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Biomedical subjects

E M Wassermann

Publications and source records attributed to E M Wassermann.

69 records · Page 4Linked to original sources

Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression.

Converging evidence points to hypofunction of the left prefrontal cortex in depression. Repetitive transcranial magnetic stimulation (rTMS) activates neurons near the surface of the brain. We questioned whether daily left prefrontal rTMS might improve mood in depressed subjects and report a pilot study of such treatment in six highly medication-resistant depressed inpatients. Depression scores significantly improved for the group as a whole (Hamilton Depression Scores decreased from 23.8 +/- 4.2 (s.d.) at baseline to 17.5 +/- 8.4 after treatment; t = 3.03, 5DF, p = 0.02, two-tailed paired t-test). Two subjects showed robust mood improvement which occurred progressively over the course of several weeks. In one subject, depression symptoms completely remitted for the first time in 3 years. Daily left prefrontal rTMS appears to be safe, well tolerated and may alleviate depression.

Affect↗

The role of reading activity on the modulation of motor cortical outputs to the reading hand in Braille readers.

We studied the cortical motor output maps of the first dorsal interosseous (FDI) of both hands and the abductor digiti minimi of the reading hand in 6 blind proficient Braille readers. The maps were generated using transcranial magnetic stimulation. We compared the maps obtained on a day in which they worked as Braille proofreaders (reading Braille for approximately 6 hours) with the maps obtained on a day they took off from work. On the work day, the maps for the FDI of the reading hand were significantly larger after the working shift than in the morning after having been off work for 2 days. These changes were not seen for the same muscle on the day off work or on any of the 2 days in the other two muscles studied. These results illustrate the rapid modulation in motor cortical outputs in relation to preceding activity and emphasize the importance of precise timing in studies of the neurophysiological correlates of skill acquisition.

Adult↗

Resetting of essential tremor and postural tremor in Parkinson's disease with transcranial magnetic stimulation.

We studied the effects of transcranial motor cortex stimulation on the electromyographic characteristics of tremor in 9 patients with familial essential tremor and in 12 patients with postural tremor associated with Parkinson's disease. Transcranial magnetic stimulation reset both types of tremor equally. The resetting depended on the stimulus intensity, but was most closely correlated with the duration of the electromyographic silent period that followed the stimulus-induced motor evoked potential. Tremor resetting was present bilaterally even after focal, unilateral stimulation. Transcranial electrical stimulation failed to reset the tremor in either patient group. These results emphasize the role of central, intracortical structures in the generation of essential tremor and postural tremor in Parkinson's disease.

Adult↗

Cortical motor representation of the ipsilateral hand and arm.

We sought to determine whether motor evoked potentials (MEPs) as well as silent periods could be produced in hand and shoulder muscles by transcranial magnetic stimulation (TMS) of the ipsilateral cerebral hemisphere and, if so, whether their cortical representations could be mapped with respect to those of contralateral muscles. In six normal subjects, we delivered ten stimuli each to a grid of sites 1 cm apart on the scalp. The EMG was recorded and averaged from the contralateral first dorsal interosseous (FDI) and risorius (facial) muscles at rest and the ipsilateral FDI muscle, which was voluntarily contracted. In four of these subjects and an additional subject, we used the same mapping technique and recorded from the deltoid muscle on the right and left sides and the contralateral FDI during activation of the ipsilateral deltoid. In all subjects, the cortical representation of the contralateral risorius was anterolateral to that of the FDI. The contralateral deltoid could be activated in only three subjects. In them, its representation was slightly medial to that of the FDI. All subjects had at least one scalp site where TMS produced MEPs in the ipsilateral FDI. Two subjects had rich ipsilateral hand representations with multiple ipsilateral MEP sites. Both had ipsilateral MEP sites near the representation of the contralateral FDI, but the largest ipsilateral MEPs occurred with TMS at more lateral sites, which were near the representation of the contralateral risorius. In these subjects, the ipsilateral deltoid was preferentially activated at sites medial and posterior to those activating the contralateral muscle. Ipsilateral TMS also produced silent periods in the FDI in all subjects. These silent periods were much more frequent than the ipsilateral MEPs and tended to occur with TMS near the representation of the contralateral FDI. The excitatory cortical representation of the ipsilateral arm muscles is accessible to TMS in normal subjects and is different from that of the homologous contralateral muscles. The hand may have two ipsilateral representations, one of which produces silent periods and the other MEPs at the same stimulus intensity.

Adult↗

Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex.

