Motor Cortical Areas Research Articles

Changes in Functional Connectivity Relate to Modulation of Cognitive Control by Subthalamic Stimulation.

Subthalamic (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients not only improves kinematic parameters of movement but also modulates cognitive control in the motor and non-motor domain, especially insituations of high conflict. The objective of this study was to investigate the relationship between DBS-induced changes in functional connectivity at rest and modulation of response- and movement inhibition by STN-DBS in a visuomotor task involving high conflict. During DBS ON and OFF conditions, we conducted a visuomotor task in 14 PD patients who previously underwent resting-state functional MRI (rs-fMRI) acquisitions DBS ON and OFF as part of a different study. In the task, participants had to move a cursor with a pen on a digital tablet either toward (automatic condition) or in the opposite direction (controlled condition) of a target. STN-DBS induced modulation of resting-state functional connectivity (RSFC) as a function of changes in behavior ON versus OFF DBS was estimated using link-wise network-based statistics. Behavioral results showed diminished reaction time adaptation and higher pen-to-target movement velocity under DBS. Reaction time reduction was associated with attenuated functional connectivity between cortical motor areas, basal ganglia, and thalamus. On the other hand, increased movement velocity ON DBS was associated with stronger pallido-thalamic connectivity. These findings suggest that decoupling of a motor cortico-basal ganglia network underlies impaired inhibitory control in PD patients undergoing subthalamic DBS and highlight the concept of functional network modulation through DBS.

Predictors for quality of life improvement following rTMS treatment in neuropathic pain patients.

Recently, Repetitive Transcranial Magnetic Stimulation (rTMS) has gained attention for its potential in relieving neuropathic pain (NP). NP encompasses central and peripheral neuralgia, characterized by sensory abnormalities and spontaneous pain. Pharmacological treatments often provide partial relief with significant side effects, making rTMS an attractive alternative. This study aimed to assess the efficacy of rTMS in treating NP and its impact on quality of life over three months. A total of 51 patients with drug-resistant NP were included, undergoing 15 sessions of rTMS targeting motor cortex areas over three weeks. Clinical response was evaluated using various psychometric scales, including VAS for pain and PGIC. Quality of life was assessed using the SF-36 questionnaire. Results showed significant clinical improvements in pain severity and quality of life following rTMS treatment. Predictive factors of quality of life improvement were identified, with mental health being crucial across all NP areas. Notably, patients with cerebral NP showed improvements linked to physical dimensions, emphasizing tailored treatment approaches. This study underscores the efficacy of rTMS in managing NP, highlighting sustained improvements in pain severity and quality of life. The findings offer valuable insights for personalized treatment approaches and optimizing patient outcomes in NP management.

Motor learning is modulated by dopamine availability in the sensorimotor putamen.

Successful motor skill acquisition requires the dynamic interaction of multiple brain regions, with the striatum playing a critical role in this network. Animal studies suggest that dopaminergic mechanisms are involved in the regulation of motor learning-associated striatal plasticity. In humans, however, the contribution of nigrostriatal dopaminergic transmission to motor learning remains elusive beyond its well-characterized role in initiation and fluent execution of movements. In this prospective observational study, we investigated motor sequence learning in individuals who had undergone 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography for the differential diagnosis of Parkinson's disease (n = 41) and age-matched healthy controls (n = 20). We found that striatal dopamine transporter depletion exhibited distinct spatial patterns that were associated with impairments in motor sequence learning and the manifestation of Parkinsonian motor symptoms, respectively. Specifically, significant associations between striatal dopamine transporter depletion and impairments in motor sequence learning were confined to posterior putaminal regions, whereas significant associations of striatal dopamine transporter depletion with Parkinsonian motor symptom severity showed a widespread spatial pattern across the entire striatal volume with an anterior maximum. Normative functional connectivity analysis revealed that both behavioural domains shared largely overlapping connectivity patterns with the basal ganglia and supplementary motor area. However, apart from connectivity with more posterior parts of the supplementary motor area, significant functional connectivity with primary motor cortical areas was only present for striatal dopamine transporter availability-related modulation of online motor learning. Our findings indicate that striatal dopaminergic signalling plays a specific role in motor sequence learning beyond its influence on mere motor execution, implicating learning-related sensorimotor striatum recruitment and cortico-striatal plasticity as dopamine-dependent mechanisms.

