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Significance: Myelin breakdown is likely a key factor in the loss of cognitive and motor function associated with many neurodegenerative diseases. Aim: New methods for imaging myelin structure are needed to characterize and quantify the degradation of myelin in standard whole-brain sections of nonhuman primates and in human brain. Approach: Quantitative birefringence microscopy (qBRM) is a label-free technique for rapid histopathological assessment of myelin structural breakdown following cortical injury in rhesus monkeys. Results: We validate birefringence microscopy for structural imaging of myelin in rhesus monkey brain sections, and we demonstrate the power of qBRM by characterizing the breakdown of myelin following cortical injury, as a model of stroke, in the motor cortex. Conclusions: Birefringence microscopy is a valuable tool for histopathology of myelin and for quantitative assessment of myelin structure. Compared to conventional methods, this label-free technique is sensitive to subtle changes in myelin structure, is fast, and enables more quantitative assessment, without the variability inherent in labeling procedures such as immunohistochemistry.

Objectives: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). Methods: Twenty two patients (10 males, 12 females, mean age 39 years, range 10–65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. Results: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). Conclusions: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.

Background: Congenital bilateral perisylvian syndrome (CBPS) is characterised by bilateral perisylvian polymicrogyria and suprabulbar paresis. Mild tetraparesis, cognitive impairment, and epilepsy are frequently associated. Sensory deficits are surprisingly rare, even though polymicrogyria often extends to auditory and sensorimotor cortex. Objectives: To study the sensorimotor and auditory cortex function and location in CBPS patients. Methods: We mapped the sensory and motor cortex function onto brain magnetic resonance images in six CBPS patients and seven control subjects using sources of somatosensory and auditory evoked magnetic fields, and of rhythmic magnetoencephalographic (MEG) activity phase-locked to surface electromyogram (EMG) during voluntary hand muscle contraction. Results: MEG-EMG coherence in CBPS patients varied from normal (if normal central sulcus anatomy) to absent, and could occur at abnormally low frequency. Coherent MEG activity was generated at the central sulcus or in the polymicrogyric frontoparietal cortex. Somatosensory and auditory evoked responses were preserved and also originated within the polymicrogyric cortex, but the locations of some source components could be grossly shifted. Conclusion: Plastic changes of sensory and motor cortex location suggest disturbed cortex organisation in CBPS patients. Because the polymicrogyric cortex of CBPS patients may embed normal functions in unexpected locations, functional mapping should be considered before brain surgery.

Objective: Drug resistant neurogenic pain can be relieved by repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. This study was designed to assess the influence of pain origin, pain site, and sensory loss on rTMS efficacy. Patients and methods: Sixty right handed patients were included, suffering from intractable pain secondary to one of the following types of lesion: thalamic stroke, brainstem stroke, spinal cord lesion, brachial plexus lesion, or trigeminal nerve lesion. The pain predominated unilaterally in the face, the upper limb, or the lower limb. The thermal sensory thresholds were measured within the painful zone and were found to be highly or moderately elevated. Finally, the pain level was scored on a visual analogue scale before and after a 20 minute session of "real" or "sham" 10 Hz rTMS over the side of the motor cortex corresponding to the hand on the painful side, even if the pain was not experienced in the hand itself. Results and discussion: The percentage pain reduction was significantly greater following real than sham rTMS (-22.9% v -7.8%, p = 0.0002), confirming that motor cortex rTMS was able to induce antalgic effects. These effects were significantly influenced by the origin and the site of pain. For pain origin, results were worse in patients with brainstem stroke, whatever the site of pain. This was consistent with a descending modulation within the brainstem, triggered by the motor corticothalamic output. For pain site, better results were obtained for facial pain, although stimulation was targeted on the hand cortical area. Thus, in contrast to implanted stimulation, the target for rTMS procedure in pain control may not be the area corresponding to the painful zone but an adjacent one. Across representation plasticity of cortical areas resulting from deafferentation could explain this discrepancy. Finally, the degree of sensory loss did not interfere with pain origin or pain site regarding rTMS effects. Conclusion: Motor cortex rTMS was found to result in a significant but transient relief of chronic pain, influenced by pain origin and pain site. These parameters should be taken into account in any further study of rTMS application in chronic pain control.

