Contralateral Primary Motor Cortex Research Articles

Decoding the individual finger movements from single‐trial functional magnetic resonance imaging recordings of human brain activity

Multivariate pattern classification analysis (MVPA) has been applied to functional magnetic resonance imaging (fMRI) data to decode brain states from spatially distributed activation patterns. Decoding upper limb movements from non-invasively recorded human brain activation is crucial for implementing a brain-machine interface that directly harnesses an individual's thoughts to control external devices or computers. The aim of this study was to decode the individual finger movements from fMRI single-trial data. Thirteen healthy human subjects participated in a visually cued delayed finger movement task, and only one slight button press was performed in each trial. Using MVPA, the decoding accuracy (DA) was computed separately for the different motor-related regions of interest. For the construction of feature vectors, the feature vectors from two successive volumes in the image series for a trial were concatenated. With these spatial-temporal feature vectors, we obtained a 63.1% average DA (84.7% for the best subject) for the contralateral primary somatosensory cortex and a 46.0% average DA (71.0% for the best subject) for the contralateral primary motor cortex; both of these values were significantly above the chance level (20%). In addition, we implemented searchlight MVPA to search for informative regions in an unbiased manner across the whole brain. Furthermore, by applying searchlight MVPA to each volume of a trial, we visually demonstrated the information for decoding, both spatially and temporally. The results suggest that the non-invasive fMRI technique may provide informative features for decoding individual finger movements and the potential of developing an fMRI-based brain-machine interface for finger movement.

Task-related modulation of crossed spinal inhibition between human lower limbs

Crossed reflex action mediated by muscle spindle afferent inputs has recently been revealed in humans. This raised the question of whether a complex spinal network involving commissural interneurons receiving inputs from proprioceptors and suprasegmental structures, as described in cats, persists in humans and contributes to the interlimb coordination during movement. First, we investigated the neurophysiological mechanisms underlying crossed reflex action between ankle plantar flexors and its corticospinal control from primary motor cortex. Second, we studied its modulation during motor tasks. We observed crossed inhibition in contralateral soleus motoneurons occurring with about 3 ms central latency, which is consistent with spinal transmission through oligosynaptic pathway. The early phase of inhibition was evoked with lower stimulus intensity than the late phase, suggesting mediation by group I and group II afferents, respectively. The postsynaptic origin of crossed inhibition is confirmed by the finding that both H-reflex and motor-evoked potential were reduced upon conditioning stimulation. Transcranial magnetic stimulation over ipsilateral and contralateral primary motor cortex reduced crossed inhibition, especially its late group II part. Last, late group II crossed inhibition was particularly depressed during motor tasks, especially when soleus was activated during the walking stance phase. Our results suggest that both group I and group II commissural interneurons participate in crossed reflex actions between ankle plantar flexors. Neural transmission at this level is depressed by descending inputs activated by transcranial magnetic stimulation over the primary motor cortex or during movement. The specific modulation of group II crossed inhibition suggests control from monoaminergic midbrain structures and its role for interlimb coordination during locomotion.

Cerebellar theta burst stimulation in stroke patients with ataxia

Evidence for effective improvement of the symptoms of cerebellar stroke is still limited. Here, we investigated the effects of repetitive transcranial magnetic stimulation (rTMS) applied over the injured cerebellar hemisphere in six patients with posterior circulation stroke. We applied a two-week course of cerebellar intermittent theta burst stimulation (iTBS). Before and after the iTBS treatment, paired-pulse TMS methods were used to explore: i) the functional connectivity between the cerebellar hemisphere and the contralateral primary motor cortex (M1), by means of the cerebellar brain inhibition (CBI) protocol; and ii) the intracortical circuits in the contralateral M1, by means of the short intra-cortical inhibition (SICI) and intra-cortical facilitation (ICF) protocols. Patients were also evaluated using the Modified International Cooperative Ataxia Rating Scale (MICARS). Cerebellar iTBS induced a decrease in CBI and an increase in ICF at an interstimulus interval of 15 msec. These neurophysiological changes were paralleled by a clinical improvement, shown by the MICARS posture and gait subscale scores. Cerebellar iTBS could be a promising tool to promote recovery of cerebellar stroke patients.

