Motor Cortex In Patients Research Articles

Repetitive transcranial magnetic stimulation focusing on patients with neuropathic pain in the upper limb: a randomized sham-controlled parallel trial

This study aimed to evaluate the efficacy and safety of navigation-guided repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in patients with neuropathic pain in the upper limb. This randomized, blinded, sham-controlled, parallel trial included a rTMS protocol (10-Hz, 2000 pulses/session) consisting of five daily sessions, followed by one session per week for the next seven weeks. Pain intensity, as well as pain-related disability, quality of life, and psychological status, were assessed. For the primary outcome, pain intensity was measured daily using a numerical rating scale as a pain diary. Thirty patients were randomly assigned to the active rTMS or sham-stimulation groups. In the primary outcome, the decrease (least square [LS] mean ± standard error) in the weekly average of a pain diary at week 9 compared to the baseline was 0.84 ± 0.31 in the active rTMS group and 0.58 ± 0.29 in the sham group (LS mean difference, 0.26; 95% confidence interval, − 0.60 to 1.13). There was no significant effect on the interaction between the treatment group and time point. Pain-related disability score improved, but other assessments showed no differences. No serious adverse events were observed. This study did not show significant pain relief; however, active rTMS tended to provide better results than sham. rTMS has the potential to improve pain-related disability in addition to pain relief.Clinical Trial Registration number: jRCTs052190110 (20/02/2020).

Exploring EEG-based motor imagery decoding: a dual approach using spatial features and spectro-spatial Deep Learning model IFNet.

In recent years, the decoding of motor imagery (MI) from electroencephalography (EEG) signals has become a focus of research for brain-machine interfaces (BMIs) and neurorehabilitation. However, EEG signals present challenges due to their non-stationarity and the substantial presence of noise commonly found in recordings, making it difficult to design highly effective decoding algorithms. These algorithms are vital for controlling devices in neurorehabilitation tasks, as they activate the patient's motor cortex and contribute to their recovery. This study proposes a novel approach for decoding MI during pedalling tasks using EEG signals. A widespread approach is based on feature extraction using Common Spatial Patterns (CSP) followed by a linear discriminant analysis (LDA) as a classifier. The first approach covered in this work aims to investigate the efficacy of a task-discriminative feature extraction method based on CSP filter and LDA classifier. Additionally, the second alternative hypothesis explores the potential of a spectro-spatial Convolutional Neural Network (CNN) to further enhance the performance of the first approach. The proposed CNN architecture combines a preprocessing pipeline based on filter banks in the frequency domain with a convolutional neural network for spectro-temporal and spectro-spatial feature extraction. To evaluate the approaches and their advantages and disadvantages, EEG data has been recorded from several able-bodied users while pedalling in a cycle ergometer in order to train motor imagery decoding models. The results show levels of accuracy up to 80% in some cases. The CNN approach shows greater accuracy despite higher instability.

How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease that, at present, has no effective cure. Evidence of increased circulating glutamate and hyperexcitability of the motor cortex in patients with amyotrophic lateral sclerosis have provided an empirical support base for the 'dying forward' excitotoxicity hypothesis. The hypothesis postulates that increased activation of upper motor neurons spreads pathology to lower motor neurons in the spinal cord in the form of excessive glutamate release, which triggers excitotoxic processes. Many clinical trials have focused on therapies that target excitotoxicity via dampening neuronal activation, but not all are effective. As such, there is a growing tension between the rising tide of evidence for the 'dying forward' excitotoxicity hypothesis and the failure of therapies that target neuronal activation. One possible solution to these contradictory outcomes is that our interpretation of the current evidence requires revision in the context of appreciating the complexity of the nervous system and the limitations of the neurobiological assays we use to study it. In this review we provide an evaluation of evidence relevant to the 'dying forward' excitotoxicity hypothesis and by doing so, identify key gaps in our knowledge that need to be addressed. We hope to provide a road map from hyperexcitability to excitotoxicity so that we can better develop therapies for patients suffering from amyotrophic lateral sclerosis. We conclude that studies of upper motor neuron activity and their synaptic output will play a decisive role in the future of amyotrophic lateral sclerosis therapy.

