Motor Cortex In Patients Research Articles

Motor cortex disinhibition in Alzheimer's disease

Objectives: To explore subclinical disturbances in the motor cortex of patients with Alzheimer's disease (AD). Methods: We used transcranial magnetic stimulation in a paired pulse technique to test intracortical inhibition (ICI) and intracortical facilitation in mildly to moderately demented AD patients with a normal neurological examination. Patients were studied before and during treatment with the cholinesterase inhibitor donepezil. Results: AD patients had a reduced ICI compared to an age-matched control group. The amount of disinhibition correlated with the severity of dementia. Treatment with 10 mg donepezil daily was associated with an increase of ICI. Conclusions: The subclinical motor cortex disinhibition in AD patients indicates a functional disturbance, and is probably associated with a cholinergic deficit.

Cortical reorganization in motor cortex after graft of both hands

Cortical organization shifts after sensory deprivation, but the reversibility of this reorganization has not been studied. Here, using functional magnetic resonance imaging (fMRI), we investigated the dynamics of cortical reorganization in a patient's motor cortex before and after bilateral hand transplantation. We found that amputation-induced cortical reorganization was reversed following hand transplantation.

The motor cortex and amyotrophic lateral sclerosis.

On theoretical grounds, abnormalities of the motor cortex in patients with amyotrophic lateral sclerosis (ALS) could lead to anterograde ("dying-forward") transneuronal degeneration of the anterior horn cells as suggested by Charcot. Conversely, retrograde ("dying-back") degeneration of the corticospinal tracts could affect the motor cortex. Evidence derived from clinical, neuropathological, static, and functional imaging, and physiological studies, favors the occurrence of anterograde degeneration. It is hypothesized that transneuronal degeneration in ALS is an active excitotoxic process in which live but dysfunctional corticomotoneurons, originating in the primary motor cortex, drive the anterior horn cell into metabolic deficit. When this is marked, it will result in more rapid and widespread loss of lower motor neurons. In contrast, slow loss of corticomotoneurons, as occurs in primary lateral sclerosis (PLS), precludes excitotoxic drive and is incompatible with anterograde degeneration. Preservation of slow-conducting non-M1 direct pathways in PLS is not associated with excitotoxicity, and anterior horn cells survive for long periods of time.

Decreased platelet glutamate uptake in patients with amyotrophic lateral sclerosis.

Decreased glutamate uptake and a loss of the astrocytic glutamate transporter EAAT2 (GLT-1) have been shown in spinal cord and motor cortex of patients with ALS. Because platelets express the three major glutamate transporter subtypes, including GLT-1, and possess a high-affinity glutamate uptake, the authors investigated glutamate uptake in platelets from patients with ALS and controls. A 43% reduction of high-affinity glutamate uptake rate (p < 0.0001) was observed in patients with ALS compared with normal controls and chronic neurologic disorder patients, suggesting a systemic impairment of glutamate uptake in ALS.

Ipsilateral activation of the unaffected motor cortex in patients with hemiparetic stroke

Background and purpose: Recent research has shown that following stroke patients can display ipsilateral activity reflecting a functional link between the undamaged hemisphere and the affected upper limb on the same side of the body. In the present study the capacity for ipsilateral activation is documented during recovery by using transcranial magnetic stimulation (TMS) and transcranial Doppler (TCD). Methods: Fourteen patients affected by hemispheric stroke were examined with TMS and TCD within 48 h of onset, and again 6 months later. Neurological signs were scored with reference to the NIHSS, and patients executed a thumb to finger opposition task so as to further estimate the motor deficit. Twenty healthy volunteers represented the control population. Results: (1) Both TMS and TCD yielded homogeneous results showing ipsilateral activity between affected hands and undamaged hemispheres. On stimulating the motor cortex 3 cm anterior and 3 cm lateral to Cz, a scalp site remote from the primary motor area, ipsilateral motor evoked potentials (iMEPs) from hand muscles were found in recovered patients. (2) In 8 controls iMEPs with smaller amplitudes than patients could be obtained by stimulating only the left hemisphere. (3) TCD revealed increased blood flow velocity in the ipsilateral MCA by activating the recovering hand (10.5±3.3%; P<0.001). Conclusion: TMS reveals a specific area in the motor cortex from which ipsilateral MEPs can be elicited and both TMS and TCD indicate that an ipsilateral corticospinal tract can be accessible in some adult controls or becomes unmasked after cerebral damage.