Objectives: Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer’s disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is due to the impairment of intracortical inhibitory circuits or to an independent abnormality of excitatory circuits. Methods: We assessed the excitability of the motor cortex with TMS in 28 patients with AD using several TMS paradigms and compared the data of cortical excitability (evaluated by measuring resting motor threshold) with the amount of motor cortex disinhibition as evaluated using the test for motor cortex cholinergic inhibition (short latency afferent inhibition) and GABAergic inhibition (short latency intracortical inhibition). The data in AD patients were also compared with that from 12 age matched healthy individuals. Results: The mean resting motor threshold was significantly lower in AD patients than in controls. The amount of short latency afferent inhibition was significantly smaller in AD patients than in normal controls. There was also a tendency for AD patients to have less pronounced short latency intracortical inhibition than controls, but this difference was not significant. There was no correlation between resting motor threshold and measures of either short latency afferent or intracortical inhibition (r = −0.19 and 0.18 respectively, NS). In 14 AD patients the electrophysiological study was repeated after a single oral dose of the cholinesterase inhibitor rivastigmine. Resting motor threshold was not significantly modified by the administration of rivastigmine. In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine. Conclusions: The change in threshold did not seem to correlate with dysfunction of inhibitory intracortical cholinergic and GABAergic circuits, nor with the central cholinergic activity. We propose that the hyperexcitability of the motor cortex is caused by an abnormality of intracortical excitatory circuits.

Objectives: To investigate if intraoperative focused high frequency repetitive transcranial magnetic stimulation (rTMS) can localise the primary motor cortex without exposure of the cortical surface. Methods: A high frequency train (357 Hz) of four suprathreshold magnetic stimuli was delivered transcranially to the region of the rolandic area during brain tumour operations in 12 patients. To induce a focal magnetoelectric field, the flat figure of eight coil (outer diameter of each loop 7 cm) was used. Motor evoked potentials (MEP) were recorded in eight muscles of the upper and lower contralateral extremities. The first stimulation site was 2.5 cm behind the bregma, the second site 2 cm, and the third site 4 cm dorsal to the first stimulation site. If no MEP were obtainable, stimulation was repeated in anteroposterior direction at more laterally located sites. Using neuronavigation, each positive stimulation site was correlated with the underlying cortical anatomy. Results: Stimulation was performed at a total of 42 sites (in two patients, maximum stimulation at the three initial sites failed to evoke a motor response). In four patients, MEP were obtained only from one stimulation site. This site exactly overlayed the primary motor cortex. In eight patients, MEP could be elicited from more than one stimulation site. In seven of the eight patients, the site from which MEP with peak amplitudes were elicited, corresponded to the primary motor cortex. In total, the primary motor cortex was correctly identified on the basis of electrophysiological findings in 11 of 12 patients (92 %). In two patients, only the more lateral stimulation sites permitted MEP recording. Conclusion: Intraoperative focused rTMS is highly sensitive for localisation of the primary motor cortex. Focused rTMS as a localising instrument alleviates the need of motor cortex exposure and, thereby, can contribute to minimise the surgical approach to brain tumours in the rolandic area.