We applied trains of focal, rapid-rate transcranial magnetic stimulation (rTMS) to the motor cortex of 14 healthy volunteers with recording of the EMG from the contralateral abductor pollicis brevis, extensor carpi radialis, biceps brachii and deltoid muscles. Modulation of the amplitude of motor evoked potentials (MEPs) produced in the target muscle during rTMS showed a pattern of inhibitory and excitatory effects which depended on the rTMS frequency and intensity. With the magnetic coil situated over the optimal scalp position for activating the abductor pollicis brevis, rTMS led to spread of excitation, as evident from the induction of progressively larger MEPs in the other muscles. The number of pulses inducing this spread of excitation decreased with increasing rTMS frequency and intensity. Latency of the MEPs produced in the other muscles during the spread of excitation was significantly longer than that produced by single-pulse TMS applied to the optimal scalp positions for their activation. The difference in MEP latency could be explained by a delay in intracortical conduction along myelinated cortico-cortical pathways. Following rTMS, a 3-4 min period of increased excitability was demonstrated by an increase in the amplitude of MEPs produced in the target muscles by single-pulse TMS. Nevertheless, repeated rTMS trains applied 1 min apart led to similar modulation of the responses and to spread of excitation after approximately the same number of pulses. This suggests that the spread might be due to the breakdown of inhibitory connections or the recruitment of excitatory pathways, whereas the post-stimulation facilitation may be due to a transient increase in the efficacy of excitatory synapses.

Adult↗

Modulation of motor cortical outputs to the reading hand of braille readers.

We used focal transcranial magnetic stimulation to map the motor cortical areas targeting the first dorsal interosseous and the abductor digiti minimi muscles bilaterally in 10 proficient braille readers and 10 blind controls who were matched for age (mean, 50.6 yr) and age at time of blindness (mean, 7.5 yr). The proficient braille readers had learned braille at age 8 to 14 years and used it daily for 5 to 10 hours. Controls had not learned braille until age 17 to 21 years and used it daily for < 1 hour. In the controls, motor representations of the right and left first dorsal interosseous and abductor digiti minimi muscles were not significantly different. However, in the proficient braille readers, the representation of the first dorsal interosseous muscle in the reading hand was significantly larger than that in the nonreading hand or in either hand of the controls. Conversely, the representation of the abductor digiti minimi muscle in the reading hand was significantly smaller than that in the nonreading hand or in either hand of the controls. These differences were not due to differences in motor thresholds. Our results suggest that the cortical representation of the reading finger in proficient braille readers is enlarged at the expense of the representation of other fingers.

Adolescent↗

Safety of rapid-rate transcranial magnetic stimulation in normal volunteers.

In 9 normal volunteers, we studied the safety of rapid-rate transcranial magnetic stimulation (rTMS) applied to different scalp positions at various frequencies and intensities. Pure tone threshold audiometry showed temporary threshold shifts in 3 subjects. In the subject stimulated at the highest intensity, rTMS induced a focal, secondarily generalized seizure despite the absence of definite risk factors for seizures. Rapid-rate TMS did not result in any important changes in the neurological examination findings, cognitive performance, electroencephalogram, electrocardiogram, and hormone levels (prolactin, adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone). In 10 additional subjects, the electromyographic activity in several contralateral muscles showed that trains of rTMS applied to the motor cortex induced a spread of cortical excitability. The spread of excitability depended on the intensity and frequency of the stimuli and probably constituted an early epileptogenic effect of rTMS. Guidelines for preventing the undesirable side effects of rTMS are offered.

Adult↗

Topography of the inhibitory and excitatory responses to transcranial magnetic stimulation in a hand muscle.

We studied the excitatory motor evoked potentials (MEPs) and the inhibitory (silent period) responses to focal transcranial magnetic stimulation (TMS) in the abductor pollicis brevis (APB) of 5 normal subjects to learn whether the scalp topography of the two responses differed. At the scalp location where stimulation produced the highest-amplitude MEP in the voluntarily activated APB, stimulus intensities below the MEP threshold produced silent periods with little or no preceding facilitation. The silent periods had a mean duration of 26.8 +/- 6.8 msec and a mean onset latency of 27.6 +/- 3.6 msec, which was 7.2 +/- 2.3 msec longer than the latency of MEPs produced in the APB by higher stimulus intensities. A period of excitation, with an onset latency of 50-80 msec, often followed the silent period. On averaged trials, a stimulus intensity just above the threshold of the MEP at its optimal position produced MEPs followed by silent periods at a cluster of scalp locations 1 cm apart on the central scalp (medial area) and silent periods with very slight or no preceding facilitation in 3-9 locations lateral to the MEP area (lateral area). This finding was confirmed in 3 subjects with maps constructed from statistical analysis of multiple trials. These maps also showed that MEPs produced from the medial area occurred 4-6 msec earlier than those produced from the lateral area. The integral of the silent period tended to be larger in the lateral area. The motor representation of APB, as defined by TMS, is not homogeneous but rather contains at least two components that differ physiologically and topographically.

Adult↗

Human motor evoked responses to paired transcranial magnetic stimuli.