Brain positron emission tomography in idiopathic normal-pressure hydrocephalus: new 18F-fluorodeoxyglucose pattern in a long-known syndrome.

Patients with idiopathic normal-pressure hydrocephalus (iNPH) can show a global reduction in cerebral glucose metabolism at [18F]Fluorodeoxyglucose (FDG) PET. The presence of caudate hypometabolism has been identified as a potential biomarker in iNPH, yet there is limited evidence of hypermetabolic findings in patients with iNPH so far. We retrieved retrospectively patients with iNPH and normal cognitive assessment, evaluated before surgery undergoing brain [18F]FDG-PET. The 18F-FDG-PET brain scans were compared to those of a control group of healthy subjects, matched for age and sex, by statistical parametric mapping (SPM) to identify areas of relative hypo- and hypermetabolism. Furthermore, the existence of a correlation between areas of hypo- and hypermetabolism in the patient group was tested. Seven iNPH patients (mean age 74 ± 6 years) were found in the hospital database. SPM group analysis revealed clusters of significant hypometabolism (P = 0.001) in the iNPH group in the dorsal striatum, involving caudate and putamen bilaterally. Clusters of significant hypermetabolism (P = 0.001) were revealed in the bilateral superior and precentral frontal gyrus (BA 4, 6). A significant inverse correlation between striatal hypometabolism and bilateral superior and precentral frontal gyrus hypermetabolism was revealed (P < 0.001 corrected for multiple comparisons). In this cohort, patients with iNPH showed subcortical hypometabolism, including bilateral dorsal striatum. To the best of our knowledge, this is the first report demonstrating a hypermetabolic pattern in the primary motor and premotor areas, and showing an inverse correlation between the striatum and motor cortex in patients with iNPH.

Role of Neural Plasticity of Motor Cortex in Gliomas Evaluated by Brain Imaging and Mapping Techniques in Pre- and Postoperative Period: A Systematic Review.

Resection of infiltrative neuroepithelial primary brain tumors, such as low-grade gliomas (LGGs) remains a neurosurgical challenge. Usual lack of clinical deficit despite LGGs growing in eloquent brain areas may be explained by reshaping and reorganization of functional networks. The development of modern diagnostic imaging techniques could disclose better understanding of the rearrangement of the brain cortex; however, mechanisms underlying such compensation and how it occurs in the motor cortex remain unclear. This systematic review aims to analyze the neuroplasticity of motor cortex in patients with LGGs, as determined by neuroimaging and functional techniques. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, medical subject headings (MeSH) and the following terms related to neuroimaging, LGGs and neuroplasticity were used with the Boolean operators AND and OR to synonymous terms in the PubMed database. Among the 118 results, 19 studies were included in the systematic review. Motor function in patients with LGG was characterized by a compensation in the contralateral and supplementary motor areas and premotor functional networks. Furthermore, ipsilateral activation in these types of gliomas was rarely described. Moreover, some studies did not reveal statistical significance in association between functional reorganization and the postoperative period, which can be explained by the low number of patients. Our findings suggest a high pattern of reorganization per different eloquent motor areas and gliomas diagnosis. Understanding this process is useful to guide safe surgical resection and to develop protocols that assess the plasticity, even though functional network rearrangement needs to be better characterized by more studies.

Altered Thalamocortical Signaling in a Mouse Model of Parkinson's Disease.

