Till Dino Waberski

Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis

RationaleMany studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-d-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2A agonist model).ObjectivesThe aim of the present study was to directly compare the two models of psychosis using an intraindividual crossover design.Materials and methodsFifteen healthy subjects participated in a randomized, double-blind, crossover study with a low and a high dose of the 5HT2A agonist dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine. During electroencephalographic recording, the subjects were performing the AX-version of a continuous performance test (AX-CPT). A source analysis of MMN was performed on the basis of a four-source model of MMN generation.ResultsNine subjects completed both experimental days with the two doses of both drugs. Overall, we found blunted MMN and performance deficits in the AX-CPT after both drugs. However, the reduction in MMN activity was overall more pronounced after S-ketamine intake, and only S-ketamine had a significant impact on the frontal source of MMN.ConclusionsThe NDMA antagonist model and the 5HT2A agonist model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis.

Spatio-temporal source imaging reveals subcomponents of the human auditory mismatch negativity in the cingulum and right inferior temporal gyrus.

We investigated the generators of the mismatch negativity by means of spatio-temporal source imaging on the basis of 64-channel electroencephalography data in order to study the time course and localization of proposed frontal sources. Results indicate that there are additional generators located both within the anterior cingulate gyrus and in the right inferior temporal gyrus, clearly separated from the supratemporal generators in space and time course. The cingulate generator is activated later than the temporal ones, which supports the hypothesis of a frontally located mechanism of involuntary switching of attention triggered by the temporal change detection system. Evidence for an additional right inferior temporal generator supports the hypothesis of right hemispheric dominance in early sound discrimination.

Fast visual evoked potential input into human area V5

STUDIES of the human visual cortex have demonstrated that an area for motion processing (V5) is located in the lateral occipito-temporal cortex. To study the timing of arrival of signals in V5 we recorded multi-channel visual evoked potentials (VEPs) to checkerboard stimuli. We then applied dipole source analysis which was computed on a grand average of 10 subjects, and on five individual subjects, respectively. We demonstrate an early VEP component with onset before 30 ms and with a peak around 45 ms, located in the vicinity of V5. This early component was independent of a second activity, which started around 50 ms and peaked around 70 ms, and was located within the striate cortex (V1). These results provide further evidence for a very fast input to V5 before activation of V1.

Sleep stage dependant changes of the high-frequency part of the somatosensory evoked potentials at the thalamus and cortex

OBJECTIVES It is known that the high-frequency oscillations (above 400 Hz) of the somatosensory evoked potentials (SEPs) diminish during sleep while the N20 persists (Neurology 38 (1988) 64; Electroenceph clin Neurophysiol 70 (1988) 126; Electroenceph clin Neurophysiol 100 (1996) 189). We investigated possible differential effects of sleep on the 600 Hz SEPs at the thalamus and cortex. METHODS SEPs from 10 subjects were recorded using 64 channels following electric stimulation at the wrist during awake state and sleep stages II, IV and REM. Dipole source analysis was applied to separate brain-stem, thalamic and cortical activity in the low-frequency (20-450 Hz) and the high-frequency (450-750 Hz) part of the signal. RESULTS The low-frequency SEPs showed a non-significant increase of the latency of the N20 and a bifid change of the waveform in 3 subjects. The high-frequency SEPs showed a significant decrease of their amplitude at the level of the thalamus and cortex but not at the brain-stem. This decrease in amplitude at the thalamus and cortex were significantly correlated. There was no effect on the latency of the signal. In addition, at the cortex, differential effects on early and late parts of the 600 Hz oscillations were found by time-frequency analysis using a wavelet transformation. CONCLUSIONS Sleep dependent decrease of the high-frequency SEPs were first observed at the thalamus pointing to the known function of the reticular thalamic nucleus regulating arousal. The results presented here provide further evidence for a thalamic origin of the 600 Hz oscillations. In addition, on the basis of the differential effects on early (up to the N20 peak) and late (between 20 and 25 ms) parts of the signal, at least one intracortical generator of these oscillations is proposed. In general, the high-frequency SEPs (600 Hz oscillations) are supposed to reflect activity of a somatosensory arousal system.

Dipole-source analysis in a realistic head model in patients with focal epilepsy.

Summary: Purpose: By the use of three different head models in EEG dipole analysis, we tried to model the origin of interictal and ictal epileptic activity as precisely as possible. Further, as a control, a second evaluation was made by an independent group to control for interindividual reliability of the dipole source analysis. With the realistic head model (CURRY) considering cortex, skull, and skin segmentation, the spike source was located.