Increased Bilateral Interactions in Middle-Aged Subjects

A hallmark of the age-related neural reorganization is that old versus young adults execute typical motor tasks by a more diffuse neural activation pattern including stronger ipsilateral activation during unilateral tasks. Whether such changes in neural activation are present already at middle age and affect bimanual interactions is unknown. We compared the amount of associated activity, i.e., muscle activity and force produced by the non-task hand and motor evoked potentials (MEPs) produced by magnetic brain stimulation between young (mean 24 years, n = 10) and middle-aged (mean 50 years, n = 10) subjects during brief unilateral (seven levels of % maximal voluntary contractions, MVCs) and bilateral contractions (4 × 7 levels of % MVC combinations), and during a 120-s-long MVC of sustained unilateral index finger abduction. During the force production, the excitability of the ipsilateral (iM1) or contralateral primary motor cortex (cM1) was assessed. The associated activity in the “resting” hand was ~2-fold higher in middle-aged (28% of MVC) versus young adults (11% of MVC) during brief unilateral MVCs. After controlling for the background muscle activity, MEPs in iM1 were similar in the two groups during brief unilateral contractions. Only at low (bilateral) forces, MEPs evoked in cM1 were 30% higher in the middle-aged versus young adults. At the start of the sustained contraction, the associated activity was higher in the middle-aged versus young subjects and increased progressively in both groups (30 versus 15% MVC at 120 s, respectively). MEPs were greater at the start of the sustained contraction in middle-aged subjects but increased further during the contraction only in young adults. Under these experimental conditions, the data provide evidence for the reorganization of neural control of unilateral force production as early as age 50. Future studies will determine if the altered neural control of such inter-manual interactions are of functional significance.

The latency of motor-evoked potentials (MEPs) can predict whether cTBS will exert an inhibitory or excitatory effect on the ipsilateral and contralateral primary motor cortex

Event Abstract Back to Event The latency of motor-evoked potentials (MEPs) can predict whether cTBS will exert an inhibitory or excitatory effect on the ipsilateral and contralateral primary motor cortex Gan Huang1* and André Mouraux1* 1 Université catholique de Louvain, Institute of Neuroscience (IONS), Belgium Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a research tool to probe the function of a given brain structure, or as a non-invasive therapeutic approach in neurology and psychiatry. However, its effect is highly variable between individuals. For example, Hamada et al. (2012) showed that continuous theta burst stimulation (cTBS) delivered over the primary motor cortex (M1) increases M1 excitability in 58% of subjects, and decreases it in 42% of subjects. The authors found that the excitatory or inhibitory effect of cTBS on M1 can be predicted by the latency of motor-evoked potentials (MEPs), suggesting that this inter-individual variability could be related to differences in the neuronal circuits preferentially activated by TMS. Here, we further explore this hypothesis by characterizing the relationship between MEP latency and the effects of cTBS on M1 excitability, measured using both MEPs and TMS-evoked brain potentials (TEPs). The recording of TEPs can provide useful information about the responsiveness and connectivity between the brain region targeted by TMS and brain regions sampled using EEG (Bonato et al. 2006). cTBS was delivered over the left or right M1 using biphasic pulses delivered over the central sulcus in an anterior-posterior (A-P) or posterior-anterior (P-A) direction. MEPs and TEPs elicited by stimulation of both the ipsilateral and contralateral M1 were recorded before (T0), immediately after (T1) and 20 minutes after (T2) cTBS. Confirming the results of Hamada et al. (2012), we found a positive correlation between MEP latency at T0 and the effect of cTBS on excitability of the ipsilateral M1. MEPs of shorter latency were associated with an increase of MEP amplitude after cTBS (i.e. M1 facilitation), whereas MEPs of longer latency were associated with a decrease of MEP amplitude after cTBS (i.e. M1 inhibition). At T1, this correlation was significant for A-P pulses (r=-0.672, p=.017) but not for P-A pulses (r=-0.137, p=.671). At T2, this correlation was no longer significant (A-P pulses: r=-0.201, p=.552; P-A pulses: r=0.082, p=.800). Most interestingly, there was also a significant but reverse relationship between MEP latency and the effect of cTBS on excitability of the contralateral M1 which was significant for A-P pulses (T1: r=+0.693, p=.012; T2: r=0.623, p=.030) but not P-A pulses (T1: r=+0.31, p=.354; T2: r=-0.03, p=0.925). Furthermore, there was a highly significant relationship between MEP latency and the effect of cTBS on the N100 peak of TEPs elicited by stimulation of the contralateral M1 (T1: r=0.730, p=.007; T2: r=0.714, p=.009). In contrast there was no relationship between MEP latency and the effect of cTBS on the N100 peak elicited by stimulation of the ipsilateral M1 (T1: r=-0.143, p=.658; T2: r=-0.088, p=.785). Taken together, our results confirm that the inter-individual variability of the effect of cTBS on M1 excitability can be predicted by MEP latency, indicating that it is related to individual differences in the neuronal circuits activated by TMS. Furthermore, our results show that variability in MEP latency also predicts the remote effect of cTBS on the contralateral M1, as measured using MEPs and TEPs. Acknowledgements This work was supported by ERC Starting Grant PROBING-PAIN (336130)

