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Biomedical subjects

Gregor Thut

Publications and source records attributed to Gregor Thut.

At least 19 recordsLinked to original sources

A glimpse into your vision.

Invasive recordings of local field potentials (LFPs) have been used to "read the mind" of monkeys in real time. Here we investigated whether noninvasive field potentials estimated from the scalp-recorded electroencephalogram (EEG) using the ELECTRA source localization algorithm could provide real-time decoding of mental states in healthy humans. By means of pattern recognition techniques on 500-ms EEG epochs, we were able to discriminate accurately from single trials which of four categories of visual stimuli the subjects were viewing. Our results show that it is possible to reproduce the decoding accuracy previously obtained in animals with invasive recordings. A comparison between the decoding results and the subjects' behavioral performance indicates that oscillatory activity (OA), elicited in specific brain regions) codes better for the visual stimulus category presented than the subjects' actual response, i.e., is insensitive to voluntary or involuntary errors. The identification of brain regions participating in the decoding process allowed us to construct 3D-functional images of the task-related OA. These images revealed the activation of brain regions known for their involvement in the processing of this type of visual stimuli. Electrical neuroimaging therefore appears to have the potential to establish what the brain is processing while the stimuli are being seen or categorized, i.e., concurrently with sensory-perceptual processes.

Adult↗

Alpha-band electroencephalographic activity over occipital cortex indexes visuospatial attention bias and predicts visual target detection.

Covertly directing visual attention toward a spatial location in the absence of visual stimulation enhances future visual processing at the attended position. The neuronal correlates of these attention shifts involve modulation of neuronal "baseline" activity in early visual areas, presumably through top-down control from higher-order attentional systems. We used electroencephalography to study the largely unknown relationship between these neuronal modulations and behavioral outcome in an attention orienting paradigm. Covert visuospatial attention shifts to either a left or right peripheral position in the absence of visual stimulation resulted in differential modulations of oscillatory alpha-band (8-14 Hz) activity over left versus right posterior sites. These changes were driven by varying degrees of alpha-decreases being maximal contralateral to the attended position. When expressed as a lateralization index, these alpha-changes differed significantly between attention conditions, with negative values (alpha_right < alpha_left) indexing leftward and more positive values (alpha_left < or = alpha_right) indexing rightward attention. Moreover, this index appeared deterministic for processing of forthcoming visual targets. Collapsed over trials, there was an advantage for left target processing in accordance with an overall negative bias in alpha-index values. Across trials, left targets were detected most rapidly when preceded by negative index values. Detection of right targets was fastest in trials with most positive values. Our data indicate that collateral modulations of posterior alpha-activity, the momentary bias of visuospatial attention, and imminent visual processing are linked. They suggest that the momentary direction of attention, predicting spatial biases in imminent visual processing, can be estimated from a lateralization index of posterior alpha-activity.

Adult↗

Neural basis of embodiment: distinct contributions of temporoparietal junction and extrastriate body area.

Embodiment, the sense of being localized within one's physical body, is a fundamental aspect of the self. Recently, researchers have started to show that self and body processing require distinct brain mechanisms, suggesting two posterior brain regions as key loci: the temporoparietal junction (TPJ), which is involved in self processing and multisensory integration of body-related information; and the extrastriate body area (EBA), which responds selectively to human bodies and body parts. Here we used evoked potential mapping and a distributed linear inverse solution to show that activations in EBA and TPJ code differentially for embodiment and self location, because the location and timing of brain activation depended on whether mental imagery is performed with mentally embodied (EBA) or disembodied (TPJ) self location. In a second experiment, we showed that only EBA activation, related to embodied self location, but not TPJ activation, related to disembodied self location, was modified by the subjects' body position during task performance (supine or sitting). This suggests that embodied self location and actual body location share neural mechanisms. Collectively, these data show that distributed brain activity at the EBA and TPJ as well as their timing are crucial for the coding of the self as embodied and as spatially situated within the human body.

Adult↗

Modulation of steady-state auditory evoked potentials by cerebellar rTMS.