Asymmetric cortico-cortical inhibition in patients with progressive limb-kinetic apraxia.

To evaluate the activity of cortico-cortical (intracortical) inhibitory circuits within the motor cortex in patients with progressive asymmetric limb-kinetic apraxia. We studied 4 patients with progressive limb-kinetic apraxia whose clinical diagnosis was corticobasal degeneration (CBD) and 7 control subjects. Cortico-cortical inhibition was measured using the technique of double pulse transcranial magnetic stimulation over the motor cortex. The effects of conditioning stimuli on the test responses were examined. In the normal control subjects, the conditioning magnetic stimulus suppressed motor evoked responses to the test stimulus at interstimulus intervals of 1 to 5 ms. This inhibition was significantly diminished on the affected side of the patients, but it was normal on the less affected side. Disruption of intracortical inhibitory circuits in the motor cortex may, at least in part, be related to severe limb clumsiness in the patients with progressive limb-kinetic apraxia.

Loss of the muscle silent period evoked by transcranial magnetic stimulation of the motor cortex in patients with cervical cord lesions

The silent period following motor evoked potentials in small hand muscles after transcranial magnetic stimulation (TMS) of the human motor cortex is considered to be cortical origin. The authors report three patients with cervical spinal cord lesions who showed loss of the cortical silent period (CSP) after TMS. One patient had traumatic cervical cord injury, and the other two patients had cervical spondylosis. All the patients had cervical cord compression on magnetic resonance imaging. TMS study showed loss of the CSP in both the hand and foot muscles in two patients and only in the foot muscle in one patient. Paired TMS study in one patient with pseudoathetotic hands showed reduced inhibition within the motor cortex. The hand weakness or interrupted sensory afferents might have caused motor cortical reorganization or hyperexcitability, leading to the loss of the CSP.

Immunocytochemical and ultrastructural study of the motor cortex in patients with lower motor neuron disease

This report conveys the results of an immunocytochemical and ultrastructural study of the motor cortices of six patients with clinically and pathologically-diagnosed lower motor neuron disease (LMND) such as progressive spinal muscular atrophy, progressive bulbar palsy, or both. These patients showed neither upper motor neuron signs nor upper motor neuron system involvement including the corticospinal tract in postmortem tissues after conventional stainings. Specimens from 12 age-matched normal individuals served as controls. All patients showed loss of brainstem motor neurons and anterior horn cells. Betz cells in LMND patients were significantly reduced in number as compared to controls ( P<0.01). However, there was no significant difference in the density of phosphorylated neurofilament (PNF) (200 kDa)-positive Betz cells between LMND patients and controls. The pyramidal cells of layer III were immunostained for PNF in four of six LMND patients, but there was no significant difference in the density of PNF-positive pyramidal cells between LMND patients and controls. The number of astrocytes immunostained for glial fibrillary acidic protein increased in layer III and at the transition between white matter and motor cortex in three out of six patients and one of 12 controls. Ultrastructural examination revealed that the Betz cells of five of six LMND patients had Bunina bodies, Lewy body-like inclusions or skein-like inclusions, all of which are characteristic of amyotrophic lateral sclerosis (ALS). These findings suggest that most patients with clinically and pathologically-diagnosed LMND should be classified into the category of ALS.

The RNA of the glutamate transporter EAAT2 is variably spliced in amyotrophic lateral sclerosis and normal individuals.

