Exercise effects on cortical excitability in pain populations: A systematic review and meta-analysis.

BACKGROUND: Transcranial Magnetic Stimulation (TMS) studies examining exercise-induced neuroplasticity in pain populations have produced contradictory findings. We conducted a systematic review to explore how exercise impacts cortical excitability in pain populations using TMS metrics. This review aims to summarize the effect sizes and to understand their sources of heterogeneity. METHODS: We searched multiple databases from inception to December 2022. We included randomized controlled trials (RCTs) with any type of pain population, including acute and chronic pain; exercise interventions were compared to sham exercise or other active interventions. The primary outcomes were TMS metrics, and pain intensity was the secondary outcome. Risk of bias assessment was conducted using the Cochrane tool. RESULTS: This review included five RCTs (n = 155). The main diagnoses were fibromyalgia and cervical dystonia. The interventions included submaximal contractions, aerobic exercise, physical therapy, and exercise combined with transcranial direct current stimulation. Three studies are considered to have a high risk of bias. All five studies showed significant pain improvement with exercise. The neurophysiological data revealed improvements in cortical excitability measured by motor-evoked potentials; standardized mean difference = 2.06, 95% confidence interval 1.35-2.78, I2 = 19%) but no significant differences in resting motor threshold. The data on intracortical inhibition/facilitation (ICI/ICF) was not systematically analyzed, but one study (n = 45) reported higher ICI and lower ICF after exercise. CONCLUSIONS: These findings suggest that exercise interventions positively affect pain relief by modifying corticospinal excitability, but their effects on ICI/ICF are still unclear. While the results are inconclusive, they provide a basis for further exploration in this area of research; future studies should focus on establishing standardized TMS measurements and exercise protocols to ensure consistent and reliable findings. A large-scale RCT that examines various exercise interventions and their effects on cortical excitability could offer valuable insights to optimize its application in promoting neuroplasticity in pain populations.

Mapping cortical excitability in the human dorsolateral prefrontal cortex.

BACKGROUND: Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an effective treatment for depression, but the neural effects after TMS remains unclear. TMS paired with electroencephalography (TMS-EEG) can causally probe these neural effects. Nonetheless, variability in single pulse TMS-evoked potentials (TEPs) across dlPFC subregions, and potential artifact induced by muscle activation, necessitate detailed mapping for accurate treatment monitoring. OBJECTIVE: To characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and specifically that conditions with larger muscle artifact may exhibit lower observed EL-TEPs due to over-rejection during preprocessing. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach. METHODS: In 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses. RESULTS: Stimulation location significantly influenced observed EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%. SIGNIFICANCE: EL-TEPs can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols.

Impact of Acute High-intensity Interval Training on Cortical Excitability, M1-related Cognitive Functions, and Myokines: A Randomized Crossover Study.

High-intensity interval training (HIIT) is a time-efficient, safe, and feasible exercise type that can be utilized across different ages and health status. This randomized cross-over study aimed to investigate the effect of acute HIIT on cortical excitability, M1-related cognitive functions, cognition-related myokines, brain-derived neurotrophic factor (BDNF), and Cathepsin B (CTSB). Twenty-three sedentary young adults (mean age: 22.78 years ± 2.87; 14 female) participated in a cross-over design involving two sessions: either 23 min of HIIT or seated rest. Before and after the sessions, cortical excitability was measured using transcranial magnetic stimulation, and M1-related cognitive functions were assessed by the n-back test and mental rotation test. Serum levels of BDNF and CTSB were assessed using the ELISA method before and after the HIIT intervention. We demonstrated that HIIT improved mental rotation and working memory, and increased serum levels of BDNF and CTSB, whereas cortical excitability did not change. Our findings provide evidence that one session of HIIT is effective on M1-related cognitive functions and cognition-related myokines. Future research is warranted to determine whether such findings are transferable to different populations, such as cognitively at-risk children, adults, and older adults, and to prescribe effective exercise programs.

Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study.

BACKGROUND: Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. MATERIALS AND METHODS: TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. RESULTS: Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50-160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220-560 ms; 190-420 ms). Patients showed a reduction of both early (50-110 ms) gamma increase and later (180-230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. CONCLUSION: Our findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics.

Phosphene and motor transcranial magnetic stimulation thresholds are correlated: A meta-analytic investigation.

