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E M Wassermann

Publications and source records attributed to E M Wassermann.

At least 55 records · Page 3Linked to original sources

Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters.

Induction of a seizure in a normal subject with trains of repetitive transcranial magnetic stimulation (rTMS) applied in close succession suggested that short inter-train intervals, a parameter not considered in our previous safety studies, may not be safe. Here, we evaluate the safety of different inter-train intervals for rTMS in 10 healthy volunteers. Ten rTMS trains at 20 Hz for 1.6 s and a stimulus intensity of 110% of motor threshold (MT) were found to be safe at the inter-train interval of 5 s. However, inter-train intervals of 1 s or less were unsafe for trains of 20 Hz for 1.6 s and stimulus intensities higher than 100% of MT. Based on these results, we propose safety guidelines for inter-train intervals at different stimulus intensities. We also analyzed the stimulus parameters, used in 3 studies, that led to seizures in normal subjects. One seizure was due to short inter-train intervals, one was likely related to intense individual rTMS trains close to the limit of our previous safety recommendations, and one was likely due to a combination of these two factors. To provide an additional safety margin, we suggest reducing the duration for individual rTMS trains by 25% from our previous recommendations. Updated safety tables currently in use at our institution are provided.

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Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial.

OBJECTIVE: Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity. The authors sought to confirm this finding by using a double-blind crossover design. METHOD: Twelve depressed adults received in random order 2 weeks of active treatment (repetitive transcranial magnetic stimulation, 20 Hz at 80% motor threshold) and 2 weeks of sham treatment. RESULTS: Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment. During the active-treatment phase, Hamilton depression scale scores decreased 5 points, while during sham treatment the scores increased or worsened by 3 points. No adverse effects were noted. CONCLUSIONS: These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters. Further controlled studies are indicated to explore optimal stimulation characteristics and location, potential clinical applications, and possible mechanisms of action.

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Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study.

OBJECTIVE: Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms. METHOD: Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients' symptoms and mood were rated for 8 hours afterward. RESULTS: Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation. CONCLUSIONS: These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder.

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Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation.

We studied the effects of low-frequency transcranial magnetic stimulation (TMS) on motor cortex excitability in humans. TMS at 0.1 Hz for 1 hour did not change cortical excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar to the parameters used to induce long-term depression (LTD) in cortical slice preparations and in vivo animal studies, led to a mean decrease in motor evoked potential (MEP) amplitude of 19.5%. The decrease in cortical excitability lasted for at least 15 minutes after the end of the 0.9 Hz stimulation. The mechanism underlying this decrease in excitability may be similar to LTD. TMS-induced reduction of cortical excitability has potential clinical applications in diseases such as epilepsy and myoclonus. Spread of excitation, which may be a warning sign for seizures, occurred in one subject and was not accompanied by increased MEP amplitude, suggesting that spread of excitation and amplitude changes are different phenomena and also indicating the need for adequate monitoring even with stimulations at low frequencies.

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Decreased postexercise facilitation of motor evoked potentials in patients with cerebellar degeneration.

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects and 11 medication-free patients with cerebellar degeneration. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until the muscle fatigued (subject became unable to maintain half maximal force). MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean preexercise MEP amplitude in normal subjects and 132% in cerebellar patients, indicating postexercise MEP facilitation in both groups. However, postexercise MEP facilitation, compared with the mean preexercise MEP amplitude, was not significant in the patients but was significant in the normal subjects. The amplitudes of MEPs recorded within the first few minutes after fatigue were 44% of the mean preexercise MEP amplitudes in both groups. We conclude that in patients with cerebellar degeneration, postexercise MEP facilitation is significantly reduced, whereas postexercise MEP depression after fatigue is similar to that of normal subjects.

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Effects of phenytoin on cortical excitability in humans.

