Two evoked responses with different recovery functions in the primary somatosensory cortex in humans.

OBJECTIVES: We investigated the recovery function of somatosensory evoked magnetic cortical fields (SEFs) to confirm the temporal aspects of the somatosensory process in humans. METHODS: SEFs were recorded following median nerve electrical stimulation in 6 healthy subjects. Double stimulation, with interstimulus intervals (ISIs) from 3 to 100 ms, was applied, and the SEF components for the second stimulation were analyzed. In a supplementary experiment, responses to single stimulations of various intensities from the sensory threshold to the motor threshold were studied. RESULTS: The first SEF component (1M) diminished when the ISI was less than 10 ms, while the second component (2M) remained even when the ISI was 3 ms. The two components showed a very similar attenuation with decrease of stimulus intensity. There was no significant difference in dipole location between 1M and 2M in the primary somatosensory cortex (SI). CONCLUSIONS: The results suggested that at least two independent pathways with different recovery functions exist in a similar area in the SI.     

The effects of focal epileptic activity on the somatosensory evoked potentials in the rat

Summary The cortical somatosensory evoked potential (SEP) of the rat, evoked by contralateral forepaw stimulation, consisted of early (P 1 and N 1) and late components (P 2 and N 2). Microelectrode recording yielded evoked unitary responses of short latencies in the range of the early components and responses of longer latencies in the range of P 2. During the development of focal epilepsy after topical application of penicillin, the late components of SEP were enhanced and the enhanced late negativity corresponded to a surface negative cortical spike. The prominent enlargement of later components was associated with prolonged, often recurrent discharges of longer latency unitary responses and with enlarged local field potentials. Early components of SEP remained relatively unaffected and so did unitary responses with short latencies.Epileptic spike-conditioned SEPs in the cuneate nucleus, thalamic sensory relay nucleus and sensory cortex were depressed from 100 ms (cuneate nucleus) to about 300 ms (thalamus and cortex) subsequent to spike discharge. Transmission in the cuneate nucleus was least affected. Thalamic and cortical early components of SEP had similar time courses of recovery, which differed markedly from that of cortical late components. Our findings suggest that two different neuronal activities generate different components of SEP and are differentially involved in the epileptic activities, which results in the different amplitude recovery following spontaneous epileptic spike discharges.This work was supported by the Deutsche Forschungsgemeinschaft (German Research Council)     

Correspondence between short-latency somatosensory evoked brain potentials and cortical magnetic fields following median nerve stimulation

We investigated the somatosensory evoked cortical magnetic field (SEF) components corresponding to the somatosensory evoked potential (SEP) components between 20 and 30 ms after median nerve stimulation. SEP and SEF were simultaneously recorded after right median nerve stimulation in seven healthy subjects. Twenty single-sweep epochs of SEF and SEP were selected, in which the first SEF component at 20 ms, 1M, and the second component at 30 ms, 2M, were identifiable. The selected epochs were re-averaged at the peaks of 1M and 2M as the triggering periods (zero ms). The width of the deflection, the temporal dispersion (TD), of SEP components, P20 and N30 (Fz-A2), N20, cP25 and cN30 (C3-Fz), N20 and pP30 (P3-A2), and N20 and P30 (P3-Fz), were compared between three averaging conditions. The N20/P20 components showed significantly smaller TDs when the epochs were averaged at the 1M peak (one-way factorial ANOVA, P<0.02) than those of the control, but averaging at the 1M peak did not decrease the TD of N30/P30. On averaging at the 2M peak, the TDs of N30/P30 components recorded from Fz-A2 and P3-Fz were smaller than those of the control. Neither the averaging at the 1M peak nor that at the 2M peak decreased the TD of the cP25 and cN30 components. Source analysis showed that the equivalent current dipoles (ECDs) for both 1M and 2M were located around the central sulcus, possibly in the primary somatosensory cortex (SI). We confirmed that the 1M and 2M temporally linked with N20/P20 and N30/P30, respectively. The difference of TD of N20/P20 and N30/P30 indicated that the neural pathways to the responses to N20/P20 and N30/P30 might be independent.     