Activation of the primary motor cortex (M1) is important for the execution of skilled movements and motor learning, and its dysfunction contributes to the pathophysiology of Parkinson's disease (PD). A well-accepted idea in PD research, albeit not tested experimentally, is that the loss of midbrain dopamine leads to decreased activation of M1 by the motor thalamus. Here, we report that midbrain dopamine loss altered motor thalamus input in a laminar- and cell type-specific fashion and induced laminar-specific changes in intracortical synaptic transmission. Frequency-dependent changes in synaptic dynamics were also observed. Our results demonstrate that loss of midbrain dopaminergic neurons alters thalamocortical activation of M1 in both male and female mice, and provide novel insights into circuit mechanisms for motor cortex dysfunction in a mouse model of PD.SIGNIFICANCE STATEMENT Loss of midbrain dopamine neurons increases inhibition from the basal ganglia to the motor thalamus, suggesting that it may ultimately lead to reduced activation of primary motor cortex (M1). In contrast with this line of thinking, analysis of M1 activity in patients and animal models of Parkinson's disease report hyperactivation of this region. Our results are the first report that midbrain dopamine loss alters the input-output function of M1 through laminar and cell type specific effects. These findings support and expand on the idea that loss of midbrain dopamine reduces motor cortex activation and provide experimental evidence that reconciles reduced thalamocortical input with reports of altered activation of motor cortex in patients with Parkinson's disease.

Deficient GABABergic and glutamatergic excitability in the motor cortex of patients with long-COVID and cognitive impairment

ObjectiveAttention, working memory and executive processing have been reported to be consistently impaired in Neuro-Long coronavirus disease (COVID). On the hypothesis of abnormal cortical excitability, we investigated the functional state of inhibitory and excitatory cortical regulatory circuits by single “paired-pulse” transcranial magnetic stimulation (ppTMS) and Short-latency Afferent Inhibition (SAI). MethodsWe compared clinical and neurophysiological data of 18 Long COVID patients complaining of persistent cognitive impairment with 16 Healthy control (HC) subjects. Cognitive status was evaluated by means of the Montreal Cognitive Assessment (MoCA) and a neuropsychological evaluation of the executive function domain; fatigue was scored by the Fatigue Severity Scale (FSS). Resting motor threshold (RMT), the amplitude of the motor evoked potential (MEP), Short Intra-cortical Inhibition (SICI), Intra-cortical Facilitation (ICF), Long-interval Intracortical Inhibition (LICI) and Short-afferent inhibition (SAI) were investigated over the motor (M1) cortex. ResultsMoCA corrected scores were significantly different between the two groups (p = 0.023). The majority of the patients’ performed sub-optimally in the neuropsychological assessment of the executive functions. The majority (77.80%) of the patients reported high levels of perceived fatigue in the FSS. RMT, MEPs, SICI and SAI were not significantly different between the two groups. On the other hand, Long COVID patients showed a reduced amount of inhibition in LICI (p = 0.003) and a significant reduction in ICF (p < 0.001). ConclusionsNeuro-Long COVID patients performing sub-optimally in the executive functions showed a reduction of LICI related to GABAb inhibition and a reduction of ICF related to glutamatergic regulation. No alteration in cholinergic circuits was found. SignificanceThese findings can help to better understand the neurophysiological characteristics of Neuro-Long COVID, and in particular, motor cortex regulation in people with “brain fog”.