Navigated Transcranial Magnetic Stimulation and Diffusion Tensor Imaging Tractography in Insular Glioma Surgery.

The surgical resection of insular gliomas is associated with a high rate of postoperative morbidity as they grow close to descending motor fibers and lenticulostriate arteries. It is believed that intraoperative perforator infarctions are the determining factor for patients' postoperative outcome, while the majority of patients with intraoperative ischemic events do not develop postoperative motor deficits. This study aims to evaluate whether navigated transcranial magnetic stimulation (nTMS) and nTMS-based fiber tracking could be valuable for the preoperative assessment of patients with insular gliomas. Thirty-two patients with insular gliomas were presurgically examined by nTMS. The resting motor threshold and cortical representation areas of legs, hands, and face were identified on both hemispheres. Motor evoked potential positive stimulation points were then used as a region of interest for diffusion tensor imaging tractographies. Somatotopic fiber tracking was performed enabling analyses of the spatial relation between tumor and cortico-spinal tract (CST) as well as the extraction of fiber tract integrity, measured by fractional anisotropy and the apparent diffusion coefficient. The performance of nTMS mappings of the motor cortex and reconstruction of descending motor fibers for legs, hands, and facial functioning was successful in all patients. Higher preoperative resting motor threshold ratios and a distance between tumor and CST of <3 mm were associated with a permanent deterioration in motor function (P = .029 and P = .007). Shorter distances between CST and tumorous tissue were correlated with lowered peritumoral fractional anisotropy values, suggesting alterations in fiber tract integrity. Lower interhemispheric peritumoral fractional anisotropy ratios showed an association with new postoperative motor deficits (P = .017). nTMS-based diffusion tensor imaging tractography enables somatotopic tract visualization and provides a valuable tool for preoperative planning, intraoperative orientation, and individual risk stratification. Thus, it may be beneficial to increase safety in insular glioma resection surgery.

An ANN models cortical-subcortical interaction during post-stroke recovery of finger dexterity.

Finger dexterity, and finger individuation in particular, is crucial for human movement, and disruptions due to brain injury can significantly impact quality of life. Understanding the neurological mechanisms responsible for recovery is vital for effective neurorehabilitation. This study explores the role of two key pathways in finger individuation: the corticospinal tract (CST) from the primary motor cortex and premotor areas, and the subcortical reticulospinal tract (RST) from the brainstem. We aimed to investigate how the cortical-reticular network reorganizes to aid recovery of finger dexterity following lesions in these areas. To provide a potential biologically plausible answer to this question, we developed an artificial neural network (ANN) to model the interaction between a premotor planning layer, a cortical layer with excitatory and inhibitory corticospinal outputs, and reticulospinal outputs controlling finger movements. The ANN was trained to simulate normal finger individuation and strength. A simulated stroke was then applied to the corticospinal (CS) area, reticulospinal (RS) area, or both, and the recovery of finger dexterity was analyzed. In the intact model, the ANN demonstrated a near-linear relationship between the forces of instructed and uninstructed fingers, resembling human individuation patterns. Post-stroke simulations revealed that lesions in both CS and RS regions led to increased unintended force in uninstructed fingers, immediate weakening of instructed fingers, improved control during early recovery, and increased neural plasticity. Lesions in the CS region alone significantly impaired individuation, while RS lesions affected strength and to a lesser extent, individuation. The model also predicted the impact of stroke severity on finger individuation, highlighting the combined effects of CS and RS lesions. This model provides insights into the interactive role of cortical and subcortical regions in finger individuation. It suggests that recovery mechanisms involve reorganization of these networks, which may inform neurorehabilitation strategies.

