Wienbruch, Christian
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Changes in cortical slow wave activity in healthy aging
A number of studies have demonstrated enhanced slow wave activity associated with pathological brain function e.g. in stroke patients, schizophrenia, depression, Morbus Alzheimer, and post-traumatic stress disorder. However, the association between slow wave activity and healthy aging has remained largely unexplored. This study examined whether the frequency at which focal generators of delta waves appear in the healthy cerebral cortex changes with age and whether this measure relates to cognitive performance. We investigated 53 healthy individuals aged 18 to 89 years and assessed MEG during a resting condition. Generators of focal magnetic slow waves were localized. Results showed a significant influence of age: dipole density decreases with increasing age. The relationship between cognitive performance and delta dipole density was not significant. The results suggest that in healthy aging slow waves decrease with aging and emphasize the importance of age-matched control groups for further studies. Increased appearance of slow waves as a marker for pathological stages can only be detected in relation to a control group of the same age.
Abnormal slow wave mapping (ASWAM) : a tool for the investigation of abnormal slow wave activity in the human brain
Slow waves in the delta and theta frequency range, normal signs of deactivated networks in sleep stages, are considered 'abnormal' when prominent in the waking state and when generated in circumscribed brain areas. Structural cortical lesions, e.g. related to stroke, tumors, or scars, generate focal electric and magnetic slow wave activity in the penumbra. Focal concentrations of slow wave activity exceeding those of healthy subjects have also been found in individuals suffering from psychiatric disorders without obvious structural brain damage. Hence, identification and mapping of abnormal slow wave activity might contribute to the investigation of cortical indications of psychopathology. Here I propose a method for abnormal slow wave mapping (ASWAM), based on a 5 min resting magnetoencephalogramm (MEG) and equivalent current dipole fitting to sources in the 1-4 Hz frequency band (delta) in anatomically defined cortical regions. The method was tested in a sample of 116 healthy subjects (59 males), with the aim to provide a basis for later comparison with patient samples. As to be expected, delta dipole density was low in healthy subjects. However, its distribution differed between genders with fronto-central>posterior dipole density in male and posterior dominance in female participants, which was not significantly related to either age or head size. Results suggest that this method allows the identification of ASWA, so that comparison against Z-scores from a larger normal control group might assist diagnostic purposes in patient groups. As specific distributions seem to reflect differences between genders, this should be considered also in the analysis of patient samples.
Source distribution of neuromagnetic slow wave activity in schizophrenic and depressive patients
Objective: Focal slow waves in the delta and theta frequency range frequently appear in psychopathological conditions. Due to their focal nature they can be localized by dipole modeling. We previously reported regional clustering of slow waves in temporal and parietal cortex of schizophrenic patients whereas such activity is largely absent in normals. Here we examine, to what extent distribution of slow wave generators differentiates schizophrenic from depressive syndromes. Methods: The regional densities of generators of focal slow waves were determined during resting conditions in patients with DSM-IV diagnoses of schizophrenia (N = 25) and depression (N = 27) and in 18 healthy controls. Results: Schizophrenic patients demonstrated accentuated temporal and parietal delta and theta dipole clustering, when compared to both the control and the depressive sample. In contrast, depressive patients had reduced frontal and prefrontal delta and theta dipole density relative to both schizophrenics and controls. This pattern was not related to age. Men generally displayed somewhat higher slow wave activity than women. For the areas of most pronounced slow wave deviances activity within each group was related to symptom scores: higher left-temporal slow wave activity was associated with hallucinations in schizophrenics, suppression of left-prefrontal slow wave activity correlated with depression scores. Conclusions: Results suggest that slow wave distribution may assist in differentially diagnosing psychopathological conditions.
Tonotopic organization of the sources of human auditory steady-state responses
Steady-state responses (SSRs) or steady-state fields (SSFs) show maximum amplitude when tone pulses are presented at repetition rates near 40 Hz. This result has led to the hypothesis that the SSR/SSF consists of superimposed transient 'middle latency' responses which display wave periods near 40 Hz and summate with one another when phase locked by 40 Hz steady-state stimulation. We evaluated this hypothesis by comparing the cortical sources of the 40 Hz auditory SSF with sources of the middle latency Pa wave which is prominent in electrical and magnetic recordings, and with the cortical sources of the familiar N1 wave, at different carrier frequencies between 250 and 4000 Hz. SSF sources determined for the different carrier frequencies were found to display a 'medial' tendency tonotopy resembling that of the N1m (sources for the higher frequencies represented more deeply within the supratemporal sulcus), opposite the 'lateral' tendency tonotopy of the middle latency Pam (sources for the higher frequencies situated more laterally). A medial SSF tonotopy was observed in each of the subjects investigated, including three subjects for whom Pam and N1m maps were also available. These findings suggest that the 40 Hz SSF may not consist of summated or entrained middle latency responses, as has previously been proposed. Alternative mechanisms for the SSR are discussed.
Distinct cognitive mechanisms in a gambling task share neural mechanisms
Distinct psychological processes have been proposed to unfold in decision-making. The time course of neural mechanisms supporting these processes has not been fully identified. The present MEG study examined spatio-temporal activity related to components of decision-making proposed to support reward valuation, reward prediction, and outcome evaluation. Each trial presented information on reward value (10 or 50 cents) and reward probability (10%, 50%, or 90%). Brain activity related to those inputs and to outcome feedback was evaluated via electromagnetic responses in source space. Distributed dipole activity reflected reward value and reward probability 150–350 ms after information arrival. Neural responses to reward-value information peaked earlier than those to reward-probability information. Results suggest that valuation, prediction, and outcome evaluation share neural structures and mechanisms even on a relatively fine time scale.