Altered Functional Connectivity of Salience Network in Mood Disorders

IntroductionDespite the significant scientific progress in the study of the mechanisms underlying mental disorders, stable biomarkers facilitating their diagnosis and differential diagnosis are lacking. Therefore, we attempted to explore possible functional connectivity (FC) differences across some of the more prevalent mental disorders, namely mood disorders.ObjectivesThe current study aimed at investigating the alterations of the functional connectivity of major seeds of the Salience Network (SN) (the Anterior Cingulate Cortex (ACC), and Anterior Insula (AI) in patients with unipolar (Major Depressive Disorder-MDD) or bipolar (Bipolar Disorder-BD) depression as compared to healthy controls (HC).MethodsFor this study 103 adult subjects underwent resting-state Magnetic Resonance Imaging of whom 60 were patients with a depressive episode (MDD: n=35; BD: n=25), and 43 were healthy controls (HC). The individuals in both groups were matched for age and gender. Each participant has provided written informed consent (Ethics Committee: P186/22.01.2021). Seed-to-voxel analysis was performed via the CONN toolbox running on MATLAB. Random Field Theory parametric statistics was used with a cluster-level FWE correction p&lt;0.05.ResultsBoth the ACC and the right AI demonstrated a statistically significant increase in the FC to the somatosensory cortex and the motor cortex in patients as opposed to HC. In addition, there was hyperconnectivity between ACC and the right Superior Frontal Gyrus, Precuneus, and the Superior Parietal Lobule bilaterally in patients as well. A reduced FC between the ACC and the hippocampus and parahippocampus was observed in depression in comparison to HC. The analysis of the left AI seed yielded no statistically significant between-group differences.ConclusionsOur results demonstrate aberrant connectivity between nodes of the SN, the Default Mode Network, and the Limbic Network which might provide clarification on the mechanisms of impaired balance between internally and externally oriented attention, affective and cognitive control in depression. In addition, the alterations of the FC between SN and the somatosensory and motor cortices may be suggested as a possible explanation of the disturbances in the psychomotor activity in mood disorders.Disclosure of InterestA. Todeva-Radneva Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, R. Paunova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, D. Stoyanov Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, T. Zdravkova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, S. Kandilarova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience

Spontaneous beta power, motor-related beta power and cortical thickness in major depressive disorder with psychomotor disturbance

IntroductionThe psychomotor disturbance is a common symptom in patients with major depressive disorder (MDD). The neurological mechanisms of psychomotor disturbance are intricate, involving alterations in the structure and function of motor-related regions. However, the relationship among changes in the spontaneous activity, motor-related activity, local cortical thickness, and psychomotor function remains unclear. MethodA total of 140 patients with MDD and 68 healthy controls performed a simple right-hand visuomotor task during magnetoencephalography (MEG) scanning. All patients were divided into two groups according to the presence of psychomotor slowing. Spontaneous beta power, movement-related beta desynchronization (MRBD), absolute beta power during movement and cortical characteristics in the bilateral primary motor cortex were compared using general linear models with the group as a fixed effect and age as a covariate. Finally, the moderated mediation model was tested to examine the relationship between brain metrics with group differences and psychomotor performance. ResultsThe patients with psychomotor slowing showed higher spontaneous beta power, movement-related beta desynchronization and absolute beta power during movement than patients without psychomotor slowing. Compared with the other two groups, significant decreases were found in cortical thickness of the left primary motor cortex in patients with psychomotor slowing. Our moderated mediation model showed that the increased spontaneous beta power indirectly affected impaired psychomotor performance by abnormal MRBD, and the indirect effects were moderated by cortical thickness. ConclusionThese results suggest that patients with MDD have aberrant cortical beta activity at rest and during movement, combined with abnormal cortical thickness, contributing to the psychomotor disturbance observed in this patient population.

TU-136. Short latency afferent inhibition and facilitation in the motor cortex of patients with progressive myoclonus epilepsy type 1 (EPM1)

TU-136. Short latency afferent inhibition and facilitation in the motor cortex of patients with progressive myoclonus epilepsy type 1 (EPM1)

Sling Exercise Can Drive Cortical Representation of the Transversus Abdominis and Multifidus Muscles in Patients With Chronic Low Back Pain.