Steady-state auditory evoked responses (SSAER) obtained via electroencephalography (EEG) co-vary in amplitude with blood flow changes in the auditory area of the cerebellum. The aim of the present EEG study was to probe the cerebellar role in the control of such SSAER. For this purpose, we investigated changes in SSAERs due to transient disruption of the cerebellar hemisphere by repetitive transcranial magnetic stimulation (rTMS). SSAERs to click-trains of three different frequencies in the gamma-band (32, 40 and 47 Hz) were recorded from 45 scalp electrodes in six healthy volunteers immediately after 1-Hz rTMS and compared to baseline SSAERs assessed prior to magnetic stimulation. Cerebellar rTMS contralateral to the stimulated ear significantly reduced the amplitude of steady-state responses to 40-Hz click-trains and showed a tendency to reduce the amplitude to 32-Hz click-trains. No effects were observed for 47-Hz click-trains, nor for magnetic stimulation of the cerebellum ipsilateral to auditory stimulation or after sham stimulation. Our results suggest that interference with cerebellar output by rTMS modifies functional activity associated with cortical auditory processing. The finding of maximum effects on 40-Hz SSAERs provides support to the notion that the cerebellum is part of a distributed network involved in the regulation of cortical oscillatory activity and points at some frequency-specificity for the control of auditory-driven neuronal oscillations.

Acoustic Stimulation↗

Electroencephalographic recording during transcranial magnetic stimulation in humans and animals.

OBJECTIVE: We report on the development of an EEG recording system, comprised of electrodes and amplifiers that are compatible with TMS (single and rapid-rate) in both human and animal studies. METHODS: We assembled a versatile multi-channel EEG recording system consisting of: (1) two types of electrodes that are safe during TMS or rTMS. (2) Low slew-rate EEG amplifiers that recover within a few milliseconds after the application of TMS pulses. RESULTS: The two electrode types: (a) a conductive-plastic surface electrode with a conductive-silver epoxy coat and (b) a subdermal silver wire electrode (SWE) are compatible to TMS pulses. The amplifiers recover within 30 ms, so that the EEG can be viewed online, essentially without interruption and/or blocking or excessive artifact. CONCLUSIONS: Our TMS compatible electrode and EEG recording system allows safe and online viewing/recording of the subject's (human or animal) EEG/EP during experiments or studies involving TMS or rTMS applications. The TMS compatible electrode/amplifier system can be used with any EEG recording instrument. SIGNIFICANCE: A simple recording technique coupled with new electrodes permit safe and readable EEG records during TMS in humans and animals. Such online monitoring of the EEG would allow control of TMS/rTMS parameters based on EEG activity.

Animals↗

Very high frequency oscillations (VHFO) as a predictor of movement intentions.

Gamma band (30-80 Hz) oscillations arising in neuronal ensembles are thought to be a crucial component of the neural code. Recent studies in animals suggest a similar functional role for very high frequency oscillations (VHFO) in the range 80-200 Hz. Since some intracerebral studies in humans link VHFO to epileptogenesis, it remains unclear if VHFO appear in the healthy human brain and if so which is their role. This study uses EEG recordings from twelve healthy volunteers, engaged in a visuo-motor reaction time task, to show that VHFO are not necessarily pathological but rather code information about upcoming movements. Oscillations within the range (30-200 Hz) occurring in the period between stimuli presentation and the fastest hand responses allow highly accurate (>96%) prediction of the laterality of the responding hand in single trials. Our results suggest that VHFO belong in functional terms to the gamma band that must be considerably enlarged to better understand the role of oscillatory activity in brain functioning. This study has therefore important implications for the recording and analysis of electrophysiological data in normal subjects and patients.

Adult↗

Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1Hz rTMS in patients with juvenile myoclonic epilepsy.

OBJECTIVE: The preliminary results of noninvasive brain stimulation for epilepsy treatment have been encouraging, but mixed. Two important factors may contribute to this heterogeneity: the altered brain physiology of patients with epilepsy and the variable presence of antiepileptic drugs. Therefore, we aimed to study the effects of 1 Hz rTMS on corticospinal excitability in patients with juvenile myoclonic epilepsy (JME) in two different conditions: low- or high-plasma valproate levels. METHODS: Fifteen patients with JME and 12 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS was assessed in JME patients with low- and high-plasma valproate levels; and these results were compared with those in healthy subjects. RESULTS: In patients with chronic use of valproate and low-plasma concentrations, 1 Hz rTMS had a similar significant inhibitory effect on corticospinal excitability as in healthy subjects. However, in the same patients when the serum valproate concentration was high, 1 Hz rTMS increased the corticospinal excitability significantly. In addition, there was a significant positive correlation between plasma valproate levels and the motor threshold changes after 1 Hz rTMS. CONCLUSIONS: Our findings can be accounted for by mechanisms of homeostatic plasticity and illustrate the dependency of the modulatory effects of rTMS on the physiologic state of the targeted brain cortex. SIGNIFICANCE: The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability.

Adolescent↗

A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy.