Effects of distraction on pain-related somatosensory evoked magnetic fields and potentials following painful electrical stimulation

We aimed to compare the effects of distraction on pain-related somatosensory evoked magnetic fields (pain SEF) following painful electrical stimulation with simultaneous recordings of evoked potentials (pain SEP). Painful electrical stimuli were applied to the right index finger of eleven healthy subjects. A table with 25 random two-digit numbers was shown to the subjects, who were asked to add 5 numbers of each line in their mind (calculation task) or to memorize the numbers (memorization task) during the recording. In the SEF recording, 3 short-latency components within 50 ms of the stimulation were generated in the primary sensory cortex (SI) of the hemisphere contralateral to the stimulated finger. Middle-latency components between 100 and 250 ms after the stimuli were recorded from the secondary somatosensory cortex (SII) in the bilateral hemispheres or the cingulate cortex. No SEF components were significantly affected by either task. In the SEP recording, the middle-latency components (N140 and P230) were identified as being maximal around the vertex. Amplitudes of the N140 and P230 were not affected by each task, but the peak-to-peak amplitude (N140-P230) was significantly decreased by both the calculation and memorization tasks, particularly by the former. Subjective pain rating was decreased in both the calculation and memorization tasks, particularly in the former. We concluded that distraction tasks reduced activities in the limbic system, in which the middle-latency EEG component probably generated, while neither the short-latency SEF components generated in SI nor the primary pain-related SEF components generated in SII-insula are affected.     

Maturation of somatosensory cortical processing from birth to adulthood revealed by magnetoencephalography

ObjectiveTo evaluate the maturation of tactile processing by recording somatosensory evoked magnetic fields (SEFs) from healthy human subjects.MethodsSEFs to tactile stimulation of the left index finger were measured from the contralateral somatosensory cortex with magnetoencephalography (MEG) in five age groups: newborns, 6- and 12–18-month-olds, 1.6–6-year-olds, and adults. The waveforms of the measured signals and equivalent current dipoles (ECDs) were analyzed in awake and sleep states in order to separate the effects of age and vigilance state on SEFs.ResultsThere was an orderly, systematic change in the measured and ECD source waveforms of the initial cortical responses with age. The broad U-shaped response in newborns (M60) shifted to a W-shaped response with emergence of a notch by 6 months of age. The adult-type response with M30 and M50 components was present by 2 years. The ECDs of M60 and M30 were oriented anteriorly and that of M50 posteriorly. These maturational changes were independent of vigilance state.ConclusionsThe most significant maturation of short latency cortical responses to tactile stimulation takes place during the first 2 years of life.SignificanceThe maturational changes of somatosensory processing can noninvasively be evaluated with MEG already in infancy.     

Effects of edrophonium bromide on neuromuscular transmission in a healthy human subject

Regional intravenous injections of different amounts (1-3 mg) of edrophonium were given to the hand of a healthy subject. The earliest change was a small negative deflection occurring at the end of the muscle response evoked by nerve stimulation, due to repetitive activity. It did not occur after a second stimulus at 30 ms or immediately after 10 s maximum voluntary contraction. Repetitive stimulation at 0.5 Hz reduced the repetitive activity. With a higher dose of edrophonium the response to a second shock (M2) at 30 ms was reduced in amplitude, but M2 at 80 ms was unaffected. An even larger dose caused depression of M2 at 80 ms also and a decremental response to 50 Hz stimulation. The amplitude of the response to a single shock was unchanged throughout.     

The P18 component of the median nerve SEP recorded from a posterior to anterior neck montage

Objective

To investigate the P18 component in the posterior to anterior neck montage after median nerve stimulation.

Methods

Somatosensory evoked potentials, through electrical wrist stimulation, were collected. In 12 subjects, the presence of the P18 component was evaluated in the posterior to anterior neck montage. In 10 subjects, the effects of simultaneous vibration of the hand were evaluated. In five subjects, responses after double-pulse stimulation (ISI 20 ms) were evaluated.

Results

The P18 component was identified in all subjects. Vibration reduced the amplitude of all components except the P18 and N18. Double-pulse stimulation reduced the amplitude of the P18 and the N18 components without significantly changing the amplitude of the other components.

Conclusions

The posterior to anterior neck montage allows for recording the P18 component. The amplitude reduction of all components during vibration, except N18 and P18, is interpreted as reflecting inhibitory activities at the cuneiform nucleus and at the segmental dorsal horn of the spinal cord, respectively. The reduction in the P18 component after double-pulse stimulation is compatible with previous observations on the positive component of cord dorsum potentials.

Significance

Studying this component may add to the knowledge of the function of the spinal cord in humans.     

