Evaluation of thalamocortical impulse propagation in the akinetic Rigd type of Parkinson's disease using high-frequency (600 Hz) SEP oscillations.

Human median nerve somatosensory evoked potentials exhibit low-amplitude, high-frequency (600 Hz) oscillations (HFOs) superimposed onto the primary cortical response 'N20.' Previous EEG-studies indicated the HFOs to reflect in part activity generated at the thalamus and within the thalamocortical radiation. Expecting impairment of thalamocortical impulse propagation in Parkinson's disease (PD) the present study aimed to explore the performance of the HFOs in a cohort of PD patients in comparison to an exactly age- and sex-matched group of controls. To avoid motor interference and to minimize the influence of central tremor oscillators to the HFOs we selected PD patients suffering from an akinetic rigid type of the disease. We recorded multichannel somatosensory evoked potentials and applied an advanced analysis combining source and time frequency analysis. Low frequency and HFO signals showed no significant differences between PD patients and the control group, neither in the source waveforms evaluation nor in the time frequency analysis. Contrasting two former studies indicating enhanced HFOs in nonselected PD patients the present results differ most probably due to the lack of motor interference effects and the missing impact of central tremor-oscillators on the signals by selecting patients without tremor. THEME: Sensory systems. TOPIC: Somatosensory cortex and thalamocortical relationships.

The impact of stimulus properties on low- and high-frequency median nerve somatosensory evoked potentials.

Questioning whether stimulation properties in median nerve somatosensory evoked potentials show interactions multichannel recordings were performed in a three-factorial repeated measures design with the parameters (i) eyes opened versus eyes closed, (ii) stimulation intensity above motor threshold versus intensity sub motor threshold, (iii) stimulation rate 0.5 Hz versus 9 Hz resulting in somatosensory evoked potentials recorded during eight different conditions. Varying the stimulation intensity revealed an impact on the amplitude and the latency of the N20 source activity and on the amplitude, the duration and the number of peaks of the high frequency oscillatory (HFOs) sources. Modifying the stimulation rate lead to an effect on the amplitude and latency of the N20 and on the amplitude of the high-frequency oscillatory sources. The condition opened/closed eyes had an impact on the duration and number of high-frequency oscillatory. No relevant interactions between the stimulation properties were found. In consequence, varying one stimulus parameter already leads to a saturation of the low as well as high-frequency somatosensory evoked potentials components. Thus, the careful choice of stimulation parameters is a condition precedent for reasonable data interpretation.

The temporal pattern of motion in depth perception derived from ERPs in humans.

Former studies have demonstrated the cortical regions being involved in visual motion processing. The strength of neuronal activation was found to depend on the direction of motion. In particular the detection of optic flow towards the observer seems of particular importance due to its obvious biological relevance. We used event related potentials (ERPs) to add data of the temporal dynamics of this neuronal processing. Using current density reconstruction, source maxima of differential activation in motion in depth versus planar motion in the time range from 50 to 400 ms after stimulus onset were localized, and the time courses of activation were elaborated. Source reconstruction revealed six regions contributing significant source activity related to the perception of motion in depth: occipital pole, bilateral fusiform gyrus, right lateral superior occipital cortex and bilateral superior parietal cortex. Our data provide evidence for an early involvement of visual occipital cortex in the perception of motion in depth stimuli, followed by activation within parietal cortex, presumably associated with attention information processing. Sub-dividing the effects of the direction of the stimuli in motion in depth perception, optic flow directed towards the observer-induced stronger activation, but this differential activation excluded the parietal cortex. Thus the temporal deconvolution of the electrophysiological data suggests that the differential processing of approaching stimuli is initiated at an early stage of visual perception within the visual association area.

Temporal activation patterns of lateralized cognitive and task control processes in the human brain.