Abnormal individualized functional connectivity: A potential stimulation target for pediatric tourette syndrome

ObjectiveIn order to examine whether individualized peak functional connectivity could potentially serve as a target for repetitive transcranial magnetic stimulation (rTMS) therapy, we investigated the location of peak functional connectivity (FC) between the cortical motor area and the key brain region, the globus pallidus internus (GPi), in Tourette syndrome, and explored the relationship between the severity of the disease and these aberrant functional connections. MethodsThe study involved a cohort of 103 children diagnosed with Tourette syndrome and 66 age-matched typically developing children. The GPi was served as the seed, and the study compared individualized peak FC strength in the supplementary motor area (SMA) and premotor area between the two groups. Spatial distribution of peak FC in the motor area and GPi-based voxel-wise FC were also analyzed. ResultsChildren with Tourette syndrome exhibited lower peak FC in the left SMA when using left GPi as the seed. This reduction in peak FC demonstrated a significant and negative correlation with the Yale Global Tic Severity Scale scores. ConclusionsSMA-GPi FC is one of the key pathological circuit in Tourette syndrome. SignificanceThe individual peak FC location in the left SMA potentially serve as stimulation targets for rTMS treatment of TS.

Psychiatric phenotype in neurodevelopmental myoclonus-dystonia is underpinned by abnormality of cerebellar modulation on the cerebral cortex

Psychiatric symptoms are common in neurodevelopmental movement disorders, including some types of dystonia. However, research has mainly focused on motor manifestations and underlying circuits. Myoclonus-dystonia is a rare and homogeneous neurodevelopmental condition serving as an illustrative paradigm of childhood-onset dystonias, associated with psychiatric symptoms. Here, we assessed the prevalence of psychiatric disorders and the severity of depressive symptoms in patients with myoclonus-dystonia and healthy volunteers (HV). Using resting-state functional neuroimaging, we compared the effective connectivity within and among non-motor and motor brain networks between patients and HV. We further explored the hierarchical organization of these networks and examined the relationship between their connectivity and the depressive symptoms. Comparing 19 patients to 25 HV, we found a higher prevalence of anxiety disorders and more depressive symptoms in the patient group. Patients exhibited abnormal modulation of the cerebellum on the cerebral cortex in the sensorimotor, dorsal attention, salience, and default mode networks. Moreover, the salience network activity was directed by the cerebellum in patients and was related to depressive symptoms. Altogether, our findings highlight the role of the cerebellar drive on both motor and non-motor cortical areas in this disorder, suggesting cerebellar involvement in the complex phenotype of such neurodevelopmental movement disorders.

Targeted deep brain stimulation of the motor thalamus improves speech and swallowing motor functions after cerebral lesions.

Speech and swallowing are complex motor acts that depend upon the integrity of input neural signals from motor cortical areas to control muscles of the head and neck. Lesions damaging these neural pathways result in weakness of key muscles causing dysarthria and dysphagia, leading to profound social isolation and risk of aspiration and suffocation. Here we show that Deep Brain Stimulation (DBS) of the motor thalamus improved speech and swallowing functions in two participants with dysarthria and dysphagia. First, we proved that DBS increased excitation of the face motor cortex, augmenting motor evoked potentials, and range and speed of motion of orofacial articulators in n = 10 volunteers with intact neural pathways. Then, we demonstrated that this potentiation led to immediate improvement in swallowing functions in a patient with moderate dysphagia and profound dysarthria as a consequence of a traumatic brain lesion. In this subject and in another with mild dysarthria, we showed that DBS immediately ameliorated impairments of respiratory, phonatory, resonatory, and articulatory control thus resulting in a clinically significant improvement in speech intelligibility. Our data provide first-in-human evidence that DBS can be used to treat dysphagia and dysarthria in people with cerebral lesions.