Impaired re-uptake of synaptic glutamate, and a reduced expression of the glutamate transporter EAAT2 have been found in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Two splice forms of the EAAT2 RNA resulting from retention of intronic sequences (EAAT2/Int) and deletion of one protein coding exon (EAAT2/C1) have been reported to account for the EAAT2 protein loss in ALS. In this study we investigated the presence of two known (EAAT2/C1; EAAT2/Int) and three novel (EAAT2/C2-4) EAAT2 RNA in motor cortex of 17 ALS cases and 11 controls. Reverse transcription and PCR were carried out to amplify the complementary DNA of the complete and variably spliced EAAT2 transcripts. Nested PCR was followed to generate amplicons specific for EAAT2/C1-4 and EAAT2/Int. EAAT2/Int was detected in 59% of ALS specimens as compared to 36% of controls showing a trend but no statistical significance of a more frequent expression in ALS (Type I error 24.6%). EAAT2/C1-4 were found to be equally expressed in ALS patients and controls. Our results indicate that the involvement of EAAT2 transcripts in ALS is unlikely to be primary, and more complex than previously recognized. Alterations of quantitative expression of distinct EAAT2 splice forms in ALS cannot be excluded from this study and remain to be investigated.

Prolonged postexcitatory inhibition after transcranial magnetic stimulation of the motor cortex in patients with cerebellar ataxia.

Postexcitatory inhibition after transcranial magnetic stimulation of the motor cortex (silent period, SP) is supposed to be predominantly mediated by the activation of inhibitory cortical interneurons. Cortical excitability seems to be reduced in patients with cerebellar ataxia. Motor threshold, central motor conduction time and the duration of the silent period after a single magnetic stimulus to the motor cortex on both sides were measured in five patients with cerebellar ataxia of different origin and 18 healthy controls. Duration of SP was highly significantly prolonged in patients compared with controls (P<0.001) while motor threshold and central motor conduction times were not different. Fifteen of 18 control subjects showed late EMG responses after magnetic stimulation but none of the patients did (P<0.001). These findings support the hypothesis that cerebellar lesions activate inhibitory cortical interneurons or cause a disruption of a normally tonic cerebellar excitation to the motor cortex. Silent period measurement appears to be a sensitive diagnostic tool in the neurophysiological examination of cerebellar diseases.

Abnormal increase in the corticomotor output to the affected hand during repetitive transcranial magnetic stimulation of the primary motor cortex in patients with writer's cramp

In fourteen right-handed patients with writer's cramp and 10 right-handed controls, 10 trains of suprathreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) were applied over the left primary motor hand area. Each rTMS train lasted for a minute with an intertrain interval of 10 s. The motor evoked potentials (MEPs) were recorded from the relaxed contralateral first dorsal interosseus muscle. The mean MEP area of each rTMS train was taken as a measure of the corticospinal motor output to the affected hand. While the mean MEP area decreased significantly in controls, patients showed a significant increase in mean MEP area during rTMS. The differential effect on MEP size was highly significant. The abnormal rTMS-associated facilitation of the corticomotor output to the affected hand demonstrates an increased excitability of the corticospinal motor system in writer's cramp.

The human motor cortex after incomplete spinal cord injury: an investigation using proton magnetic resonance spectroscopy

OBJECTIVES(1) A biochemical investigation of the motor cortex in patients with incomplete spinal cord injury and normal control subjects using proton magnetic resonance spectroscopy (MRS). (2) To relate any altered...

Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements.

To determine the motor cortex degeneration in patients with amyotrophic lateral sclerosis (ALS) using proton magnetic resonance spectroscopy, and to prove that proton magnetic resonance spectroscopy is suited to monitor the course of disease with follow-up examinations. We studied 33 patients with ALS whose conditions were diagnosed according to the El Escorial World Federation of Neurology criteria. Nine patients with ALS were followed up for up to 2 years. The control group included 20 healthy volunteers and 4 patients with multifocal motor neuropathy. Proton magnetic resonance spectroscopy determined levels of the brain metabolites N-acetylaspartate (NAA), choline, inositol-containing compounds, glutamate/glutamine, and phosphocreatine. Patients with ALS showed a significant reduction in the NAA-choline (P <.001) and NAA-phosphocreatine (P <.005) metabolite ratios and significantly elevated choline-phosphocreatine (P <.005) ratios compared with controls. Inositol-phosphocreatine ratios were also elevated in case patients, but the increase was less pronounced (P <.05). No differences in glutamate/glutamine-phosphocreatine ratios were detected between case patients and controls. An analysis of subgroups demonstrated less significant differences in NAA-choline metabolite ratios (P<.05), even in patients with pure lower motor neuron syndrome (suspected ALS). No changes in metabolite T1 and T2 relaxation times were observed. Patients with multifocal motor neuropathy showed normal metabolic ratios. Progressive alterations in affected metabolite ratios could be documented in the follow-up examinations. Spectroscopic changes in the motor cortices of patients with ALS correspond with a reduction in levels of NAA and an elevation in levels of choline and inositol compounds. Since NAA is exclusively expressed in neurons, the observed decrease of NAA reflects neuronal loss or dysfunction. Inositol and choline are associated with plasma membrane metabolism, so the release of these compounds may be related to membrane disorders.