Transcranial magnetic stimulation (TMS) is commonly delivered at an intensity defined by the resting motor threshold (rMT), which is thought to represent cortical excitability, even if the TMS target area falls outside of the motor cortex. This approach rests on the assumption that cortical excitability, as measured through the motor cortex, represents a 'global' measure of excitability. Another common approach to measure cortical excitability relies on the phosphene threshold (PT), measured through the visual cortex of the brain. However, it remains unclear whether either estimate can serve as a singular measure to infer cortical excitability across different brain regions. If PT and rMT can indeed be used to infer cortical excitability across brain regions, they should be correlated. To test this, we systematically identified previous studies that measured PT and rMT to calculate an overall correlation between the two estimates. Our results, based on 16 effect sizes from eight studies, indicated that PT and rMT are correlated (ρ = 0.4), and thus one measure could potentially serve as a measure to infer cortical excitability across brain regions. Three exploratory meta-analyses revealed that the strength of the correlation is affected by different methodologies, and that PT intensities are higher than rMT. Evidence for a PT-rMT correlation remained robust across all analyses. Further research is necessary for an in-depth understanding of how cortical excitability is reflected through TMS.

Always expect the unexpected: eye position modulates visual cortex excitability in a stimulus-free environment.

Stimuli that potentially require a rapid defensive or avoidance action can appear from the periphery at any time in natural environments. de Wit et al. (Cortex 127: 120-130, 2020) recently reported novel evidence suggestive of a fundamental neural mechanism that allows organisms to effectively deal with such situations. In the absence of any task, motor cortex excitability was found to be greater whenever gaze was directed away from either hand. If modulation of cortical excitability as a function of gaze location is a fundamental principle of brain organization, then one would expect its operation to be present outside of motor cortex, including brain regions involved in perception. To test this hypothesis, we applied single-pulse transcranial magnetic stimulation (TMS) to the right lateral occipital lobe while participants directed their eyes to the left, straight-ahead, or to the right, and reported the presence or absence of a phosphene. No external stimuli were presented. Cortical excitability as reflected by the proportion of trials on which phosphenes were elicited from stimulation of the right visual cortex was greater with eyes deviated to the right as compared with the left. In conjunction with our previous findings of change in motor cortex excitability when gaze and effector are not aligned, this eye position-driven change in visual cortex excitability presumably serves to facilitate the detection of stimuli and subsequent readiness to act in nonfoveated regions of space. The existence of this brain-wide mechanism has clear adaptive value given the unpredictable nature of natural environments in which human beings are situated and have evolved.NEW & NOTEWORTHY For many complex tasks, humans focus attention on the site relevant to the task at hand. Humans evolved and live in dangerous environments, however, in which threats arise from outside the attended site; this fact necessitates a process by which the periphery is monitored. Using single-pulse transcranial magnetic stimulation (TMS), we demonstrated for the first time that eye position modulates visual cortex excitability. We argue that this underlies at least in part what we term "surveillance attention."

Tmod2 Is a Regulator of Cocaine Responses through Control of Striatal and Cortical Excitability and Drug-Induced Plasticity.

Drugs of abuse induce neuroadaptations, including synaptic plasticity, that are critical for transition to addiction, and genes and pathways that regulate these neuroadaptations are potential therapeutic targets. Tropomodulin 2 (Tmod2) is an actin-regulating gene that plays an important role in synapse maturation and dendritic arborization and has been implicated in substance abuse and intellectual disability in humans. Here, we mine the KOMP2 data and find that Tmod2 knock-out mice show emotionality phenotypes that are predictive of addiction vulnerability. Detailed addiction phenotyping shows that Tmod2 deletion does not affect the acute locomotor response to cocaine administration. However, sensitized locomotor responses are highly attenuated in these knock-outs, indicating perturbed drug-induced plasticity. In addition, Tmod2 mutant animals do not self-administer cocaine indicating lack of hedonic responses to cocaine. Whole-brain MR imaging shows differences in brain volume across multiple regions, although transcriptomic experiments did not reveal perturbations in gene coexpression networks. Detailed electrophysiological characterization of Tmod2 KO neurons showed increased spontaneous firing rate of early postnatal and adult cortical and striatal neurons. Cocaine-induced synaptic plasticity that is critical for sensitization is either missing or reciprocal in Tmod2 KO nucleus accumbens shell medium spiny neurons, providing a mechanistic explanation of the cocaine response phenotypes. Combined, these data, collected from both males and females, provide compelling evidence that Tmod2 is a major regulator of plasticity in the mesolimbic system and regulates the reinforcing and addictive properties of cocaine.