Sustained attention modulates the immediate effect of de-afferentation on the cortical representation of the digits: source localization of somatosensory evoked potentials in humans

Long-term cortical reorganization of the somatotopic arrangement of the digits after alterations of the peripheral input is well established. Studies on the immediate effects of manipulating peripheral input have shown conflicting results indicating that additional factors might modulate cortical reorganization. We present a source localization study using somatosensory evoked potentials (SEP) following electric stimulation of digits one and five before and during anaesthesia of digits two, three and four in 10 normal volunteers. When attention was directed to a stimulus at the dorsal hand, the 3D-distance between digits one and five decreased during as compared to before anaesthesia. In contrast, this distance enlarged when subjects were not attending a particular stimulus. In this condition most subjects focused their attention on the clear sensation of the de-afferented hand region. These results indicate that attention modulates the effect of immediate cortical reorganization of the hand area during partial deafferentation. As an hypothesis: it may be speculated that the sensation of the de-afferentation results in increased synchronized activity of the de-afferented somatosensory cortex and, thus, to its enlarged representation. Conversely, if attention is directed to a different hand region, the representations of the neighboring digits may expand into the de-afferented cortex.

Timing of visuo-spatial information processing: Electrical source imaging related to line bisection judgements

This study deconvolves the temporal dynamics of the neural processes underlying line bisection judgements (i.e., the landmark task). Event-related potentials (ERPs) were recorded from 96 scalp electrodes in 10 healthy right-handed male subjects while they were judging whether horizontal lines were correctly prebisected. In the control task, subjects judged whether or not the horizontal line was transected by a vertical line, irrespective of its position. Using a current density reconstruction approach, source maxima in the time range from 50 to 400ms after stimulus onset were localized and the time courses of activation were elaborated. Five regions, corresponding to those revealed by our previous fMRI studies (e.g., [Fink, G. R., Marshall, J. C., Shah, N. J., Weiss, P. H., Halligan, P. W., Grosse-Ruyken, et al. (2000). Line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI. Neurology, 54, 1324-1331]), were identified as contributing significant source activity related to line bisection judgements: right middle occipital gyrus (Brodmann area; BA18); bilateral inferior occipital gyrus (BA19); right superior posterior parietal cortex (BA7) and right inferior posterior parietal cortex (BA40). Temporal deconvolution indicated sequential activation of these regions starting at BA18 as early as 90ms post-stimulus onset, followed by the successive activation of the right superior posterior parietal (BA7), bilateral inferior occipital (BA19) and right inferior posterior parietal cortex (BA40). Three of these areas (BA18, BA17 and BA19) became reactivated within 250ms of stimulus onset. The data provide evidence for an early involvement of the right hemispheric parietal network in visuo-spatial information processing. Furthermore, the temporal deconvolution of the electrophysiological data suggest that iterative processes between and within parietal (dorsal path) and occipital areas (ventral path) mediate bisection judgements.

Comparison of realistically shaped boundary-element and spherical head models in source localization of early somatosensory evoked potentials.

SummarySource localizations of early somatosensory evoked potentials and electrical potentials produced by dipoles in the region of the central sulcus were computed using realistically shaped boundary-element head models (BEM) and compared to localizations obtained using 3-shell spherical models. Realistically shaped 3-shell boundary-element-models were constructed on the basis of the individual anatomy obtained from 3D-MR-tomography in 6 subjects. Spherical head models were fitted to the actual locations of the electrodes and to the surface of the heads, respectively. Source locations calculated within the spherical head models differed by an average of 4 mm (range: 2 to 7 mm) with respect to the 3-shell BEM, taking into account the limited accuracy of this model. This mislocation was most prominently due to deeper source locations predicted using a spherical head model and caused by incorrect modelling of the geometry of the heads, although sources were located in a favourable region of the heads.

Differential effects of pain and spatial attention on digit representation in the human primary somatosensory cortex

Reorganization of primary somatosensory cortex subsequent to either reduced or enhanced peripheral input is well established. Recently, plastic changes following arm amputation in humans were shown to correlate with phantom limb pain. This raised the question whether spatial attention and pain may cause cortical reorganization in the absence of deafferentation. Using non-invasive neuroelectric imaging to study the digit representation in the human primary somatosensory cortex, we report a delayed shift of the representation of digits 2–3 due to pain on the digits 4–5, which outlasted the pain by several minutes. In contrast, reorganization during spatial attention was less pronounced, was seen almost immediately and only during the condition. These data indicate that spatial attention and pain without peripheral deafferentation cause cortical reorganization by different mechanisms. The differential time course of reorganizational effects observed at the cortex may be due to modulation of the lemniscal pathways by nociceptive input from the spinal cord dorsal horn.

Functional dissociation of a subcortical and cortical component of high-frequency oscillations in human somatosensory evoked potentials by motor interference

To identify the possibly divergent impact on early and late high-frequency oscillations (HFOs) in human somatosensory evoked potentials (SEPs), we have studied motor interference effects on the HFOs, and the relevance of such effects for the controversy concerning their origins. While the late HFO is thought to be generated in the somatosensory cortex, there is an ongoing discussion whether the early burst is of cortical or subcortical origin. Movements of the index finger were performed in parallel with median nerve SEP recordings. The intracortically generated N20-SEP and the late HFO were attenuated by the motor task, while the brainstem low-frequency P14-SEP and the early HFO remained unaffected. These differing effects are consistent with a generation of the early HFOs by cortical presynaptic activity in terminals of the thalamocortical projection, and confirm a postsynaptic intracortical origin of the late burst subcomponent.