Intracortical modulation of somatosensory evoked fields during movement: evidence for selective suppression of postsynaptic inhibition.

As accurate finger movements depend on guidance by afferent sensory feedback information, it is of interest to examine how the cortical processing of afferent signals is altered during movement states compared with rest. In the present study we evaluated afferent input to the primary somatosensory cortex (SI) in human subjects performing a finger opposition task. We recorded somatosensory evoked magnetic fields (SEFs) in 6 healthy subjects to stimulation of left and right median nerves in a resting condition and during active right-sided finger movements. At the left SI, the SEFs to right (moving hand) median nerve stimulation showed a selective and robust reduction of the P35m deflection during movement compared with rest, while there were only minor non-significant changes in the other SEF deflections, including N20m, which represents the 1st excitatory cortical event after stimulation. In contrast, at the right SI the SEFs to left (non-moving hand) median nerve stimulation were modified in the opposite direction: the P35m deflection was slightly enhanced during right-sided movement, there being no significant changes in the other deflections. The results thus show that the P35m SEF deflection can be selectively reduced during finger movements of the stimulated hand, and selectively enhanced if the movement is being performed with the fingers of the opposite hand. Because N20m was not changed, the modulation took place at the cortical level rather than in the afferent pathways. As the P35m SEF deflection likely represents postsynaptic IPSPs at SI, the results suggest that postsynaptic inhibition to somatosensory impulses from the moving part of the body is suppressed. Comparison of the present results with recent intracellular studies in behaving mice suggests that the P35m reduction specifically corresponds to a reduction in the activity of parvalbumin-containing fast-spiking inhibitory interneurons during movement. The results provide evidence that precision movements can be executed without this type of cortical postsynaptic inhibition.

In search of augmentation at human SI: Somatosensory cortical responses to stimulus trains and their modulation by motor activity.

In many animal preparations, repeated stimulation at ca. 10 Hz in thalamic nuclei leads to rapid changes in the cortical evoked responses, known as the augmenting response. The present study was undertaken to evaluate whether anything similar to the augmenting response can be observed in awake human subjects when a peripheral nerve is stimulated, and whether a possible human correlate of augmenting would be modified when the subject is engaged in an active motor task. Somatosensory-evoked magnetic fields (SEFs) were recorded in healthy human subjects in response to stimulus trains (15 pulses at 10 Hz) applied to the left median nerve. SEFs were recorded in a resting condition and during a finger-tapping task performed with the stimulated hand. In the resting condition, the most marked change in the SEF configuration was a reduction of the P35m deflection and a concurrent enhancement of the N45m deflection during the 1st few stimuli of the trains. Another conspicuous feature was a prolongation of the latencies of the N45m and P60m deflections toward the end of the train. In the motor task, the response modulation during the pulse trains was in general similar to the resting condition. The most notable difference was that the P35m amplitude was markedly reduced already for the 1st pulse of the train when compared with rest. Also, the latencies of N45m and P60m were not prolonged during the train. We discuss the possibility that the reduction of P35m and a concurrent increase of N45m during a pulse train constitute a human analogue to the augmenting response, and suggest that these changes may reflect a decrease of inhibitory postsynaptic potentials (IPSPs, P35m) and an increase of secondary excitatory postsynaptic potentials (N45m) during stimulus train presentation. The reduction of P35m during motor activity compared with rest already at the beginning of stimulus trains suggests that postsynaptic IPSPs in response to afferent stimulation are reduced during active movement. Otherwise the short-term plastic changes were similar during rest and motor activity. Finally, the results suggest slowing down of intracortical network processing with repeated stimulation, and that this slowing is not present during an active motor task which depends on afferent feedback information.

Modulation of somatosensory evoked fields from SI and SII by acute GABA A-agonism and paired-pulse stimulation.

The purpose of the present study was to shed light on the physiology underlying somatosensory evoked magnetic fields (SEFs) by means of pharmacological manipulation with the GABA A agonist lorazepam and paired-pulse stimulation. SEFs were recorded from the primary (SI) and secondary (SII) somatosensory cortices following median nerve stimulation. Responses were obtained to single stimuli every 2 s and to paired stimuli with interpulse intervals (IPIs) of 20 ms and 100 ms. Recordings were performed in 2 sessions, once after the intravenous injection of lorazepam and once after the injection of placebo. The underlying neural generators of the response components were modelled with single equivalent current dipoles (ECDs). In the single-stimulus condition, lorazepam slightly increased the ECD strength of the 1st excitatory deflection (N20m) from the contralateral SI and reduced the strengths of the following P35m, P60m and N140m deflections from the contralateral SI and the response from the ipsilateral SII. Under placebo, paired-pulse stimulation with the IPI of 20 ms diminished all SEF components compared with single-pulse stimulation. At the IPI of 100 ms, the N20m and the P60m deflections from SI had recovered to nearly baseline levels, being consistent with recovery cycles of excitatory postsynaptic potentials (EPSPs). In contrast, the P35m and N140m, as well as the SII deflections, did not recover at 100 ms. Lorazepam had no effect on the paired-pulse depression (PPD) or recovery thereof for the N20m deflection. The attenuation of the P35m deflection by lorazepam and its lack of recovery in the 100-ms paired-pulse condition are expected behaviours of inhibitory postsynaptic potentials (IPSPs) in intracellular recordings, thus lending further support to our previous suggestion that P35m largely represents IPSPs. The lack of PPD modulation of N20m by lorazepam suggests that paired-pulse depression of the first cortical excitatory response (N20m) may be caused by mechanisms other than GABA A receptor-mediated inhibition.