Acute aerobic exercise at different intensities modulates inhibitory control and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD).

BACKGROUND: This study aimed to investigate the effects of different aerobic exercise intensities on inhibitory control and cortical excitability in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: The study was conducted in a within-subject design. Twenty-four adults with ADHD completed a stop signal task and received cortical excitability assessment by transcranial magnetic stimulation (TMS) before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. RESULTS: Acute moderate-, and high-intensity aerobic exercise improved inhibitory control in adults with ADHD. Moreover, the improving effect was similar between moderate-, and high-intensity aerobic exercise conditions. As shown by the brain physiology results, short interval intracortical inhibition was significantly increased following both, moderate- and high-intensity aerobic exercise intervention conditions. Additionally, the alteration of short interval intracortical inhibition and inhibitory control improvement were positively correlated. CONCLUSIONS: The moderate-, and high-intensity aerobic exercise-dependent alterations of cortical excitability in adults with ADHD might partially explain the inhibitory control-improving effects of aerobic exercise in this population.

Effects of dry needling on spasticity, cortical excitability, and range of motion in a patient with multiple sclerosis: a case report.

BACKGROUND: Dry needling is an intervention used by physiotherapists to manage muscle spasticity. We report the effects of three sessions of dry needling on ankle plantar flexor muscle spasticity and cortical excitability in a patient with multiple sclerosis. CASE PRESENTATION: The patient was a 40-year-old Iranian woman with an 11-year history of multiple sclerosis. The study outcomes were measured by the modified modified Ashworth scale, transcranial magnetic stimulation parameters, and active and passive ankle range of motion. They were assessed before (T0), after three sessions of dry needling (T1), and at 2-week follow-up (T2). Our result showed: the modified modified Ashworth scale was improved at T2 from, 2 to 1. The resting motor threshold decreased from 63 to 61 and 57 at T1 and T2, respectively. The single test motor evokes potential increased from 76.2 to 78.3. The short intracortical inhibition increased from 23.6 to 35.4 at T2. The intracortical facilitation increased from 52 to 76 at T2. The ankle active and passive dorsiflexion ROM increased ~ 10° and ~ 6° at T2, respectively. CONCLUSION: This case study presented a patient with multiple sclerosis who underwent dry needling of ankle plantar flexors with severe spasticity, and highlighted the successful use of dry needling in the management of spasticity, ankle dorsiflexion, and cortical excitability. Further rigorous investigations are warranted, employing randomized controlled trials with a sufficient sample of patients with multiple sclerosis. Trial registration IRCT20230206057343N1, registered 9 February 2023, https://en.irct.ir/trial/68454.

Electroencephalography oscillations can predict the cortical response following theta burst stimulation.

BACKGROUND: Continuous theta burst stimulation and intermittent theta burst stimulation are clinically popular models of repetitive transcranial magnetic stimulation. However, they are limited by high variability between individuals in cortical excitability changes following stimulation. Although electroencephalography oscillations have been reported to modulate the cortical response to transcranial magnetic stimulation, their association remains unclear. This study aims to explore whether machine learning models based on EEG oscillation features can predict the cortical response to transcranial magnetic stimulation. METHOD: Twenty-three young, healthy adults attended two randomly assigned sessions for continuous and intermittent theta burst stimulation. In each session, ten minutes of resting-state electroencephalography were recorded before delivering brain stimulation. Participants were classified as responders or non-responders based on changes in resting motor thresholds. Support vector machines and multi-layer perceptrons were used to establish predictive models of individual responses to transcranial magnetic stimulation. RESULT: Among the evaluated algorithms, support vector machines achieved the best performance in discriminating responders from non-responders for intermittent theta burst stimulation (accuracy: 91.30%) and continuous theta burst stimulation (accuracy: 95.66%). The global clustering coefficient and global characteristic path length in the beta band had the greatest impact on model output. CONCLUSION: These findings suggest that EEG features can serve as markers of cortical response to transcranial magnetic stimulation. They offer insights into the association between neural oscillations and variability in individuals' responses to transcranial magnetic stimulation, aiding in the optimization of individualized protocols.

Assessing cortical excitability with electroencephalography: A pilot study with EEG-iTBS.