Cortical activation associated with asterixis in manifest hepatic encephalopathy

Severe hepatic encephalopathy gives rise to asterixis, a striking motor symptom also called flapping tremor, which is characterized by a sudden ceasing of muscle tone in all muscles of a limb. In this study, we aimed at scrutinizing the cortical activation associated with asterixis and unraveling the underlying pathophysiological mechanisms. We recorded simultaneously neural activity with magnetoencephalography (MEG) and muscle activity with surface EMG in nine patients with manifest hepatic encephalopathy showing asterixis. Asterixis events were detected semiautomatically and served as triggers for averaging MEG signals. Evoked responses averaged time-locked to asterixis events were subjected to equivalent current dipole (ECD) modeling. Additionally, we localized the strongest cortico-muscular coherence in the frequency of the co-occurring tremulousness. Evoked fields averaged time-locked to asterixis events were best explained by a single dipolar source in the contralateral primary motor cortex (M1, Talairach coordinates of mean localization: -40, -20, and 64; Brodmann area 4). This dipole showed a twofold field reversal, that is biphasic wave, with frontal dipole orientation at 49 ms before flap onset and 99 ms after flap onset. Conversely, two maxima with occipital dipole orientation were observed 2 ms and 160 ms after flap onset. Cortico-muscular coherence for the tremulousness was likewise localized in the contralateral M1 confirming earlier findings in the present patient cohort. Our results reveal an involvement of M1 in the generation of asterixis. As also tremulousness, also called mini-asterixis, was shown to originate in M1, asterixis and mini-asterixis may share common pathophysiological mechanisms.

Preserved Foot Motor Cortex in Patients With Complete Spinal Cord Injury

Background. Since the brain is intact, persons with a spinal cord injury (SCI) might benefit from a brain–computer interface (BCI) to improve mobility by making use of functional near-infrared spectroscopy (fNIRS). Objective. We aimed to use fNIRS to detect contralateral primary motor cortex activity during attempted foot movements in participants with complete SCI. Methods. A 6-channel fNIRS, including 2 reference channels, measured relative concentration changes of oxy- (HbO) and deoxy-hemoglobin (HbR) in the contralateral motor cortex for the right foot. Seven subjects, studied within 18 months after injury, performed 12 trials of attempted right foot and real hand movements. Results. T tests revealed significant HbO and HbR responses of the left motor cortex for attempted foot movements, but not for right hand movements. A 2-way repeated-measures analysis of variance revealed a larger decrease in HbR for attempted foot movements compared to hand movements. Individual results show major interindividual differences in (number of) channels activated and the sensitive chromophore (HbR or HbO). Conclusions. On group level, activity in the motor cortex of the foot can be measured with fNIRS in patients with complete SCI during attempted foot movements and might in principle be used in future BCI studies and applications.

Rearrangement of motor centers and its relationship to the neurological status of low-grade glioma examined on pre- and postoperative fMRI

