Offline low-frequency rTMS of the primary and premotor cortices does not impact motor sequence memory consolidation despite modulation of corticospinal excitability.

Motor skills are acquired and refined across alternating phases of practice (online) and subsequent consolidation in the absence of further skill execution (offline). Both stages of learning are sustained by dynamic interactions within a widespread motor learning network including the premotor and primary motor cortices. Here, we aimed to investigate the role of the dorsal premotor cortex (dPMC) and its interaction with the primary motor cortex (M1) during motor memory consolidation. Forty-eight healthy human participants (age 22.1 ± 3.1 years) were assigned to three different groups corresponding to either low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of left dPMC, rTMS of left M1, or sham rTMS. rTMS was applied immediately after explicit motor sequence training with the right hand. Motor evoked potentials were recorded before training and after rTMS to assess potential stimulation-induced changes in corticospinal excitability (CSE). Participants were retested on motor sequence performance after eight hours to assess consolidation. While rTMS of dPMC significantly increased CSE and rTMS of M1 significantly decreased CSE, no CSE modulation was induced by sham rTMS. However, all groups demonstrated similar significant offline learning indicating that consolidation was not modulated by the post-training low-frequency rTMS intervention despite evidence of an interaction of dPMC and M1 at the level of CSE. Motor memory consolidation ensuing explicit motor sequence training seems to be a rather robust process that is not affected by low-frequency rTMS-induced perturbations of dPMC or M1. Findings further indicate that consolidation of explicitly acquired motor skills is neither mediated nor reflected by post-training CSE.

Clinical Benefit of Rehabilitation Training in Spinal Cord Injury: A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: This study was performed to evaluate the effects of different rehabilitation interventions in spinal cord injury. SUMMARY OF BACKGROUND DATA: Several activity-based interventions have been widely applied in spinal cord injury in the past, but the effects of these rehabilitation exercises are controversial. METHODS: Publications were searched from databases (PubMed, Embase, Cochrane, the database of the U.S. National Institutes of Health and World Health Organization International Clinical Trials Registry Platform) using the searching terms like spinal cord injury, transcranial magnetic stimulation, functional electrical stimulation, activity-based therapy, and robotic-assisted locomotor training. Randomized controlled trials and controlled trials were included. The primary outcomes included functional upper/lower extremity independence, walking capacity, spasticity, and life quality of individuals with spinal cord injury. Meta-analysis was performed using Revman 5.0 software. RESULTS: Thirty-one articles were included. Meta-analysis showed that transcranial magnetic stimulation improved walking speed (95% confidence interval [CI] 0.01, 0.16) and lower extremity function (95% CI 1.55, 7.27); functional electrical stimulation significantly increased upper extremity independence (95% CI 0.37, 5.48). Robotic-assisted treadmill training improved lower extremity function (95% CI 3.44, 6.56) compared with related controls. CONCLUSION: Activity-based intervention like transcranial magnetic stimulation, functional electrical stimulation, and robotic-assisted treadmill training are effective in improving function in individuals with spinal cord injury.Level of Evidence: 1.

Transcranial Magnetic Stimulation and the Understanding of Behavior.

The development of the use of transcranial magnetic stimulation (TMS) in the study of psychological functions has entered a new phase of sophistication. This is largely due to an increasing physiological knowledge of its effects and to its being used in combination with other experimental techniques. This review presents the current state of our understanding of the mechanisms of TMS in the context of designing and interpreting psychological experiments. We discuss the major conceptual advances in behavioral studies using TMS. There are meaningful physiological and technical achievements to review, as well as a wealth of new perceptual and cognitive experiments. In doing so we summarize the different uses and challenges of TMS in mental chronometry, perception, awareness, learning, and memory.

Effect of psychotropic drugs on cortical excitability of patients with major depressive disorders: A transcranial magnetic stimulation study.

Transcranial magnetic stimulation (TMS) can be used to evaluate the effects of pharmacological interventions. The aim of this study was to assess the impact of the selective serotonin reuptake inhibitor, sertraline, and the atypical antipsychotic drugs quetiapine and olanzapine, on cortical excitability in unmedicated patients with major depressive disorder (MDD). The study included 45 medication-free MDD patients diagnosed according to DSM V. They were divided randomly into three groups who received a single oral dose of one of the three drugs sertraline (50 mg), quetiapine (100 mg) and olanzapine (10 mg). Psychological evaluation was conducted using the Mini-Mental State Examination (MMSE) and Beck Depression Inventory Scale (BDI). Resting and active motor thresholds (rMT and aMT) together with contralateral and ipsilateral cortical silent periods (cSP, and iSP) were measured for each participant before and at the time of maximum concentration of drug intake. There was significant increase in excitability of motor cortex after sertraline without changes in GABAB neurotransmission. Quetiapine and olanzapine potentiated inhibitory GABAB neurotransmission (prolongation of cSP); olanzapine additionally prolonged the iSP. Thus TMS can differentiate between the impact of different psychotropic drugs on excitatory and inhibitory transmission in motor cortex.

Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial.

BACKGROUND: Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) to the left dorsal lateral prefrontal cortex (LDLPFC) transiently reduces smoking craving, decreases cigarette consumption, and increases abstinence rates. OBJECTIVE: We investigated whether 10 daily MRI-guided rTMS sessions over two weeks to the LDLPFC paired with craving cues could reduce cigarette consumption and induce smoking cessation. METHODS: We enrolled 42 treatment-seeking nicotine-dependent smokers (≥10 cigarettes per day) in a randomized, double-blind, sham-controlled trial. Participants received 10 daily sessions over 2 weeks of either active or sham MRI-guided rTMS (10Hz, 3000 pulses each session) to the LDLPFC concurrently with video smoking cues. The primary outcome was a reduction in biochemically confirmed cigarette consumption with a secondary outcome of abstinence on the target quit date. We also recorded cue-induced craving and withdrawal symptoms. RESULTS: Compared to sham (n = 17), participants receiving active rTMS (n = 21) smoked significantly fewer cigarettes per day during the 2-week treatment (mean [SD], 13.73[9.18] vs. 11.06[9.29], P < .005) and at 1-month follow-up (12.78[9.53] vs. 7.93[7.24], P < .001). Active rTMS participants were also more likely to quit by their target quit rate (23.81%vs. 0%, OR 11.67, 90% CL, 0.96-141.32, x2 = 4.66, P = .031). Furthermore, rTMS significantly reduced mean craving throughout the treatments and at follow-up (29.93[13.12] vs. 25.01[14.45], P < .001). Interestingly across the active treatment sample, more lateral coil location was associated with more success in quitting (-43.43[0.40] vs. -41.79[2.24], P < .013). CONCLUSIONS: Daily MRI-guided rTMS to the LDLPFC for 10 days reduces cigarette consumption and cued craving for up to one month and also increases the likelihood of smoking cessation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02401672.

Changes in interleukin-1 beta induced by rTMS are significantly correlated with partial improvement of cognitive dysfunction in treatment-resistant depression: a pilot study.

The impairment experienced by many individuals with depression is closely related to the cognitive symptoms of the disorder. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method that provides a promising technique for improving cognitive symptoms in treatment-resistant depression (TRD). It has recently been demonstrated that TRD is associated with increased inflammatory process. In the present study, we investigated whether a relationship exists between changes in cognitive function and those in inflammatory cytokines before and after rTMS treatment. Eleven patients with TRD were enrolled in a high-frequency (10 Hz) rTMS study. Cognitive function, depressive symptoms and serum concentration of inflammatory cytokines (interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α) were measured at baseline and at the endpoint of rTMS treatment. rTMS treatment significantly improved depressive symptom scores and some subscales of cognitive dysfunction. The present study has demonstrated that partial changes in cognitive function and changes in IL-1ß were significantly correlated. The partial improvement of cognitive dysfunction by rTMS in the present study might be attributable to the reduction of peripheral IL-1ß levels. The present results should be replicated for verification in future studies.

Repetitive transcranial magnetic stimulation ameliorates recognition memory impairment induced by hindlimb unloading in mice associated with BDNF/TrkB signaling.

Repetitive transcranial magnetic stimulation (rTMS), which could improve learning and memory, is widely used in psychiatry and neurology as a therapeutic approach. There are few studies reporting effective countermeasures to cognition decline in astronauts during space flight. Accordingly, we examined whether rTMS was able to significantly alleviate the learning and memory deficits induced by hindlimb unloading (HU), a general accepted rodent model to simulate microgravity, in mice. Male C57BL/6 J mice were randomly divided into four groups: Sham, rTMS, HU, and HU + rTMS groups. The hindlimb unloading procedure continued for consecutive 14 days. Meanwhile, high frequency rTMS (15 Hz) was applied for 14 days from the 1st day of HU procedure. The novel object recognition test showed that the recognition memory was evidently impaired in the HU group compared to that in the Sham group, however, rTMS significantly attenuated the impairment of the memory. Furthermore, rTMS significantly improved the HU-induced LTP impairment and increased spine density in the hippocampal dentate gyrus region. Additionally, rTMS enhanced the expressions of postsynaptic function-associated proteins N-methyl-d-aspartic acid receptors (NR2B and NR2 A) and postsynaptic density protein (PSD95), upregulated BDNF/TrkB signaling and increased phosphorylation of protein kinase B (Akt) in the HU + rTMS group. In conclusion, the data suggest that high frequency rTMS may be an effective countermeasure against the learning and memory deficiency, induced by simulated microgravity.