In a recent fMRI study with identical word stimuli we demonstrated task-dependent lateralization of brain activity during visual processing, with left-hemispheric activations for letter decisions and right-hemispheric activations for visuospatial decisions (Stephan, K.E., Marshall, J.C., Friston, K.J., Rowe, J.B., Ritzl, A., Zilles, K., Fink, G.R., 2003. Lateralized Cognitive Processes and Lateralized Task Control in the Human Brain. Science 301, 384-386). In order to explore the temporal dynamics of these lateralized processes we here recorded multichannel event-related potentials (ERPs) using the same stimuli. ERP data were analysed with current source density reconstruction (CDR). Contrasting the ERP results elicited by the two tasks, source deconvolution showed enhanced activity during letter decisions in Broca's area from 200-250 ms during letter decisions and during visuospatial decisions in the right posterior parietal cortex (PPC) from 175-200 ms and 250-275 ms. Prior to these activations ERP data revealed an initiation of activity within the anterior cingulate cortex (ACC) from 125-150 ms followed by a late activation of this region from 400-425 ms. Consistent with our previous fMRI study the current electrophysiological data support the notion that lateralized cognitive processes may depend on task requirements rather than stimulus properties. The current results extend our previous findings as they allow insights into the temporal dynamics of these lateralized processes and their relations to task control processes. The temporal deconvolution of ERPs suggests an early differential involvement of Broca's area in letter-processing and of PPC during visuospatial processing. In addition, activation of ACC prior and after this differential activation is consistent with previous findings suggesting that this area may be involved in cognitive control.

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.

Loudness dependence of evoked dipole source activity during acute serotonin challenge in females.

OBJECTIVES: Direct challenge of cortical serotonergic (5-hydroxytryptamine, 5-HT) availability by tryptophan depletion test (TDT) was used to assess the hypothesized inverse relationship between central 5-HT function and loudness dependence of auditory evoked potentials (LDAEPs). Gender must be taken into particular account here, since there are gender differences in 5-HT brain synthesis, with women reacting more strongly to TDT. METHODS: In a double-blind, controlled cross-over study, 16 healthy females were ingested two highly concentrated amino acid mixtures with (+TRP) or without TRP (-TRP). While monitoring TRP levels and mood states, the AEP of different loudness stimuli were recorded, followed by dipole source analysis. RESULTS: Under the -TRP condition, free plasma TRP levels decreased by 81.10% (+/-5.14). Most of the loudness change rates of the relevant N1/P2 tangential dipole activities were significantly increased under -TRP, but calculated LDAEP did not differ significantly between treatments. LDAEP and states of mood were not correlated. CONCLUSIONS: Despite strong TRP depletion, the results did not reach sufficient evidence that LDAEP is a valid biological marker of central 5-HT activity in females when using TDT. This agrees with the literature and supports the view that LDAEP indicates predominantly biological vulnerability in predisposed individuals.

Cerebral processing of spontaneous reversals of the rotating Necker cube.

The cerebral processing of spontaneous perceptive reversals of the rotating Necker cube was studied in humans by combined functional MRI and electroencephalography. These reversals prefer certain positions of the Necker cube and can be studied without external reference of the perception. Functional MRI revealed six bilaterally active regions in the visual, parietal, and premotor cortex. A new method determined phase-locked electroencephalography-activations in the regions of interest and showed a significant stimulus-locked activity that started in the left Brodmann area 18. This activity started 38 ms after passing the symmetric position of the Necker cube and spread along the dorsal stream. We suggest that a further portion of the event-related potential signal reflects additional top-down processing, dependent on the position of the Necker cube.

Comparative source localization of electrically and pressure-stimulated multichannel somatosensory evoked potentials.

The purpose of the study was to determine if there is a difference in the determination of the cortical hand area by dipole source estimation after artificial and natural stimuli. In principle, there are advantages of both methods: pressure stimulation is less invasive and compatible to fMRI, whereas electrical stimulation can be applied with higher stimulus rates and elicits sharper waveforms. Electrical and pressure stimulation was performed simultaneously on the thumb and fifth finger on eight healthy volunteers. The somatosensory evoked potentials after electrical stimulation showed sharper peaks and higher amplitudes than the pressure stimulated potentials. For the two stimulus qualities, cortical source positions of thumb and fifth finger separated significantly in the vertical z-axis. Both methods deliver reliable stimulation and therefore allow separate source localization of thumb and fifth finger. For cortical plasticity studies, peripheral somatosensory stimulation is of great importance. According to these findings, the choice of method, electrical or mechanical stimulation, may depend on practical criteria.