An analysis of the human brain stem auditory evoked response yielding new criteria for defining its abnormality

The human brain stem auditory evoked response (BAER) is analysed into 3 main constituent components: a slow background wave, a repetitive wave, and a 3rd (delayed) component which is of relatively short duration, and which does not begin until about 5 ms after the click stimulus. In a group of responses from healthy subjects, the amplitude and latency variabilities of the delayed component are found to be small. In the BAER, as usually recorded from vertex-ipsilateral earlobe electrodes, the peaks I, II, III, IV and VI are identified with the crests of the repetitive wave. Based on this correlation, it is suggested that these peaks may be generated from a common source. Existing criteria for defining abnormality of the BAER are interpreted in terms of the constituent components found from the analysis. New criteria are proposed which involve the amplitudes and latencies of these components.     

Altered response to repetitive transcranial magnetic stimulation in patients with chronic primary insomnia

BackgroundWe aimed at evaluating the amplitude changes of the motor evoked potentials (MEPs) induced by of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) in10 patients with primary insomnia (PI) and in 10 age-matched healthy controls.MethodsMedian peak-to-peak MEP amplitudes were assessed in all subjects at three times: at baseline (T₀), after the first train of a single rTMS session (T₁), and after the whole rTMS procedure (T₂). This consists of 20 trains of 1 Hz stimulation with 50 stimuli per train and an intertrain interval of 30 s.ResultsResting motor threshold (RMT) and MEPs amplitude did not differ between the two groups at T₀. A reduction of MEP size was observed at both T₁ and T₂ in all subjects, but this was significantly less pronounced in patients than in control subjects.ConclusionsThe lack of MEP inhibition reflects an altered response to LF rTMS in patients with PI. These rTMS findings are indicative of an altered cortical plasticity in inhibitory circuits within M1 in PI. Subjects with PI exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus providing further support to the involvement of GABA neurotransmission in the pathophysiology of PI.     

Head extensor reflex evoked by trigeminal stimulation in humans.

OBJECTIVE: Excitatory and inhibitory responses have been recognized in human cervical muscles following trigeminal stimulation. However, no evidence has so far been published of a crossed, short-latency, excitatory response resembling the early head extensor reflex seen in the cat. We seek its existence in humans. METHODS: The study was carried out in 14 voluntary healthy subjects. Percutaneous and surface electrical stimulation of the supraorbital and infraorbital nerves was performed with single, double and repetitive stimuli. Signals were recorded from the relaxed splenius and sternomastoid muscles bilaterally. RESULTS: Percutaneous stimulation of infraorbital nerve with single stimuli evoked an early response in the contralateral splenius muscle, with onset latency ranging from 11 to 14 ms (HR1). This response was greatly facilitated by double or repetitive stimuli. Single stimuli also gave rise to two larger responses in all 4 muscles in the latency ranges 50-70 ms (HR2) and 100-160 ms (HR3). Surface stimulation of one nerve alone could not elicit any early activity. Single surface stimuli delivered simultaneously to the supraorbital and infraorbital nerves evoked HR1 in only 5 subjects. CONCLUSIONS: We detected a crossed early reflex of the head extensor muscles to trigeminal stimuli. Its timing is similar to the 8-ms response seen in cats. The evidence provided suggests that the reflex is mediated by an oligosynaptic circuit and that it needs a strong spatial summation at central synapses.     

Acute and chronic effects of ethanol on cortical excitability.

OBJECTIVE: We designed this study to find out whether 5Hz repetitive transcranial magnetic stimulation (rTMS) would disclose changes in cortical plasticity after acute intake of ethanol and in patients with chronic alcohol consumption. METHODS: Ten stimuli-5Hz-rTMS trains were applied over the primary motor cortex in 10 healthy subjects before and after acute ethanol intake and in 13 patients with chronic ethanol abuse, but negative blood ethanol levels when studied. The motor evoked potential (MEP) amplitude and the cortical silent period (CSP) duration during the course of rTMS trains were measured. Short-interval intracortical inhibition (3ms) and intracortical facilitation (10ms) were studied by paired-pulse TMS in 4 healthy subjects and 4 patients. RESULTS: In healthy subjects before and after acute ethanol intake, 5Hz-rTMS produced a significant increase in the MEP size and CSP duration during rTMS. The first CSP in the train was significantly longer after than before ethanol intake. In patients 5Hz-rTMS failed to produce the normal MEP facilitation but left the CSP increase unchanged. CONCLUSIONS: Acute and chronic ethanol intake alters cortical excitability and short-term plasticity of the primary motor cortex as tested by the MEP size facilitation and CSP lengthening after 5Hz-rTMS. SIGNIFICANCE: This finding suggests that rTMS is a valid tool for investigating the effects of ethanol on cortical plasticity in humans.     

