RESUMEN
It has already been described that transcutaneous spinal direct current stimulation (tsDCS) can selectively influence nociceptive evoked potentials. This study is the first aiming to prove an influence of tsDCS on pain-related evoked potentials (PREP) using concentric surface electrodes (CE), whose nociceptive specificity is still under discussion. 28 healthy subjects participated in this sham-controlled, double-blind cross-over study. All subjects underwent one session of anodal and one session of sham low-thoracic tsDCS. Before and after the intervention, PREP using CE, PREP-induced pain perception and somatosensory evoked potentials (SEP) were assessed on the right upper and lower limb. We found a decrease in PREP amplitude at the lower limb after sham stimulation, but not after anodal tsDCS, while SEP remained unchanged under all studied conditions. There was no difference between the effects of anodal tsDCS and sham stimulation on the studied parameters assessed at the upper limb. PREP-induced pain of the upper and lower limb increased after anodal tsDCS. The ability of influencing PREP using a CE at the spinal level in contrast to SEP suggests that PREP using CE follows the spinothalamic pathway and supports the assumption that it is specifically nociceptive. However, while mainly inhibitory effects on nociceptive stimuli have already been described, our results rather suggest that anodal tsDCS has a sensitizing effect. This may indicate that the mechanisms underlying the elicitation of PREP with CE are not the same as for the other nociceptive evoked potentials. The effects on the processing of different types of painful stimuli should be directly compared in future studies.
Asunto(s)
Estimulación Eléctrica Transcutánea del Nervio , Humanos , Voluntarios Sanos , Estudios Cruzados , Estimulación Eléctrica Transcutánea del Nervio/métodos , Dolor , Potenciales Evocados Somatosensoriales , Electrodos , Médula Espinal/fisiología , Potenciales Evocados Motores/fisiologíaRESUMEN
Perception is subject to ongoing alterations by learning and top-down influences. Although abundant studies have shown modulation of perception by attention, motivation, content and context, there is an unresolved controversy whether these examples provide true evidence that perception is penetrable by cognition. Here we show that tactile perception assessed as spatial discrimination can be instantaneously and systematically altered merely by the semantic content during hypnotic suggestions. To study neurophysiological correlates, we recorded EEG and SEPs. We found that the suggestion "your index finger becomes bigger" led to improved tactile discrimination, while the suggestion "your index finger becomes smaller" led to impaired discrimination. A hypnosis without semantic suggestions had no effect but caused a reduction of phase-locking synchronization of the beta frequency band between medial frontal cortex and the finger representation in somatosensory cortex. Late SEP components (P80-N140 complex) implicated in attentional processes were altered by the semantic contents, but processing of afferent inputs in SI remained unaltered. These data provide evidence that the psychophysically observed modifiability of tactile perception by semantic contents is not simply due to altered perception-based judgments, but instead is a consequence of modified perceptual processes which change the perceptual experience.
Asunto(s)
Semántica , Percepción del Tacto , Percepción del Tacto/fisiología , Sugestión , Tacto , Corteza Somatosensorial/fisiologíaRESUMEN
Transcutaneous spinal direct current stimulation (tsDCS) is a safe and convenient method of neuromodulation. It has been proven to alter sensory processing at cervicomedullary level by amplitude changes of the P30 response of tibial nerve somatosensory evoked potentials (TN SEPs). With knowledge that tsDCS affects cortical circuits, we hypothesized that tsDCS may also affect intracortical excitability of the somatosensory cortex assessed by paired stimulation suppression (PSS). Fourteen healthy men were included in this prospective, single-blinded, placebo-controlled crossover study. Single (SS) and paired stimulation (PS) TN SEPs were recorded over the scalp before, immediately as well as 30 and 60 min after applying 15 min of tsDCS over the twelfth thoracic vertebra. Each volunteer underwent three independent and randomized sessions of either cathodal, anodal or sham stimulation. tsDCS showed no effect on peak-to-peak amplitudes or latencies of cortical P40-N50 response after SS. Furthermore, tsDCS failed to induce significant changes on amplitude ratios of PSS, thus showing no impact on intracortical excitability of the somatosensory cortex in healthy subjects. Further research is required to reveal the different mechanisms and to strengthen clinical use of this promising technique.
