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Abstract Background The hippocampus is a brain region that is particularly affected by age-related morphological changes. It is generally assumed that a loss in hippocampal volume results in functional deficits that contribute to age-related cognitive decline. In a combined cross-sectional behavioural and magnetoencephalography (MEG) study we investigated whether hippocampal-associated neural current flow during a transverse patterning task - which requires learning relational associations between stimuli - correlates with age and whether it is modulated by cognitive competence. Results Better performance in several tests of verbal memory, verbal fluency and executive function was indeed associated with higher hippocampal neural activity. Age, however, was not related to the strength of hippocampal neural activity: elderly participants responded slower than younger individuals but on average produced the same neural mass activity. Conclusions Our results suggest that in non-pathological aging, hippocampal neural activity does not decrease with age but is rather related to cognitive competence.

Abstract Background Repeated traumatic experiences, e.g. torture and war, lead to functional and structural cerebral changes, which should be detectable in cortical dynamics. Abnormal slow waves produced within circumscribed brain regions during a resting state have been associated with lesioned neural circuitry in neurological disorders and more recently also in mental illness. Methods Using magnetoencephalographic (MEG-based) source imaging, we mapped abnormal distributions of generators of slow waves in 97 survivors of torture and war with posttraumatic stress disorder (PTSD) in comparison to 97 controls. Results PTSD patients showed elevated production of focally generated slow waves (1–4 Hz), particularly in left temporal brain regions, with peak activities in the region of the insula. Furthermore, differential slow wave activity in right frontal areas was found in PTSD patients compared to controls. Conclusion The insula, as a site of multimodal convergence, could play a key role in understanding the pathophysiology of PTSD, possibly accounting for what has been called posttraumatic alexithymia, i.e., reduced ability to identify, express and regulate emotional responses to reminders of traumatic events. Differences in activity in right frontal areas may indicate a dysfunctional PFC, which may lead to diminished extinction of conditioned fear and reduced inhibition of the amygdala.

Abstract Background Slow waves in the delta (0.5–4 Hz) frequency range are indications of normal activity in sleep. In neurological disorders, focal electric and magnetic slow wave activity is generated in the vicinity of structural brain lesions. Initial studies, including our own, suggest that the distribution of the focal concentration of generators of slow waves (dipole density in the delta frequency band) also distinguishes patients with psychiatric disorders such as schizophrenia, affective disorders, and posttraumatic stress disorder. Methods The present study examined the distribution of focal slow wave activity (ASWA: abnormal slow wave activity) in116 healthy subjects, 76 inpatients with schizophrenic or schizoaffective diagnoses and 42 inpatients with affective (ICD-10: F3) or neurotic/reactive (F4) diagnoses using a newly refined measure of dipole density. Based on 5-min resting magnetoencephalogram (MEG), sources of activity in the 1–4 Hz frequency band were determined by equivalent dipole fitting in anatomically defined cortical regions. Results Compared to healthy subjects the schizophrenia sample was characterized by significantly more intense slow wave activity, with maxima in frontal and central areas. In contrast, affective disorder patients exhibited less slow wave generators mainly in frontal and central regions when compared to healthy subjects and schizophrenia patients. In both samples, frontal ASWA were related to affective symptoms. Conclusion In schizophrenic patients, the regions of ASWA correspond to those identified for gray matter loss. This suggests that ASWA might be evaluated as a measure of altered neuronal network architecture and communication, which may mediate psychopathological signs.

Abstract Background The aim of this study was to investigate brain responses triggered by different wordclasses in dyslexic and control children. The majority of dyslexic children have difficulties to phonologically assemble a word from sublexical parts following grapheme-to-phoneme correspondences. Therefore, we hypothesised that dyslexic children should mainly differ from controls processing low frequent words that are unfamiliar to the reader. Methods We presented different wordclasses (high and low frequent words, pseudowords) in a rapid serial visual word (RSVP) design and performed wavelet analysis on the evoked activity. Results Dyslexic children had lower evoked power amplitudes and a higher spectral frequency for low frequent words compared to control children. No group differences were found for high frequent words and pseudowords. Control children had higher evoked power amplitudes and a lower spectral frequency for low frequent words compared to high frequent words and pseudowords. This pattern was not present in the dyslexic group. Conclusion Dyslexic children differed from control children only in their brain responses to low frequent words while showing no modulated brain activity in response to the three word types. This might support the hypothesis that dyslexic children are selectively impaired reading words that require sublexical processing. However, the lacking differences between word types raise the question if dyslexic children were able to process the words presented in rapid serial fashion in an adequate way. Therefore the present results should only be interpreted as evidence for a specific sublexical processing deficit with caution.