We studied the effects of a loading dose of phenytoin on motor cortex excitability in five healthy volunteers. Phenytoin elevated motor thresholds to transcranial magnetic stimulation (TMS) in all subjects, but had no effects on motor-evoked potential amplitudes, silent period durations, and intracortical excitability tested by paired TMS during rest and voluntary muscle activation. These results are consistent with the hypothesis that blockade of voltage-gated sodium channels decreases membrane excitability and elevates the threshold to TMS, but will not reduce intracortical excitability.

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Impaired inhibition in writer's cramp during voluntary muscle activation.

We used paired transcranial magnetic stimulation (TMS) to evaluate inhibitory mechanisms in eight patients with writer's cramp during rest and isometric wrist extension. Both stimuli were 110% of the motor threshold; the interstimulus intervals (ISIs) were 20 to 200 ms in increments of 10 ms. Surface EMG was recorded from wrist extensors. In the symptomatic hemisphere, there was no significant difference in the amplitude of the test (second) motor evoked-potential (MEP) between patients and age-matched controls at rest. However, with voluntary muscle activation, inhibition of the test MEP by the conditioning MEP was significantly less in writer's cramp patients than in controls (p = 0.02). The difference was most prominent at ISIs of 60 to 80 ms in which inhibition is maximum. In the asymptomatic hemisphere, there was no significant difference between patients and controls in both rest and active conditions. The silent period was shorter in patients than controls on the symptomatic side (p = 0.003) but not on the asymptomatic side. We conclude that the inhibitory effects induced by magnetic stimulation are reduced in patients with writer's cramp, but only on the symptomatic side during muscle activation. This may relate to the overflow of muscle activity that characterizes this condition.

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Locating the motor cortex on the MRI with transcranial magnetic stimulation and PET.

Transcranial magnetic stimulation with a focal coil was used to map the cortical representation of a hand muscle in four healthy subjects. In each subject, the three-dimensional locations of the magnetic stimulation positions and about 400 positions on the surface of the head were digitized. The amplitude-weighted center of gravity of each subject's map was found, and a line perpendicular to the local head surface was projected inward. The digitized heads were registered with the subjects' MRIs using the scalp contours. The coordinate transformations yielded by this process were used to map the stimulation positions and the perpendicular line into the MRIs. Brain areas imaged with positron emission tomography (PET) and 15O-labeled water, activated by movement of the same muscle, were registered with the MRIs using the brain contours. In all cases, the magnetic stimulation lines encountered the surface of the brain at the anterior lip of the central sulcus and ran along the precentral gyrus a few millimeters anterior to the central sulcus, coming within 5-22 mm of all the PET activation maxima. This technique demonstrates the accuracy of transcranial magnetic stimulation for locating the primary motor area.

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Responses to paired transcranial magnetic stimuli in resting, active, and recently activated muscles.

Transcranial magnetic stimulation (TMS) causes the corticospinal system to become refractory to subsequent stimuli for up to 200 ms. We examined the phenomenon of paired pulse inhibition with TMS under conditions of rest, ongoing voluntary activation (isometric force generation), and at variable delays following activation (postactivation) of the wrist extensors of seven normal subjects. Paired stimuli were delivered to the motor cortex with a circular coil at 1.1 times motor evoked potential (MEP) threshold, with various interstimulus intervals. Voluntary activation caused a marked decrease in the variability of the ratio of the amplitude of the MEP evoked by the test pulse to that of the MEP evoked by the conditioning pulse. Marked inhibition of the MEP evoked by the test pulse was still present. Postactivation, however, caused a dramatic reversal of the inhibitory effect of the conditioning pulse in all subjects at interstimulus intervals ranging from 40 to 120 ms. This effect lasted for up to 10 s following the cessation of activation. MEPs to transcranial electrical stimulation were also inhibited by conditioning TMS, but postactivation did not reverse this inhibition, indicating that the reversal of paired pulse inhibition is intracortical. We conjecture that paired pulse inhibition reflects activity of inhibitory interneurons or inhibitory connections between cortical output cells that are inactivated in the postactivation state.