Activity-Dependent Changes in Rat Ventral Horn Neurons in vitro; Summation of Prolonged Afferent Evoked Postsynaptic Depolarizations Produce a d-2-Amino-5-Phosphonovaleric Acid Sensitive Windup

The synaptic responses of lumbar ventral horn neurons including identified flexor motoneurons, to graded stimulation of peripheral nerves have been recorded in vitro in the young rat spinal cord-hindlimb preparation. Single shock stimulation of low threshold myelinated afferents evoked short latency (< 20 ms) short duration (< 1.0 s, 391 +/- 42 ms n=43 SEM) compositive mono- and polysynaptic potentials. Recruitment of both thinly myelinated (A delta) and unmyelinated (C) afferent fibres elicited a prolonged postsynaptic depolarization (> 1 s) in all cells. In the majority of cells (67.4%), this depolarization exceeded 4.0 s in duration (8.01 +/- 0.4 s, n=26, maximum 14 s). In the remainder, shorter responses were evoked (< 3.0 s, mean=1.74 +/- 0.4 s, n=18). In those cells where the postsynaptic response to a single A delta or C fibre strength stimulus exceeded 4 s, low frequency (0.5 - 1.0 Hz) repetitive stimulation resulted in a temporal summation of the postsynaptic depolarizations, which generated a cumulatively increasing depolarization. This incrementing depolarization was sufficient in 33% of the cells to produce a progressive increase in spike discharge (windup). On cessation of the train of stimuli the depolarization decayed slowly (65 +/- 27 s). The N-methyl d-aspartic acid (NMDA) receptor antagonist d-2-amino-5-phosphonovaleric acid (d-APV) reduced the duration and amplitude of the prolonged postsynaptic depolarizations elicited by a single shock stimulation of small diameter afferents by 57% and 50% respectively. A smaller effect was produced on the low threshold afferent evoked early excitatory postsynaptic potentials (EPSP) (3% decrease in amplitude and 24% decrease in duration). In the presence of d-APV the cumulatively incrementing depolarization produced by repetitive stimulation was substantially reduced and windup failed to occur. Activity-dependent amplifications of primary afferent evoked responses in spinal neurons therefore involves a temporal summation of d-APV sensitive prolonged postsynaptic depolarizations.     

Exploring the contributions of the supplementary eye field to subliminal inhibition using double‐pulse transcranial magnetic stimulation

It is widely accepted that the supplementary eye fields (SEF) are involved in the control of voluntary eye movements. However, recent evidence suggests that SEF may also be important for unconscious and involuntary motor processes. Indeed, Sumner et al. ([2007]: Neuron 54:697–711) showed that patients with micro‐lesions of the SEF demonstrated an absence of subliminal inhibition as evoked by masked‐prime stimuli. Here, we used double‐pulse transcranial magnetic stimulation (TMS) in healthy volunteers to investigate the role of SEF in subliminal priming. We applied double‐pulse TMS at two time windows in a masked‐prime task: the first during an early phase, 20–70 ms after the onset of the mask but before target presentation, during which subliminal inhibition is present; and the second during a late phase, 20–70 ms after target onset, during which the saccade is being prepared. We found no effect of TMS with the early time window of stimulation, whereas a reduction in the benefit of an incompatible subliminal prime stimulus was found when SEF TMS was applied at the late time window. These findings suggest that there is a role for SEF related to the effects of subliminal primes on eye movements, but the results do not support a role in inhibiting the primed tendency. Hum Brain Mapp 38:339–351, 2017. © 2016 Wiley Periodicals, Inc.     

Innocuous-related sural nerve-evoked and finger-evoked potentials generated in the primary somatosensory and supplementary motor cortices.

