Reliability of transcranial magnetic stimulation for mapping swallowing musculature in the human motor cortex.

OBJECTIVE: Although transcranial magnetic stimulation (TMS) has been widely used to study motor cortex organization and excitability, the reliability of this technique has not been thoroughly investigated. Furthermore, previous reports of TMS reliability have been restricted to upper limb musculature. We sought to determine the test-retest reliability for TMS mapping of motor representations for swallowing musculature. METHODS: Twenty healthy volunteers were tested twice over two weeks using TMS to determine motor threshold, map area, map volume, maximal MEP site location and maximal MEP site size for the suprahyoid complex and pharyngeal musculature. RESULTS: Good test-retest reliability was found in both swallowing muscle sites for the following test parameters: motor map area, maximal MEP site location: lateral coordinate, maximal MEP site size and motor threshold (ICC=0.76-0.98). Moderate reliability was observed for motor map volume and maximal MEP site location: anterior-posterior coordinate (ICC=0.68-0.74). CONCLUSIONS: TMS assessments of motor representation size, location and excitability appear to be highly reproducible, although the reliability of these measures may vary according to the specific muscle under investigation. SIGNIFICANCE: These works provide much needed psychometric data to validate the use of TMS to assess the cortical representation of swallowing musculature.

Dissociation of neglect subtypes with transcranial magnetic stimulation.

OBJECTIVE: To identify two forms of hemispatial neglect, attentional and intentional, in healthy volunteers using frontal and parietal repetitive transcranial magnetic stimulation (rTMS). METHODS: Ten healthy volunteers performed line bisection tasks while viewing stimuli on closed circuit TV. Direct view of the exploring hand and the target was precluded and the TV monitor guided performance. In the normal condition, the direction of hand movement on the table (workspace) was congruent with that on the monitor, and in the reversed condition, the lateral movement in the workspace occurred in the opposite direction on the monitor. The line bisections were performed in three conditions: without rTMS (control), with right frontal rTMS, and with right parietal rTMS. RESULTS: In the normal condition, both right frontal and right parietal rTMS caused a significant rightward deviation (left hemispatial neglect). In the reversed condition, right frontal rTMS continued to cause rightward deviation in the workspace corresponding to leftward bias on the monitor, whereas right parietal rTMS caused leftward deviation in the workspace, corresponding to rightward bias on the monitor. CONCLUSIONS: Right frontal repetitive transcranial magnetic stimulation causes motor-intentional neglect, whereas right parietal repetitive transcranial magnetic stimulation causes sensory-attentional neglect. Alternatively, these findings can also be explained based on a dichotomy related to an egocentric-oriented system.

Reliability of motor cortex transcranial magnetic stimulation in four muscle representations.

OBJECTIVE: Motor cortex plasticity may underlie motor recovery after stroke. Numerous studies have used transcranial magnetic stimulation (TMS) to investigate motor system plasticity. However, research on the reliability of TMS measures of motor cortex organization and excitability is limited. We sought to test the reliability of these TMS measurements. METHODS: Twenty healthy volunteers were tested twice over a two-week period using TMS to determine motor threshold, map topography, and stimulus-response curves for first dorsal interosseous (FDI), abductor pollicis brevis (APB), extensor digitorum communis (EDC), and flexor carpi radialis (FCR) muscles. RESULTS: We found moderate to good test-retest reliability TMS measurements of motor threshold (ICC=0.90-0.97), map area (ICC=0.63-0.86) and location (ICC=0.69-0.86), and stimulus-response curves (ICC=0.60-0.83). CONCLUSIONS: TMS assessments of motor representation size, location, and excitability are generally reliable measures, although their reliability may vary according to the muscle under investigation. SIGNIFICANCE: These results suggest that TMS measurements of motor cortex function are reliable enough to be potentially useful in investigation of motor system plasticity.

Proximal myotonic myopathy: clinical, neuropathologic, and molecular genetic features.