Interaction of motor behaviour, cortical oscillations and deep brain stimulation in Parkinson disease

Abstract Recent progress in the study of Parkinson's disease (PD) has highlighted the pivotal role of beta oscillations within the basal ganglia-thalamo-cortical network in modulating motor symptoms. Predominantly manifesting as transient bursts, these beta oscillations are central to the pathophysiology of PD motor symptoms, especially bradykinesia. Our central hypothesis is that increased bursting duration in cortex, coupled with kinematics of movement, disrupts the typical flow of neural information, leading to observable changes in motor behavior in PD. To explore this hypothesis, we employed an integrative approach, analyzing the interplay between moment-to-moment brain dynamics and movement kinematics, and the modulation of these relationships by therapeutic deep brain stimulation (DBS). Local field potentials were recorded from the hand motor (M1) and premotor cortical (PM) areas, and internal Globus Pallidus (GPi) in 26 PD patients undergoing DBS implantation surgery. Participants executed rapid alternating hand movements in 30-second blocks, both with and without therapeutic pallidal stimulation. Behaviorally, the analysis revealed bradykinesia, with hand movement cycle width increasing linearly over time during DBS-OFF blocks. Crucially, there was a moment-to-moment correlation between M1 low beta burst duration and movement cycle width, a relationship that dissipated with therapeutic DBS. Further analyses suggest that high gamma activity correlates with enhanced motor performance with DBS-ON. Regardless of the nature of coupling, DBS’s modulation of cortical bursting activity appeared to amplify the brain signals’ informational content regarding instantaneous movement changes. Our findings underscore that DBS significantly reshapes the interaction between motor behavior and neural signals in PD, not only modulating specific bands but also expanding the system's capability to process and relay information for motor control. These insights shed light on the possible network mechanisms underlying DBS therapeutic effects, suggesting a profound impact on both neural and motor domains.

A comparative study of simulated electric fields of transcranial magnetic stimulation targeting different cortical motor regions.

This computational simulation study investigates the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EF) in primary motor cortex (M1) and secondary motor areas. Our results reveal high interindividual variability in the strength of TMS-induced EF responses in secondary motor areas, relative to the stimulation threshold in M1. Notably, the activation of the supplementary motor area requires high-intensity stimulation, which could be attributed to the greater scalp-to-cortex distance observed over this area. These findings emphasize the importance of individualized planning using computational simulation for optimizing neuromodulation strategies targeting the cortical motor system.

Neuroanatomical and functional correlates in tic disorders and Tourette's syndrome: A narrative review

AbstractTic disorders represent a developmental neuropsychiatric condition whose causes can be attributed to a variety of environmental, neurobiological, and genetic factors. From a neurophysiological perspective, the disorder has classically been associated with neurochemical imbalances (particularly dopamine and serotonin) and structural and functional alterations affecting, in particular, brain areas and circuits involved in the processing and coordination of movements: the basal ganglia, thalamus, motor cortical area, and cingulate cortex; however, more recent research is demonstrating the involvement of many more brain regions and neurotransmission systems than previously observed, such as the prefrontal cortex and cerebellum. In this paper, therefore, we summarize the evidence to date on these abnormalities with the intent to illustrate and clarify the main neuroanatomical differences between patients with tic disorders and healthy individuals.

Effects of gait retraining in knee joint position sense

BackgroundJoint position sense (JPS) is crucial for maintaining posture, protecting joints, and carrying out daily activities such as walking. Studies show that exercises to strengthen muscles and improve proprioception can positively impact JPS during passive and less complex activities. Evidence suggests that motor training can effectively enhance sensory function, including JPS, due to the extensive connections between the motor cortex and somatosensory areas. Gait retraining using real-time feedback has improved outcomes among patients with musculoskeletal disorders. The effect of gait retraining on JPS has not been investigated. This study assessed the effects of gait retraining to reduce knee extension in joint position sense in individuals with knee hyperextension walking patterns. MethodsTen women with asymptomatic knee hyperextension (KH) >5° during overground walking participated in this study. Sagittal-plane kinematics were assessed using a three-dimensional (3D) motion analysis system. The JPS was assessed using the Knee Position Active Reproduction Test. The knee with the highest hyperextension was the focus of the gait retraining intervention, which consisted of six 1-h sessions using verbal instructions and visual kinematic feedback. Comparisons of peak knee extension during walking and knee JPS overall error (RMSE) were made using a paired t-test. ResultsGait retraining intervention significantly reduced knee extension angle during walking (83.8 % change; p < 0.001; Cohen's d = −1.6) and improved knee JPS (62 % change; p = 0.023; Cohen's d = 0.8) post-training. In addition, the improvements in joint kinematics (36.7 % change; p = 0.005; Cohen's d = −1.2) and JPS (52.6 % change; p = 0.015; Cohen's d = 0.9) were observed in the untrained knee. SignificanceGait retraining can improve joint position sense. This study addresses a gap in our understanding of how gait retraining can influence JPS. Our results corroborate that gait retraining is an evolving and promising strategy for improving gait outcomes, particularly in individuals with KH walking patterns.

