Precise finger somatotopy revealed by focal motor cortex injury.

BACKGROUND: Somatotopy is considered the hallmark of the primary motor cortex. While this is fundamentally true for the major body parts (head, upper and lower extremities), evidence supporting the existence of within-limb somatotopy is scarce. METHOD: We report a young man presenting recurrent ischemic strokes with selective finger weakness in whom serial motor cortex mapping procedures were performed. RESULT: Following the first stroke, which largely spared the motor cortex, motor mapping displayed overlap of the motor representations of the hand muscles. The second focal stroke, affecting the lateral part of the hand knob, resulted in selective loss of the first dorsal interosseous muscle motor evoked potentials while sparing those of the adductor digiti minimi muscle. This observation is in apparent contradiction with the first mapping results that suggested complete overlap of motor representations. DISCUSSION: Our mapping results provide evidence for the existence of very precise within-limb somatotopy and confirm the proposed homuncular order, whereby lateral fingers are represented laterally and medial fingers medially. The discrepancy between the initial and subsequent mapping results is discussed in light of functional organization of the primary motor cortex.

The Hand Motor Hotspot is not Always Located in the Hand Knob: A Neuronavigated Transcranial Magnetic Stimulation Study.

The hand motor hot spot (hMHS) is one of the most salient parameters in transcranial magnetic stimulation (TMS) practice, notably used for targeting. It is commonly accepted that the hMHS corresponds to the hand representation within the primary motor cortex (M1). Anatomical and imaging studies locate this representation in a region of the central sulcus called the "hand knob". The aim of this study was to determine if the hMHS location corresponds to its expected location at the hand knob. Twelve healthy volunteers and eleven patients with chronic neuropathic pain of various origins, but not related to a brain lesion, were enrolled. Morphological magnetic resonance imaging of the brain was normal in all participants. Both hemispheres were studied in all participants except four (two patients and two healthy subjects). Cortical mapping of the hand motor area was conducted using a TMS-dedicated navigation system and recording motor evoked potentials (MEPs) in the contralateral first dorsal interosseous (FDI) muscle. We then determined the anatomical position of the hMHS, defined as the stimulation site providing the largest FDI-MEPs. In 45 % of hemispheres of normal subjects and 25 % of hemispheres of pain patients, the hMHS was located over the central sulcus, most frequently at the level of the hand knob. However, in the other cases, the hMHS was located outside M1, most frequently anteriorly over the precentral or middle frontal gyrus. This study shows that the hMHS does not always correspond to the hand knob and M1 location in healthy subjects or patients. Therefore, image-guided navigation is needed to improve the anatomical accuracy of TMS targeting, even for M1.

Central and peripheral motor drive to the palatal muscles.

AIM OF THE STUDY: To characterize the motor command of the soft palate muscles using a magnetic stimulation technique. MATERIAL AND METHODS: Motor evoked potentials (MEPs) were recorded in 10 right-handed and 5 left-handed subjects at the midline of the palate or on the right or left hemipalate to peripheral and cortical magnetic stimulation. RESULTS: Mean palatal MEP amplitude ranged from 0.06 to 0.26mV to peripheral stimulation and from 0.36 to 1.09mV to cortical stimulation. In hemipalate recordings, MEPs to peripheral stimulation had greater amplitude when recorded ipsilaterally to the stimulation side, whereas MEPs to cortical stimulation were symmetrical. In midline recordings, right-handed subjects showed greater palatal MEP amplitude to right (rather than left) peripheral stimulation and to left (rather than right) cortical stimulation. Mean palatal MEP latency ranged from 4.0 to 4.1ms to peripheral stimulation and from 9.0 to 10.2ms to cortical stimulation; mean central conduction time ranged from 4.9 to 6.2ms. CONCLUSION: Palatal MEPs were easily and reliably obtained, including selective responses in each hemipalate. A bilateral cortical command of the palate is supported by our results, with a possible predominant motor drive from the left hemisphere in right-handed subjects.

Tremor in multiple sclerosis: The intriguing role of the cerebellum.

Tremor is frequently encountered in multiple sclerosis (MS) patients. However, its underlying pathophysiological mechanisms remain poorly understood. Our aim was to assess the potential role of the cerebellum and brain stem structures in the generation of MS tremor.We performed accelerometric (ACC) and electromyographic(EMG) assessment of tremor in 32MS patients with manual clumsiness. In addition to clinical examination, patients underwent a neurophysiological exploration of the brainstem and cerebellar functions,which consisted of blink and masseter inhibitory reflexes, cerebello-thalamo-cortical inhibition (CTCi), and somatosensory evoked potentials. Tremor was clinically visible in 18 patients and absent in 14. Patients with visible tremor had more severe score of ataxia and clinical signs of cerebellar dysfunction, as well as a more reduced CTCi on neurophysiological investigation. However, ACC and EMG recordings confirmed the presence of a real rhythmic activity in only one patient. In most MS patients, the clinically visible tremor corresponded to a pseudorhythmic activity without coupling between ACC and EMG recordings. Cerebellar dysfunction may contribute to the occurrence of this pseudorhythmic activity mimicking tremor during posture and movement execution.