Efficacy and tolerability of deep transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to investigate the efficacy of deep transcranial magnetic stimulation (dTMS) for treatment-resistant depression (TRD). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Medline, PsycINFO, Embase, and Cochrane Library were systematically searched from the time of their inception until July 17, 2019. Data were pooled using a random-effects model. Primary outcomes were mean change of depression and anxiety severity. Secondary outcomes were response and remission rate of depression. RESULTS: Fifteen studies including three randomized controlled trials (RCTs) (n = 417, mean age: 50.6 years) and twelve uncontrolled clinical trials (n = 284, mean age: 46.4 years) were included. dTMS significantly improved the depressive (Hedges' g = -1.323, 95% CI = -1.651 to -0.995, p < .001) and anxiety symptoms (Hedges' g = -1.282, 95% CI = -1.514 to -1.051, p < .001) in patients with TRD. Subgroup analysis showed that non-RCTs had a larger effect size than RCTs (-1.461 vs -0.756) on depression severity. Although the response and remission rates of the dTMS group were high, only studies using both dTMS and antidepressant medications achieved significance. The anxiolytic effect of dTMS was more heterogeneous, and the results were obtained mainly from non-RCTs. Importantly, the dTMS group showed favorable tolerability without major adverse events. CONCLUSIONS: dTMS is a safe and effective intervention in patients with TRD. Studies combining dTMS and antidepressant medications seemed to show greater therapeutic effects. Future studies are needed to address the interaction effect of dTMS with different classes of antidepressant medications.

Does rTMS on brain areas of mirror neurons lead to higher improvements on symptom severity and empathy compared to the rTMS standard procedure? - Results from a double-blind interventional study in individuals with major depressive disorders.

BACKGROUND: A key feature of major depressive disorders is the lack of emotional processing such as empathy. To counter this, we tested, if brain stimulation on areas rich of mirror neurons on the left inferior parietal lobe (lIPL) might improve emotional processing, including empathy, compared to a standard brain stimulation on the left dorsolateral prefrontal cortex (lDLPFC). METHODS: Twenty inpatients (mean age: 38.9 years; 55% females) with severe major depressive disorders and stable treatment of sertraline at therapeutic dosages were randomly assigned to either the rTMS condition on areas of mirror neuron stimulation, that is, the left inferior parietal lobe (rTMS-lIPL), or to the left dorsolateral prefrontal cortex (rTMS-lDLPFC; control condition). Interventions lasted for two consecutive weeks (2 × 5 interventions of 30'). At baseline and at the end of the study, patients completed questionnaires on current mood state and emotion regulation. In parallel, experts rated patients' depression severity. RESULTS: Mood improved over time, but more so in the control condition, compared to the rTMS-lIPL condition (medium-large effect sizes). Emotion regulation improved over time; specifically, empathy improved, but only in the rTMS-lIPL condition, compared to the control condition. Symptoms of depression decreased over time, but more so in the rTMS- lIPL condition. CONCLUSIONS: The pattern of results suggests that among inpatients with severe major depressive disorders, and compared to a standard procedure of rTMS, rTMS targeting on areas rich of mirror neurons appeared to improve emotion regulation, and specifically empathy, while there was no advantage on acute mood.

Potential predictors of depressive relapse following repetitive Transcranial Magnetic Stimulation: A systematic review.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is widely approved treatment for major depressive disorder (MDD). However, around 50% of individuals who recover from depression following rTMS interventions experience a relapse of depressive symptomatology by 12 months. The short-term durability of the rTMS treatment effect has been systematically investigated. However, variables relating to the long-term durability of the antidepressant effect produced by rTMS are less understood. Therefore, the current review systematically assessed the research on variables relating to relapse following rTMS. METHOD: This systematic review was performed according to PRISMA guidelines. A comprehensive electronic literature search for terms related to relapse following rTMS treatment for MDD was performed on studies published before the end of October 2018. RESULTS: A total of 18 studies assessing relapse related variables were identified. While there is some indication that comorbid anxiety, acute response, and residual symptomatology may hold predictive potential for depressive relapse following rTMS treatment, findings were not sufficient to draw reliable conclusions. DISCUSSION: Identified studies assessed three main categories of variables including demographic information, clinical characteristics and rating scale scores, and rTMS treatment specific factors. Only a small number of studies were available, and considerable inconsistency exists between studies, only limited conclusions were able to be drawn. CONCLUSION: More studies assessing a wider range of predictor variables such as cognitive or neuroimaging markers are needed.