Asunto(s)
Corteza Somatosensorial/fisiología , Columna Vertebral/fisiología , Estimulación Eléctrica Transcutánea del Nervio , Potenciales Evocados Somatosensoriales/fisiología , Humanos , Masculino , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
INTRODUCTION: Our hands are the primary means for motor interaction with the environment, and their neural organization is fundamentally asymmetric: While most individuals can perform easy motor tasks with two hands equally well, only very few individuals can perform complex fine motor tasks with both hands at a similar level of performance. The reason why this phenomenon is so rare is not well understood. Professional drummers represent a unique population to study it, as they have remarkable abilities to perform complex motor tasks with their two limbs independently. METHODS: Here, we used a multimethod neuroimaging approach to investigate the structural, functional, and biochemical correlates of fine motor behavior in professional drummers (n = 20) and nonmusical controls (n = 24). RESULTS: Our results show that drummers have higher microstructural diffusion properties in the corpus callosum than controls. This parameter also predicts drumming performance and GABA levels in the motor cortex. Moreover, drummers show less activation in the motor cortex when performing a finger-tapping task than controls. CONCLUSION: In conclusion, professional drumming is associated with a more efficient neuronal design of cortical motor areas as well as a stronger link between commissural structure and biochemical parameters associated with motor inhibition.
Asunto(s)
Cuerpo Calloso/diagnóstico por imagen , Corteza Motora/metabolismo , Desempeño Psicomotor/fisiología , Ácido gamma-Aminobutírico/metabolismo , Adulto , Neuroimagen Funcional/métodos , Mano/fisiología , Humanos , Masculino , Actividad Motora/fisiología , Música , Profesionalismo , Análisis Espectral/métodosRESUMEN
BACKGROUND: Repetitive sensory stimulation (RSS) adapts the timing of stimulation protocols used in cellular studies to induce synaptic plasticity. In healthy subjects, RSS leads to widespread sensorimotor cortical reorganization paralleled by improved sensorimotor behavior. Here, we investigated whether RSS reduces sensorimotor upper limb impairment in patients with subacute stroke more effectively than conventional therapy. METHODS: A single-blinded sham-controlled clinical trial assessed the effectiveness of RSS in treating sensorimotor deficits of the upper limbs. Patients with subacute unilateral ischemic stroke were randomly assigned to receive standard therapy in combination with RSS or with sham RSS. Patients were masked to treatment allocation. RSS consisted of intermittent 20 Hz electrical stimulation applied on the affected hand for 45 min/day, 5 days per week, for 2 weeks, and was transmitted using custom-made stimulation-gloves with built-in electrodes contacting each fingertip separately. Before and after the intervention, we assessed light-touch and tactile discrimination, proprioception, dexterity, grip force, and subtasks of the Jebsen Taylor hand-function test for the non-affected and the affected hand. Data from these quantitative tests were combined into a total performance index serving as primary outcome measure. In addition, tolerability and side effects of RSS intervention were recorded. RESULTS: Seventy one eligible patients were enrolled and randomly assigned to receive RSS treatment (n = 35) or sham RSS (n = 36). Data of 25 patients were not completed because they were transferred to another hospital, resulting in n = 23 for each group. Before treatment, sensorimotor performance between groups was balanced (p = 0.237). After 2 weeks of the intervention, patients in the group receiving standard therapy with RSS showed significantly better restored sensorimotor function than the control group (standardized mean difference 0.57; 95% CI -0.013-1.16; p = 0.027) RSS treatment was superior in all domains tested. Repetitive sensory stimulation was well tolerated and accepted, and no adverse events were observed. CONCLUSIONS: Rehabilitation including RSS enhanced sensorimotor recovery more effectively than standard therapy alone. Rehabilitation outcome between the effects of RSS and standard therapy was largest for sensory and motor improvement; however, the results for proprioception and everyday tasks were encouraging warranting further studies in more severe patients. TRIAL REGISTRATION: The trial was retrospectively registered January 31, 2012 under DRKS00003515 ( https://www.drks.de/drks_web/navigate.do;jsessionid=AEE2585CCB82A22A2B285470B37C47C8?navigationId=results ).