Short-term cortical reorganization by deafferentation of the contralateral sensory cortex.

The topographic arrangement of the human primary somatosensory cortex following deafferentation of the contralateral cortex has been investigated by means of dipole source analysis. Somatosensory-evoked potentials were obtained by electrical stimulation of digit 1 and digit 5 of the left hand before and after anesthesia of digits 2-4 of the right hand during different terms of attention. Anesthesia induced an expansion of the three-dimensional distance between digits 1 and 5. This suggests intercortical plasticity modulated between bilateral primary somatosensory cortical areas, which is unaffected by spatial attention. These changes occur rapidly and are probably mediated by disinhibition of intercortical connections, leading to hyperexcitability of the primary sensory cortex that is contralateral to the region undergoing deafferentation.

Human high frequency somatosensory evoked potential components are refractory to circadian modulations of tonic alertness.

The impact of vigilance states, such as sleep or arousal changes, on the high-frequency (600 Hz) components (HFOs) of somatosensory evoked potentials (SEPs) is known. The present study sought to characterize the effects of circadian fluctuations of tonic alertness on HFOs in awake humans. Median nerve SEPs were recorded at four times during a 24-hour waking period. In parallel to the SEP recordings, a reaction-time (RT) task was performed to assess tonic alertness. Additionally, the spontaneous EEG was monitored. The low-frequency SEP component N20 and the early and late HFO parts did not change across the measurement sessions. In contrast, RTs were clearly prolonged at night and on the second morning. EEG also showed increased delta power at night. HFOs are sensitive to pronounced vigilance changes, such as sleep, but are refractory to fluctuations of tonic alertness. Tonic alertness is regarded to be the top-down cognitive control mechanism of wakefulness, whereas sleep is mediated by overwhelming bottom-up regulation, which seems apparently more relevant for, at least in part, subcortically triggered high-frequency burst generation in the ascending somatosensory system.

Transcranial direct current stimulation applied over the somatosensory cortex - differential effect on low and high frequency SEPs.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has an influence on the excitability of the human motor cortex measured by motor evoked potentials (MEPs) after transcranial magnetic stimulation. Low and high frequency (HFOs) components of somatosensory evoked potentials (SEPs) were studied questioning whether a comparable effect can be observed after applying tDCS to the human somatosensory cortex. METHODS: Multichannel median nerve SEPs were recorded before and after applying tDCS of 1mA over a period of 9min with the cathode placed over the somatosensory cortex and the anode over the contralateral forehead and vice versa in a second session. The source activity of the N20, N30 and HFOs was evaluated before and after application of tDCS. RESULTS: After cathodal tDCS to the somatosensory cortex we found a significant reduction of the N20 source amplitude while there was no effect after anodal stimulation. For the N30 component and HFOs no change in source activity was observed. CONCLUSIONS: Corresponding to the results for the motor cortex a sustained reduction of the excitability of the somatosensory cortex after cathodal tDCS was shown. SIGNIFICANCE: We demonstrated differential effects of tDCS on the high and low frequency components of SEPs confirming the hypothesis of locally and functionally distinct generators of these two components.

Temporal pattern of source activities evoked by different types of motion onset stimuli.

