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Introduction: Transcranial magnetic stimulation (TMS) permits stimulation of the cerebral cortex in humans without requiring open access to the brain and is one of the newest tools available in neuroscience. There are two main types of application: single-pulse TMS and repetitive TMS., Development: The magnetic stimulator is composed of a series of capacitors that store the voltage necessary to generate a stimulus of the sufficient intensity of generate an electric field in the stimulation coil. The safety of TMS is supported by the considerable experience derived from studies involving electrical stimulation of the cortex in animals and humans, and also specific studies on the safety of TMS in humans., Conclusions: In this article we review historical and technical aspects of TMS, describe its adverse effects and how to avoid them, summarize the applications of TMS in the investigation of different cerebral functions, and discuss the possibility of using TMS for the treatment of neuropsychiatric disorders.

Transcranial magnetic stimulation (TMS) can be applied in different paradigms to obtain a measure of various aspects of cortical excitability. These different TMS paradigms provide information about different neurotransmitter systems, enhance our understanding about the pathophysiology of neuropsychiatric conditions, and in the future may be helpful as a guide for pharmacological interventions. In addition, repetitive TMS (rTMS) modulates cortical excitability beyond the duration of the rTMS trains themselves. Depending on rTMS parameters, a lasting inhibition or facilitation of cortical excitability can be induced. These effects can be demonstrated neurophysiologically or by combining rTMS with neuroimaging techniques. The effects do not remain limited to the cortical area directly targeted by rTMS, but affect a wider neural network transynaptically. Modulation of cortical excitability by rTMS may in the future be useful not only as a research tool but also as a therapeutic intervention in neurology, psychiatry, and neurorehabilitation.

Functional imaging studies of people who were blind from an early age have revealed that their primary visual cortex can be activated by Braille reading and other tactile discrimination tasks. Other studies have also shown that visual cortical areas can be activated by somatosensory input in blind subjects but not those with sight. The significance of this cross-modal plasticity is unclear, however, as it is not known whether the visual cortex can process somatosensory information in a functionally relevant way. To address this issue, we used transcranial magnetic stimulation to disrupt the function of different cortical areas in people who were blind from an early age as they identified Braille or embossed Roman letters. Transient stimulation of the occipital (visual) cortex induced errors in both tasks and distorted the tactile perceptions of blind subjects. In contrast, occipital stimulation had no effect on tactile performance in normal-sighted subjects, whereas similar stimulation is known to disrupt their visual performance. We conclude that blindness from an early age can cause the visual cortex to be recruited to a role in somatosensory processing. We propose that this cross-modal plasticity may account in part for the superior tactile perceptual abilities of blind subjects.

We studied the changes in excitability of the corticospinal projection evoked by self-induced sad and happy thoughts. Corticospinal excitability was probed using focal, single-pulse transcranial magnetic stimulation (TMS) applied to the optimal scalp position for evoking motor potentials in the contralateral first dorsal interosseus muscle. Fourteen right-handed subjects were studied while counting mentally, thinking sad thoughts, or thinking happy thoughts. In each of these three conditions TMS was applied in each subject randomly, 20 times to the right and 20 times to the left hemisphere. Sad thoughts resulted in a significant facilitation of the motor potentials evoked by left-hemispheric stimulation, while happy thoughts facilitated motor potentials evoked by right-hemispheric TMS, but decreased the amplitude of those evoked by left-hemispheric TMS. In two subjects an additional experiment using H-reflex measurements suggests that these changes are caused by changes in cortical rather than spinal excitability. These results further illustrate the lateralized control of mood in normal volunteers.

The objective of our work was to measure plasma melatonin levels in patients with Parkinson's Disease (PD) following electrical stimulation of the internal globus pallidus (GPi), and to compare these levels with groups of PD patients under drug therapy and healthy controls. The levels of melatonin were measured twice daily at 1000 and 1200. The GPi stimulation at 130 Hz lowered melatonin levels, while no changes were observed in the absence of stimulation. The melatonin levels from healthy subjects were lower than those observed in PD patients. The melatonin levels from PD patients under drug therapy were also measured during the night (2000-2400-0400) and at 0800 in order to observe their circadian changes. The Internal Globus Pallidus (GPi) stimulation was effective in lowering the melatonin levels during the day and, therefore returned these levels to those observed in normal subjects.

We report the results of serial transcranial magnetic stimulation mapping of cortical motor outputs to the face and upper extremity in a subject studied before and repeatedly after traumatic amputation of the right arm immediately below the elbow. The results of the mapping studies illustrate the time course of plastic changes in the motor cortical representation in humans following a traumatic amputation and allow the correlation of subjective perceptions of phantom limbs with the reorganization of cortical outputs.

Background: Lesion and neuroimaging studies suggest that left prefrontal lobe dysfunction is pathophysiologically linked to depression. Rapid-rate transcranial magnetic stimulation (rTMS) to prefrontal structures has a lateralised effect on mood in normal volunteers, and several preliminary studies suggest a beneficial effect of rTMS on depression. However, adequately controlled studies have not been conducted., Methods: We have studied the effects of focal rTMS on the depressive symptoms in 17 patients with medication-resistant depression of psychotic subtype. The study was designed as a multiple cross-over, randomised placebo-controlled trial. Sham rTMS and stimulation of different cortical areas were used as controls., Findings: Left dorsolateral prefrontal cortex rTMS resulted in a significant decrease in scores on the Hamilton depression rating scale HDRS (from 25.2 to 13.8) and the self-rated Beck questionnaire BQ (from 47.9 to 25.7). 11 of the 17 patients showed pronounced improvement that lasted for about 2 weeks after 5 days of daily rTMS sessions. No patient experienced any significant undesirable side-effects., Interpretation: Our findings emphasise the role of the left dorsolateral prefrontal cortex in depression, and suggest that rTMS of the left dorsolateral prefrontal cortex might become a safe, non-convulsive alternative to electroconvulsive treatment in depression.