BACKGROUND: Cortical excitability measures neural reactivity to stimuli, usually delivered via Transcranial Magnetic Stimulation (TMS). Excitation/inhibition balance (E/I) is the ongoing equilibrium between excitatory and inhibitory activity of neural circuits. According to some studies, E/I could be estimated in-vivo and non-invasively through the modeling of electroencephalography (EEG) signals and termed 'intrinsic excitability' measures. Several measures have been proposed (phase consistency in the gamma band, sample entropy, exponent of the power spectral density 1/f curve, E/I index extracted from detrend fluctuation analysis, and alpha power). Intermittent theta burst stimulation (iTBS) of the primary motor cortex (M1) is a non-invasive neuromodulation technique allowing controlled and focal enhancement of TMS cortical excitability and E/I of the stimulated hemisphere. OBJECTIVE: Investigating to what extent E/I estimates scale with TMS excitability and how they relate to each other. METHODS: M1 excitability (TMS) and several E/I estimates extracted from resting state EEG recordings were assessed before and after iTBS in a cohort of healthy subjects. RESULTS: Enhancement of TMS M1 excitability, as measured through motor-evoked potentials (MEPs), and phase consistency of the cortex in high gamma band correlated with each other. Other measures of E/I showed some expected results, but no correlation with TMS excitability measures or strong consistency with each other. CONCLUSIONS: EEG E/I estimates offer an intriguing opportunity to map cortical excitability non-invasively, with high spatio-temporal resolution and with a stimulus independent approach. While different EEG E/I estimates may reflect the activity of diverse excitatory-inhibitory circuits, spatial phase synchrony in the gamma band is the measure that best captures excitability changes in the primary motor cortex.

Effect of neuronavigated repetitive Transcranial Magnetic Stimulation on pain, cognition and cortical excitability in fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome is a widespread chronic pain condition identified by body-wide pain, fatigue, cognitive fogginess, and sleep issues. In the past decade, repetitive transcranial magnetic stimulation has emerged as a potential management tool.. In the present study, we enquired whether repetitive transcranial magnetic stimulation could modify pain, corticomotor excitability, cognition, and sleep. METHODS: Study is a randomized, sham-controlled, double-blind, clinical trial; wherein after randomizing thirty-four fibromyalgia patients into active or sham therapy (n = 17 each), each participant received repetitive transcranial magnetic stimulation therapy. In active therapy was given at 1 Hz for 20 sessions were delivered on dorsolateral prefrontal cortex (1200 pulses, 150 pulses per train for 8 trains); while in sham therapy coil was placed at right angle to the scalp with same frequency. Functional magnetic resonance imaging was used to identify the therapeutic site. Pain intensity, corticomotor excitability, cognition, and sleep were examined before and after therapy. RESULTS: Baseline demographic and clinical parameters for both active and sham groups were comparable. In comparison to sham, active repetitive transcranial magnetic stimulation showed significant difference in pain intensity (P < 0.001, effect size = 0.29, large effect) after intervention. Other parameters of pain perception, cognition, and sleep quality also showed a significant improvement after the therapy in active therapy group only, as compared to sham. CONCLUSIONS: Findings suggest that repetitive transcranial magnetic stimulation intervention is effective in managing pain alongside cognition and sleep disturbances in patients of fibromyalgia. It may prove to be an important tool in relieving fibromyalgia-associated morbidity.

Abnormal cortical excitability in patients with spinocerebellar ataxia type 12.

BACKGROUND: Spinocerebellar ataxia type 12 (SCA-12) is an uncommon autosomal dominant cerebellar ataxia characterized by action tremors in the upper limbs, dysarthria, head tremor, and gait ataxia. We aimed to evaluate the motor cortical excitability in patients with SCA-12 using transcranial magnetic stimulation (TMS). METHODS: The study was done in the department of Neurology at the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore. Nine patients with SCA-12 (2 females) and 10 healthy controls (2 females) were included in the study. TMS was performed in all the subjects and various parameters such as resting motor threshold (RMT), central motor conduction time (CMCT) and contralateral silent period (cSP) were recorded. The left motor cortex was stimulated and the recording was done from right first dorsal interossei muscle. The severity of ataxia was assessed using the scale for assessment and rating in ataxia (SARA). RESULTS: The mean age of the patients was 58.11 ± 7.56 years mean age at onset: 51.67 ± 4.18 years. The mean duration of illness was 9.44 ± 4.88 years. The mean SARA score was 13.83 ± 3.60. Patients with SCA-12 had significantly increased RMT (88.80 ± 12.78 %) compared to HC (44.90 ± 9.40 %, p < 0.05). A significantly prolonged CMCT was observed in patients (13.70 ± 2.52 msec) compared to HC (7.31 ± 1.21 msec, p < 0.05). In addition, cSP was significantly increased in SCA-12 patients (144.43 ± 25.79 msec) compared to HC (82.14 ± 28.90 msec, p < 0.05). CONCLUSIONS: Patients with SCA-12 demonstrate a reduced cortical excitability and increased cortical inhibition suggesting an increase in the GABAergic neurotransmission.