Responses of thenar muscles to transcranial magnetic stimulation of the motor cortex in patients with incomplete spinal cord injury

OBJECTIVETo investigate changes in electromyographic (EMG) responses to transcranial magnetic stimulation (TMS) of the motor cortex after incomplete spinal cord injury in humans.METHODSA group of 10 patients with incomplete spinal...

Functional Magnetic Resonance Mapping of Sensory Motor Cortex for Image-Guided Neurosurgical Intervention

This paper describes the potentials of functional magnetic resonance imaging (fMRI) to map sensory motor cortex in patients with mass lesions near primary motor cortex and to guide neurosurgical procedures located close to eloquent brain regions. 7 patients with mass lesions near the central sulcus and 10 healthy volunteers were studied using a blood oxygenation level dependent 2D multislice multishot T2* weighted gradient echo EPI sequence on a 1.5T Phillips Gyroscan during alternating epochs of rest and motor activation of hand, foot and tongue. Sites of neuronal activation were identified by statistical analysis of the signal time course using Kolmogorov Smirnov statistics. Neuronal activation following motor tasks consistently localised to the contralateral precentral gyrus and the supplementary motor area, even in the presence of local brain pathology. Additionally we could observe activation in primary sensory areas (post-central gyrus) and supplementary motor area (SMA) in some cases. fMRI is capable of mapping sensory motor cortex even in the presence of distorting brain lesions. Since this information will provide valuable information to the neurosurgeon during pre-operative planning, we consider this method for neurosurgical navigation a valuable tool in the routine diagnostic of intracerebral interventions.

Epidural electrical stimulation of the motor cortex in patients with facial neuralgia

Chronic facial neuralgias often do not respond sufficiently to standard treatment methods. Alternative modalities are needed for long-term reduction of pain in such cases. The present preliminary report describes two patients with trigeminal and glossopharyngeal neuralgia, respectively, treated with standard methods without obtaining satisfactory pain relief. Electrical stimulation of the motor cortex contralateral to the pain area was employed in both cases and proved able to produce a long-term facial pain reduction. Alleviation of pain occurred after activation of the flat quadripolar electrode placed epidurally on the precentral cortical area and lasted as long as the stimulator was working. By changing the polarity of the electrodes, it was possible to induce tingling sensations and muscle activation not only contralaterally to the stimulated motor cortex, but also in the ipsilateral part of the face. No stimulator-independent pain reduction resulted from long-term use of the stimulation device. During a follow-up period of 18 months, a sufficient and relatively stable analgesic effect of electrostimulation was observed. One major complication of motor cortex stimulation during the follow-up period was a single generalized epileptic seizure in one of the patients.

Functional MRI: primary motor cortex localization in patients with brain tumors.