The aim of this study was to compare the time course of motion-related source activities evoked by the onset of different kinds of visual motion stimuli in human subjects. Event-related potentials (ERP) were recorded from 64 scalp electrodes in ten healthy subjects while they were viewing four different types of motion stimuli (translation, rotation, expansion and contraction). Following a new approach combining a current density reconstruction with clustering algorithms, source maxima in the time range from 50 to 400 ms after the onset of the visual stimulus were localized and the time courses of activation were elaborated. Six regions contributed significantly to source activity, half originating in the occipital lobe and half in the right parietal and right temporal cortex. The comparison of their time courses led to the following conclusions: (i) the different kinds of motion stimuli activated about the same areas of the brain but with different temporal patterns. (ii) Mainly parietal and extrastriate areas, but not V1/V2, were significantly involved in the differentiation of different kinds of motion. (iii) Contrasting the different kinds of motion onsets, responses from parietal areas were found mainly before those from lateral occipital areas. (iv) The classically defined N2 and P2 components were significantly different among the four motion conditions, but not P1. The N2 motion-related component was elicited not only by lateral occipital areas and middle temporal areas but also by right parietal areas. (v) The rotation condition evoked a novel component P180, concomitant with an increased activity in the left middle temporal gyrus.

Electrophysiological evidence for altered early cerebral somatosensory signal processing in schizophrenia.

Various studies have indicated an impairment of sensory signal processing in schizophrenic patients. Anatomical and functional imaging studies have indicated morphological and metabolic abnormalities in the thalamus in schizophrenia. Other results give evidence for an additional role of cortical dysfunction in sensory processing in schizophrenia. Advanced analysis of human median nerve somatosensory evoked potentials (SEPs) reveals a brief oscillatory burst of low-amplitude and high-frequency activity ( approximately 600 Hz), the so-called high frequency oscillations (HFOs). The present study explores the behavior of HFOs in a cohort of schizophrenic patients in comparison to a group of controls. HFOs in the group of patients appeared with a delayed latency. In the low-frequency part of the SEPs an increase in amplitude was found. These results are interpreted to reflect a lack of somatosensory inhibition in the somatosensory pathway, either at a thalamic or a cortical level.

High-frequency somatosensory thalamocortical oscillations and psychopathology in schizophrenia.

Human cortical somatosensory evoked potentials (SEPs), which are presumably generated in afferent thalamocortical and early cortical fibers, reveal a burst of superimposed early (N20) high-frequency oscillations (HFOs), around 600 Hz. There is increasing evidence of an imbalance of thalamocortical systems in schizophrenic patients. In order to assess correlations between somatosensory evoked oscillations and symptoms of schizophrenia, we investigated median nerve SEPs in 20 inpatients and their age-matched and gender-matched healthy controls using a multichannel EEG. Dipole source analysis and wavelet transformation were performed before and after application of a 450-Hz high-pass filter. In schizophrenics, the maximum HFOs occurred with a significantly prolonged latency. There was also a higher amplitude (energy) in the low-frequency range of the N20 component compared with the controls. Importantly, amplitudes (energy) of HFOs were inversely correlated with symptoms of formal thought disorder and delusions. Alterations of the thalamocortical somatosensory signal processing in schizophrenia with absence of an early HFO - assumed to be of inhibitory nature - could indicate a dysfunctional thalamic inhibition with increased amplitudes of N20, paralleled by enhanced positive schizophrenic symptoms.

Patterns of disturbed impulse propagation in multiple sclerosis identified by low and high frequency somatosensory evoked potential components.

In human median nerve somatosensory evoked potentials (SSEPs), high frequency (600 Hz) oscillations (HFOs) are superimposed onto the low frequency SSEP component N20. High frequency oscillations are generated both in deep axon segments of thalamo-cortical projection neurons and at the primary somatosensory cortex. The present study aimed to test the hypothesis that HFOs might be more sensitive to temporal dispersion caused by demyelinating lesions in multiple sclerosis (MS) than the N20. The authors recorded HFOs in median nerve SSEPs in 50 patients with definite MS and in 30 healthy controls. Three patterns of SSEP alterations were found: (1) abolished HFOs with either normal (11% of stimulated limbs), or delayed N20 (16% of stimulated limbs); (2) an attenuation of N20 amplitude with preserved HFOs (13%); and (3) a mixture of both patterns (21%). The first pattern--normal N20 with abolished HFOs--indicates that the HFOs are a sensitive marker of slight demyelination. The second pattern is suggestive of a mainly axonal lesion type, while the third pattern points to a combined axonal/demyelinating process or a conduction block. Analysis of HFOs allows identification of slight demyelinating processes in MS patients in whom the N20 SSEP component remains unaffected. The HFOs provide a tool to distinguish different patterns of disturbed impulse propagation.