Prediction of rTMS treatment response in major depressive disorder using machine learning techniques and nonlinear features of EEG signal.

BACKGROUND: Prediction of therapeutic outcome of repetitive transcranial magnetic stimulation (rTMS) treatment is an important purpose that eliminates financial and psychological consequences of applying inefficient therapy. To achieve this goal we proposed a method based on machine learning to classify responders (R) and non- responders (NR) to rTMS treatment for major depression disorder (MDD) patients. METHODS: 19 electrodes resting state EEG was recorded from 46 MDD patients before treatment. Then patients underwent 7 weeks of rTMS, and 23 of them responded to treatment. Features extracted from EEG include Lempel-Ziv complexity (LZC), Katz fractal dimension (KFD), correlation dimension (CD), the power spectral density, features based on bispectrum, frontal and prefrontal cordance and combination of them. The most relevant features were selected by the minimal-redundancy-maximal-relevance (mRMR) feature selection algorithm. For classifying two groups of R and NR, k-nearest neighbors (KNN) were applied. The performance of the proposed method was evaluated by leave-1-out cross-validation. For further study, the capability of features in differentiating R and NR was investigated by a statistical test. RESULTS: Effective EEG features for prediction of rTMS treatment response were found. EEG beta power, the sum of bispectrum diagonal elements in delta and beta bands and CD were the most discriminative features. Power of beta classified R and NR with the high performance of 91.3% accuracy, 91.3% specificity, and 91.3% sensitivity. LIMITATIONS: Lack of large sample size restricted our method for using in clinical applications. CONCLUSION: This considerable high accuracy indicates that our proposed method with power and some of the nonlinear and bispectral features can lead to promising results in predicting treatment outcome of rTMS for MDD patients only by one session pretreatment EEG recording.

Patient- and Technician-Oriented Attitudes Toward Transcranial Magnetic Stimulation Devices.

Four transcranial magnetic stimulation (TMS) devices are currently approved for use in treatment-resistant depression. The authors present the first data-driven study examining the patient- and technician-experience using three of these distinct devices. A retrospective survey design with both patient and technician arms was utilized. The study population included patients who received TMS for treatment-resistant depression at the Berenson Allen Center for Noninvasive Brain Stimulation for the first time between 2013 and 2016 and technicians who worked in the program from 2009 to 2017. Statistical analysis included t tests and analyses of variance to assess differences between and across the multiple groups, respectively. Patients treated with the NeuroStar device reported greater confidence that the treatment was being performed correctly compared with those treated with the Magstim device. Conversely, with regard to tolerability, patients treated with the Magstim device reported less pain in the last week and less pain on average compared with those treated with the NeuroStar device. On average, technicians reported feeling that both the Magstim and NeuroStar devices were significantly easier to use than the Brainsway Deep TMS H-Coil device. Additionally, they found the former two devices to be more reliable and better tolerated. Furthermore, the technicians reported greater confidence in the Magstim and NeuroStar devices compared with the Brainsway Deep TMS H-Coil device and indicated that they would be more likely to recommend the two former devices to other treatment centers.

Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia.

Impaired neural plasticity may be a core pathophysiological process underlying the symptomatology of schizophrenia. Plasticity-enhancing interventions, including repetitive transcranial magnetic stimulation (rTMS), may improve difficult-to-treat symptoms; however, efficacy in large clinical trials appears limited. The high variability of rTMS-related treatment response may be related to a comparably large variation in the ability to generate plastic neural changes. The aim of the present study was to determine whether negative symptom improvement in schizophrenia patients receiving rTMS to the left dorsolateral prefrontal cortex (DLPFC) was related to rTMS-related brain volume changes. A total of 73 schizophrenia patients with predominant negative symptoms were randomized to an active (n=34) or sham (n=39) 10-Hz rTMS intervention applied 5 days per week for 3 weeks to the left DLPFC. Local brain volume changes measured by deformation-based morphometry were correlated with changes in negative symptom severity using a repeated-measures analysis of covariance design. Volume gains in the left hippocampal, parahippocampal and precuneal cortices predicted negative symptom improvement in the active rTMS group (all r⩽-0.441, all P⩽0.009), but not the sham rTMS group (all r⩽0.211, all P⩾0.198). Further analyses comparing negative symptom responders (⩾20% improvement) and non-responders supported the primary analysis, again only in the active rTMS group (F(9, 207)=2.72, P=0.005, partial η 2=0.106). Heterogeneity in clinical response of negative symptoms in schizophrenia to prefrontal high-frequency rTMS may be related to variability in capacity for structural plasticity, particularly in the left hippocampal region and the precuneus.