This study investigated the applicability of statistical parametric mapping (SPM) for analysing individual preoperative brain mapping studies in patients with cerebral mass lesions for neurosurgical planning. The study further investigated if hints on functional reorganisation processes can be found.Nine adult patients with cerebral mass lesions underwent activation [(15)O]water-PET under stimulation by finger (n=9) and foot (n=4) movement. Individual SPM-t-maps were computed without anatomical normalisation and coregistered to the individual magnetic resonance imaging. Relative cerebral blood flow change maps were calculated for comparison.The spatial relation between the sensorimotor cortex and the lesion could be determined in all cases. Additional activations covered the ipsilateral sensorimotor cortex and the bilateral cerebellum, premotor cortices and supplementary motor areas. Patients with motor symptoms of the stimulated hand (paresis, focal seizures) activated the ipsilateral premotor cortices and contralateral cerebellum more often than patients without motor symptoms. The SPM results for p0.005 and cerebral blood flow change maps showed considerably overlapping motor area activations. For p0.001, SPM missed three sensorimotor cortex activations depicted by cerebral blood flow change maps and by SPM for p0.005 in typical localisation. SPM analyses showed less activations probably unrelated to task performance.It is concluded that SPM provides an efficient method for analysing individual preoperative PET activation studies. Activations of the ipsilateral premotor cortices and contralateral cerebellum may indicate an enhanced recruitment of ipsilateral motor pathways evoked by functional reorganisation processes. However, this changed activation pattern was not necessarily associated with a better neurological status.

Objective: Intraoperative localisation of the sensorimotor cortex using the phase reversal of somatosensory evoked potentials (SEPs) is an essential tool for surgery in and around the perirolandic gyri, but unsuccessful and perplexing results have been reported. This study examines the effect of tumour masses on the waveform characteristics and feasibility of SEP compared with functional neuronavigation and electrical motor cortex mapping. Methods: In 230 patients with tumours of the sensorimotor region the SEP phase reversal of N20-P20 was recorded from the exposed cortex using a subdural grid or strip electrode. In one subgroup of 80 patients functional neuronavigation was performed with motor and sensory magnetic source imaging and in one subgroup of 40 patients the motor cortex hand area was localised by electrical stimulation mapping. Results: The intraoperative SEP method was successful in 92% of all patients, it could be shown that the success rate rather depended on the location of the lesion than on preoperative neurological deficits. In 13% of the patients with postcentral tumours no N20-P20 phase reversal was recorded but characteristic polyphasic and high amplitude waves at 25 ms and later made the identification of the postcentral gyrus possible nevertheless. Electrical mapping of the motor cortex took up to 30 minutes until a clear result was obtained. It was successful in 37 patients, but failed in three patients with precentral and central lesions. Functional neuronavigation indicating the tumour margins and the motor and sensory evoked fields was possible in all patients. Conclusion: The SEP phase reversal of N20-P20 is a simple and reliable technique, but the success rate is much lower in large central and postcentral tumours. With the use of polyphasic late waveforms the sensorimotor cortex may be localised. By contrast with motor electrical mapping it is less time consuming. Functional neuronavigation is a desirable tool for both preoperative surgical planning and intraoperative use during surgery on perirolandic tumours, but compensation for brain shift, accuracy, and cost effectiveness are still a matter for discussion.

Objective: To clarify the clinical usefulness of preoperative fibre-tracking in affected pyramidal tracts for intraoperative monitoring during the removal of brain tumours from patients with motor weakness. Methods: We operated on 10 patients with mild to moderate motor weakness caused by brain tumours located near the pyramidal tracts under local anaesthesia. Before surgery, we performed fibre-tracking imaging of the pyramidal tracts and then transferred this information to the neuronavigation system. During removal of the tumour, motor function was evaluated with motor evoked potentials elicited by cortical/subcortical electrical stimulation and with voluntary movement. Results: In eight patients, the locations of the pyramidal tracts were estimated preoperatively by fibre-tracking; motor evoked potentials were elicited on the motor cortex and subcortex close to the predicted pyramidal tracts. In the remaining two patients, in which fibre-tracking of the pyramidal tracts revealed their disruption surrounding the tumour, cortical/subcortical electrical stimulation did not elicit responses clinically sufficient to monitor motor function. In all cases, voluntary movement with mild to moderate motor weakness was extensively evaluated during surgery and was successfully preserved postoperatively with appropriate tumour resection. Conclusions: Preoperative fibre-tracking could predict the clinical usefulness of intraoperative electrical stimulation of the motor cortex and subcortical fibres (ie, pyramidal tracts) to preserve affected motor function during removal of brain tumours. In patients for whom fibre-tracking failed preoperatively, awake surgery is more appropriate to evaluate and preserve moderately impaired muscle strength.