Differential effects of theta-gamma tACS on motor skill acquisition in young individuals and stroke survivors: A double-blind, randomized, sham-controlled study

BackgroundTheta-gamma transcranial alternating current stimulation (tACS) was recently found to enhance thumb acceleration in young, healthy participants, suggesting a potential role in facilitating motor skill acquisition. Given the relevance of motor skill acquisition in stroke rehabilitation, theta-gamma tACS may hold potential for treating stroke survivors. ObjectiveWe aimed to examine the effects of theta-gamma tACS on motor skill acquisition in young, healthy participants and stroke survivors. MethodsIn a pre-registered, double-blind, randomized, sham-controlled study, 78 young, healthy participants received either theta-gamma peak-coupled (TGP) tACS, theta-gamma trough-coupled (TGT) tACS or sham stimulation. 20 individuals with a chronic stroke received either TGP or sham. TACS was applied over motor cortical areas while participants performed an acceleration-dependent thumb movement task. Stroke survivors were characterized using standardized testing, with a subgroup receiving additional structural brain imaging. ResultsNeither TGP nor TGT tACS significantly modified general motor skill acquisition in the young, healthy cohort. In contrast, in the stroke cohort, TGP diminished motor skill acquisition compared to sham. Exploratory analyses revealed that, independent of general motor skill acquisition, healthy participants receiving TGP or TGT exhibited greater peak thumb acceleration than those receiving sham. ConclusionAlthough theta-gamma tACS increased thumb acceleration in young, healthy participants, consistent with previous reports, it did not enhance overall motor skill acquisition in a more complex motor task. Furthermore, it even had detrimental effects on motor skill acquisition in stroke survivors.

Local organization of spatial and shape information in the primate prefrontal cortex.

The current understanding of sensory and motor cortical areas has been defined by the existence of topographical maps across the brain surface, however, higher cortical areas, such as the prefrontal cortex, seem to lack an equivalent organization, and only limited evidence of functional clustering of neurons with similar stimulus properties is evident in them. We thus sought to examine whether neurons that represent similar spatial and object information are clustered in the monkey prefrontal cortex and whether such an organization only emerges as a result of training. To this end, we analyzed neurophysiological recordings from male macaque monkeys before and after training in spatial and shape working memory tasks. Neurons with similar spatial or shape selectivity were more likely than chance to be encountered at short distances from each other. Some aspects of organization were present even in naïve animals, however other changes appeared after cognitive training. Our results reveal that prefrontal microstructure automatically supports orderly representations of spatial and object information.

Spontaneous running wheel exercise during pregnancy prevents later neonatal-anoxia-induced somatic and neurodevelopmental alterations