Decoding the clinical effects of low-grade glioma-induced cortical excitability.

OBJECTIVE: Patients with low-grade glioma (LGG) in eloquent regions often present with seizures, and findings on detailed neuropsychological testing are often abnormal. This study evaluated the association between cortical excitability, seizures, and cognitive function in patients with LGG. METHODS: LGG patients who underwent transcranial magnetic stimulation (TMS) from January 2021 to December 2022 were studied. Cortical excitability was measured using the resting motor thresholds (RMTs) of the upper and lower extremities. Early postoperative seizures served as the seizure endpoint. Neuropsychological assessment was completed prior to surgery contemporaneous with the TMS studies. RESULTS: A total of 31 patients were analyzed for seizure outcome. Median (interquartile range [IQR]) upper-extremity RMT was 39% (34%-46%) of maximum stimulator output, and the median (IQR) lower-extremity RMT was 69% (51%-79%). Lower-extremity RMT was higher in patients with early postoperative seizures, especially in those with motor region tumors (p = 0.02); however, RMT was not associated with seizures at presentation or long-term seizure control. A total of 26 patients completed neuropsychological assessment. There were significant negative correlations between upper-extremity RMT and psychomotor processing speed (Wechsler Adult Intelligence Scale-Fourth Edition [WAIS-IV] Processing Speed Index r = -0.42, p = 0.031; WAIS-IV Coding r = -0.41, p = 0.036; WAIS-IV Symbol Search r = -0.39, p = 0.048), executive function (Trail Making Test Part B r = -0.41, p = 0.036), and hand dexterity (Grooved Pegboard Test r = -0.50, p = 0.047). CONCLUSIONS: RMT was positively correlated with early postoperative seizure risk and negatively correlated with psychomotor processing speed, executive function, and hand dexterity. These findings support the theory of local and regional resting oscillatory network dysfunction from a glioma-brain network.

Age- and region-dependent cortical excitability in the zQ175 Huntington disease mouse model.

The neurodegenerative disorder, Huntington disease (HD), manifests as disorders of movement, cognition and mood. Although studies report abnormal corticostriatal synaptic function early in HD mouse models, less is known about cortical-cortical activity across brain regions and disease stages. Recently, we reported enhanced mesoscale spread of cortical responses to sensory stimulation in vivo at early-manifest stages of two HD mouse models. Here, we investigated cortical excitability of zQ175 HD-model mice compared to their wild-type littermates across different cell types, ages and/or cortical regions using ex vivo electrophysiology. Cortical pyramidal neurons (CPNs) in somatosensory cortex of zQ175 mice showed intrinsic hyper-excitability at 3-4 months, but hypo-excitability at early-manifest stage (8-9 months); reduced frequency of spontaneous excitatory postsynaptic currents (sEPSCs) was seen at both ages. In contrast, motor cortex CPNs in early-manifest zQ175 mice showed increased intrinsic excitability and sEPSC frequency. Large-amplitude excitatory discharges recorded from CPNs in early-manifest zQ175 mice showed increased frequency only in somatosensory cortex, suggesting the intrinsic hypo-excitability of these CPNs may be compensatory against cortical network hyper-excitability. Similarly, in early-manifest zQ175 mice, region-dependent differences were seen in fast-spiking interneurons (FSIs): somatosensory but not motor FSIs from early-manifest zQ175 mice had reduced intrinsic excitability. Moreover, CPNs showed decreased frequency of spontaneous inhibitory postsynaptic currents and increased excitatory-inhibitory (E-I) balance of evoked synaptic currents in somatosensory cortex. Aberrant large-amplitude discharges and reduced inhibitory drive may therefore underlie E-I imbalances that result in circuit changes and synaptic dysfunction in early-manifest HD.

A comparative transcranial magnetic stimulation study: Assessing cortical excitability and plasticity in Alzheimer's disease, dementia with Lewy bodies and Frontotemporal dementia.