To determine the relationship of cerebral degeneration with survival in amyotrophic lateral sclerosis (ALS).Patients with probable or definite ALS underwent magnetic resonance spectroscopic imaging (MRSI) of the brain between July 1996 and May 2002, and were followed prospectively until March 2004. Creatine (Cr), choline (Cho) and the neuronal marker N-acetylaspartate (NAA) were quantified as ratios in the motor cortex.In 63 patients compared with 18 healthy people, NAA/Cho was reduced by 13% (p0.001), NAA/Cr was reduced by 5% (p = 0.01) and Cho/Cr was increased by 8% (p = 0.01). NAA/Cho was used for survival analysis, given its larger effect size and superior test accuracy (a sensitivity of 67% and a specificity of 83%). Median survival after MRSI was 24 months. Multivariate analysis showed reduced survival for lower NAA/Cho (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.08 to 0.72, p = 0.01), older age (HR 1.03, 95% CI 1.00 to 1.06, p = 0.04) and shorter symptom duration (HR 0.96, 95% CI 0.93 to 0.99, p = 0.01). Patients with NAA/Cho2.11 had a reduced survival of 19.4 v 31.9 months (HR 2.05, 95% CI 1.12 to 4.03, p = 0.02).Cerebral degeneration is predictive of reduced survival in ALS.

Background: A comprehensive characterisation of grey and white matter changes in progressive supranuclear palsy (PSP), the second most common extrapyramidal syndrome after Parkinson disease, is still not available. Objective: To evaluate grey and white matter changes in mild PSP patients by voxel based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. Methods: 14 mild PSP patients and 14 healthy controls entered the study and underwent a clinical and neuropsychological evaluation according with a standardised assessment. Each subject had a structural magnetic resonance imaging (MRI) study. Processing analysis of MRI data was carried out according to optimised VBM and fractional anisotropy was determined. Results: Compared with the controls, in PSP patients VBM analysis showed a significant clusters of reduced grey matter in premotor cortex, frontal operculum, anterior insula, hippocampus, and parahippocampal gyrus, bilaterally. With regard to subcortical brain regions, the pulvinar, dorsomedial and anterior nuclei of the thalamus, and superior and inferior culliculum were affected bilaterally. A bilateral decrease in fractional anisotropy in superior longitudinal fasciculus, anterior part of corpus callosum, arcuate fascicolus, posterior thalamic radiations, and internal capsule, probably involving the cortico-bulbar tracts, was present in PSP patients. Conclusions: These data provide evidence for both grey and white matter degeneration in PSP from the early disease stage. These structural changes suggest that atrophy of cortical and subcortical structures and neurodegeneration of specific fibre tracts contribute to neurological deficits in PSP.

Background: Mirror movements (MM) are not widely appreciated in parkinsonism and no report has evaluated this clinical sign in detail. Objectives: To define the parkinsonian clinical features associated with MM in patients with early, asymmetric parkinsonism. Methods: Twenty seven patients with early Parkinson’s disease were evaluated using a standardised videotaping protocol. MM were scored from blinded video assessment using a clinical scale that rates the amplitude, distribution, and proportion of mirroring in the less affected limb. Parkinsonian features were combined into axial and lateralised scores using related items of the Unified Parkinson’s Disease Rating Scale. Results: MM were present in 24 of 27 patients. There was a significant linear correlation between the degree of asymmetry of motor deficits and MM on the less affected side. The effect of asymmetry was greater when the proportional rather than the absolute motor difference between sides was largest. Asymmetry in leg rigidity was the most important examination feature in the prediction of contralateral foot mirroring. Conclusions: MM are a clinical feature of the unaffected or less affected side in mild asymmetric parkinsonism. Their presence may be a useful clinical finding in early parkinsonism.