Sensorimotor cortex localization: comparison of magnetoencephalography, functional MR imaging, and intraoperative cortical mapping.

PURPOSE: To prospectively evaluate magnetoencephalography (MEG) and functional magnetic resonance (MR) imaging, as compared with intraoperative cortical mapping, for identification of the central sulcus. MATERIALS AND METHODS: Fifteen patients (six men, nine women; age range, 25-58 years) with a lesion near the primary sensorimotor cortex (13 gliomas, one cavernous hemangioma, and one meningioma) were examined after institutional review board approval and written informed consent from each patient were obtained. At MEG, evoked magnetic fields to median nerve stimulation were recorded; at functional MR imaging, hemodynamic responses to self-paced palmar flexion of the wrist were imaged. General linear model analysis with contextual clustering (P < .01) was used to analyze functional MR imaging data, and dipole modeling was used to analyze MEG data. MEG and functional MR localizations were compared with intraoperative cortical mappings. The distance from the area of functional MR imaging activation to the tumor margin was compared between the patients with discordant and those with concordant intraoperative mapping findings by using unpaired t testing. RESULTS: MEG depicted the central sulcus correctly in all 15 patients, as verified at intraoperative mapping. The functional MR imaging localization results agreed with the intraoperative mappings in 11 patients. In all four patients with a false localization, the primary activation was in the postcentral sulcus region, but it did not differ significantly from the primary activation in the patients with correct localization with respect to proximity to the tumor (P = .38). Furthermore, at functional MR imaging, multiple nonprimary areas were activated, with considerable interindividual variation. CONCLUSION: Although both MEG and functional MR imaging can provide useful information for neurosurgical planning, in the present study, MEG proved to be superior for locating the central sulcus. Activation of multiple nonprimary cerebral areas may confound the interpretation of functional MR imaging results.

Spatial dynamics of population activities at S1 after median and ulnar nerve stimulation revisited: an MEG study.

In a number of studies, magnetoencephalography (MEG) has been successfully employed in localizing cortical neural population activities after stimulation of peripheral nerves. Little attention has been paid, however, to the spatiotemporal dynamics of these activations within the primary somatosensory cortex (SI). Here we report on the activation sequence at the right SI after left median and ulnar nerve stimulation. The results show that at least three macroscopically separable sources within or near SI are activated within 100 ms after the stimulus, corresponding to the somatosensory evoked field (SEF) deflections N20m, P35m and P60m. As P60m was localized significantly more posteriorly and also tended to be deeper than the two earlier deflections, its underlying source may be more extensive than during N20m and P35m, and it may get contribution from the postcentral gyrus and sulcus, possibly Brodmann areas 1 and 2. The source separation between the neural populations activated by the 2 nerves was 12 mm during N20m, 6 mm during P35m and 4 mm during P60m. Thus, at longer latencies, the centers of gravity of the activations were closer to each other for the 2 nerves. We argue that this reflects spreading of the activation with time from the site of initial excitation to encompass larger and more overlapping neural populations at longer latencies.

Effects of scopolamine on MEG spectral power and coherence in elderly subjects.

OBJECTIVE: Scopolamine, a muscarinic receptor antagonist, can produce temporary cognitive impairments as well as electroencephalographic changes that partially resemble those observed in Alzheimer's disease. In order to test the sensitivity of spectral power and hemispheric coherence to changes in cholinergic transmission, we evaluated quantitative magnetoencephalogram (MEG) after intravenous injection of scopolamine. METHODS: MEG of 8 elderly healthy subjects (59-80 years) were measured with a whole-head magnetometer after intravenous injection of scopolamine. An injection of glycopyrrolate, a peripheral muscarinic antagonist, was used as the placebo in a double-blind, randomized, cross-over design. Spectral power and coherence were computed over 7 brain regions in 3 frequency bands. RESULTS: Scopolamine administration increased theta activity (4-8 Hz) and resulted in the abnormal pattern of MEG desynchronization in eyes-open vs. eyes-closed conditions in the alpha band (8-13 Hz). These effects were most prominent over the posterior regions. Interhemispheric and left intrahemispheric coherence was significantly decreased in the theta band (4-8 Hz). CONCLUSIONS: Spontaneous cortical activity at the theta and alpha range and functional coupling in the theta band are modulated by the cholinergic system. MEG may provide a tool for monitoring brain dynamics in neurological disorders associated with cholinergic abnormalities.