ObjectiveWell-developed compensatory mechanisms, based on the phenomenon of brain plasticity, exist in patients with neuroepithelial tumors, especially with highly differentiated gliomas (WHO grade II). We studied phenomenon of rearrangement of sensorimotor cortex using functional magnetic resonance imaging (fMRI), and verified relationship between observed changes and results of neurological and neuropsychological assessment. MethodsStudy group included 20 patients with WHO grade II gliomas located within motor or sensory cortex. fMRI examination, as well as clinical, neurological (Karnofsky performance score [KPS] and Lovett's scale [Lo]), and neuropsychological assessment (Digit Coding Symbol Test and Digit Span Test) were performed pre-operatively and 3 months post-surgery. ResultsThere were no significant differences in pre- and postoperative performance status of patients. Although statistically insignificant, an increase in frequency of activation of primary and secondary cortical motor centers was observed postoperatively (p>0.05). Prior to surgery, motor centers were characterized by lower values of t-statistics than in postoperative period (p>0.05). In contrast, values of parameters describing the size of examined centers, i.e. mean number of clusters, were lower, but not statistically significant on postoperative examination (p>0.05). Compared to individuals without motor deficit, patients with preoperative Lo3/Lo4 paralysis showed significantly higher mean values of t-statistics in the accessory motor area on postoperative examination (p<0.05). ConclusionsThe processes of motor cortex rearrangement seemed to be associated with the pre- and postoperative neurological and neuropsychological status of patients. After contralateral primary motor cortex, accessory motor area was the second most frequently activated center, both pre- and postoperatively.

Transcranial Direct Current Stimulation (tDCS) of the Cortical Motor Areas in Three Cases of Cerebellar Ataxia

The excitability of the motor areas of the cerebral cortex is reduced in ataxia. Since transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique able to increase the cortical excitability, we assessed the effect of anodal tDCS over the motor cortex in three patients with ataxia. A clinical evaluation, a video-taped SARA rating scale and a gait analysis with cinematic parameters, were performed pre- and post-sham and anodal tDCS cycle. The full cycle was composed by five consecutive constant current sessions of stimulation. Anodal tDCS (2.0 mA, 20 min,max current density: 0.0278 mA/cm2, max total charge:0.033 C/cm2) was performed on the M1 area of the most affected side. The contralateral primary motor cortex underwent cathodal stimulation (2.0 mA, 20 min, max current density:0.0278 mA/cm2, max total charge: 0.033 C/cm2). After anodal tDCS, gait analysis revealed an improvement of the symmetry of step execution and reduction of base-width lasting 30 days associated to patients’ perception of amelioration. No relevant changes were found after sham stimulation. Our results suggest tDCS can improve gait symmetry in patients with ataxia for a short-term period. Future researches are needed in order to standardize time, amplitude, and area of stimulation in order to reach a long lasting effect on cerebellar ataxia.

A Liquid Crystal Polymer-Based Neuromodulation System: An Application on Animal Model of Neuropathic Pain

We developed a custom-made miniaturized neural stimulation system with a liquid crystal polymer (LCP)-based electrode array for animal experiments. In order to verify the feasibility of the system, motor cortex stimulation (MCS) was applied on the rat pain model induced by sciatic nerve injury.LCP is mechanically stable and chemically inert and has a much lower water absorption rate than other biocompatible polymers such as polyimide or parylene. In the present study, a film-type LCP substrate is used to microfabricate the cortical stimulation electrode array. A miniaturized electrical neuromodulation system is implemented using an application-specific integrated chip for generation of electrical stimulation current. In vivo experiment was performed using a rat neuropathic pain model induced by sciatic nerve injury. The electrodes were attached to the contralateral primary motor cortex, which processes the hind limb movement. Mechanical allodynia was measured before, during, and after electrical stimulation to determine the effects on pain threshold.Electrical stimulation into the brain structure processing pain perception was effective in alleviating neuropathic pain. The pain threshold of the rats increased more than fivefold during the electrical stimulation.We developed a miniaturized electrical stimulation system with a novel flexible LCP electrode array for MCS in rats. This system is expected to be used in studying various neurological diseases and examining in vivo brain function.

Theta Burst Stimulation Modulates Cerebellar-Cortical Connectivity in Patients with Progressive Supranuclear Palsy