The primary genetic abnormality in myotonic dystrophy (DM) is an expansion of the CTG trinucleotide repeat on chromosome 19q. Recently, patients with similar clinical features, but without this genetic alteration, have been designated as proximal myotonic myopathy (PROMM). We describe two additional cases of PROMM, both of whom presented with clinical features suggestive of myotonic dystrophy. The patients had electromyographic (EMG) evidence of myotonia, normal cardiac evaluation, and no cataracts. Genetic analysis of peripheral blood leukocytes revealed no expansion of the trinucleotide repeat by polymerase chain reaction (PCR) and Southern blot analysis. Muscle biopsies in both cases were significant with features suggestive of myotonic dystrophy, such as large numbers of fibers containing multiple internal nuclei, occasional nuclear chains, and fiber atrophy, although sarcoplasmic masses and ring fibers were absent. These cases illustrate the clinical and neuropathologic findings of PROMM and underline the importance of correlating these aspects with genetic studies in patients with myotonic muscle disorders.

Emotional conversations in Parkinson's disease.

OBJECTIVE: To learn how PD influences verbal description of emotional events. BACKGROUND: Individuals with PD exhibit emotional processing deficits. Emotional experience likely involves several dimensions (e.g., valence, arousal, motor activation) subserved by a distributed modular network involving cortical, limbic, basal ganglia, diencephalic, and mesencephalic regions. Although the neurodegeneration in PD likely affects components in this network, little is known about how PD influences emotional processing. Because PD is associated with activation deficits, one could predict that the discourse of emotional experiences involving high activation would be reduced in patients with PD compared to control subjects. Alternatively, because patients with PD exhibit paradoxical sensitivity to externally evoked motor activation (kinesia paradoxica), it is possible that emotional stimuli may facilitate verbal emotional expression more so in patients with PD than in control subjects. METHODS: The authors measured verbal descriptions of personal emotional experiences in subjects with PD and normal controls. RESULTS: Compared with control subjects, individuals with PD showed a relative increase in the number of words spoken and in discourse duration when talking about emotional experiences that are usually associated with high levels of arousal and motor activation. Although the authors did not measure arousal or activation, prior research has shown that, when asked to recall an emotional experience, people will often re-experience the emotion previously experienced during that episode. CONCLUSIONS: Recalling emotional episodes induces verbal kinesia paradoxica in patients with PD. Although recall of these emotional episodes may have been associated with increased arousal and activation, the mechanism underlying emotional verbal kinesia paradoxica is unclear.

Listeria spinal cord abscess responsive to trimethoprim-sulfamethoxazole monotherapy.

OBJECTIVE: To describe an alternative antibiotic regimen for the treatment of central nervous system Listeria monocytogenes infection. BACKGROUND: Classical treatment of listeria infections of the brain and spinal cord has included ampicillin in combination with gentamicin and chloramphenicol. Antibiotic resistance to L. monocytogenes is extraordinarily low, and the combined risks of nephrotoxicity, ototoxicity, and agranulocytosis in an already critically ill patient make the potential use of trimethoprim-sulfamethoxazole monotherapy for coverage or treatment of listeria an important alternative. METHODS: Case report. RESULTS: A 58-year-old woman presented with a two-week history of progressive quadriplegia. Gadolinium enhanced MRI showed diffuse edema of the cervical and thoracic spine with ring-enhancing lesions. Cerebrospinal fluid and blood cultures both grew L. monocytogenes. Spinal cord biopsy of the lesion revealed inflammation with necrosis and also grew listeria. Intravenous trimethoprim-sulfamethoxazole (8 mg/kg in four divided doses) was administered for six weeks with resultant arrest of neurological symptoms and stabilization of the clinical course. Although the patient was quadraparetic she was able to be discharged to a rehabilitation facility. CONCLUSIONS: Trimethoprim-sulfamethoxazole monotherapy may be a potential alternative option for critically ill patients with central nervous system L. monocytogenes infection.

The effects of selective response preparation on corticospinal excitability.

OBJECTIVE: Both motor imagery and selective motor cues enhance performance. Motor cortex is activated during motor imagery. We wanted to learn if selective motor cueing also activates motor cortex. METHODS: We gave normal right-handed subjects information about which hand to use to respond to an imperative stimulus (selective intention) or where in space an imperative stimulus would occur (selective attention). To minimize anticipatory responses, warning stimulus validity was 80%. During this choice reaction time task, we recorded magnetic motor evoked potentials. Imperative stimuli and transcranial magnetic stimulation were presented randomly to assess the effect of warning cues on reaction times and corticospinal excitability. RESULTS: Selective intentional and attentional warning cues reduced reaction times, but neither stimulus altered motor evoked potentials. CONCLUSIONS: These results suggest that unlike motor imagery, selective intention to respond to an imperative stimulus and shifting spatial attention to an imperative stimulus do not alter corticospinal excitability.