Effects of an acute D2-dopaminergic blockade on the somatosensory cortical responses in healthy humans: evidence from evoked magnetic fields.

We tested the possible role of dopaminergic activity in the processing of somatosensory afferent information in healthy humans. Somatosensory evoked magnetic fields (SEFs) were recorded in seven subjects in response to left median nerve stimulation. SEFs were obtained in all subjects after oral administration of 2 mg haloperidol, an antagonist to dopaminergic D2 receptors, and placebo, which were given in a randomized, double-blind cross-over design. SEFs were analyzed using a multiple equivalent current dipole (ECD) model, with one dipole at the right primary somatosensory cortex (SI) and at both left and right secondary somatosensory cortices (SII). The earliest responses from SI, peaking at about 20 ms (N20m) and 35 ms (P35m), were not affected by haloperidol. A later deflection peaking at about 75 ms (P60m), however, was slightly reduced (p < 0.05). Responses arising from SII were not significantly changed. The results suggest that dopaminergic activity may be involved in modulating somatosensory processing after the initial stages of cortical activation.

Dopamine modulates involuntary attention shifting and reorienting: an electromagnetic study.

OBJECTIVE: Dopaminergic function has been closely associated with attentional performance, but its precise role has remained elusive. METHODS: Electrophysiological and behavioral methods were used to assess the effects of dopamine D2-receptor antagonist haloperidol on involuntary attention shifting using a randomized, double-blind, placebo-controlled cross-over design. Eleven subjects were instructed to discriminate equiprobable 200 and 400ms tones in a forced-choice reaction-time (RT) task during simultaneous measurement of whole-head magnetoencephalography and high-resolution electroencephalography. RESULTS: Occasional changes in task-irrelevant tone frequency (10% increase or decrease) caused marked distraction on behavioral performance, as shown by significant RT increases to deviant stimuli and subsequent standard tones. Furthermore, while the standard tones elicited distinct P1-N1-P2-N2-P3 waveforms, deviant tones elicited additional mismatch negativity (MMN), P3a, and reorienting negativity (RON) responses, indexing brain events associated with involuntary attention shifting. While haloperidol did not affect the source loci of the responses of magnetic N1 and MMN, the amplitude of the electric P3a and that of RON were significantly reduced and the latency of magnetic RON were delayed following haloperidol administration. CONCLUSIONS: The present results suggest that dopamine modulates involuntary attention shifting to task-irrelevant deviant events. It appears that dopamine may disrupt the subsequent re-orienting efforts to the relevant task after distraction.

Memory-based comparison process not attenuated by haloperidol: a combined MEG and EEG study.

Auditory P50 and N100 responses reflect preattentive processing, whereas subsequent mismatch negativity (MMN) response indexes memory-based comparison process. Divergent ERP responses have been found in schizophrenia and in Parkinson's disease (PD), which have abnormalities in cerebral dopamine activity. We used simultaneously magnetoencephalography and electroencephalography to investigate, whether a single dose of haloperidol, a dopamine D2-receptor antagonist, modulates preattentive auditory processing using a randomized, double-blind, placebo-controlled crossover design. Our results showed that haloperidol did not alter MMN to frequency and duration changes, whereas the magnetic MMN to frequency change was significantly accelerated. The amplitude and latency changes of the electric and magnetic P50 and N100 were insignificant. Our results indicate that memory-based sound comparison and preceding cortical processing underlying stimulus detection are not attenuated by haloperidol, whereas haloperidol appears to accelerate preattentive sound comparison.

Ipsi- and contralateral EEG reactions to transcranial magnetic stimulation.

OBJECTIVES: Transcranial magnetic stimulation (TMS) and high-resolution electroencephalography (EEG) were used to study the spreading of cortical activation in 6 healthy volunteers. METHODS: Five locations in the left sensorimotor cortex (within 3cm(2)) were stimulated magnetically, while EEG was recorded with 60 scalp electrodes. A frameless stereotactic method was applied to determine the anatomic locus of stimulation and to superimpose the results on magnetic resonance images. Scalp potential and cortical current-density distributions were derived from averaged electroencephalographic (EEG) data. RESULTS: The maxima of the ipsilateral activation were detected at the gyrus precentralis, gyrus supramarginalis, and lobulus parietalis superior, depending on the subject. Activation over the contralateral cortex was observed in all subjects, appearing at 22plus minus2ms (range 17--28); the maxima were located at the gyrus precentralis, gyrus frontalis superior, and the lobulus parietalis inferior. Contralateral EEG waveforms showed consistent changes when different sites were stimulated: stimulation of the two most medial points evoked the smallest responses fronto-parietally. CONCLUSIONS: With the combination of TMS, EEG, and magnetic resonance imaging, an adequate spatiotemporal resolution may be achieved for tracing the intra- and interhemispheric spread of activation in the cortex caused by a magnetic pulse.