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The role of the dorsolateral prefrontal cortex in implicit procedural learning.

We studied the role of the dorsolateral prefrontal cortex in procedural learning. Normal subjects completed several blocks of a serial reaction time task using only one hand without or with concurrent non-invasive repetitive transcranial magnetic stimulation. To disrupt their function transiently, stimulation was applied at low intensity over the supplementary motor area or over the dorsolateral prefrontal cortex contralateral or ipsilateral to the hand used for the test. Stimulation to the contralateral dorsolateral prefrontal cortex markedly impaired procedural implicit learning, as documented by the lack of significant change in response times during the task. Stimulation over the other areas did not interfere with learning. These results support the notion of a critical role of contralateral dorsolateral prefrontal structures in learning of motor sequences.

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Cortical modulation of spinal excitability: an F-wave study.

F-waves are known to be highly sensitive to changes in the excitatory state of the spinal cord. This paper describes the effects of subthreshold transcranial magnetic stimulation on the F-waves evoked in hand and foot muscles. In the abductor pollicis brevis muscle, the F-wave was significantly enhanced when the cortical stimulus was given with a delay corresponding approximately to the expected time of collision, i.e., the difference between the mean latency of the F-wave and the mean latency of the motor evoked potential. A second, usually larger facilitatory phase follows the first phase after 2-3 msec, and later peaks of enhancement often occurred. After the enhancement periods, a significant inhibition of the F-wave was usually observed. In the extensor digitorum brevis muscle, the first facilitatory phase was observed some milliseconds earlier than expected in 4 of 5 subjects, and the inhibitory phase was less pronounced. We argue that the sequential arrival of I-waves at the spinal segment could be responsible for the changes observed in the F-wave recorded from the small hand muscle. In the foot muscle, anatomical and technical factors could contribute to the generation of a D-wave. The strong inhibition observed in the F-wave recorded from the hand muscle is likely to be due to the arrival on alpha-motoneurons of inhibitory postsynaptic potentials (IPSPs) generated by the cortical stimulus. Our data show that the F-wave ia a probe for changes in the spinal cord excitatory state.

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Changes in mood and hormone levels after rapid-rate transcranial magnetic stimulation (rTMS) of the prefrontal cortex.

Rapid-rate transcranial magnetic stimulation (rTMS) was administered to 10 healthy volunteers on different days over the right or left prefrontal cortex, midfrontal cortex, occipital cortex, or cerebellum. Mood (self-rated), reaction time, and hormone levels were serially measured. Consistent with a previous study, comparison of hemispheres revealed significant associations with decreased happiness after left prefrontal rTMS and decreased sadness after right prefrontal rTMS. Stimulation of all three prefrontal regions, but not the occipital or cerebellar regions, was associated with increases in serum thyroid-stimulating hormone. There was no effect on serum prolactin. rTMS applied to prefrontal cortex is safe and well tolerated and produces regionally and laterally specific changes in mood and neuroendocrine measures in healthy adults. rTMS is a promising tool for investigating prefrontal cortex functions.

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Transcranial magnetic stimulation: a neuropsychiatric tool for the 21st century.

Neuroscientists have constantly sought new methods of evaluating brain function, with progressive improvement in the last century in imaging brain structure and function. However, except for direct surgical stimulation, neuropsychiatrists can only infer causality between the signal obtained on an image and a behavior or disease. Transcranial magnetic stimulation (TMS) is a new, noninvasive technique for directly stimulating cortical neurons. It has been used to map attention, memory, movement, speech, and vision. Preliminary investigations have also used rapid-rate TMS to improve motor speed in Parkinson's disease and mood in depression. TMS is likely to be an important future neuropsychiatric tool.

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Abnormal cortical motor excitability in dystonia.