Cortical excitability changes over time in progressive multiple sclerosis.

In 25 patients with progressive forms of multiple sclerosis (MS), motor cortex excitability was longitudinally studied over one year by means of transcranial magnetic stimulation (TMS). The following TMS parameters were considered: resting and active motor thresholds (MTs), input-output curve, short-interval intracortical inhibition (SICI), and intracortical facilitation. Clinical evaluation was based on the Expanded Disability Status Scale (EDSS). In the 16 patients not receiving disease-modifying drugs, the EDSS score worsened, resting MT increased, and SICI decreased. By contrast, no clinical for neurophysiological changes were found over time in the nine patients receiving immunomodulatory therapy. The natural course of progressive MS appears to be associated with a decline in cortical excitability of both pyramidal neurons and inhibitory circuits. This pilot study based on a small sample suggests that disease-modifying drugs may allow cortical excitability to remain stable, even in patients with progressive MS.

Reappraisal of the anatomical landmarks of motor and premotor cortical regions for image-guided brain navigation in TMS practice.

Image-guided navigation systems dedicated to transcranial magnetic stimulation (TMS) have been recently developed and offer the possibility to visualize directly the anatomical structure to be stimulated. Performing navigated TMS requires a perfect knowledge of cortical anatomy, which is very variable between subjects. This study aimed at providing a detailed description of sulcal and gyral anatomy of motor cortical regions with special interest to the inter-individual variability of sulci. We attempted to identify the most stable structures, which can serve as anatomical landmarks for motor cortex mapping in navigated TMS practice. We analyzed the 3D reconstruction of 50 consecutive healthy adult brains (100 hemispheres). Different variants were identified regarding sulcal morphology, but several anatomical structures were found to be remarkably stable (four on dorsoventral axis and five on rostrocaudal axis). These landmarks were used to define a grid of 12 squares, which covered motor cortical regions. This grid was used to perform motor cortical mapping with navigated TMS in 12 healthy subjects from our cohort. The stereotactic coordinates (x-y-z) of the center of each of the 12 squares of the mapping grid were expressed into the standard Talairach space to determine the corresponding functional areas. We found that the regions whose stimulation produced almost constantly motor evoked potentials mainly correspond to the primary motor cortex, with rostral extension to premotor cortex and caudal extension to posterior parietal cortex. Our anatomy-based approach should facilitate the expression and the comparison of the results obtained in motor mapping studies using navigated TMS.

Stroke rehabilitation using noninvasive cortical stimulation: motor deficit.

Noninvasive cortical stimulation (NICS) has been used during the acute, postacute and chronic poststroke phases to improve motor recovery in stroke patients having upper- and/or lower-limb paresis. This paper reviews the rationale for using the different NICS modalities to promote motor stroke rehabilitation. The changes in cortical excitability after stroke and the possible mechanisms of action of cortical stimulation in this context are outlined. A number of open and placebo-controlled trials have investigated the clinical effect of repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) of the primary motor cortex in patients with motor stroke. These studies attempted to improve motor performance by increasing cortical excitability in the stroke-affected hemisphere (via high-frequency rTMS or anodal tDCS) or by decreasing cortical excitability in the contralateral hemisphere (via low-frequency rTMS or cathodal tDCS). The goal of these studies was to reduce the inhibition exerted by the unaffected hemisphere on the affected hemisphere and to then restore a normal balance of interhemispheric inhibition. All these NICS techniques administered alone or in combination with various methods of neurorehabilitation were found to be safe and equally effective at the short term on various aspects of poststroke motor abilities. However, the long-term effect of NICS on motor stroke needs to be further evaluated before considering the use of such a technique in the daily routine management of stroke.

Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery.

Stroke rehabilitation using noninvasive cortical stimulation: hemispatial neglect.

The rehabilitation of neuropsychological sequels of cerebral stroke such as hemispatial neglect by noninvasive cortical stimulation (NICS) attracts increasing attention from the scientific community. The NICS techniques include primarily repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). They are based on the concept of either reactivating a hypoactive cortical region affected by the stroke (the right hemisphere in case of neglect) or reducing cortical hyperactivity of the corresponding cortical region in the contralateral hemisphere (the left hemisphere). In the studies published to date on the topic of neglect rehabilitation, rTMS was used to inhibit the left parietal cortex and tDCS to either activate the right or inhibit the left parietal cortex. Sham-controlled NICS studies assessed short-term effects, whereas long-term effects were only assessed in noncontrolled rTMS studies. Further controlled studies of large series of patients are necessary to determine the best parameters of stimulation (including the optimal cortical target location) according to each subtype of neglect presentation and to the time course of stroke recovery. To date, even if there are serious therapeutic perspectives based on imaging data and experimental studies, the evidence is not compelling enough to recommend any particular NICS protocol to treat this disabling condition in clinical practice.