OBJECTIVE: To study the antiepileptic effects of rTMS in patients with refractory epilepsy and malformations of cortical development in a randomized, double-blind, sham-controlled trial. METHODS: Twenty-one patients with malformations of cortical development and refractory epilepsy underwent five consecutive sessions of low-frequency rTMS, either sham or active (1Hz, 1,200 pulses), focally targeting the malformations of cortical development. The number of epileptiform discharges in the electroencephalogram and the number of clinical seizures were measured before (baseline), immediately after, as well as 30 and 60 days after rTMS treatment. RESULTS: rTMS significantly decreased the number of seizures in the active compared with sham rTMS group (p < 0.0001), and this effect lasted for at least 2 months. Furthermore, there was a significant decrease in the number of epileptiform discharges immediately after (p = 0.01) and at week 4 (p = 0.03) in the active rTMS group only. There were few mild adverse effects equally distributed in both groups. The preliminary cognitive evaluation suggests improvement in some aspects of cognition in the active rTMS group only. INTERPRETATION: Noninvasive brain stimulation for epilepsy may be an alternative treatment for pharmaco-resistant patients with clearly identifiable seizure foci in the cortical convexity and who are not eligible for surgical treatment.

Adult↗

Arm folding, hand clasping, and Luria's concept of "latent left-handedness".

Luria (1947/1970) proposed left-top positions in arm folding (AF) and hand clasping (HC) to be signs of "latent left-handedness". However, research since has revealed that (1) left-top positions are canonical for European right-handers and (2) combined AF/HC measures may provide more information about cerebral laterality than either measure considered alone. We tested whether AF and HC or AF/HC combinations predicted diminished right-handedness for 12 handedness items. Results from 509 healthy participants showed that (1) left-top positions in AF and HC were dominant across participants, as was right-handedness, and a right-top position in HC was associated with attenuated right-handedness, (2) right-hand preference was more frequently associated with congruent AF/HC combinations, especially of the LL type (AF: left-top / HC: left-top), and (3) non-right-hand preference was associated with non-congruent, predominantly LR combinations. We conjecture that the LL type combination indicates left hemispheric dominance for motor actions, whereas the LR combination, in which HC as the distally innervated posture deviates from the canonical pattern, indicates attenuated hemispheric asymmetry. Our data support Luria's proposition that a left-top preference in AF points to "latent" left-handedness, but only if associated with a right-top preference in HC. Consistent left-top preference for the combined AF/HC measure appears to predict right-handedness.

Adolescent↗

Effect of low-frequency transcranial magnetic stimulation on an affective go/no-go task in patients with major depression: role of stimulation site and depression severity.

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a therapeutic tool in major depression. However, a means to assess the effects of a single rTMS session on mood to guide subsequent sessions would be desirable. The present study examined the effects of a single rTMS session on an affective go/no-go task known to measure emotional-cognitive deficits associated with major depression. Ten patients with an acute episode of unipolar major depression and eight partially or completely remitted (improved) patients underwent 1 Hz rTMS over the left and right dorsolateral prefrontal cortex prior to task performance. TMS over the mesial occipital cortex was used as a control. We observed significantly improved performance in depressed patients following right prefrontal rTMS. This beneficial effect declined with decreasing depression severity and tended to reverse in the improved group. Left prefrontal rTMS had no significant effect in the depressed group, but it resulted in impaired task performance in the improved group. Our findings indicate that the acute response of depressed patients to rTMS varies with the stimulation site and depression severity. Further studies are needed to determine whether the present paradigm could be used to predict antidepressant treatment success or to individualize stimulation parameters according to specific pathology.

Antidepressive Agents↗

Two electrophysiological stages of spatial orienting towards fearful faces: early temporo-parietal activation preceding gain control in extrastriate visual cortex.

Visuo-spatial attention tends to be prioritized towards emotionally negative stimuli such as fearful faces, as opposed to neutral or positive stimuli. Using a covert orienting task, we previously showed that a lateral occipital P1 component, with extrastriate neural sources, was selectively enhanced to lateralized visual targets replacing a fearful face (fear-valid trial) than the same targets replacing a neutral face (fear-invalid trial), providing evidence for exogenous spatial orienting of attention towards threat cues. Here, we describe a new analysis of these data, using topographic evoked potentials mapping methods combined with a distributed source localization technique. We show that an early field topography (40-80 ms post-target onset) with a centro-parietal negativity and a left posterior parietal source distinguished fear-valid from fear-invalid trials, whereas a distinct activity with anterior cingulate sources was selectively evoked during fear-invalid trials. At the same latency, or later, no difference in field topography was found for valid compared to invalid trials with happy faces. The early parietal map preceded a modulation in amplitude of the field strength (approximately 130 ms), corresponding to the enhanced lateral occipital P1 during valid trials in the fear condition. Furthermore, this early topography at 40-80 ms was positively correlated with the subsequent amplitude modulation of P1 at 130-160 ms in the fear condition, suggesting a possible functional coupling between these two successive events. These data have important implications for models of spatial attention and interactions with emotion. They suggest two successive stages of neural activity during exogenous orienting of attention towards visual targets following fearful faces, including an early posterior parietal negativity, followed by gain control mechanisms enhancing visual responses in extrastriate occipital cortex.