BackgroundProgressive Supranuclear Palsy (PSP) is an atypical degenerative Parkinsonism characterized by postural instability, supranuclear gaze palsy and frontal deficits. Recent imaging studies revealed that the volume of cerebellar peduncles and midbrain were reduced in PSP. Transcranial magnetic stimulation (TMS) studies demonstrated a cerebellar involvement in PSP showing an impairment of functional connectivity between the cerebellar hemisphere (Cb) and the contralateral primary motor cortex (M1) (cerebellar brain inhibition-CBI). ObjectiveTo investigate the plasticity of the cerebello-thalamo-cortical circuits in ten PSP patients after two-week course of cerebellar intermittent theta burst stimulation (iTBS), a form of repetitive TMS. MethodsBefore and after the iTBS sessions we measured functional connectivity between Cb and contralateral M1 (CBI), short intracortical inhibition (SICI) and intracortical facilitation (ICF) and short latency afferent inhibition (SLAI) in contralateral M1. We also performed resting state functional magnetic resonance (rs-fMRI) and we administered clinical rating scale (PSP-RS). ResultsAt baseline PSP patients had decreased efficiency of CBI, SICI and SLAI in comparison to PD patients and healthy subjects. Cerebellar iTBS increased the deficient functional cerebellar-motor connectivity as assessed by CBI. No effect was seen for SICI/ICF and SLAI circuits. Following iTBS there was an increased signal in the head of the caudate nucleus bilaterally as shown by rs-fMRI. Moreover, PSP-RS showed an improvement of dysarthria in all patients. ConclusionsiTBS enhanced functional connectivity between the cerebellar hemisphere, the caudate nucleus and the cortex, that was paralleled by some clinical improvement. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.

The Aging Motor System as a Model for Plastic Changes of GABA-Mediated Intracortical Inhibition and Their Behavioral Relevance

Since GABAA-mediated intracortical inhibition has been shown to underlie plastic changes throughout the lifespan from development to aging, here, the aging motor system was used as a model to analyze the interdependence of plastic alterations within the inhibitory motorcortical network and level of behavioral performance. Double-pulse transcranial magnetic stimulation (dpTMS) was used to examine inhibition by means of short-interval intracortical inhibition (SICI) of the contralateral primary motor cortex in a sample of 64 healthy right-handed human subjects covering a wide range of the adult lifespan (age range 20-88 years, mean 47.6 ± 20.7, 34 female). SICI was evaluated during resting state and in an event-related condition during movement preparation in a visually triggered simple reaction time task. In a subgroup (N = 23), manual motor performance was tested with tasks of graded dexterous demand. Weak resting-state inhibition was associated with an overall lower manual motor performance. Better event-related modulation of inhibition correlated with better performance in more demanding tasks, in which fast alternating activation of cortical representations are necessary. Declining resting-state inhibition was associated with weakened event-related modulation of inhibition. Therefore, reduced resting-state inhibition might lead to a subsequent loss of modulatory capacity, possibly reflecting malfunctioning precision in GABAAergic neurotransmission; the consequence is an inevitable decline in motor function.

Corticomuscular Coherence Modulation With the Pattern of Finger Force Coordination

We assess the corticomuscular coherence (CMC) of the contralateral primary motor cortex and the hand muscles during a finger force-tracking task and explore whether the pattern of finger coordination has an impact on the CMC level. Six healthy subjects (three men and three women) were recruited to conduct the force-tracking tasks comprising two finger patterns, i.e., natural combination of index and middle fingers and unnatural combination of index and middle fingers (i.e., simultaneously producing equal force strength in index and middle finger). During the conducting of the tasks with right index and middle finger, MEG and sEMG signals were recorded from left primary motor cortex (M1) and right flexor digitorum superficialis (FDS), respectively; the contralateral CMC was calculated to assess the neuromuscular interaction. Finger force-tracking tasks of Common-IM only induce beta-band CMC, whereas Uncommon-IM tasks produce CMC in both beta and low-gamma band. Compared to the force-tracking tasks of Common-IM, the Uncommon-IM task is associated with the most intensive contralateral CMC. Our study demonstrated that the pattern of finger coordination had significant impact on the CMC between the contralateral M1 and hand muscles, and more corticomuscular interaction was necessary for unnaturally coordinated finger activities to regulate the fixed neural drive of hand muscles.

Reversed timing-dependent associative plasticity in the human brain through interhemispheric interactions

Spike timing-dependent plasticity (STDP) has been proposed as one of the key mechanisms underlying learning and memory. Repetitive median nerve stimulation, followed by transcranial magnetic stimulation (TMS) of the contralateral primary motor cortex (M1), defined as paired-associative stimulation (PAS), has been used as an in vivo model of STDP in humans. PAS-induced excitability changes in M1 have been repeatedly shown to be time-dependent in a STDP-like fashion, since synchronous arrival of inputs within M1 induces long-term potentiation-like effects, whereas an asynchronous arrival induces long-term depression (LTD)-like effects. Here, we show that interhemispheric inhibition of the sensorimotor network during PAS, with the peripheral stimulation over the hand ipsilateral to the motor cortex receiving TMS, results in a LTD-like effect, as opposed to the standard STDP-like effect seen for contralateral PAS. Furthermore, we could show that this reversed-associative plasticity critically depends on the timing interval between afferent and cortical stimulation. These results indicate that the outcome of associative stimulation in the human brain depends on functional network interactions (inhibition or facilitation) at a systems level and can either follow standard or reversed STDP-like mechanisms.