Cognitive and vestibulo-proprioceptive components of spatial ability in Parkinson's disease.

Visual-spatial deficits are often associated with Parkinson's Disease (PD). Recent theories suggest that frontal-basal ganglionic dysfunction affects cognition in PD. Although this hypothesis does not entirely explain spatial deficits in PD, the inappropriate utilization of cues associated with executive dysfunction may induce spatial deficits. Alternatively, the vestibular system is also involved in spatial cognition, and vestibular dysfunction may affect visual-spatial ability in PD. To test these hypotheses, we administered the Water Jar Test, while perturbing vestibulo-proprioceptive input. Non-demented PD patients were significantly less accurate than controls in judging horizontal, and appeared to inappropriately utilize cues. No group effect was found for head tilt. These findings suggest the visual-spatial difficulties seen in PD are related to executive dysfunction that is associated with a disruption of the frontal-basal ganglionic and frontal-parietal systems.

Predicting hand preference with performance on motor tasks.

Handedness may be defined as preference or hand-differences in task performance. The strength and significance of the relationship between hand preference and hand performance asymmetries have been contested. To evaluate this relationship, we administered the Edinburgh Handedness Inventory and measured asymmetries in finger tapping, Purdue Pegboard, and grip strength in 30 subjects who prefer their right hand and 30 subjects who prefer their left hand. Hand asymmetries in finger tapping, Purdue Pegboard, and grip strength each predicted hand preference scores. However, a multiple regression equation best predicted hand preference by using performance of each task. Hand asymmetries in finger tapping correlated strongly with asymmetries in Purdue Pegboard performance, but neither of these asymmetries correlated strongly with asymmetries in grip strength. These findings indicate that hand preference and asymmetries in motor proficiency are strongly related, but suggest that preference and proficiency for different aspects of motor performance may be independently lateralized.

Bilateral medial pectoral neuropathy in a weight lifter.

Weight lifting has occasionally been associated with focal neuropathies of unknown cause. We describe a case of progressive bilateral medial pectoral neuropathy in a body builder. Whereas the medial pectoral nerve passes through pectoralis minor to reach the pectoralis major, the lateral pectoral nerve has no such intramuscular course. We postulate that weight lifting and concomitant pectoralis minor hypertrophy in our patient produced intramuscular entrapment of the medial pectoral nerves.

Transcranial magnetic stimulation identifies upper motor neuron involvement in motor neuron disease.

OBJECTIVE: To evaluate the sensitivity of transcranial magnetic stimulation (TMS) to identify upper motor neuron involvement in patients with motor neuron disease. BACKGROUND: Diagnosis of ALS depends on upper and lower motor neuron involvement. Lower motor neuron involvement may be documented with electromyography, whereas definite evidence of upper motor neuron involvement may be elusive. A sensitive, noninvasive test of upper motor neuron function would be useful. METHODS: TMS and clinical assessment in 121 patients with motor neuron disease. RESULTS: TMS revealed evidence of upper motor neuron dysfunction in 84 of 121 (69%) patients, including 30 of 40 (75%) patients with only probable upper motor neuron signs and unsuspected upper motor neuron involvement in 6 of 22 (27%) patients who had purely lower motor neuron syndromes clinically. In selected cases, upper motor neuron involvement identified with TMS was verified in postmortem examination. Increased motor evoked potential threshold was the abnormality observed most frequently and was only weakly related to peripheral compound muscle action potential amplitude. In a subset of 12 patients reexamined after 11+/-6 months, TMS showed progression of abnormalities, including progressive inexcitability of central motor pathways and loss of the normal inhibitory cortical stimulation silent period. CONCLUSIONS: TMS provides a sensitive means for the assessment and monitoring of excitatory and inhibitory upper motor neuron function in motor neuron disease.