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.

Enhanced intensity dependence as a marker of low serotonergic neurotransmission in borderline personality disorder.

Dysfunction of central serotonergic activity has been assumed in patients with borderline personality disorder (BPD) characterized by a prominent impulsive behavioral style. Following the high serotonergic innervation of the primary auditory cortex, there is increasing evidence of the intensity dependence of auditory evoked potentials (AEP), especially the N1/P2 component, indicating serotonergic neurotransmission in animals and humans. 15 females who met the IPDE-criteria for BPD and a group of comparative healthy females (controls) completed extensive personality questionnaires which gave special regard to impulsiveness. We obtained event-related AEP through the application of various loudness stimuli. We examined the relevant N1/P2 amplitude of the tangential dipole of the auditory evoked response using dipole source analysis. The augmentation of the N1/P2 amplitude of tangential dipole source activity with rising stimulus intensity was significantly pronounced in BPD as opposed to controls, accompanied by a reduction in N1 and P2 latencies. The strong loudness dependency of AEP correlated with aspects of impulsiveness. These data imply reduced inhibiting control over cortical sensory processing in BPD. Our findings contribute a further argument to the hypothesis of low serotonergic neurotransmission in BDP and may point to a trait character of impulsiveness in this personality disorder.

Dissociation of human thalamic and cortical SEP gating as revealed by intrathalamic recordings under muscle relaxation.

'Gating' refers to a reduction of cortical somatosensory evoked potentials (SEP) under multiple simultaneous afferent inputs. This study used the opportunity for intrathalamic recordings in patients with movement disorders to clarify to what extent cortical SEP gating is preceded by thalamic gating. Recordings were performed in 10 patients, narcotised by intravenous propofol when receiving implantation of a therapeutic deep brain stimulator system. SEP were elicited by an 8.1-Hz median nerve stimulation at twice motor threshold and were recorded simultaneously from both intrathalamic and scalp electrodes before and after the application of the depolarising muscle blocker succinylcholine which eliminated both the background muscular tone and the repetitive muscle twitches caused by the median nerve stimulation. Peripheral compound action potentials recorded at the upper arm remained unchanged after complete muscle relaxation, proving a continuously effective nerve stimulation. In contrast, the primary cortical SEP component (N20) was significantly increased under succinylcholine (+17%). This cortical release from gating was not paralleled, however, by an increased thalamic response; rather, the primary thalamic response (P16) showed a slight (-9%) but highly significant amplitude reduction. As the recordings were performed in narcotised patients, any potentially variable attentional bias on part of the subjects can be excluded as confounding factor when comparing the two experimental conditions with vs. without reafferent somatosensory inflow. Thus, given the high signal-to-noise ratio of intrathalamically recorded SEP, the present study shows a distinct thalamo-cortical dissociation with the primary somatosensory cortex representing the predominant level exhibiting SEP gating.

Spatial direction of attention enhances right hemispheric event-related gamma-band synchronization in humans.

Gamma-band oscillations are related to sensory information processing and attention. To further illuminate the relationship of gamma-band activity and selective somatic attention, we have studied the effects of direction of attention on the stimuli of somatosensory evoked potentials. Responses during focused attention to stimulation of the right median nerve and ignored stimulation at the right tibial nerve were compared with responses of ignored stimulation of the right median nerve but focused attention to stimulation at the right tibial nerve. Subtraction of the data demonstrated a significant predominantly right hemispheric event-related synchronization in the gamma-band by attention to the right median nerve in the time period between 280 and 325 ms post-stimulus. This finding implicates the involvement of a right temporoparietal network in selective spatial attention.