, once every other day, 2 weeks as one course, 3 courses were required. Before and after treatment, the scores of fatigue scale-14 (FS-14) and the MOS 36-item short form health survey (SF-36) were observed, and cortical excitability (the resting motor threshold [RMT], amplitude of motor-evoked potential [MEP-A] and latency of motor-evoked potential [MEP-L]) was detected in the two groups. After treatment, the physical fatigue score, mental fatigue score and total score of FS-14, as well as RMT of motor cortex in the EA group were decreased compared with those before treatment (P<0.01), the physical fatigue score and total score of FS-14 in the sham EA group were decreased compared with those before treatment (P<0.05); each item score and total score of FS-14 and RMT of motor cortex in the EA group were lower than those in the sham EA group (P<0.01, P<0.05). After treatment, each item score and total score of SF-36 and MEP-A of motor cortex in the EA group were increased compared with those before treatment (P<0.01), which were higher than those in the sham EA group (P<0.01, P<0.05). EA at back-shu points of five zang can effectively improve the fatigue status and quality of life in patients with CFS, its mechanism may be related to the up-regulating excitability of cerebral motor cortex.

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity.

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n=14; 61 ± 7yrs) or abnormally enlarged (hyperechogenic; n=9; 60 ± 6yrs) area of SN echogenicity. Thirteen of these participants (7 SN- and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p=.005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10-12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.