Augmenting LTP-Like Plasticity in Human Motor Cortex by Spaced Paired Associative Stimulation.

Paired associative stimulation (PASLTP) of the human primary motor cortex (M1) can induce LTP-like plasticity by increasing corticospinal excitability beyond the stimulation period. Previous studies showed that two consecutive PASLTP protocols interact by homeostatic metaplasticity, but animal experiments provided evidence that LTP can be augmented by repeated stimulation protocols spaced by ~30 min. Here we tested in twelve healthy selected PASLTP responders the possibility that LTP-like plasticity can be augmented in the human M1 by systematically varying the interval between two consecutive PASLTP protocols. The first PASLTP protocol (PAS1) induced strong LTP-like plasticity lasting for 30-60 min. The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2. At 10 min, PAS2 prolonged the PAS1-induced LTP-like plasticity. At 30 min, PAS2 augmented the LTP-like plasticity induced by PAS1, by increasing both magnitude and duration. At 60 min and 180 min, PAS2 had no effect on corticospinal excitability. The cumulative LTP-like plasticity after PAS1 and PAS2 at 30 min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60 min and 180 min. In summary, consecutive PASLTP protocols interact in human M1 in a time-dependent manner. If spaced by 30 min, two consecutive PASLTP sessions can augment LTP-like plasticity in human M1. Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases.

[Interactive rTMS protocols in psychiatry]. / Protocoles de rTMS interactives en psychiatrie.

BACKGROUND: The efficiency of repetitive transcranial magnetic stimulation (rTMS) in the treatment of psychiatric disorders is robust for major depressive episode (MDE) while results are encouraging for schizophrenia. However, rTMS protocols need to be optimized. Basic researches in TMS led to the concept of "state dependency TMS". This concept suggests that the neural circuits' activation states, before and during the stimulation, influence the pulse effect. Indeed, TMS effect must be seen, not simply as a stimulus, but also as the result of an interaction between a stimulus and a level of brain activity. Those data suggest that rTMS efficiency could be increased in psychiatric disorders by triggering patients' neurocognitive activities during stimulation. Thus "interactive rTMS protocols" have been submitted. OBJECTIVES: This article provides a review and a classification of different interactive protocols implemented in the treatment of MDE and schizophrenia. Protocols' interactions with cognitive activities and brain electrical activities will be discussed. LITERATURE FINDINGS: Interactive rTMS protocols that manipulate cognitive activities have been developed for MDE treatments. They aim at regulating emotional states of depressed patients during the stimulation. The patients perform emotional tasks in order to activate cortical networks involving the left dorsolateral prefrontal cortex (DLPFC) into a state that may be more sensitive to the rTMS pulse effect. Simultaneous cognitive behavioral therapy ("CBT rTMS") and cognitive-emotional reactivation ("affective rTMS") have thus been tested during left DLPFC rTMS in MDE. Interactive rTMS protocols that manipulate brain electrical activities have been developed for MDE and schizophrenia treatments. Two categories of protocols should be identified. In the first set, personalized brain activity has been analyzed to determine the parameters of stimulation (i.e. frequency of stimulation) matching the patient ("personalized rTMS"). Personalized rTMS protocols can be made "online" or "offline" depending on whether the EEG activity is measured during or prior to rTMS. Online protocol is called "contingent rTMS": it consists in stimulating the brain only when a specific EEG pattern involving the intensity of alpha rhythm is recorded and recognized. Offline protocol is called "alpha rTMS", and relies on ascertaining frequency of stimulation in accordance with personalized alpha peak frequency prior to rTMS. In the second set, electrical brain activity is modulated before or during rTMS in order to stimulate the DLPFC in optimal conditions. Brain activity modulation may be obtained by transcranial direct current stimulation ("tDCS rTMS") or EEG-biofeedack ("EEG-biofeedback rTMS"). CONCLUSION: Interactive rTMS studies have various limitations, notably their exploratory character on a small sample of patients. Furthermore, their theoretical neurocognitive framework justification remains unclear. Nonetheless, interactive rTMS protocols allow us to consider a new field of rTMS, where cognitive and cerebral activities would no longer be considered as simple neural noise, leading to a kind of "first person rTMS", and certainly to innovative therapy in psychiatry.