Adult↗

Left prefrontal repetitive transcranial magnetic stimulation impairs performance in affective go/no-go task.

Functional neuroimaging studies have associated affective go/no-go function with lateral prefrontal activation, but they have not established a causal role and have not determined whether one hemisphere is predominantly engaged. In the present study, 11 normal volunteers underwent slow repetitive transcranial magnetic stimulation of the left and right dorsolateral prefrontal cortex, and the occipital cortex prior to performance of a picture-based affective go/no-go task. We found an interfering effect of left prefrontal repetitive transcranial magnetic stimulation compared with both right prefrontal and occipital repetitive transcranial magnetic stimulation. This impairment concerned positive and negative task stimuli to a similar extent, and tended to be greater in shift compared with nonshift blocks. Our findings demonstrate a functionally relevant lateralization of the prefrontal contribution to affective go/no-go tasks.

Adult↗

A new device and protocol for combining TMS and online recordings of EEG and evoked potentials.

We describe an electroencephalographic (EEG) device and protocol that allows recording of electrophysiological signals generated by the human brain during transcranial magnetic stimulation (TMS) despite the TMS-induced high-voltage artifacts. The key hardware components include slew-rate limited preamplifiers to prevent saturation of the EEG system due to TMS. The protocol involves artifact subtraction to isolate the electrophysiological signals from residual TMS-induced contaminations. The TMS compatibility of the protocol is illustrated with examples of two data sets demonstrating the feasibility of the approach in the single-pulse TMS design, as well as during repetitive TMS. Our data show that both high-amplitude potentials evoked by visual checkerboard stimulation and low-amplitude steady-state oscillations induced by auditory click-trains can be retrieved with the present protocol. The signals recorded during TMS perfectly matched control EEG responses to the same visual and auditory stimuli. The main field of application of the present protocol is in cognitive neuroscience complementing behavioral studies that use TMS to induce transient, 'virtual lesions'. Combined EEG-TMS techniques provide neuroscientists with a unique method to test hypothesis on functional connectivity, as well as on mechanisms of functional orchestration, reorganization, and plasticity.

Adult↗

Linking out-of-body experience and self processing to mental own-body imagery at the temporoparietal junction.

The spatial unity of self and body is challenged by various philosophical considerations and several phenomena, perhaps most notoriously the "out-of-body experience" (OBE) during which one's visual perspective and one's self are experienced to have departed from their habitual position within one's body. Although researchers started examining isolated aspects of the self, the neurocognitive processes of OBEs have not been investigated experimentally to further our understanding of the self. With the use of evoked potential mapping, we show the selective activation of the temporoparietal junction (TPJ) at 330-400 ms after stimulus onset when healthy volunteers imagined themselves in the position and visual perspective that generally are reported by people experiencing spontaneous OBEs. Interference with the TPJ by transcranial magnetic stimulation (TMS) at this time impaired mental transformation of one's own body in healthy volunteers relative to TMS over a control site. No such TMS effect was observed for imagined spatial transformations of external objects, suggesting the selective implication of the TPJ in mental imagery of one's own body. Finally, in an epileptic patient with OBEs originating from the TPJ, we show partial activation of the seizure focus during mental transformations of her body and visual perspective mimicking her OBE perceptions. These results suggest that the TPJ is a crucial structure for the conscious experience of the normal self, mediating spatial unity of self and body, and also suggest that impaired processing at the TPJ may lead to pathological selves such as OBEs.

Adult↗

Prediction of response speed by anticipatory high-frequency (gamma band) oscillations in the human brain.