Mapping the brain's orchestration during speech comprehension : task-specific facilitation of regional synchrony in neural networks
Background: How does the brain convert sounds and phonemes into comprehensible speech? In the present magnetoencephalographic study we examined the hypothesis that the coherence of electromagnetic oscillatory activity within and across brain areas indicates neurophysiological processes linked to speech comprehension.
Results: Amplitude-modulated (sinusoidal 41.5 Hz) auditory verbal and nonverbal stimuli served to drive steady-state oscillations in neural networks involved in speech comprehension. Stimuli were presented to 12 subjects in the following conditions (a) an incomprehensible string of words, (b) the same string of words after being introduced as a comprehensible sentence by proper articulation, and (c) nonverbal stimulations that induced a 600-Hz tone, a scale, and a melody. Coherence, defined as correlated activation of magnetic steady state fields across brain areas and measured as simultaneous activation of current dipoles in source space (Minimum-Norm-Estimates), increased within left-temporal-posterior areas when the sound string was perceived as a comprehensible sentence. Intra-hemispheric coherence was larger within the left than the right within the right than the left hemisphere for the sentence (condition (b) relative to all other conditions), and tended to be larger within the right than the left hemisphere for nonverbal stimuli (condition (c), tone and melody relative to the other conditions), leading to a more pronounced hemispheric asymmetry for nonverbal than verbal material.
Conclusions: We conclude that coherent neuronal network activity may index encoding of verbal information on the sentence level and can be used as a tool to investigate auditory speech comprehension.
Input-increase and input-decrease types of cortical reorganization after upper extremity amputation in humans
A plastic remodeling of regions in somatosensory cortex has previously been observed to occur in separate experimental paradigms in response to loss of somatosensory input and to increase in input. In this study, both types of cortical reorganization have been observed to occur concurrently in the same adult human nervous system as a result of a single intervention. Following upper extremity amputation, magnetic source imaging revealed that tactile stimulation of the lip evoked responses not only in the area of the somatosensory cortex corresponding to the face, but also within the cortical region that would normally correspond to the now absent hand. This "invasion" of the cortical amputation zone was accompanied by a significant increase in the size of the representation of the digits of the intact hand, presumably as a result of an increased importance of sensory stimulation consequent to increased dependence on that hand imposed by the loss of the contralateral extremity.
Adverse experiences in childhood influence brain responses to emotional stimuli in adult psychiatric patients
Previous results suggest that early life stress (ELS) may be related to altered cortical responses to emotional stimuli. In a previous study, we found suppressed cortical responses to emotional pictures in psychiatric patients with high-ELS. The present study explored the stability of this effect across time and stimulation conditions. In addition, the relationship between ELS and current life stress was examined, and we probed whether this current life stress was related to the cortical responses. Fifteen patients with high, 16 patients with low-ELS and 15 psychiatrically healthy subjects with low-ELS participated in two sessions 8 months apart. Subjects monitored a rapid serial presentation of pleasant, neutral and unpleasant pictures during magnetoencephalographic recording. In both sessions, estimated neural activity in occipital parietal temporal regions between 70 and 250 ms after picture onset was smaller in patients, particularly in those with high-ELS, compared to healthy subjects. Modulation of activity by arousing (pleasant and unpleasant) compared to neutral stimuli around 200 ms post-stimulus did not differ between groups, whereas around 300 ms, patients did not show the pronounced cortical response to pleasant stimuli exhibited by healthy subjects. Results suggest that ELS and psychiatric disorder (1) diminish early perceptual processing (b200 ms) of emotional stimuli without substantially affecting activity modulation by stimulus arousal value, (2) diminish later attention allocation processes (N300 ms), and (3) are related to more recent life stress. High intraindividual correlations of activity patterns between sessions suggest lasting effects of ELS on processing modes.
Source distribution of neuromagnetic slow-wave activity in schizophrenic patients : effects of activation
When slow waves in the EEG delta and theta frequency range appear in the waking state, they may indicate pathological conditions including psychopathology. The generators of focal slow waves can be mapped using magnetic source imaging. The resulting brain maps may possibly characterize dysfunctional brain areas. The present study examined the stability of the density and distribution of MEG slow waves during three conditions-rest, mental arithmetic and imagery-in 30 schizophrenic patients and 17 healthy controls. Schizophrenic patients displayed a higher density of delta and theta generators primarily in temporal and parietal areas. The group difference was not affected by the particular conditions. The focal concentration of delta and theta slow waves did not differ between patients with and without neuroleptic medication, whereas the prominence of theta dipoles in the temporal area correlated with neuroleptic dosage. The relative amount of temporal slow waves was correlated with the negative symptoms score (PANSS-N) suggesting that temporal dysfunction may be related to negative symptomatology. Results suggest that the distribution of slow-wave activity, measured in a standardized setting, might add diagnostic information about brain abnormalities in schizophrenia.
Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients
The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study. Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG) recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 qcm cubicles containing at least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spikes generated in deep temporomesial structures may escape the MEG registration.