Hierarchical organization of parietofrontal circuits during goal-directed action.

Two parietofrontal networks share the control of goal-directed movements: a dorsomedial circuit that includes the superior parieto-occipital sulcus (sPOS) and a dorsolateral circuit comprising the anterior intraparietal sulcus (aIPS). These circuits are thought to independently control either reach and grip components (a functional dissociation), or planning and execution phases of grasping movements (a temporal dissociation). However, recent evidence of functional and temporal overlap between these circuits has undermined those models. Here, we test an alternative model that subsumes previous accounts: the dorsolateral and dorsomedial circuits operate at different hierarchical levels, resulting in functional and temporal dependencies between their computations. We asked human participants to grasp a visually presented object, manipulating movement complexity by varying object slant. We used concurrent single-pulse transcranial magnetic stimulation and electroencephalography (TMS-EEG) to probe and record neurophysiological activity in the two circuits. Changes in alpha-band oscillations (8-12 Hz) characterized the effects of task manipulations and TMS interferences over aIPS and sPOS. Increasing the complexity of the grasping movement was accompanied by alpha-suppression over dorsomedial parietofrontal regions, including sPOS, during both planning and execution stages. TMS interference over either aIPS or sPOS disrupted this index of dorsomedial computations; early when aIPS was perturbed, later when sPOS was perturbed, indicating that the dorsomedial circuit is temporally dependent on aIPS. TMS over sPOS enhanced alpha-suppression in inferior parietal cortex, indicating that the dorsolateral circuit can compensate for a transient sPOS perturbation. These findings suggest that both circuits specify the same grasping parameters, with dorsomedial computations depending on dorsolateral contributions.

Abnormal sensorimotor plasticity in CADASIL correlates with neuropsychological impairment.

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small vessel disease of the brain caused by mutations in the NOTCH3 gene. CADASIL progresses, in some cases, to subcortical dementia with a particular cognitive impairment. Different diseases in the dementia spectrum share a central cholinergic and sensorimotor plasticity alteration. We aimed to study different intracortical circuits and sensorimotor plasticity in CADASIL patients using transcranial magnetic stimulation protocols, and to determine whether these characteristics correlated with the results of clinical neuropsychological evaluation. METHODS: Ten CADASIL patients and 10 healthy subjects were included in the study. All subjects underwent a transcranial magnetic stimulation study examining different intracortical circuits. Sensorimotor plasticity was also assessed using a paired associative stimulation and extensive neuropsychological tests. RESULTS: CADASIL patients showed a lack of intracortical facilitation, short latency afferent inhibition and sensorimotor plasticity when compared with control subjects. CADASIL patients also showed an altered neuropsychological profile. Correlation between sensorimotor plasticity and neuropsychological alterations was observed in CADASIL patients. CONCLUSIONS: These results suggest that acetylcholine and glutamate could be involved in the dementia process in CADASIL and that abnormal sensorimotor plasticity correlates with the neuropsychological profile in CADASIL patients.

The impact of high-frequency repetitive transcranial magnetic stimulation on fine motor functions in medication-resistant major depression.

OBJECTIVES: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been reported to improve mood symptoms in major depressive disorder (MDD), research on its impact on psychomotor symptoms is scarce. This study assessed the psychomotor effects of 1 and 10 sessions, respectively, of HF-rTMS over the left DLPFC. METHODS: Ten HF-rTMS sessions were applied in 21 medication-free MDD patients over a 2-week period. At the beginning, one placebo (sham)-controlled rTMS session was also applied in a cross-over, single-blind design. Psychomotor variables were digitally recorded during completion of a Fitts' task, at baseline, after the first and second real/sham session and at the end point. RESULTS: The total 10-session treatment period resulted in a decrease of depression severity. One HF-rTMS session resulted in improvements on the Fitts' task, without a difference between active and sham stimulation, however. No further improvements occurred from session 2 to session 10. CONCLUSIONS: No evidence was provided to link the observed psychomotor improvements to HF-rTMS stimulation, as a practice effect could have impacted the significant psychomotor outcomes.