OBJECTIVE: Our earlier work revealed two components of the somatosensory evoked potential, which we have labeled SP1 and SP4a, that appear to be generated by neurons involved in the innocuous aspects of somatosensation. The objective of the present study was to examine a hypothesis developed in our earlier work, namely that SP1 and SP4a are generated in the primary somatosensory cortex. METHODS: The dipole source localization method was applied to SP1 and SP4a evoked by electrical stimulation of the fingers and of the sural nerve in 20 subjects. The subjects rated the subjective magnitude of each stimulus on a 9 point scale. RESULTS: The finger-evoked and sural nerve-evoked SP1 were best-fit by single sources located in the primary somatosensory cortex (SI) hand and foot areas, respectively. Both the finger-evoked and the sural nerve-evoked SP4a, on the other hand, were best-fit by a single source located in the supplementary motor area (SMA). CONCLUSIONS: These results are consistent with our hypothesis that SP1 reflects the activity of SI neurons that are involved in innocuous somatosensation. SP4a is not generated in SI as we originally hypothesized, but rather in the SMA. The SP4a amplitude-stimulus intensity function and the dependence of the SP4a source location on the evoking stimulus site and not the hand registering the magnitude rating suggests that SP4a reflects the response of SMA neurons to afferent input from the innocuous somatosensory pathways. Hence, SP4a may be generated by SMA activity involved in the sensory-guided selection and/or generation of motor responses.     

Somatosensory evoked potentials in patients with hypocalcaemia after parathyroidectomy

Summary The effects of hypocalcaemia on somatosensory evoked potentials (SEPs) were studied in five patients after parathyroidectomy. Despite normal latencies the mean value of amplitudes of the SEPs in hypocalcaemic patients was greater than that in normocalcaemic subjects. Recovery functions of the SEPs showed a significant decrease in hypocalcaemic patients at interstimulus intervals of about 10 ms compared with those in normocalcaemic patients and in normal volunteers. Recovery functions appear to be a valid indicator of synaptic efficacy, especialy for evaluation of the reduction in conduction efficacy of the central nervous system in hypocalcaemia.     

Cerebral magnetic responses to stimulation of tibial and sural nerves

We report somatosensory evoked magnetic fields (SEFs) to stimulation of the mixed posterior tibial nerve (PTN) and the sensory sural nerve (SN) in 6 healthy subjects. The first peak of the responses occurred at 39-50 ms (P40m), with a 2-3 ms longer latency for SN than PTN stimulation. Within 200 ms several other deflections followed, with interindividually varying waveforms and latencies. Magnetic field mappings indicated that the source of P40m for PTN can be modelled by a single equivalent current dipole at the primary sensorimotor cortex; for the smaller responses to SN stimulation the single dipole model was less applicable. Field patterns for later deflections differed from those of P40m, indicating that several current sources within or near the primary foot projection area are sequentially activated after stimulation of both a mixed and a sensory lower limb nerve. These late deflections could not always be satisfactorily explained by single current dipoles, suggesting more complex geometries for the underlying neural activity.     

Characterising the central mechanisms of sensory modulation in human swallowing motor cortex.

OBJECTIVE: Pharyngeal stimulation can induce remarkable increases in the excitability of swallowing motor cortex, which is associated with short-term improvements in swallowing behaviour in dysphagic stroke patients. However, the mechanism by which this input induces cortical change remains unclear. Our aims were to explore the stimulus-induced facilitation of the cortico-bulbar projections to swallowing musculature and examine how input from the pharynx interacts with swallowing motor cortex. METHODS: In 8 healthy subjects, a transcranial magnetic stimulation (TMS) paired-pulse investigation was performed comprising a single conditioning electrical pharyngeal stimulus (pulse width 0.2 ms, 240 V) followed by cortical TMS at inter-stimulus intervals (ISI) of 10-100 ms. Pharyngeal sensory evoked potentials (PSEP) were also measured over the vertex. In 6 subjects whole-brain magnetoencephalography (MEG) was further acquired following pharyngeal stimulation. RESULTS: TMS evoked pharyngeal motor evoked potentials were facilitated by the pharyngeal stimulus at ISI between 50 and 80 ms (Delta mean increase: 47+/-6%, P < 0.05). This correlated with the peak latency of the P1 component of the PSEP (mean 79.6+/-8.5 ms). MEG confirmed that the equivalent P1 peak activities were localised to caudolateral sensory and motor cortices (BA 4, 1, 2). CONCLUSIONS: Facilitation of the cortico-bulbar pathway to pharyngeal stimulation relates to coincident afferent input to sensorimotor cortex. SIGNIFICANCE: These findings have mechanistic importance on how pharyngeal stimulation may increase motor excitability and provide guidance on temporal windows for future manipulations of swallowing motor cortex.     