Background: In vivo evaluation of cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI). SAI is reduced in Alzheimer's disease ( AD) and drugs enhancing cholinergic transmission increase SAI. Methods: We evaluated whether SAI testing, together with SAI test-retest, after a single dose of the acetylcholinesterase (AChE) inhibitor rivastigmine, might be useful in predicting the response after 1 year treatment with rivastigmine in 16 AD patients. Results: Fourteen AD patients had pathologically reduced SAI. SAI was increased after administration of a single oral dose of rivastigmine in AD patients with abnormal baseline SAI, but individual responses to rivastigmine varied widely, with SAI change ranging from an increase in inhibition of similar to 50% of test size to no change. Baseline SAI and the increase in SAI after a single dose of rivastigmine were correlated with response to long term treatment. A normal SAI in baseline conditions, or an abnormal SAI in baseline conditions that was not greatly increased by a single oral dose of rivastigmine, were invariably associated with poor response to long term treatment, while an abnormal SAI in baseline conditions in conjunction with a large increase in SAI after a single dose of rivastigmine was associated with good response to long term treatment in most of the patients. Conclusions: Evaluation of SAI may be useful for identifying AD patients likely to respond to treatment with AChE inhibitors.

Background and objective: A single session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex had been reported to produce short term relief of some types of chronic pain. The present study investigated whether five consecutive days of rTMS would lead to longer lasting pain relief in unilateral chronic intractable neuropathic pain. Patients and methods: Forty eight patients with therapy resistant chronic unilateral pain syndromes (24 each with trigeminal neuralgia (TGN) and post-stroke pain syndrome (PSP)) participated. Fourteen from each group received 10 minutes real rTMS over the hand area of motor cortex (20 Hz, 10x10 s trains, intensity 80% of motor threshold) every day for five consecutive days. The remaining patients received sham stimulation. Pain was assessed using a visual analogue scale (VAS) and the Leeds assessment of neuropathic symptoms and signs (LANSS) scale, before, after the first, fourth, and fifth sessions, and two weeks after the last session. Results: No significant differences were found in basal pain ratings between patients receiving real- and sham-rTMS. However, a two factor ANOVA revealed a significant "± TMS" x "time" interaction indicating that real and sham rTMS had different effects on the VAS and LANSS scales. Post hoc testing showed that in both groups of patients, real-rTMS led to a greater improvement in scales than sham-rTMS, evident even two weeks after the end of the treatment. No patient experienced adverse effects. Conclusion: These results confirm that five daily sessions of rTMS over motor cortex can produce longlasting pain relief in patients with TGN or PSP.

Background: Epilepsy is often complicated by depression requiring antidepressant treatment. Such treatment might be proconvulsive. Objective: To examine the effects of the noradrenergic and specific serotonergic antidepressant mirtazapine on motor cortex excitability in epilepsy patients with depression and in healthy controls, using transcranial magnetic stimulation (TMS). Methods: Seven clinically depressed epilepsy patients treated with anticonvulsant drugs and six healthy volunteers were studied. Before intake of mirtazapine and 24 hours afterwards (and also three weeks afterwards in the patients), the active and resting motor threshold (AMT, RMT), the size of the motor evoked potential (MEP), the cortical silent period (SP), and intracortical inhibition/facilitation and intracortical facilitatory I wave interactions were determined using single and paired pulse TMS. Results: At baseline, AMT and RMT were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP area greater in patients (p = 0.041). In patients but not in healthy subjects AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had no significant effect on the MEP size, duration of the SP, or the ratio of SP duration to MEP size in patients. The duration of the SP was longer (p = 0.037) but the ratio of SP duration to MEP size remained similar in healthy subjects after mirtazapine. There were no significant differences in paired pulse measures between the two groups either at baseline or after mirtazapine. Conclusions: Mirtazapine increased neuronal excitability of pyramidal tract axons in an activated state in both healthy controls and epilepsy patients with major depression.