IntroductionAbout 15–20 % of babies that suffer perinatal asphyxia die and around 25 % of the survivors exhibit permanent neural outcomes. Minimization of this global health problem has been warranted. This study investigated if the offspring of pregnant female rats allowed to spontaneously exercise on running wheels along a 11-day pregnancy period were protected for somatic and neurodevelopmental disturbs that usually follow neonatal anoxia. Methodsspontaneous exercise was applied to female rats which were housed in cages allowing free access to running wheels along a 11-day pregnancy period. Their offspring were submitted to anoxia 24–36 h after birth. Somatic and sensory-motor development of the pups were recorded until postnatal day 21 (P21). Myelin basic protein (MBP)-stained areas of sensory and motor cortices were measured at P21. Neuronal nuclei (NeuN)-immunopositive cells and synapsin-I levels in hippocampal formation were estimated at P21 and P75. Resultsgestational exercise and / or neonatal anoxia increased the weight and the size of the pups. In addition, gestational exercise accelerated somatic and sensory-motor development of the pups and protected them against neonatal-anoxia-induced delay in development. Further, neonatal anoxia reduced MBP stained area in the secondary motor cortex and decreased hippocampal neuronal estimates and synapsin-I levels at P21; gestational exercise prevented these effects. Therefore, spontaneous exercise along pregnancy is a valuable strategy to prevent neonatal-anoxia-induced disturbs in the offspring. Conclusionspontaneous gestational running wheel exercise protects against neonatal anoxia-induced disturbs in the offspring, including (1) physical and neurobehavioral developmental impairments, and (2) hippocampal and cortical changes. Thus, spontaneous exercise during pregnancy may represent a valuable strategy to prevent disturbs which usually follow neonatal anoxia.

Pathology reduction and motor behavior improvement associated with ultrasound-mediated delivery of arctiin to the motor cortex in a mutant SOD1 mouse model of amyotrophic lateral sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with microbubbles (FUS/MB) for opening the blood–brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders. ObjectivesWe aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model. MethodsThe ALS mouse model with the SOD1G93A mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining. ResultsCompared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord. ConclusionThese preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.

Dynamic causal modelling highlights the importance of decreased self-inhibition of the sensorimotor cortex in motor fatigability

Motor fatigability emerges when challenging motor tasks must be maintained over an extended period of time. It is frequently observed in everyday life and affects patients as well as healthy individuals. Motor fatigability can be measured using simple tasks like finger tapping at maximum speed for 30 s. This typically results in a rapid decrease of tapping frequency, a phenomenon called motor slowing. In a previous study (Bächinger et al, eLife, 8 (September), https://doi.org/10.7554/eLife.46750, 2019), we showed that motor slowing goes hand in hand with a gradual increase in blood oxygen level dependent signal in the primary sensorimotor cortex (SM1), supplementary motor area (SMA), and dorsal premotor cortex (PMd). It is unclear what drives the activity increase in SM1 caused by motor slowing and whether motor fatigability affects the dynamic interactions between SM1, SMA, and PMd. Here, we performed dynamic causal modelling (DCM) on data of 24 healthy young participants collected during functional magnetic resonance imaging to answer this question. The regions of interest (ROI) were defined based on the peak activation within SM1, SMA, and PMd. The model space consisted of bilateral connections between all ROI, with intrinsic self-modulation as inhibitory, and driving inputs set to premotor areas. Our findings revealed that motor slowing was associated with a significant reduction in SM1 self-inhibition, as uncovered by testing the maximum à posteriori against 0 (t(23)=-4.51, p < 0.001). Additionally, the model revealed a significant decrease in the driving input to premotor areas (t(23) > 2.71, p < 0.05) suggesting that structures other than cortical motor areas may contribute to motor fatigability.

Improving efficacy of repetitive transcranial magnetic stimulation for treatment of Parkinson disease gait disorders.