Hand preference and transcranial magnetic stimulation asymmetry of cortical motor representation.

Human handedness may be associated with asymmetry in the corticospinal motor system. Previous studies measuring the threshold for eliciting motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) have provided evidence consistent with this hypothesis. However, TMS asymmetry observed in previous studies may have reflected cortical or spinal differences. We therefore undertook this investigation to test the hypothesis that handedness is associated with asymmetry in cortical motor representations. We used TMS to map contralateral cortical motor representations of the right and left abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles in nine normal subjects (three left-handed). Using focal stimulation with a figure-of-8 shaped magnetic coil, we found no differences in MEP threshold or MEP size between the preferred and the nonpreferred hand. However, we observed that the number of scalp stimulation sites eliciting MEPs was statistically greater for APB and FCR muscles of the preferred limb. We found significant asymmetry between right-handed and left-handed subjects, such that in right-handers, the representation of the right APB was larger than that of the left APB, but in left-handers the representation of right APB was smaller than that of the left APB. These results suggest that handedness is associated with asymmetry in cortical motor representation.

Effects of left frontal transcranial magnetic stimulation on depressed mood, cognition, and corticomotor threshold.

BACKGROUND: The pathophysiology of depression may include synaptic hypoactivity of left prefrontal cortex. Several groups of investigators have described improved mood associated with rapid transcranial magnetic stimulation (rTMS) but have not looked for possible cognitive side effects associated with left prefrontal magnetic stimulation. METHODS: We measured the effects of left prefrontal rTMS on mood, cognition, and motor evoked potential threshold in 10 patients with medication-resistant major depression. RESULTS: In a 2-week open trial of left prefrontal rTMS off antidepressant medications, scores on the Hamilton Rating Scale for Depression and the Beck Depression Inventory decreased by 41% and 40%, respectively. After resuming pre-rTMS antidepressant medication, improvement in mood was still significant at 1 and 3 months later. rTMS had no adverse effects on neuropsychological performance. rTMS treatments were associated with significant decreases in motor evoked potential threshold in the 9 of 10 patients who remained off psychotropic medications during the 2-week treatment period. CONCLUSIONS: These preliminary data suggest that left prefrontal rTMS is safe and improves mood in patients with medication-resistant major depression. Changes in motor evoked potential threshold suggest that prefrontal rTMS may alter brain activity at sites remote from the stimulation. Double-blind, sham-controlled studies are needed.

Cervical root stimulation at C5/6 excites C8/T1 roots and minimizes pneumothorax risk.

Needle electrical cervical root stimulation may be performed lateral to the C5/C6 or C7/T1 spinous process interspaces. Pneumothorax has been reported following C7/T1 root stimulation. We evaluated the efficacy of a modified C5/C6 stimulation technique in exciting C8/T1 roots in 15 normal subjects and 36 patients with motor neuron disease (204 procedures). No instances of a 50% or greater amplitude decline occurred. C5/C6 interspace stimulation, therefore, may be used to excite C8/T1 roots while minimizing pneumothorax risk.

Topographic differences in task-dependent facilitation of magnetic motor evoked potentials.

OBJECTIVE: To look for differences in task-dependent facilitation of magnetic motor evoked potentials (MEPs) in proximal and distal upper extremity muscles. BACKGROUND: Postexercise facilitation of MEPs has been demonstrated repeatedly in forearm muscles. Proximal muscles are prominently involved in limb stabilization, a largely isometric activity. In contrast, distal hand muscles specialize in precision movements. Based on these functional differences between proximal and distal muscles, we postulated that there might be topographic differences in task-dependent facilitation of MEPs. METHODS: We studied the effects of isometric exercise and a precision grip task on MEPs in proximal and distal upper extremity muscles. RESULTS: Isometric exercise of the target muscle was associated with significant facilitation of MEPs in biceps and extensor carpi radialis muscles, but not in first dorsal interosseous or abductor digiti minimi muscles. In contrast, a precision grip task was associated with significant post-task facilitation of MEPs in first dorsal interosseous, but not in extensor carpi radialis. CONCLUSIONS: These differences in the facilitation of MEPs depending on the motor task and whether the muscle is proximal or distal may reflect the relative importance of proximal muscles in maintaining posture.