ObjectiveThe transversus abdominis (TrA) and multifidus (MF) muscles are essential in preventing chronic low back pain (CLBP) recurrence by maintaining segmental stabilization and stiffness. Sling exercise is a high-level core stability training to effectively improve the activities of the TrA and MF muscles. However, the neural mechanism for sling exercise-induced neural plasticity change in the primary motor cortex (M1) remains unclear. This study aimed to investigate the role of sling exercise in the reorganization of the motor cortical representation of the TrA and MF muscles.MethodsTwenty patients with CLBP and 10 healthy individuals were recruited. For map volume, area, the center of gravity (CoG) location (medial-lateral location and anterior-posterior location), and latency, two-way ANOVA was performed to compare the effects of groups (the CLBP-pre, CLBP-post, and healthy groups) and the two muscles (the TrA and MF muscles). The Visual Analog Scale (VAS), the Oswestry Disability Index (ODI), and postural balance stability were assessed at baseline and at the end of 2 weeks of sling exercise. Linear correlations between VAS or ODI and CoG locations were assessed by Pearson's correlation test.Results2 weeks of sling exercise induced both the anterior-medial (P < 0.001) and anterior-posterior (P = 0.025) shifts of the MF muscle representation at the left motor cortex in patients with CLBP. Anterior-medial (P = 0.009) shift of the TrA muscle representation at the right motor cortex was observed in patients with CLBP. The motor cortical representation of the two muscles in patients with CLBP after sling exercise (TrA: 2.88 ± 0.27 cm lateral and 1.53 ± 0.47 cm anterior of vertex; MF: 3.02 ± 0.48 cm lateral and 1.62 ± 0.40 cm anterior of vertex) closely resembled that observed in healthy individuals (TrA: 2.83 ± 0.48 cm lateral and 2.00 ± 0.43 cm anterior of vertex; MF: 2.94 ± 0.43 cm lateral and 1.77 ± 0.48 cm anterior of vertex). The VAS and the ODI were reduced following the sling exercise (VAS: P < 0.001; ODI: P < 0.001).ConclusionThis study provides evidence that sling training can drive plasticity changes in the motor system, which corresponds with the reduction in pain and disability levels in patients with CLBP. This study was registered in the Chinese Clinical Trial Registry (Clinical Trial Registration Number: ChiCTR2100045904, http://www.chictr.org.cn/showproj.aspx?proj=125819).Clinical Trial RegistrationChiCTR2100045904.

Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait.

Freezing of gait is a debilitating symptom in advanced Parkinson’s disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson’s disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might reveal unique information on understanding and improving therapy for freezing of gait.Here, we directly recorded potentials in the primary motor cortex using subdural electrocorticography and synchronously captured gait freezing using optoelectronic motion-tracking systems in 16 freely-walking patients with Parkinson’s disease who received subthalamic nucleus deep brain stimulation surgery. Overall, we recorded 451 timed up-and-go walking trials and quantified 7073 s of stable walking and 3384 s of gait freezing in conditions of on/off-stimulation and with/without dual-tasking.We found that (i) high beta-gamma phase-amplitude coupling in the primary motor cortex was detected in freezing trials (i.e. walking trials that contained freezing), but not non-freezing trials, and the high coupling in freezing trials was not caused by dual-tasking or the lack of movement; (ii) non-freezing episodes within freezing trials also demonstrated abnormally high couplings, which predicted freezing severity; (iii) deep brain stimulation of subthalamic nucleus reduced these abnormal couplings and simultaneously improved freezing; and (iv) in trials that were at similar coupling levels, stimulation trials still demonstrated lower freezing severity than no-stimulation trials.These findings suggest that elevated phase-amplitude coupling in the primary motor cortex indicates higher probabilities of freezing. Therapeutic deep brain stimulation alleviates freezing by both decoupling cortical oscillations and enhancing cortical resistance to abnormal coupling. We formalized these findings to a novel ‘bandwidth model,’ which specifies the role of cortical dysfunction, cognitive burden and therapeutic stimulation on the emergence of freezing. By targeting key elements in the model, we may develop next-generation deep brain stimulation approaches for freezing of gait.

Effects of repeated transcranial magnetic stimulation in the dorsolateral prefrontal cortex versus motor cortex in patients with neuropathic pain after spinal cord injury: a study protocol

IntroductionNeuropathic pain is one of the common complications of spinal cord injuries (SCI), which will slow down the recovery process and result in lower quality of life. Previous studies have...

