Oscillatory magnetic brain activity is related to dissociative symptoms and childhood adversities - A study in women with multiple trauma.

BACKGROUND: Individuals with trauma-related disorders are complex and heterogeneous; part of this complexity derives from additional psychopathology like dissociation as well as environmental adversities such as traumatic stress, experienced throughout the lifespan. Understanding the neurophysiological abnormalities in Post-traumatic stress disorder (PTSD) requires a simultaneous consideration of these factors. METHODS: Resting state magnetoencephalography (MEG) recordings were obtained from 41 women with PTSD and comorbid depressive symptoms, and 16 healthy women. Oscillatory brain activity was extracted for five frequency bands and 11 source locations, and analyzed in relation to shutdown dissociation and adversity-related measures. RESULTS: Dissociative symptoms were related to increased delta and lowered beta power. Adversity-related measures modulated theta and alpha oscillatory power (in particular childhood sexual abuse) and differed between patients and controls. LIMITATIONS: Findings are based on women with comorbid depressive symptoms and therefore may not be applicable for men or groups with other clinical profiles. In respect to childhood adversities, we had no reliable source for the early infancy. CONCLUSION: Trauma-related abnormalities in neural organization vary with both exposure to adversities as well as their potential to evoke ongoing shutdown responses.

Electromagnetic brain activity in higher frequency bands during automatic word processing indicates recovery of function in aphasia.

AIM: Little is known about how treatment affects the neural substrate of language function in stroke sufferers. In the present study authors investigated neuronal correlates of treatment induced recovery of language functions in patients with chronic aphasia. METHODS: In 10 chronic aphasia patients and 10 age- and gender-matched control participants, evoked high-frequency activity (HFA, >20 Hz) was determined from the magnetoencephalogram in an automatic word recognition task, in which content, function, and pseudowords were visually presented at fast rate (350-ms). Recording was repeated after 2 weeks, in aphasics after intensive language training to evaluate training effects, in controls to establish HFA stability. RESULTS: In the first recording, bilateral HFA distribution in controls contrasted right-hemispheric predominance in the patients. After training, this right>left asymmetry in aphasics was reduced to a bilateral pattern similar to controls. While word class did not substantially affect HFA patterns in the two groups, enhanced right-hemispheric HFA in the patients varied with better language function (test performance) prior to training, while after training, left-temporal function- and pseudoword evoked HFA varied with performance in tests of written language. CONCLUSION: Results suggest that HFA might serve as a measure in the evaluation of rehabilitation efforts in chronic aphasia: enhanced right-hemispheric HFA might indicate compensatory activation of contralateral language areas, which tends towards patterns comparable to normal subjects after effective language training.

One set of sounds, two tonotopic maps: exploring auditory cortex with amplitude-modulated tones.

OBJECTIVE: The possibility of simultaneously observing activation of primary and secondary auditory cortices has been demonstrated by Engelien et al. [Hear Res 2000;148:153-60]. METHODS: Such a dual monitoring by means of neuromagnetic recordings can be achieved when a subject is stimulated by brief pulses of 40Hz-modulated tones. Depending on the frequency filter applied, either the steady-state field (SSF) or the N1m can be extracted from the evoked magnetic field complex. RESULTS: Using this "combined" (two-maps) paradigm with 4 carrier frequencies, we show that it is possible to synchronously screen two tonotopic maps--one map each reflected either by the SSF or the N1m. Indicators are the systematic variation in the location (higher frequencies are more posterior) and orientation (higher frequencies oriented differently in the sagittal plane) of the equivalent current dipole (ECD). These parameters were compared with those obtained from "classic" (one map) paradigms in which either a pure tone elicits an N1m or a 40 Hz continuous (3 s) stimulation produces an SSF. Overall the results were similar, however, systematic differences between the paradigms were found for ECD localization, dipole strength, amplitude, and phase. CONCLUSIONS AND SIGNIFICANCE: One possible interpretation of these results is that different tonotopically arranged cortical fields were involved in the generation of the components.

Human large-scale oscillatory brain activity during an operant shaping procedure.