Amygdalar injection of FeCl3 causes spontaneous recurrent seizures.

Rats were microinjected with a 100 mM aqueous solution of ferric chloride into the left amygdaloid body. Behavior was observed and depth electroencephalograms were recorded over the 30 days following injection. All of the FeCl3-injected rats developed isolated epileptiform discharges from the ipsilateral amygdala soon after injection. Within 5 days epileptiform discharges were arising as well from the contralateral amygdala and behavioral seizures were observed. These spontaneous seizures occurred in a pattern associated with stage 4 kindling, with rearing and bilateral forelimb clonus. Seizures persisted during the 30 days of the experiment. Recording from chronically implanted depth electrodes showed development of spike discharges, with recurrent seizures arising from amygdalar regions with propagation into both hippocampi. Aqueous iron is known to initiate lipid peroxidation by free radical mechanisms. Our observations suggest that epileptogenesis followed by chronic, spontaneous seizures could be initiated by deposition of iron-containing compounds into limbic structures of the rat.

Effect of stimulator orientation on F-wave persistence.

Most electrodiagnosis texts advocate cathode distal stimulation (CDS) for nerve conduction, but suggest cathode proximal stimulation (CPS) for F waves, because of anodal block. We postulated that CDS and CPS elicit F waves of similar persistence. We studied 657 (207 median, 204 ulnar, 136 tibial, and 110 peroneal) nerves in 225 consecutive subjects. In the median nerve, CDS elicited F waves of slightly greater persistence than CPS. Stimulator orientation did not affect F-wave persistence in the remaining nerves.

Stereotactic pallidotomy lengthens the transcranial magnetic cortical stimulation silent period in Parkinson's disease.

We compared the duration of the EMG cortical stimulation silent period (CSSP) elicited in abductor pollicis brevis using transcranial magnetic stimulation (TMS) before and after stereotactic unilateral globus pallidus internus pallidotomy (PAL) in 12 patients with Parkinson's disease. We used TMS stimulus intensities of 200, 150, 120, and 100% of motor evoked potential (MEP) threshold before and after (86 +/- 25 days) PAL. PAL increased CSSP duration at stimulus intensities of 200% of MEP threshold in the hand contralateral to the stereotactic lesion. In a subset of five patients able to remain at rest during pre-PAL testing sessions, PAL decreased the resting MEP/M-wave area ratio in the hand contralateral to the lesion at a stimulus intensity of 120% of MEP threshold. PAL did not significantly modify the effects of TMS in the hand ipsilateral to the globus pallidus lesion. The results suggest that PAL improves the function of cortical motor inhibitory circuits in Parkinson's disease.

Transcranial magnetic stimulation reveals a hemispheric asymmetry correlate of intermanual differences in motor performance.

Hemispheric asymmetries in the threshold for eliciting motor evoked potentials (MEPs) with transcranial magnetic stimulation (TMS) are associated with hand preference. We posited that hemispheric asymmetries in TMS thresholds may be strongly correlated with some hand-differences in motor performance. MEPs result from the activation of neuronal networks targeting large cortical motoneurons. Thus, MEP thresholds might reflect physiological features of the corticospinal motor system. Considering the role of corticospinal pathways in the control of independent finger movement, we hypothesized that MEP thresholds would better predict speed and dexterity than strength. In 30 right-handers and 30 left-handers, we correlated right and left hand-differences in the threshold for eliciting MEPs with hand-differences in the performance of three manual tasks: finger-tapping speed, pegboard dexterity, and grip strength. Correlations of hand-differences in TMS thresholds with hand-differences in performance indicated that a lower TMS threshold for one hand is strongly associated with greater ability with that hand. The correlations of hand-differences in TMS thresholds with hand-differences in finger-tapping and pegboard dexterity were significantly larger than the correlation of hand-differences in TMS thresholds with hand-differences in grip strength. Our results indicate that hemispheric asymmetries in MEP thresholds may have functional significance related to basic parameters of movement. These results are consistent with the critical role of the corticospinal motor system in the control of independent finger movement. Furthermore, they imply that asymmetry in the corticospinal motor system may be an important substrate for asymmetries in hand preference and performance.