Our goal was (a) to test the ability of functional MRI (fMRI) to localize the hand primary motor cortex in patients with brain neoplasms using a conventional scanner and (b) to compare within the same subject the location and morphology of the activated motor areas in the affected hemisphere with the contralateral ones. Seventeen right-handed patients with frontoparietal intra- and extraaxial tumors were studied. Hand motor performance ranged from normal to slight impairment of finger dexterity. The fMRI study was based on a series of FLASH images. Two or three contiguous slices parallel to the bicommissural plane were acquired through the level of frontoparietal cortex. Each patient was requested to perform with each hand a finger-tapping task or a simpler repetitive flexion-extension of the last four fingers. Pseudo-color activation maps were then calculated by a Z-score method and superimposed on high resolution images. Five patients were excluded because of gross motion artifacts. In all other patients, areas of significant signal increase were detected on the precentral gyrus. They had a spot-like appearance, and no substantial side-to-side differences in shape or extension could be observed. In the presence of severe compression of the gyri, a displacement of the activated areas in the affected hemisphere with respect to the contralateral ones was noticeable. fMRI localization of the primary motor area using a conventional scanner can be obtained also in patients with brain tumors, although with a lower success rate than in normal volunteer studies, mainly because of subject compliance problems. Areas of significantly increased signal are detectable even in cortex where normal anatomical patterns are lost.

Serotonergic neurotransmission in the spinal cord and motor cortex of patients with motor neuron disease and controls: quantitative autoradiography for 5-HT 1a and 5-HT 2 receptors

Serotonin 5-HT is a potent modulator of motor neuron excitability in the spinal cord. Serotonergic neurotransmission, because of its effects on glutamatergic excitation, may be relevant to the pathogenesis and therapy of motor neuron disease (MND). The human motor system was studied at two levels, spinal cord and motor cortex, by autoradiography for the 5-HT 1A and 5-HT 2 receptor subclasses. In addition, biochemical estimations of indole metabolites were performed in the spinal cord. Post mortem tissue from control cases and MND patients showed a reduction in 5-HT 1A receptor binding in the cervical ( p < 0.01) but not lumbar ventral horn in MND. 5-HT 2 receptors were preserved in the ventral horn at both levels and were focally abundant around motor neuron somata. Tissue levels of 5-HT were unchanged in the spinal cord in MND. The metabolite 5-HIAA was increased in the cervical spinal cord in MND as was the molar ratio of 5HIAA:5-HT, implying that there may be an increased turnover of 5HT. In the motor cortex and premotor cortex the 5-HT 1A receptor remained unchanged in MND. There was a 20% reduction in 5-HT 2 receptor binding sites ( p < 0.05) across all the cortical laminae with preservation of the normal pattern of laminar binding. These changes in two levels of the motor system in MND most likely represent physiological adaptations in the spinal cord and motor cortex rather than primary involvement of the serotonergic system in the pathogenesis of the disease.

Enhancement of inhibitory mechanisms in the motor cortex of patients with cerebellar degeneration: a study with transcranial magnetic brain stimulation

The excitatory state of the primary motor cortex can be studied by measuring either the postexcitatory inhibition after transcranial magnetic single stimulation (pI-S) or the refractory period with magnetic double stimulation (rP-D). The cerebellum may influence the excitability of the motor cortex by cerebellar inputs and outputs from side loops of transcortical projections. Therefore, we studied pI-S and rP-D in 24 patients with autosomal dominant cerebellar ataxia or idiopathic cerebellar ataxia, who were allocated to one group (Group A) with mild to moderate ataxia ( n = 11) and to another group (Group B) with severe ataxia ( n = 13). The results were compared with those obtained in 21 normal age-matched control subjects. The central motor conduction time (CMCT) was delayed in approximately half of the patients, demonstrating that the degenerative process, beyond the cerebellum, also affects the pyramidal tract. Mean CMCT was significantly delayed only in patients of Group B. pI-S was prolonged in 10 of our 24 patients; incidence of pathology in pI-S did not differ between the two patient groups. In 5 patients with normal CMCT, pathological pI-S results were found. Mean pI-S was prolonged in the whole patient group and in both subgroups as well. rP-D was prolonged in two patients of Group B only, but mean rP-D was significantly prolonged in the whole patient group. Prolonged postexcitatory inhibition and refractory period may be a consequence of a transient facilitation of cortical inhibitory interneurons, which results in a decreased excitability of primary motor cortex in patients with cerebellar degeneration.

Activation of the motor cortex in patients with mirror movements evaluated with functional MR imaging

Activation of the motor cortex in patients with mirror movements evaluated with functional MR imaging