Study of Cerebello-Thalamocortical Pathway by Transcranial Magnetic Stimulation in Parkinson's Disease

BackgroundAlthough functional changes in the activation of the cerebellum in Parkinson's disease (PD) patients have been consistently described, it is still debated whether such altered cerebellar activation is a natural consequence of PD pathophysiology or rather it involves compensatory mechanisms. Objective/HypothesisWe used different forms of cerebellar transcranial magnetic stimulation to evaluate the hypothesis that altered cerebello-cortical interactions can be observed in PD patients and to evaluate the role of dopaminergic treatment. MethodsWe studied the effects of a single cerebellar magnetic pulse over the excitability of the contralateral primary motor cortex tested with motor-evoked potentials (MEPs) (cerebellar-brain inhibition—CBI) in a group of 16 PD patients with (ON) and without dopaminergic treatment (OFF), and in 16 age-matched healthy controls. Moreover, we also tested the effects of cerebellar continuous theta-burst stimulation (cTBS) on MEP amplitude, short intracortical inhibition (SICI) and short intracortical facilitation (SICF) tested in the contralateral M1 in 13 PD patients in ON and OFF and in 16 age-matched healthy controls. ResultsCBI was evident in controls but not in PD patients, even when tested in both ON and OFF conditions. Similarly, cerebellar cTBS reduced MEP amplitude and SICI in controls but not in PD patients under any condition. Conclusion(s)These results demonstrate that PD patients have deficient short-latency and long-lasting cerebellar-thalamocortical inhibitory interactions that cannot be promptly restored by standard dopaminergic medication.

Detection of motor execution using a hybrid fNIRS-biosignal BCI: a feasibility study

BackgroundBrain-computer interfaces (BCIs) were recently recognized as a method to promote neuroplastic effects in motor rehabilitation. The core of a BCI is a decoding stage by which signals from the brain are classified into different brain-states. The goal of this paper was to test the feasibility of a single trial classifier to detect motor execution based on signals from cortical motor regions, measured by functional near-infrared spectroscopy (fNIRS), and the response of the autonomic nervous system. An approach that allowed for individually tuned classifier topologies was opted for. This promises to be a first step towards a novel form of active movement therapy that could be operated and controlled by paretic patients.MethodsSeven healthy subjects performed repetitions of an isometric finger pinching task, while changes in oxy- and deoxyhemoglobin concentrations were measured in the contralateral primary motor cortex and ventral premotor cortex using fNIRS. Simultaneously, heart rate, breathing rate, blood pressure and skin conductance response were measured. Hidden Markov models (HMM) were used to classify between active isometric pinching phases and rest. The classification performance (accuracy, sensitivity and specificity) was assessed for two types of input data: (i) fNIRS-signals only and (ii) fNIRS- and biosignals combined.ResultsfNIRS data were classified with an average accuracy of 79.4%, which increased significantly to 88.5% when biosignals were also included (p=0.02). Comparable increases were observed for the sensitivity (from 78.3% to 87.2%, p=0.008) and specificity (from 80.5% to 89.9%, p=0.062).ConclusionsThis study showed, for the first time, promising classification results with hemodynamic fNIRS data obtained from motor regions and simultaneously acquired biosignals. Combining fNIRS data with biosignals has a beneficial effect, opening new avenues for the development of brain-body-computer interfaces for rehabilitation applications. Further research is required to identify the contribution of each modality to the decoding capability of the subject’s hemodynamic and physiological state.