Asunto(s)
Terapia por Estimulación Eléctrica , Mano/fisiopatología , Paresia/fisiopatología , Paresia/rehabilitación , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/fisiopatología , Humanos , Resultado del TratamientoRESUMEN
Transcutaneous spinal direct current stimulation (tsDCS) is a noninvasive method that can modulate spinal reflexes, sensory afferent conduction, and even pain perception. Although neurophysiological evidence suggests that tsDCS alters somatosensory and nociceptive afferent conduction to the cortex, its supraspinal effects have not yet been investigated by using functional imaging to investigate tsDCS-induced alterations in intrinsic functional connectivity (FC). Therefore, we hypothesize that tsDCS-induced changes in neurophysiological measures might also be reflected in spontaneous brain activity. We investigated tsDCS-induced changes in somatosensory cortical connectivity by using seed-to-voxel-based analyses from the bilateral primary somatosensory cortex (S1) and the thalamus in a double-blind, crossover study design. Resting state FC was measured by using blood oxygenation level-dependent, functional magnetic resonance imaging (3T Philips) before and after anodal, cathodal, and sham tsDCS (20 min, 2.5 mA, active electrode centered over T11 spinous process, reference electrode over left shoulder blade) in a double-blind, crossover study of 20 healthy men (24 ± 0.7 years). As compared with sham, anodal tsDCS resulted in a decreased connectivity between the S1 and the ipsilateral posterior insula for both left and right hemispheres. Anodal tsDCS also resulted in decreased thalamic connectivity with the anterior cingulate cortex, and increased connectivity between S1 and the thalamus. Cathodal tsDCS showed increased FC between the right thalamus and both left and right posterior insulae, and decreased connectivity between the S1 seeds and the occipital cortex. Our results provide evidence of supraspinal effects of tsDCS and suggest that tsDCS may provide a noninvasive intervention that is able to target cortical sensory networks.
Asunto(s)
Corteza Cerebral/fisiología , Estimulación de la Médula Espinal , Tálamo/fisiología , Estimulación Eléctrica Transcutánea del Nervio , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Estudios Cruzados , Método Doble Ciego , Lateralidad Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Oxígeno/sangre , Descanso , Tálamo/diagnóstico por imagen , Adulto JovenRESUMEN
UNLABELLED: Techniques employed in rehabilitation of visual field disorders such as hemianopia are usually based on either visual or audio-visual stimulation and patients have to perform a training task. Here we present results from a completely different, novel approach that was based on passive unimodal auditory stimulation. Ten patients with either left or right-sided pure hemianopia (without neglect) received one hour of unilateral passive auditory stimulation on either their anopic or their intact side by application of repetitive trains of sound pulses emitted simultaneously via two loudspeakers. Immediately before and after passive auditory stimulation as well as after a period of recovery, patients completed a simple visual task requiring detection of light flashes presented along the horizontal plane in total darkness. The results showed that one-time passive auditory stimulation on the side of the blind, but not of the intact, hemifield of patients with hemianopia induced an improvement in visual detections by almost 100% within 30 min after passive auditory stimulation. This enhancement in performance was reversible and was reduced to baseline 1.5 h later. A non-significant trend of a shift of the visual field border toward the blind hemifield was obtained after passive auditory stimulation. These results are compatible with the view that passive auditory stimulation elicited some activation of the residual visual pathways, which are known to be multisensory and may also be sensitive to unimodal auditory stimuli as were used here. TRIAL REGISTRATION: DRKS00003577.