The present study aimed at examining the oscillatory brain-electric correlates of human operant learning using high-density electroencephalography (EEG). Induced gamma-band activity (GBA) was studied using a fixed-interval reinforcement schedule with a variable limited hold period, which was decreased depending on response accuracy. Thus, participants' behavior was shaped during the course of the learning session. After each response, numbers indicating the money value of that response served as reinforcing stimuli. Random reinforcement and self-paced button pressing without reinforcement were added as control conditions. GBA around 40 Hz was enhanced at posterior electrodes in response to visual feedback stimuli during shaping and random reward compared to the self-paced pressing condition where no visual feedback was provided. Furthermore, shaping was associated with a pronounced left frontal lower gamma (20-30 Hz) increase in response to feedback stimuli, whereas this pattern was not observed in the random reinforcement and self-paced pressing conditions. The present findings are in line with the notion that macroscopic high-frequency dynamics of neuronal cell assemblies may be regarded as a mechanism involved in learning and memory formation.

Effects of emotional arousal in the cerebral hemispheres: a study of oscillatory brain activity and event-related potentials.

OBJECTIVE: The present study aimed at examining the time course and topography of oscillatory brain activity and event-related potentials (ERPs) in response to laterally presented affective pictures. METHODS: Electroencephalography was recorded from 129 electrodes in 10 healthy university students during presentation of pictures from the international affective picture system. Frequency measures and ERPs were obtained for pleasant, neutral, and unpleasant pictures. RESULTS: In accordance with previous reports, a modulation of the late positive ERP wave at parietal recording sites was found as a function of emotional arousal. Early mid gamma band activity (GBA; 30-45 Hz) at 80 ms post-stimulus was enhanced in response to aversive stimuli only, whereas the higher GBA (46-65 Hz) at 500 ms showed an enhancement of arousing, compared to neutral pictures. ERP and late gamma effects showed a pronounced right-hemisphere preponderance, but differed in terms of topographical distribution. CONCLUSIONS: Late gamma activity may represent a correlate of widespread cortical networks processing different aspects of emotionally arousing visual objects. In contrast, differences between affective categories in early gamma activity might reflect fast detection of aversive stimulus features.

Source distribution of neuromagnetic slow waves and MEG-delta activity in schizophrenic patients.

BACKGROUND: Schizophrenic patients exhibit more activity in the electroencephalographic delta and theta frequency range than do control subjects. Using magnetic source imaging (MSI) our study aimed to explore this phenomenon in the magnetoencephalogram (MEG), the distribution of its sources, and associations between symptom profiles and sources of low-frequency activity in the brain. METHODS: Whole-head MEG recordings were obtained from 28 schizophrenic patients and 20 healthy control subjects during a resting condition. The generators of the focal magnetic slow waves were located employing a single moving dipole model. Distributed or multiple delta and theta sources were captured by the minimum norm estimate. RESULTS: Both localization procedures showed slow wave activity to be enhanced in schizophrenic patients compared with control subjects. Focal slow wave activity differed most between groups in frontotemporal and in posterior regions. Slow wave activity was associated with symptom characteristics in that positive symptoms varied with frontal delta and theta activity. CONCLUSIONS: Results indicate that activity in low-frequency bands in schizophrenic patients exceeds the activity of control subjects in distinct areas, and that this focal clustering of neuromagnetic slow waves may be related to psychopathologic characteristics.

Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables in schizophrenia.

BACKGROUND: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. METHODS: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables ("ba") delivered to the left and right ears in separate runs were compared between schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. CONCLUSIONS: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.

Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees.

The relationship between phantom limb phenomena and cortical reorganization was examined in five subjects with congenital absence of an upper limb and nine traumatic amputees. Neuromagnetic source imaging revealed minimal reorganization of primary somatosensory cortex in the congenital amputees (M=0.69 cm, SD 0.24) and the traumatic amputees without phantom limb pain (M=0.27 cm, SD 0.25); the amputees with phantom limb pain showed massive cortical reorganization (M=2.22 cm, SD 0.78). Phantom limb pain and nonpainful phantom limb phenomena were absent in the congenital amputees. Whereas phantom limb pain was positively related to cortical reorganization (r=0.87), nonpainful phantom phenomena were not significantly correlated with cortical reorganization (r=0.34). Sensory discrimination was normal and mislocalization (referral of stimulation-induced sensation to a phantom limb) was absent in the congenital amputees. The role of peripheral and central factors in the understanding of phantom limb pain and phantom limb phenomena is discussed in view of these findings.

Methohexital-induced changes in spectral power of neuromagnetic signals: beta augmentation is smaller over the hemisphere containing the epileptogenic focus.