Parkinson disease (PD) is a neurodegenerative disorder that causes motor and cognitive deficits, presenting complex challenges for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a type of neuromodulation that can produce plastic changes in neural activity. rTMS has been trialed as a therapy to treat motor and non-motor symptoms in persons with Parkinson disease (PwP), particularly treatment-refractory postural instability and gait difficulties such as Freezing of Gait (FoG), but clinical outcomes have been variable. We suggest improving rTMS neuromodulation therapy for balance and gait abnormalities in PwP by targeting brain regions in cognitive-motor control networks. rTMS studies in PwP often targeted motor targets such as the primary motor cortex (M1) or supplementary motor area (SMA), overlooking network interactions involved in posture-gait control disorders. We propose a shift in focus toward alternative stimulation targets in basal ganglia-cortex-cerebellum networks involved in posture-gait control, emphasizing the dorsolateral prefrontal cortex (dlPFC), cerebellum (CB), and posterior parietal cortex (PPC) as potential targets. rTMS might also be more effective if administered during behavioral tasks designed to activate posture-gait control networks during stimulation. Optimizing stimulation parameters such as dosage and frequency as used clinically for the treatment of depression may also be useful. A network-level perspective suggests new directions for exploring optimal rTMS targets and parameters to maximize neural plasticity to treat postural instabilities and gait difficulties in PwP.

Brain modulation after exergaming training in advanced forms of Parkinson’s disease: a randomized controlled study

BackgroundPhysical activity combined with virtual reality and exergaming has emerged as a new technique to improve engagement and provide clinical benefit for gait and balance disorders in people with Parkinson’s disease (PD).ObjectiveTo investigate the effects of a training protocol using a home-based exergaming system on brain volume and resting-state functional connectivity (rs-FC) in persons with PD.MethodsA single blind randomized controlled trial was conducted in people with PD with gait and/or balance disorders. The experimental (active) group performed 18 training sessions at home by playing a custom-designed exergame with full body movements, standing in front of a RGB-D Kinect® motion sensor, while the control group played using the computer keyboard. Both groups received the same training program. Clinical scales, gait recordings, and brain MRI were performed before and after training. We assessed the effects of both training on both the grey matter volumes (GVM) and rs-FC, within and between groups.ResultsTwenty-three patients were enrolled and randomly assigned to either the active (n = 11) or control (n = 12) training groups. Comparing pre- to post-training, the active group showed significant improvements in gait and balance disorders, with decreased rs-FC between the sensorimotor, attentional and basal ganglia networks, but with an increase between the cerebellar and basal ganglia networks. In contrast, the control group showed no significant changes, and rs-FC significantly decreased in the mesolimbic and visuospatial cerebellar and basal ganglia networks. Post-training, the rs-FC was greater in the active relative to the control group between the basal ganglia, motor cortical and cerebellar areas, and bilaterally between the insula and the inferior temporal lobe. Conversely, rs FC was lower in the active relative to the control group between the pedunculopontine nucleus and cerebellar areas, between the temporal inferior lobes and the right thalamus, between the left putamen and dorsolateral prefrontal cortex, and within the default mode network.ConclusionsFull-body movement training using a customized exergame induced brain rs-FC changes within the sensorimotor, attentional and cerebellar networks in people with PD. Further research is needed to comprehensively understand the neurophysiological effects of such training approaches.Trial registration ClinicalTrials.gov NCT03560089.

Volume electron microscopy analysis of synapses in primary regions of the human cerebral cortex.

Functional and structural studies investigating macroscopic connectivity in the human cerebral cortex suggest that high-order associative regions exhibit greater connectivity compared to primary ones. However, the synaptic organization of these brain regions remains unexplored. In the present work, we conducted volume electron microscopy to investigate the synaptic organization of the human brain obtained at autopsy. Specifically, we examined layer III of Brodmann areas 17, 3b, and 4, as representative areas of primary visual, somatosensorial, and motor cortex. Additionally, we conducted comparative analyses with our previous datasets of layer III from temporopolar and anterior cingulate associative cortical regions (Brodmann areas 24, 38, and 21). 9,690 synaptic junctions were 3D reconstructed, showing that certain synaptic characteristics are specific to particular regions. The number of synapses per volume, the proportion of the postsynaptic targets, and the synaptic size may distinguish one region from another, regardless of whether they are associative or primary cortex. By contrast, other synaptic characteristics were common to all analyzed regions, such as the proportion of excitatory and inhibitory synapses, their shapes, their spatial distribution, and a higher proportion of synapses located on dendritic spines. The present results provide further insights into the synaptic organization of the human cerebral cortex.