Cerebellar theta burst stimulation modulates short latency afferent inhibition in Alzheimer's disease patients

The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's disease (AD). Previous findings demonstrated that high density of cholinergic receptors is found in the thalamus and the cerebellum compared with the cerebral cortex and the hippocampus. We aimed at investigating whether activation of the cerebello-thalamo-cortical pathway by means of cerebellar theta burst stimulation (TBS) could modulate central cholinergic functions evaluated in vivo by using the neurophysiological determination of Short-Latency Afferent Inhibition (SLAI). We tested the SLAI circuit before and after administration of cerebellar continuous TBS (cTBS) in 12 AD patients and in 12 healthy age-matched control subjects (HS). We also investigated potential changes of intracortical circuits of the contralateral primary motor cortex (M1) by assessing short intracortical inhibition (SICI) and intracortical facilitation (ICF). SLAI was decreased in AD patients compared to HS. Cerebellar cTBS partially restored SLAI in AD patients at later inter-stimulus intervals (ISIs), but did not modify SLAI in HS. SICI and ICF did not differ in the two groups and were not modulated by cerebellar cTBS. These results demonstrate that cerebellar magnetic stimulation is likely to affect mechanisms of cortical cholinergic activity, suggesting that the cerebellum may have a direct influence on the cholinergic dysfunction in AD.

Modulation of human corticospinal excitability by paired associative stimulation

Paired Associative Stimulation (PAS) has come to prominence as a potential therapeutic intervention for the treatment of brain injury/disease, and as an experimental method with which to investigate Hebbian principles of neural plasticity in humans. Prototypically, a single electrical stimulus is directed to a peripheral nerve in advance of transcranial magnetic stimulation (TMS) delivered to the contralateral primary motor cortex (M1). Repeated pairing of the stimuli (i.e., association) over an extended period may increase or decrease the excitability of corticospinal projections from M1, in manner that depends on the interstimulus interval (ISI). It has been suggested that these effects represent a form of associative long-term potentiation (LTP) and depression (LTD) that bears resemblance to spike-timing dependent plasticity (STDP) as it has been elaborated in animal models. With a large body of empirical evidence having emerged since the cardinal features of PAS were first described, and in light of the variations from the original protocols that have been implemented, it is opportune to consider whether the phenomenology of PAS remains consistent with the characteristic features that were initially disclosed. This assessment necessarily has bearing upon interpretation of the effects of PAS in relation to the specific cellular pathways that are putatively engaged, including those that adhere to the rules of STDP. The balance of evidence suggests that the mechanisms that contribute to the LTP- and LTD-type responses to PAS differ depending on the precise nature of the induction protocol that is used. In addition to emphasizing the requirement for additional explanatory models, in the present analysis we highlight the key features of the PAS phenomenology that require interpretation.

How equivalent are the action execution, imagery, and observation of intransitive movements? Revisiting the concept of somatotopy during action simulation

Jeannerod (2001) hypothesized that action execution, imagery, and observation are functionally equivalent. This led to the major prediction that these motor states are based on the same action-specific and even effector-specific motor representations. The present study examined whether hand and foot movements are represented in a somatotopic manner during action execution, imagery, and action observation.The experiment contained ten conditions: three execution conditions, three imagery conditions, three observation conditions, and one baseline condition. In the nine experimental conditions, participants had to execute, observe, or imagine right-hand extension/flexion movements or right-foot extension/flexion movements. The fMRI results showed a somatotopic organization within the contralateral premotor and primary motor cortex during motor imagery and motor execution. However, there was no clear somatotopic organization of action observation in the given regions of interest within the contralateral hemisphere, although observation of these movements activated these areas significantly.

Differences between the somatotopic corticospinal tract for the fingers and toes in the human brain

The corticospinal tract (CST) is the most important motor tract in the human brain. The authors compared CST fibers of the fingers and toes using diffusion tensor imaging. Eleven normal healthy subjects were recruited for this study. Functional MRI stimulation was performed using finger grasp-release movements and toe flexion-extension movements (1 Hz). CST fibers of the fingers and toes were determined by selecting fibers passing through seed (the CST portion in the pons) and target regions of interest (the activation areas of the cerebral cortex during active finger and toe movements, respectively). No significant differences were observed between CST fibers of the fingers and toes in terms of fractional anisotropy, mean diffusivity, or tract volume (P> 0.05), and no differences were observed between the connectivities of CST fibers of the fingers and toes and the dorsal premotor cortex or the supplementary motor area (P>0.05). However, the connectivities between CST fibers of legs and the contralateral primary motor cortex were greater than those of CST fibers of the fingers (P< 0.05). It was found that somatotopic CST fibers of the fingers and toes did not differ in terms of diffusion tensor imaging characteristics, but that transcallosal fibers to the contralateral motor cortex were more frequent for CST fibers of the toes than for CST fibers of the fingers.