Background: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. Objective: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. Methods: A role for altered neocortical–cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. Results: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. Conclusions: Changes in apparent cerebellar–neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.

Objectives: Subcortical lesions in the sensorimotor strip are often considered to be inoperable. The purpose of this study was to evaluate the usefulness of a combined approach for surgery in this region, aided by a robotic neuronavigation system under electrophysiological control. Methods: In a prospective study on 10 patients, space occupying lesions in the sensorimotor central area were removed using the Surgiscope® robotic navigation system and the Nicolet Viking IV® electrophysiological system. Results: Precise tumour localisation with the neuronavigation system and the information on the patient's cortical motor distribution obtained by bipolar cortical stimulation led to postoperative improvement in motor function in all but one patient. Seven of the patients had focal, defined pathology (four metastases; two cavernoma; one aspergilloma). Conclusion: Due to the implementation of two recent technologies, surgery of lesions in the subcortical sensorimotor region can be performed with greater confidence.

OBJECTIVES: Functional reorganisation of the motor or sensory cortex has been demonstrated in animals after section of mixed peripheral nerves. Here functional changes in the motor cortex specifically after peripheral motor denervation in humans are investigated. METHODS: Functional MRI (fMRI) was used to study brain activation during a finger flexion-extension task in patients with a late onset, acquired pure motor neuropathy (n=6), contrasting results with those from patients with pure sensory neuropathies (n=4) or healthy controls (n=7). RESULTS: Increases in the extent of activation in the motor cortex both ipsilateral and contralateral to the hand moved were found in the patients with motor neuropathy. The neuroanatomical localisation of the mixed contralateral sensorimotor cortex activation volume was more posterior for the patients with motor neuropathy than for the healthy controls (mean difference, 12 mm, p

Objectives: The study aimed at addressing the issue of the precise nature of gait apraxia and the cerebral dysfunction responsible for it. Methods: The case of a patient, affected by a bilateral infarction limited to a portion of the anterior cerebral artery territory is reported. The patient's ability to walk was formally assessed by means of a new standardised test. Results: Due to an anomaly within the anterior cerebral artery system, the patient's lesion was centred on the supplementary motor regions of both hemispheres. He presented with clear signs of gait apraxia that could not be accounted for by paresis or other neurological deficits. No signs of any other form of apraxia were detected. Conclusions: The clinical profile of the patient and the analysis of 49 cases from previous literature suggest that gait apraxia should be considered a clinical entity in its own right and lesions to the supplementary motor areas are responsible for it.

Significance: This study is a preliminary step toward the identification of a noninvasive and reliable tool for monitoring the presence and progress of gaiting dysfunctions. Aim: We present the results of a pilot study for monitoring the motor cortex hemodynamic response function (HRF) in freely walking subjects, with time-domain functional near-infrared spectroscopy (TD fNIRS). Approach: A compact and wearable single-channel TD fNIRS oximeter was employed. The lower limb motor cortex area of three healthy subjects was monitored while performing two different freely moving gaiting tasks: forward and backward walking. Results: The time course of oxygenated and deoxygenated hemoglobin was measured during the different walking tasks. Brain motor cortex hemodynamic activations have been analyzed throughout an adaptive HRF fitting procedure, showing a greater involvement of motor area in the backward walking task. By comparison with the HRF obtained in a finger-tapping task performed in a still condition, we excluded any effect of motion artifacts in the gaiting tasks. Conclusions: For the first time to our knowledge, the hemodynamic motor cortex response was measured by TD fNIRS during natural, freely walking exercises. The cortical response during forward and backward walking shows differences, possibly related to the diverse involvement of the motor cortex in the two types of gaiting.