Asunto(s)
Estimulación Acústica , Hemianopsia/fisiopatología , Hemianopsia/terapia , Visión Ocular/fisiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Campos Visuales , Adulto JovenRESUMEN
Age-related changes occur on all stages of the human somatosensory pathway, thereby deteriorating tactile, haptic, and sensorimotor performance. However, recent studies show that age-related changes are not irreversible but treatable through peripheral stimulation paradigms based on neuroplasticity mechanisms. We here applied repetitive electric stimulation (rES) to the fingers on a bi-weekly basis for 4 weeks to induce enduring amelioration of age-related changes in healthy individuals aged 60-85 years. Tactile, haptic, and motor performance gradually improved over time of intervention. After termination of rES, tactile acuity recovered to baseline within 2 weeks, while the gains in haptic and motor performance were preserved for 2 weeks. Sham stimulation showed no comparable changes. Our data indicate that age-related decline of sensorimotor performance can be ameliorated by rES and can be stabilized by the repeated application. Thus, long-term application of rES appears as a prime candidate for maintaining sensorimotor functions in elderly individuals.
Asunto(s)
Envejecimiento/fisiología , Terapia por Estimulación Eléctrica/métodos , Trastornos del Movimiento/terapia , Trastornos de la Sensación/terapia , Vías Aferentes/fisiología , Anciano , Encéfalo/fisiología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/terapia , Aprendizaje Discriminativo/fisiología , Retroalimentación Sensorial/fisiología , Femenino , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/terapia , Humanos , Masculino , Destreza Motora/fisiología , Movimiento/fisiología , Trastornos del Movimiento/etiología , Trastornos del Movimiento/fisiopatología , Plasticidad Neuronal/fisiología , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología , Trastornos de la Sensación/etiología , Trastornos de la Sensación/fisiopatología , Células Receptoras Sensoriales/fisiología , Tacto/fisiología , Percepción del Tacto/fisiología , Resultado del TratamientoRESUMEN
Sound localization was investigated in patients with homonymous hemianopia, a visual field defect characterized by a loss of vision in one hemifield that is caused by unilateral brain lesions involving the visual cortex or its afferents. The primary aim was to clarify whether or not the known distortion of visual space in hemianopia results in processes of long-term cross-modal spatial adaptation, thus eventually inducing related alterations in auditory space perception. For this purpose, patients were tested by using tasks of either head pointing or manual pointing to acoustic targets in the azimuthal plane, under anechoic conditions in total darkness. The results obtained with both tasks consistently indicated slight, but significant, systematic errors compared with normal controls. In particular, the errors found can be interpreted by both rotation and compression of auditory space toward the anopic side. These findings can be explained by a visual miscalibration of the auditory space, as has been analogously demonstrated in studies on normal-sighted subjects after exposure to consistent auditory-visual disparity, for example by wearing prism lenses. The precision in sound localization of hemianopic patients was generally reduced across both hemispaces. Taken together, one may conclude that processes of cross-modal spatial adaptation, but not those of compensatory plasticity, occurred in patients with hemianopia.
Asunto(s)
Hemianopsia , Localización de Sonidos , Estimulación Acústica , Adulto , Percepción Auditiva , Oscuridad , Femenino , Mano , Cabeza , Humanos , Masculino , Persona de Mediana Edad , Psicoacústica , Rotación , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
Several studies have shown that patients with schizophrenia underactivate brain regions involved in theory of mind relative to controls during functional brain imaging. However, in most studies the samples were fairly heterogeneous in terms of clinical symptomatology. We examined a group of nine patients with first episode or recurrent episodes, who clinically presented with predominant "passivity" symptoms such as third-person auditory hallucinations or delusion of control, using a cartoon-based theory of mind task and compared activation patterns with a group of 13 healthy controls. All patients responded well to antipsychotic treatment and were only mildly symptomatic at the time of testing. The patient group showed significantly less activation of the right anterior cingulate cortex (ACC) and right insula compared with controls, but greater activation in dorsal areas of the medial prefrontal cortex, right temporal areas and left temporo-parietal junction. Patients with schizophrenia with predominant "passivity" symptoms and good response to antipsychotic treatment show a markedly diverging pattern of brain activation during theory of mind task performance compared with healthy controls. These findings suggest abnormal activation of those brain areas involved in the evaluation of self-reference during mental state attribution.