Long-term prophylactic efficacy of transcranial direct current stimulation in chronic migraine. A randomised, patient-assessor blinded, sham-controlled trial

ObjectiveTo assess the prophylactic effect of anodal tDCS of the left motor cortex in patients with resistant chronic migraine (CM) and its long-term maintenance. MethodsIn a patient-assessor blinded, sham-controlled trial, 36 patients were randomized to receive anodal tDCS (active group, n = 18) or sham tDCS (sham group, n = 18). The studied population was characterized by a previous failure of at least 3 classes of preventive drugs and a mean duration of migraine history of 26 years. The tDCS procedure consisted of an induction phase of 5 consecutive daily sessions (week 1) followed by a maintenance phase of 1 weekly session during the next 4 weeks and two bimonthly sessions in the next month, for a total of 11 sessions during 2 months. Anodal tDCS was delivered at 2 mA intensity for 20 min over the left motor cortex. The primary endpoint was the reduction in the monthly number of migraine attacks from baseline to each period of follow-up (months 1, 2, 3, 5) between the active and sham groups. ResultsThe monthly number of migraine attacks expressed as the percentage of reduction from baseline was significantly reduced in the active versus the sham group, from the end of first month (−21% ± 22 vs. −2% ±25, p = 0.019) to the end of follow-up (3-month post-treatment) (−32% ± 33 vs. −6% ±39, p = 0.011). At this time, the rate of responders, defined as a reduction of the monthly number of migraine attacks ≥30% from baseline, was significantly higher in the active group than in the sham group (50% vs. 14%, p = 0.043). ConclusionOur results show a marked prophylactic effect of anodal tDCS of the left motor cortex in resistant CM extending several months after the stimulation period, and suggest that this neuromodulatory approach may be part of the prophylactic alternatives available for CM.

Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study

ObjectiveHepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. Methods23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. ResultsMEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. ConclusionsOur study revealed reduced synaptic plasticity of the primary motor cortex in HE. SignificanceReduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients.

The Suppressive Effect of the Motor System on the Sensory System in Patients With Tourette Syndrome.

Objective: Tourette syndrome (TS) is a complicated sensorimotor disorder. Some patients with TS relieve their involuntary premonitory urges via tics. However, the effect of the motor system on the sensory system has not yet been elucidated. The purpose of the present study was to investigate changes in the excitability of the sensory cortex following repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with TS.Methods: Twenty-nine patients with TS and 20 healthy, age-matched controls were enrolled in this study. All subjects were divided into four groups: patients with rTMS, patients with sham-rTMS, controls with rTMS, and controls with sham-rTMS. The clinical severity of tics was evaluated using the Yale Global Tic Severity Scale. Single somatosensory evoked potentials (SEPs) and paired SEPs were recorded by stimulating the median nerve at the wrist of all subjects. The resting motor threshold (RMT) was tested in each subject in the rTMS group. Afterwards, all four groups were administered rTMS (1 Hz, 90% RMT) or sham-rTMS for 200 s, followed by a 15-min rest. Finally, single SEPs and paired SEPs were repeated for each subject.Results: No significant differences in RMT, the amplitudes of single SEPs, or the suppression of paired SEPs were observed between patients with TS and controls at baseline. After rTMS, a significant suppression of the peak-to-peak amplitude of the N20–P25 responses of single SEPs was observed in both controls (p = 0.049) and patients (p < 0.0001). The suppression of the N20–P25 peak-to-peak amplitude was more significant in patients than in controls (p = 0.039). A significant difference in the suppression of paired SEPs after rTMS was not observed between groups.Conclusions: The more significant suppression of N20–P25 components of single SEPs with normal suppressed paired SEPs in patients with TS after 1-Hz rTMS of the motor cortex suggests that the suppressive effect of the motor system on the sensory system might originate from the motor-sensory cortical circuits rather than the sensory system itself.

Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain

ObjectiveThe role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity. MethodsCross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging. ResultsWe included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = −0.25, p = 0.04). ConclusionThere is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity. SignificanceThese findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.

Serial assessment of iron in the motor cortex in limb-onset amyotrophic lateral sclerosis using quantitative susceptibility mapping

Dysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with amyotrophic lateral sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based quantitative susceptibility mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a 6-month period. Iron concentration was investigated using magnetic resonance based QSM in the primary motor cortex and the pre-motor area in 13 limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and 11 age- and sex-matched control subjects. Nine ALS patients underwent follow-up scans at 6 months. Significantly increased QSM values were observed in the left posterior primary motor area (P=0.02, Cohen's d =0.9) and right anterior primary motor area (P=0.02, Cohen's d =0.92) in the group of limb-onset ALS patients compared to that of control subjects. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to control subjects. No significant change in QSM was observed at the 6-month follow-up scans in the ALS patients. The findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a quantitative radiological indicator in early disease diagnosis in limb-onset ALS and its subtypes. Our serial scans results suggest a longer period than 6 months is needed to detect significant quantitative changes in the motor cortex.

Long-term treatment of chronic orofacial, pudendal, and central neuropathic limb pain with repetitive transcranial magnetic stimulation of the motor cortex

ObjectiveTo assess the long-term analgesic effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with chronic pain syndrome. MethodsThe study included 57 patients (orofacial pain, n = 26, pudendal neuralgia, n = 18, and neuropathic limb pain, n = 13) with an “induction phase” of 12 daily rTMS sessions for 3 weeks, followed by a “maintenance phase” of bi-monthly sessions for the next five months. ResultsAll pain measures significantly decreased from baseline to the end of the induction phase. Analgesic response, defined as pain intensity decrease ≥ 30% compared to baseline, was observed in 39 patients (68%), who could be differentiated from non-responders from the 7th rTMS session. At the end of the maintenance phase (D180), 27 patients (47%) were still responders. Anxio-depressive symptoms and quality of life also improved. The analgesic response at the end of the induction phase was associated with lower pain score at baseline, and the response at the end of the maintenance phase was associated with lower anxio-depressive score at baseline. ConclusionThe analgesic efficacy of motor cortex rTMS can be maintained in the long term in various chronic pain conditions. Patients with high pain level and severe anxio-depressive symptoms may have a less favorable profile to respond to the procedure. SignificanceThe overall impact of rTMS treatment on daily life requires a multidimensional evaluation that goes beyond the analgesic effect that can be achieved.

Distortion of the cortical motor map in patients with Unverricht-Lundborg disease: A combined TMS-MRI study

ObjectiveTo assess functional organization of the motor cortex in patients with Unverricht-Lundborg disease (EPM1A) using a combined neurophysiologic and imaging approach. MethodsEPM1A patients underwent transcranial magnetic stimulation (TMS)-based cortical mapping of the motor hand area. Moreover, they performed neuroimaging studies to assess functional magnetic resonance imaging (fMRI) activation maps related to motor hand task and cortical thickness (CTH) on T1-weighted 3D images. ResultsThe hand cortical representation was different in EPM1A patients from that of the control subjects both in TMS and in fMRI brain mapping, characterized by a posterior dislocation and a mild reduction in the activation of motor areas. CTH analysis revealed a thinning of both precentral and paracentral areas in the patients. ConclusionsWe hypothesize that the altered cortical motor map reflects a functional reorganization of the residual cortical neuronal pool of the sensorimotor hand areas driven by plastic reorganization and/or pathophysiological mechanisms. SignificanceBoth pathophysiological process and plastic changes may represent two sides of the same phenomenon in the EPM1A patients; structural and functional brain mapping may help to identify functional reorganization of the cortical motor system.