BACKGROUND: Here, we aimed to investigate the roles of long-term potentiation-like (LTP-like) plasticity using intermittent theta burst (iTBS) protocol and resting motor threshold (rMT) in the differential diagnosis of Alzheimer's disease (AD), diffuse dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). METHOD: We enrolled 21 subjects with AD, 28 subjects with DLB, 14 subjects with FTD, and 33 elderly subjects with normal cognitive functions into the study. We recorded rMT and percentage amplitude change of motor evoked potentials (MEPs) after the iTBS protocol in each group. RESULTS: In patients with AD and DLB, the percentage amplitude change of MEPs, and rMTs were significantly lower than in healthy subjects. However, no significant difference was observed in individuals with FTD. CONCLUSION: Our findings showed that transcranial magnetic stimulation measures, particularly rMTs and LTP-like plasticity, may be potential biomarkers to distinguish between different dementia subtypes. Impaired motor cortical excitability and synaptic plasticity were more prominent in AD and DLB than in FTD. This aligns with the evidence that cortical motor networks are usually spared in FTDs in early-to-middle stages.

Caffeine and cortical excitability, as measured with paired-pulse transcranial magnetic stimulation.

INTRODUCTION/AIMS: The transcranial magnetic stimulation tests of short-interval intracortical inhibition (SICI) by both conventional amplitude measurements (A-SICI) and threshold-tracking (T-SICI) are important methods to investigate intracortical inhibitory circuits, and T-SICI has been proposed to aid the diagnosis of amyotrophic lateral sclerosis. Beverages containing caffeine are widely consumed, and caffeine has been reported to affect cortical excitability. The aim of this study was to determine whether these SICI tests are affected by caffeine. METHODS: Twenty-four healthy subjects (13 females, 11 males, aged from 19 to 31, mean: 26.2 ± 2.4 years) were studied in a single fixed-dose randomized double-blind placebo-controlled cross-over trial of 200 mg caffeine or placebo ingested as chewing gum. A-SICI and T-SICI, using parallel tracking (T-SICIp), were performed before and after chewing gum. RESULTS: There was no significant change in SICI parameters after placebo in A-SICI (p > .10) or T-SICIp (p > .30), and no significant effect of caffeine was found on A-SICI (p > .10) or T-SICIp (p > .50) for any of the interstimulus intervals. DISCUSSION: There is no need for caffeine abstention before measurements of SICI by either the T-SICI or A-SICI measurements.

GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy: A Positron Emission Tomography and Transcranial Magnetic Stimulation Study.

INTRODUCTION: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls. METHODS: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability. RESULTS: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT. CONCLUSION: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Acute Aerobic Exercise at Different Intensities Modulates Motor Learning Performance and Cortical Excitability in Sedentary Individuals.

Converging evidence indicates the beneficial effects of aerobic exercise on motor learning performance. Underlying mechanisms might be an impact of aerobic exercise on neuroplasticity and cortical excitability. Evidence suggests that motor learning and cortical excitability alterations correlate with the intensity of aerobic exercise and the activity level of participants. Thus, this study aims to investigate the effects of different aerobic exercise intensities on motor learning and cortical excitability in sedentary individuals. The study was conducted in a crossover and double-blind design. Twenty-six healthy sedentary individuals (13 women and 13 men) performed a motor learning task and received a cortical excitability assessment before and after a single session of low-, moderate-, and high-intensity aerobic exercise or a control intervention. The study revealed that motor learning performance and cortical excitability were significantly enhanced in the moderate-intensity aerobic exercise, compared with the other conditions. These findings suggest aerobic exercise intensity-dependent effects on motor learning in sedentary adults. The underlying mechanism might be an exercised-induced alteration of cortical excitability, specifically a reduction of GABA activity.

Cardiac activity impacts cortical motor excitability.

Human cognition and action can be influenced by internal bodily processes such as heartbeats. For instance, somatosensory perception is impaired both during the systolic phase of the cardiac cycle and when heartbeats evoke stronger cortical responses. Here, we test whether these cardiac effects originate from overall changes in cortical excitability. Cortical and corticospinal excitability were assessed using electroencephalographic and electromyographic responses to transcranial magnetic stimulation while concurrently monitoring cardiac activity with electrocardiography. Cortical and corticospinal excitability were found to be highest during systole and following stronger neural responses to heartbeats. Furthermore, in a motor task, hand-muscle activity and the associated desynchronization of sensorimotor oscillations were stronger during systole. These results suggest that systolic cardiac signals have a facilitatory effect on motor excitability-in contrast to sensory attenuation that was previously reported for somatosensory perception. Thus, it is possible that distinct time windows exist across the cardiac cycle, optimizing either perception or action.