Previous research has suggested that methohexital, a short-term barbiturate, alters activity in the primary epileptogenic area. It can be assumed that drug-induced activation of the epileptogenic focus provides a rapid and safe method to obtain a sufficient amount of information relevant for the lateralization and localisation of the primary epileptogenic area. This study shows that methohexital changes spectral power in the beta band derived from magnetoencephalographic (MEG) signals over the hemisphere ipsilateral to the primary epileptogenic area. This effect was demonstrated for 10/13 of the investigated patients suffering from unilateral temporal lobe epilepsy (TLE). The side and location of the primary epileptogenic area of these patients (5 left TLE, 8 right TEL) was determined invasively during presurgical evaluation. During a 1-2 minute interval after intravenous bolus injection of 100 mg methohexital a clear lateralization effect in the beta band was observed, which differed marginally between fronto-central, fronto-temporal and temporo-parietal brain regions. In addition, bilateral spectral power changes were obtained in the theta, alpha and gamma bands that differed between brain regions. Analyses of simultaneously recorded scalp electroencephalographic (EEG) data revealed effects consistent with those of the MEG analysis. The reduced enhancement of beta band spectral power of MEG recordings provides a potential application for the non-invasive lateralization of the primary epileptogenic area.

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 cm3 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 spike generated in deep temporomesial structures may escape the MEG registration.

Combined EEG and MEG recordings of visual 40 Hz responses to illusory triangles in human.

EEG and MEG were simultaneously recorded to study the visual gamma-band (30-70 Hz) responses. The electrical gamma-band response phase-locked to stimulus onset can be subdivided into a central component at 39 Hz and an occipital component at 36 Hz. A new high-frequency magnetic phase-locked response recorded over the occipital lobe is described. Its topography is complex and probably reflects the activity of multiple sources. Both electrical and magnetic high-frequency responses differ in topography from the low-frequency responses in the same latency range, suggesting that at least partially distinct sources are involved. The existence of a non-phase-locked 40 Hz component around 280 ms is confirmed in EEG data but is not detectable in MEG data.

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.

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.

Increased cortical representation of the fingers of the left hand in string players.

Magnetic source imaging revealed that the cortical representation of the digits of the left hand of string players was larger than that in controls. The effect was smallest for the left thumb, and no such differences were observed for the representations of the right hand digits. The amount of cortical reorganization in the representation of the fingering digits was correlated with the age at which the person had begun to play. These results suggest that the representation of different parts of the body in the primary somatosensory cortex of humans depends on use and changes to conform to the current needs and experiences of the individual.

Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.

Although phantom-limb pain is a frequent consequence of the amputation of an extremity, little is known about its origin. On the basis of the demonstration of substantial plasticity of the somatosensory cortex after amputation or somatosensory deafferentation in adult monkeys, it has been suggested that cortical reorganization could account for some non-painful phantom-limb phenomena in amputees and that cortical reorganization has an adaptive (that is, pain-preventing) function. Theoretical and empirical work on chronic back pain has revealed a positive relationship between the amount of cortical alteration and the magnitude of pain, so we predicted that cortical reorganization and phantom-limb pain should be positively related. Using non-invasive neuromagnetic imaging techniques to determine cortical reorganization in humans, we report a very strong direct relationship (r = 0.93) between the amount of cortical reorganization and the magnitude of phantom limb pain (but not non-painful phantom phenomena) experienced after arm amputation. These data indicate that phantom-limb pain is related to, and may be a consequence of, plastic changes in primary somatosensory cortex.

Neuromagnetic source analysis using magnetic resonance images for the construction of source and volume conductor model.

Sources of the somatosensory evoked fields (SEF) for one subject were estimated using constraints from the magnetic resonance images (MRI) of the same subject. A realistic volume conductor model was shaped corresponding to the inside of the skull. Sources were restricted to a dipole patch riding on the surface of the cortex, reconstructed from the individual MRI. Such a patch can be considered as a uniformly activated cortical area giving rise to distributed currents which flow perpendicular to the cortical surface. Source locations obtained for the SEF in response to separate stimulations of lower lip, first and fifth digit, and collarbone followed the course of the contralateral central sulcus. The order of the estimated source locations was in agreement with the somatosensory homunculus of Penfield and Rasmussen. Similar results were obtained with the simple model of a current dipole in a homogeneous sphere. In contrast, combining a current dipole model with a realistic volume conductor model was rather problematic as it overestimates the radial dipole component by an order of magnitude.