To assess the excitability of the motor system, we studied 11 patients with task-specific dystonia and 11 age-matched normal subjects. The dominant side was affected in nine of the patients. We delivered transcranial magnetic stimuli at different stimulus intensities and with different levels of muscle facilitation to the side contralateral to the side of electromyographic recording, and recorded motor evoked potentials (MEPs) from the flexor carpi radialis muscles bilaterally. The threshold intensity for eliciting MEPs at rest did not differ between patients and normal subjects. We compared the affected side in patients with the dominant side in normal subjects. With facilitation, the percentage of the area of the MEP to the M wave (MEP area%) was similar in both groups at low stimulus intensities, but with increasing stimulus intensity the increase in the MEP area% was greater in patients than in normal subjects (ANOVA, p < 0.001). The increase in MEP area% was similar in both groups with increasing facilitation levels. The duration of the silent period was similar in patients and normal subjects. We conclude that cortical motor excitability is increased in dystonia.

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Characterization of postexercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation.

We studied the effects of exercise on motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES). Subjects performed 30-second periods of isometric exercise of the extensor carpi radialis until fatigue, which was defined as the inability to maintain half maximum force. The amplitude of MEPs to TMS recorded from the resting muscle after each exercise period was on average more than twice the pre-exercise value (postexercise MEP facilitation). After fatigue occurred, the MEP amplitudes were approximately 60% of the pre-exercise value (postexercise MEP depression). There was a gradual recovery of the depressed MEPs to pre-exercise values over several minutes of rest. Postexercise MEP facilitation was constant when exercise intensity ranged from 10 to 50% of maximum voluntary contraction and it decayed to baseline over several minutes after the end of exercise. There was no postexercise MEP facilitation to TES. We hypothesize that both postexercise MEP facilitation and MEP depression are due to intracortical mechanisms.

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Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression.

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects, 12 patients with chronic fatigue syndrome, and 10 depressed patients. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until they were unable to maintain half maximal force. MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean pre-exercise MEP amplitude in normal subjects, 126% in chronic fatigue patients, and 155% in depressed patients, indicating postexercise MEP facilitation in all three groups. The increases in the patient groups, however, were significantly lower than normal. The mean amplitudes of MEPs recorded within the first few minutes after the last exercise sets in all three groups were approximately half their mean pre-exercise MEP amplitudes. This postexercise MEP depression was similar in all groups. We conclude that postexercise cortical excitability is significantly reduced in patients with chronic fatigue syndrome and in depressed patients compared with that of normal subjects.

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Use and safety of a new repetitive transcranial magnetic stimulator.

In order to test a new repetitive transcranial magnetic stimulator, the Dantec MagPro, we administered transcranial magnetic stimulation (TMS) at 1 Hz and 125% of motor threshold for an average of 204 s (until the coil temperature reached 40 degrees C) and 20 Hz stimulation at 100% of motor threshold for 2 s every minute for 10 min, on different days to 10 healthy volunteers. We stimulated 6 scalp positions (primary motor area (M1) and sites 5 cm anterior and posterior on each hemisphere) with an 8-shaped coil. We tested immediate and delayed memory, verbal fluency, prolactin levels and EEG at the beginning of the study and after stimulation on each day. No abnormalities were found. Motor evoked potentials evoked with 1 Hz stimulation diminished progressively in amplitude, and 1 Hz stimulation of M1 caused inhibition lasting at least 1 min in 3 of 4 subjects who were tested with 0.1 Hz stimulation before and after the 1 Hz stimulation period. This did not occur with 20 Hz stimulation. Finger tapping frequency was tested at the beginning of the study and after TMS at each scalp site. Finger tapping rate data from 6 additional subjects who were stimulated in an identical fashion with a different stimulator were also analyzed. There was an increase in tapping rate after TMS which was independent of scalp site. This was most pronounced with 1 Hz stimulation at 125% of threshold and reached statistical significance in the hand contralateral to the stimulation. The results of this study indicate that rTMS with the MagPro stimulator is safe at specific combinations of intensity, frequency and train duration.

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