Response to a stimulus is faster when a subject is attending and knows beforehand how to respond. It has been suggested recently that this occurs because ongoing neuronal activity is spatially and temporally structured during states of expectancy preceding a stimulus. This mechanism is believed to mediate top-down processing, facilitating the early grouping and selection of distributed neuronal ensembles implicated in ensuing sensory-motor processing. To validate this model, it must be shown that some features of this early ongoing neural activity are correlated with subsequent perceptual decisions or behavioral events. We investigated this hypothesis in an electrophysiologic study in 12 subjects carrying out a simple visuomotor reaction-time task. Local field potentials (LFP) at each brain voxel were estimated using a linear distributed inverse solution termed "ELECTRA" for each single trial of each subject. The energy of oscillations for different frequency bands was computed for the period between the warning cue and visual stimuli by applying a time-frequency decomposition to the estimated LFP. A nonparametric correlation coefficient was then calculated between energy of oscillations and reaction times for each single sweep. Gamma band oscillatory activity in a frontoparietal network before stimulus onset significantly correlated with reaction time for a significant amount of subjects. These results provide direct evidence for the role of neural oscillations as a top-down attentional control mechanism that mediates the speed of motor actions.

Adult↗

Actual and mental motor preparation and execution: a spatiotemporal ERP study.

Studies evaluating the role of the executive motor system in motor imagery came to a general agreement in favour of the activation of the primary motor area (M1) during imagery, although in reduced proportion as compared to motor execution. It is still unclear whether this difference occurs within the preparation period or the execution period of the movement, or both. In the present study, EEG was used to investigate separately the preparation and the execution periods of overt and covert movements in adults. We designed a paradigm that randomly mixed actual and kinaesthetic imagined trials of an externally paced sequence of finger key presses. Sixty channel event-related potentials were recorded to capture the cerebral activations underlying the preparation for motor execution and motor imagery, as well as cerebral activations implied in motor execution and motor imagery. Classical waveform analysis was combined with data-driven spatiotemporal segmentation analysis. In addition, a LAURA source localization algorithm was applied to functionally define brain related motor areas. Our results showed first that the difference between actual and mental motor acts takes place at the late stage of the preparation period and consists of a quantitative modulation of the activity of common structures in M1. Second, they showed that primary motor structures are involved to the same extent in the actual or imagined execution of a motor act. These findings reinforce and refine the functional equivalence hypothesis between actual and imagined motor acts.

Adult↗

Dorsal posterior parietal rTMS affects voluntary orienting of visuospatial attention.

Patients with lesions in posterior parietal cortex (PPC) are relatively unimpaired in voluntarily directing visual attention to different spatial locations, while many neuroimaging studies in healthy subjects suggest dorsal PPC involvement in this function. We used an offline repetitive transcranial magnetic stimulation (rTMS) protocol to study this issue further. Ten healthy participants performed a cue-target paradigm. Cues prompted covert orienting of spatial attention under voluntary control to either a left or right visual field position. Targets were flashed subsequently at the cued or uncued location, or bilaterally. Following rTMS over right dorsal PPC, (i) the benefit for target detection at cued versus uncued positions was preserved irrespective of cueing direction (left- or rightward), but (ii) leftward cueing was associated with a global impairment in target detection, at all target locations. This reveals that leftward orienting was still possible after right dorsal PPC stimulation, albeit at an increased overall cost for target detection. In addition, rTMS (iii) impaired left, but (iv) enhanced right target detection after rightward cueing. The finding of a global drop in target detection during leftward orienting with a spared, relative detection benefit at the cued (left) location (i-ii) suggests that right dorsal PPC plays a subsidiary rather than pivotal role in voluntary spatial orienting. This finding reconciles seemingly conflicting results from patients and neuroimaging studies. The finding of attentional inhibition and enhancement occurring contra- and ipsilaterally to the stimulation site (iii-iv) supports the view that spatial attention bias can be selectively modulated through rTMS, which has proven useful to transiently reduce visual hemispatial neglect.

Adult↗

Feeling by sight or seeing by touch?

We have addressed the role of occipital and somatosensory cortex in a tactile discrimination task. Sight-ed and congenitally blind subjects rated the roughness and distance spacing for a series of raised dot patterns. When judging roughness, intermediate dot spacings were perceived as being the most rough, while distance judgments generated a linear relation. Low-frequency rTMS applied to somatosensory cortex disrupted roughness without affecting distance judgments, while rTMS to occipital cortex disrupted distance but not roughness judgments. We also tested an early blind patient with bilateral occipital cortex damage. Her performance on the roughness determination task was normal; however, she was greatly impaired with distance judgments. The findings suggest a double-dissociation effect in which roughness and distance are primarily processed in somatosensory and occipital cortex, respectively. The differential effect of rTMS on task performance and corroborative clinical evidence suggest that occipital cortex is engaged in tactile tasks requiring fine spatial discrimination.

Adult↗