We studied the effects of rapid-rate transcranial magnetic stimulation (rTMS) of different scalp positions on mood. Ten normal volunteers rated themselves before and after rTMS on five analog scales labeled "Tristeza" (Sadness), "Ansiedad" (Anxiety), "Alegria" (Happiness), "Cansancio" (Tiredness), and "Dolor/Malestar" (Pain/Discomfort). rTMS was applied to the right lateral prefrontal, left prefrontal, or midline frontal cortex in trains of 5 seconds' duration at 10 Hz and 110% of the subject's motor threshold intensity. Each stimulation position received 10 trains separated by a 25-second pause. No clinically apparent mood changes were evoked by rTMS to any of the scalp positions in any subject. However, left prefrontal rTMS resulted in a significant increase in the Sadness ratings (Tristeza) and a significant decrease in the Happiness ratings ("Alegria") as compared with right prefrontal and midfrontal cortex stimulation. These results show differential effects of rTMS of left and right prefrontal cortex stimulation on mood and illustrate the lateralized control of mood in normal volunteers.

We report the results of an intervention trial comparing the counseling (group A) of the general practitioner to encourage to quit smoking in dissonant smokers and an intervention based on counseling and offer of follow up at 2 and 3 weeks and at 3 and 6 months (group B). Both interventions were globally evaluated to assess the influence of the smoking habits of health professionals on the results. In the 93 group B patients there was a higher quitting rate than in group A. The rates of success after one year follow up were 26.9% and 11.9% (p less than 0.05). Forty-seven of the 152 patients were counseled by smoking physicians and 105 by non-smoking physicians; at one-year follow-up, the verified quitting rates were 10.6% and 25.7%, although the difference was not significant. It was concluded that the reinforcement of counseling by follow-up may increase the rate of quitting smoking in dissonant smokers in a primary care setting, and that the influence of the habit of the health professional can be limited through more systematic interventions.

Male adult albino rats were divided into six groups: two pinealectomized (Px); two sham-operated (Sh) and two serving as controls (C). Half of these groups were studied in daylight and the other half at night. The animals were open-field tested and then conditioned by the avoidance behavior test in the appropriate light period. No differences were observed among the groups when they were conditioned in the dark; however, the Px were conditioned significantly more rapidly than Sh or C in daylight. Intragroup comparisons between night/day conditioning showed them to be similar in Px but more rapid at night in both Sh and C. The Sh group is unique and not comparable to controls.

Pineal weight and serotonin (5-HT) and norepinephrine (NE) contents were studied in male Sprague-Dawley rats that were maintained under controlled light:dark conditions (LD 14:10; lights on 0700-2100) and that received daily subcutaneous injections of either melatonin (20 micrograms in 0.1 ml per animal) or the same volume (0.1 ml) of vehicle alone, at one of two times (0800-0900 or 1800-1900). Animals were sacrificied at four times (1000, 1400, 2000, or 2300) on the day after the last of the 7 consecutive d of injection. Pineal glands were quickly weighed and then frozen for 5-HT and NE assay by the Maickel and Miller extraction and fluorescence methods. Pineal NE content showed differences related to time of day, in confirmation of early work. But no effects attributable specifically to melatonin were found. Melatonin also failed to affect pineal 5-HT content significantly. But injection of either melatonin or vehicle at 1800-1900 led to a reduction in 5-HT content averaging 36% when sampled at either 2000 or 2300, and in comparison with animals injected at 0800-0900. It is suggested that a stresslike or zeitgeberlike effect of injections within a critical period at the end of the daily light phase can cause an earlier-than-normal daily fall in pineal 5-HT content.

Pineals from male Long-Evans rats (60-65 days old; adapted to a 0700-1900 photoperiod) were cultured for 6 h either in light (1200-1800) or in dark (1800-2400). The objective was to ascertain the effects of tryptophan (trp) and phenylalanine (phe) levels and ratios in the culture medium on melatonin levels in the pineals and their respective media. Total culture (pineal + medium) melatonin levels, determined by RIA, were similar under all conditions. However, in cultures during the early dark phase (1800-2400) lower trp:phe ratios in the medium led to lower pineal:medium ratios of melatonin content. In cultures during the late light phase (1200-1800) the trp:phe ratio had little impact on the pineal:medium distribution of melatonin. Trp:phe ratio rather than absolute level of either amino acid appeared responsible for this effect. Functionally this means that during early dark phase, but not late light phase, movement of melatonin from cultured pineal to medium is progressively facilitated by lower trp:phe ratios. It remains to be determined to what extent darkness per se and/or endogenous pineal rhythmic mechanisms have a permissive role in the action of trp:phe ratio on pineal melatonin release. A melatonin compartmentalization/release effect of these or other amino acids, or their ratios, has not been reported previously and may possibly contribute to mechanisms for melatonin's transport or release at night.