Asunto(s)
Corteza Cerebral/fisiopatología , Emociones , Expresión Facial , Imagen por Resonancia Magnética/estadística & datos numéricos , Reconocimiento en Psicología/fisiología , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Percepción Visual/fisiología , Adulto , Antipsicóticos/uso terapéutico , Grupos Control , Deluciones/fisiopatología , Emociones/fisiología , Femenino , Lateralidad Funcional/fisiología , Alucinaciones/fisiopatología , Humanos , Masculino , Modelos Neurológicos , Vías Nerviosas/fisiología , Pruebas Neuropsicológicas/estadística & datos numéricos , Reconocimiento Visual de Modelos/fisiología , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/fisiopatología , Percepción Social , Tálamo/fisiopatología , Insuficiencia del TratamientoRESUMEN
Sensorimotor functions decrease in old age. The well-documented loss of tactile acuity in elderly is accompanied by deterioration ofhaptic performance and fine manipulative movements. Physical training and exercise can maintain sensorimotor fitness into high age. However, regular schedules of training require discipline and physical fitness. We here present an alternative interventional paradigm to enhance tactile, haptic, and fine motor performance based on passive, sensory stimulation by means of tactile coactivation. This approach is based on patterned, synchronous tactile stimulation applied to the fingertips for 3 hours. The stimulation drives plastic reorganizational changes in somatosensory cortex that affect perception and behavior: We demonstrate that following 3 hours of coactivation tactile acuity as well as haptic object exploration and fine motor performance are improved for at least 96 hours. Because this kind of intervention does not require active participation or attention of the subjects, we anticipate that coactivation is a prime candidate for future therapeutic interventions in patients with impaired sensorimotor abilities. It can be assumed that the maintenance and restoration of sensorimotor functions can ensure and preserve independence of daily living. Further optimizing of the stimulation protocol can be assumed to strengthen both the range and durability of its efficacy.
Asunto(s)
Envejecimiento/fisiología , Destreza Motora/fisiología , Manipulaciones Musculoesqueléticas/métodos , Trastornos Psicomotores/terapia , Percepción del Tacto/fisiología , Anciano , Condicionamiento Psicológico , Aprendizaje Discriminativo , Femenino , Dedos/fisiología , Humanos , Masculino , Estimulación Física/métodos , Umbral Sensorial/fisiologíaRESUMEN
Acupuncture treatment is frequently sought for tension-type headache (TTH), but there is conflicting evidence as to its effectiveness. This randomised, controlled, multicentre, patient-and observer-blinded trial was carried out in 122 outpatient practices in Germany on 409 patients with TTH, defined as > or =10 headache days per month of which < or =1 included migraine symptoms. Interventions were verum acupuncture according to the practice of traditional Chinese medicine or sham acupuncture consisting of superficial needling at nonacupuncture points. Acupuncture was administered by physicians with specialist acupuncture training. Ten 30-min sessions were given over a six-week period, with additional sessions available for partial response. Response was defined as >50% reduction in headache days/month at six months and no use of excluded concomitant medication or other therapies. In the intent-to-treat analysis (all 409 patients), 33% of verum patients and 27% of sham controls (p=0.18) were classed as responders. Verum was superior to sham for most secondary endpoints, including headache days (1.8 fewer; 95% CI 0.6, 3.0; p=0.004) and the International Headache Society response criterion (66% vs. 55% response, risk difference 12%, 95% CI: 2%-21%; p=0.024).). The relative risk on the primary and secondary response criterion was very similar ( approximately 0.8); the difference in statistical significance may be due to differences in event rate. TTH improves after acupuncture treatment. However, the degree to which treatment benefits depend on psychological compared to physiological effects and the degree to which any physiological effects depend on needle placement and insertion depth are unclear.