Dermatome versus homunculus; detailed topography of the primary somatosensory cortex following trunk stimulation.

OBJECTIVE: Identification of a detailed topography of the receptive area for each of the thoracic dermatomes in humans using somatosensory evoked magnetic fields (SEF). METHODS: We analyzed the location of the equivalent current dipole (ECD) of SEF following electrical stimulation of the skin at Th4, Th6, Th8, Th10 and Th12 dermatomes in 14 normal subjects. RESULTS: Three deflections, M18, M25 and M40, were obtained within 60 ms of stimulation of Th6, Th8 and Th10 dermatomes. No consistent deflection could be identified following Th4 and Th12 dermatomal stimulation, probably due to a poor signal-to-noise ratio and difficulty in fixing the stimulation electrodes. M18 was absent or small in amplitude. The latency of M25 ranged from short to long in the order Th6, Th8 and Th10 (P<0.05). ECDs of all components for each site stimulation were located in the truncal area of the primary somatosensory cortex. Although the locations of the ECDs tend to be arranged from lateral to medial in the sequence Th6, Th8 and Th10, the difference was not significant. CONCLUSION: The representation area of the trunk is small, and the receptive areas for the stimulation of Th6, Th8 and Th10 dermatomes are considered to be very close or to overlap.     

Evaluation of lip sensory disturbance using somatosensory evoked magnetic fields

ObjectiveTo evaluate lip sensory dysfunction in patients with inferior alveolar nerve injury by lip-stimulated somatosensory evoked fields (SEFs).MethodsSEFs were recorded following electrical lip stimulation in 6 patients with unilateral lip sensory disturbance and 10 healthy volunteers. Lip stimulation was applied non-invasively to each side of the lip with the same intensity using pin electrodes.ResultsAll healthy volunteers showed the earliest response clearly and consistently at around 25 ms (P25m) and at least one of the following components, P45m, P60m, or P80m, over the contralateral hemisphere. The ranges of the peak latencies were 23–33, 42–50, 56–67, and 72–98 ms for right-side stimulation and 23–34, 46–49, 52–68, and 71–90 ms for left-side stimulation. Affected-side stimulation did not evoke P25m component in any patients, but invoked traceable responses in 5 patients whose latencies were 57, 89, 65, 53, and 54 ms. Unaffected-side stimulation induced P25m in 2 patients at 27 and 25 ms, but not in the other 4 patients.ConclusionThe P25m component of lip SEFs can be an effective parameter to indicate lip sensory abnormality.SignificanceLip sensory dysfunction can be objectively evaluated using magnetoencephalography.     

Long-term plasticity of visually evoked potentials in humans is altered in major depression.

BACKGROUND: Long-term synaptic plasticity is a ubiquitous form of neuronal plasticity that regulates the strength of synaptic transmission in many brain areas. However, most data on long-term potentiation and long-term depression rely on research in animal brain slices. The role of synaptic plasticity in physiology and pathology of the functioning human brain remains obscure. Considering recent studies that provided evidence for a dysfunction of brain plasticity as the neurobiological basis of affective disorders, we assessed neural transmission and its plastic modulation in the visual pathway in healthy control subjects and patients with major depression. METHODS: Recordings of visually evoked potentials (VEPs) in humans. RESULTS: Prolonged visual presentation of checkerboard reversals resulted in a sustained amplitude modulation of early components of subsequent VEPs. After a 10-min block of visual stimulation (two checkerboard reversals per second), the C1 component was reduced, whereas P1 and N1 were both significantly increased for >30 min. Chronic application of the selective serotonin reuptake inhibitor sertraline in healthy control subjects augmented these effects, whereas the polarity of the modulation was inverted in patients with severe major depression. Moreover, early VEP amplitudes were decreased in depressed patients when compared with matched control subjects and increased in normal control subjects after chronic intake of an antidepressant. CONCLUSIONS: Our results demonstrate that stimulus-induced response plasticity of VEPs can be induced in the human brain and is sharing properties with hebbian forms of synaptic plasticity. Major depression and antidepressant treatment of healthy control subjects differentially modulate amplitude and plasticity of evoked potentials. This study provides direct evidence in humans for a central role of synaptic plasticity in the pathophysiology of depression.