We studied the changes in motor pathway excitability induced by transcranial magnetic stimulation of the motor cortex, using paired stimuli (conditioning and test stimulus) and varying interstimulus interval (ISI). The effects induced depended on the stimulus intensity. At a low intensity, there was inhibition of the response to the test stimulus at ISIs of 5-40 msec, followed by facilitation at ISIs of 50-90 msec. At a high intensity, there was facilitation at ISIs of 25-50 msec, followed by inhibition at ISIs of 60-150 msec and, occasionally, by another phase of facilitation at ISIs of more than 200 msec. Only tentative explanations are currently possible for these effects: the inhibition observed at low intensities and short ISIs may be due to activation of cortical inhibitory mechanisms. The facilitation that follows may arise from the coincidence of various factors that transiently increase the excitability in alpha motoneurons. The early facilitation observed at high intensities seems to be a consequence of a rise in cortical excitability induced by the conditioning stimulus, causing an increase in the number or size, or both, of descending volleys from the test stimulus. The profound inhibition that follows probably results from a combination of both segmental and suprasegmental inhibitory mechanisms.

Adult↗

Noninvasive mapping of muscle representations in human motor cortex.

We used transcranial magnetic stimulation to map the cortical representations of 4 upper extremity muscles (abductor pollicis brevis, flexor carpi radialis, biceps, and deltoid) of 10 normal subjects. Three stimuli were delivered to scalp positions 1 cm apart, and the amplitude and latency of the motor evoked potentials (MEPs) were averaged for each position. Maps were described in terms of number of excitable scalp positions, amplitude of MEPs, scalp positions for evoking largest amplitude MEPs, and threshold for producing MEPs. We compared different muscles across subjects and the same muscles on the left and right sides in individual subjects. Distal muscles had larger representations with higher amplitude MEPs and lower thresholds. Biceps and deltoid on the left had larger representations and higher MEP amplitudes than on the right. Maps showed a somatotopic progression on the scalp of proximal to distal muscles along a posteromedial to anterolateral axis.

Adult↗

Effects of focal transcranial magnetic stimulation on simple reaction time to acoustic, visual and somatosensory stimuli.

In a simple reaction time (RT) paradigm, magnetic stimulation of different intensities was delivered over different scalp positions and at variable delays before (negative) or after (positive) the go-signal. Magnetic stimulation shortened RT to different go-signals (auditory, visual and somatosensory stimuli) by approximately 30 ms when delivered over the motor cortex contralateral to the responding arm at intensities below motor threshold. This effect was maximal at a delay of approximately +10 ms. A similar effect was found with suprathreshold stimulation to the ipsilateral motor cortex. Magnetic stimulation over other scalp areas did not affect RT regardless of the delay. No differences were found between the effects on elbow flexion and thumb abduction. The shortening of RT was not associated with changes in the timing development of premovement excitability increase in the motor cortex. We conclude that magnetic stimulation shortens RT by inducing an earlier initiation of this excitability increase.

Acoustic Stimulation↗

No evidence of hearing loss in humans due to transcranial magnetic stimulation.

Prompted by the description of hearing loss in rabbits exposed to the acoustic artifact of magnetic stimulation, we compared the results of audiologic studies before and after exposure to transcranial magnetic stimulation in humans. We found no evidence of temporary or permanent threshold shifts in any of the subjects, even in those exposed to transcranial magnetic stimulation repeatedly for several years. Risk of hearing loss from the acoustic artifact of magnetic stimulation, as evaluated by audiograms, tympanograms, acoustic reflexes, and auditory evoked potentials, seems to be small in humans.

Adult↗

Magnetic stimulation of the human cerebral cortex, an indicator of reorganization in motor pathways in certain pathological conditions.

Basic principles of magnetic stimulation of biological tissues are reviewed. Noninvasive magnetic stimulation of the brain delivered over sensorimotor areas evokes movements and less commonly paresthesias in contralateral limbs. We have evaluated the maps of motor outputs in patients with (1) congenital mirror movements, which resulted in marked derangement of the map of outputs of distal hand muscles with enlarged and ipsilateral representations; (2) amputations, which resulted in plastic reorganization of motor outputs targeting muscles immediately proximal to the stump; (3) spinal cord injury, which also resulted in enlargement of the map of outputs targeting muscles proximal to the lesion level; and (4) hemispherectomy performed at an early age for intractable seizures, which resulted in the remaining hemisphere controlling ipsilateral arm muscles. These results demonstrate the potential for reorganization in motor systems following lesions in the peripheral as well as in the central nervous system.

Brain Mapping↗

Effects of transcranial magnetic stimulation on ipsilateral muscles.

We studied the effects of transcranial magnetic stimulation of the motor cortex on ipsilateral upper extremity muscles in six normal men. Stimulation had inhibitory and excitatory effects on the muscles during voluntary activation. Transient inhibition, an ipsilateral silent period (ISP), occurred in all muscles tested, often without any preceding excitatory response. Motor evoked potentials (MEPs) occurred ipsilaterally in the proximal muscles of some subjects. Ipsilateral MEPs and ISPs were delayed relative to the MEPs evoked by the same stimulus in the corresponding contralateral muscles. The excitability of the alpha motoneuron pool, assessed during the period of the ISP by eliciting H-reflexes, showed no change, suggesting that ipsilateral inhibition acts at a level above the alpha motoneuron. Connections from motor cortex to ipsilateral muscles could be via the corpus callosum and contralateral hemisphere or via purely ipsilateral pathways.

Adult↗