Asunto(s)
Analgesia por Acupuntura/métodos , Puntos de Acupuntura , Músculo Esquelético/fisiopatología , Cefalea de Tipo Tensional/terapia , Analgesia por Acupuntura/efectos adversos , Adulto , Método Doble Ciego , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Efecto Placebo , Recurrencia , Factores de Riesgo , Cefalea de Tipo Tensional/prevención & control , Cefalea de Tipo Tensional/psicología , Resultado del TratamientoRESUMEN
BACKGROUND: Our aim was to assess the efficacy of a part-standardised verum acupuncture procedure, in accordance with the rules of traditional Chinese medicine, compared with that of part-standardised sham acupuncture and standard migraine prophylaxis with beta blockers, calcium-channel blockers, or antiepileptic drugs in the reduction of migraine days 26 weeks after the start of treatment. METHODS: This study was a prospective, randomised, multicentre, double-blind, parallel-group, controlled, clinical trial, undertaken between April 2002 and July 2005. Patients who had two to six migraine attacks per month were randomly assigned verum acupuncture (n=313), sham acupuncture (n=339), or standard therapy (n=308). Patients received ten sessions of acupuncture treatment in 6 weeks or continuous prophylaxis with drugs. Primary outcome was the difference in migraine days between 4 weeks before randomisation and weeks 23-26 after randomisation. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN52683557. FINDINGS: Of 1295 patients screened, 960 were randomly assigned to a treatment group. Immediately after randomisation, 125 patients (106 from the standard group) withdrew their consent to study participation. 794 patients were analysed in the intention-to-treat popoulation and 443 in the per-protocol population. The primary outcome showed a mean reduction of 2 .3 days (95% CI 1.9-2.7) in the verum acupuncture group, 1.5 days (1.1-2.0) in the sham acupuncture group, and 2.1 days (1.5-2.7) in the standard therapy group. These differences were statistically significant compared with baseline (p<0.0001), but not across the treatment groups (p=0.09). The proportion of responders, defined as patients with a reduction of migraine days by at least 50%, 26 weeks after randomisation, was 47% in the verum group, 39% in the sham acupuncture group, and 40% in the standard group (p=0.133). INTERPRETATION: Treatment outcomes for migraine do not differ between patients treated with sham acupuncture, verum acupuncture, or standard therapy.
Asunto(s)
Terapia por Acupuntura/métodos , Trastornos Migrañosos/prevención & control , Adolescente , Adulto , Anciano , Intervalos de Confianza , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In complex regional pain syndrome (CRPS) many clinical symptoms suggest involvement of the central nervous system. Neuropathic pain as the leading symptom is often resistant to therapy. In the present study we investigated the analgesic efficiency of repetitive transcranial magnetic simulation (rTMS) applied to the motor cortex contralateral to the CRPS-affected side. Seven out of ten patients reported decreased pain intensities. Pain relief occurred 30 s after stimulation, whereas the maximum effect was found 15 min later. Pain re-intensified increasingly 45 min after rTMS. In contrast, sham rTMS did not alter pain perception. These findings provide evidence that in CRPS I pain perception can be modulated by repetitive motor cortex stimulation.
Asunto(s)
Terapia por Estimulación Eléctrica , Corteza Motora/fisiología , Manejo del Dolor , Distrofia Simpática Refleja/terapia , Estimulación Magnética Transcraneal , Adulto , Anciano , Terapia por Estimulación Eléctrica/métodos , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Dolor/fisiopatología , Dimensión del Dolor , Percepción/fisiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
A combination of 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the left primary somatosensory cortex together with tactile coactivation applied to the right index-finger representation (coac + rTMS) boosted tactile discrimination ability tested on the right index-finger. Applying coactivation alone caused a 0.25 mm lowering in tactile discrimination thresholds. In contrast, after coac + rTMS we found a significant further improvement of discrimination thresholds in comparison to the coactivation-induced perceptual changes alone. We demonstrate that the individual further improvement after coac + rTMS depended on the effectiveness of the coactivation protocol when applied alone. Subjects, who showed little gain in tactile performance after coactivation alone, showed the largest improvement after coac + rTMS implying that the combined application was selective for poor learners. The selective effects of coac + rTMS are discussed in respect to N-methyl-D-aspartate receptor activation.