Abstract Background The present study was dedicated to investigate the influence of Methylphenidate (MPH) on cortical processing of children who were diagnosed with different subtypes of Attention Deficit Hyperactivity Disorder (ADHD). As all of the previous studies investigating power differences in different frequency bands have been using EEG, mostly with a relatively small number of electrodes our aim was to obtain new aspects using high density magnetoencephalography (MEG). Methods 35 children (6 female, 29 male) participated in this study. Mean age was 11.7 years (± 1.92 years). 17 children were diagnosed of having an Attention-Deficit/Hyperactivity Disorder of the combined type (ADHDcom, DSM IV code 314.01); the other 18 were diagnosed for ADHD of the predominantly inattentive type (ADHDin, DSM IV code 314.0). We measured the MEG during a 5 minute resting period with a 148-channel magnetometer system (MAGNES™ 2500 WH, 4D Neuroimaging, San Diego, USA). Power values were averaged for 5 bands: Delta (D, 1.5–3.5 Hz), Theta (T, 3.5–7.5 Hz), Alpha (A, 7.5–12.5 Hz), Beta (B, 12.5–25 Hz) and Global (GL, 1.5–25 Hz).). Additionally, attention was measured behaviourally using the D2 test of attention with and without medication. Results The global power of the frequency band from 1.5 to 25 Hz increased with MPH. Relative Theta was found to be higher in the left hemisphere after administration of MPH than before. A positive correlation was found between D2 test improvement and MPH-induced power changes in the Theta band over the left frontal region. A linear regression was computed and confirmed that the larger the improvement in D2 test performance, the larger the increase in Theta after MPH application. Conclusion Main effects induced by medication were found in frontal regions. Theta band activity increased over the left hemisphere after MPH application. This finding contradicts EEG results of several groups who found lower levels of Theta power after MPH application. As relative Theta correlates with D2 test improvement we conclude that MEG provide complementary and therefore important new insights to ADHD.

Abstract 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 included 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 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.

Abstract Background Focal clusters of slow wave activity in the delta frequency range (1–4 Hz), as measured by magnetencephalography (MEG), are usually located in the vicinity of structural damage in the brain. Such oscillations are usually considered pathological and indicative of areas incapable of normal functioning owing to deafferentation from relevant input sources. In the present study we investigated the change in Delta Dipole Density in 28 patients with chronic aphasia (>12 months post onset) following cerebrovascular stroke of the left hemisphere before and after intensive speech and language therapy (3 hours/day over 2 weeks). Results Neuropsychologically assessed language functions improved significantly after training. Perilesional delta activity decreased after therapy in 16 of the 28 patients, while an increase was evident in 12 patients. The magnitude of change of delta activity in these areas correlated with the amount of change in language functions as measured by standardized language tests. Conclusions These results emphasize the significance of perilesional areas in the rehabilitation of aphasia even years after the stroke, and might reflect reorganisation of the language network that provides the basis for improved language functions after intensive training.

Enduring physical strain is an important ability and prototypically required in athletic activities. However, little is known about the psychological determinants of endurance performance and their underlying neural mechanisms. Here, we investigated self-regulation as one such factor. We recruited 60 participants who hold intertwined rings for as long as possible while avoiding contacts between them, either with a goal intention or an implementation intention to perform well. Performance was measured in terms of time-to-failure and contact errors. Additionally, we repeatedly assessed ratings of perceived exertion (RPE) and pain (RPP) and used functional near-infrared spectroscopy (fNIRS) to continuously monitor cerebral oxygenation in dorsal and ventral parts of the lateral prefrontal cortex (LPFC), brain regions associated with effortful attentional control and response inhibition, respectively. Performance, RPE and RPP were similar in the goal and the implementation intention condition. LPFC activity increased over time, but its activation level was generally lower in the implementation intention condition. Both effects were particularly pronounced in the dorsal LPFC. Moreover, the balance between effortful and more automatic regulation seems to differ between self-regulation strategies. Our results indicate that self-regulation plays an important role in endurance performance and that self-regulatory processes during endurance performance might be reflected in LPFC activation.

Schizophrenia patients exhibit less gamma-frequency EEG/MEG activity (>30 Hz), a finding interpreted as evidence of poor temporal neural organization and functional network communication. Research has shown that neuroplasticity-oriented training can improve task-related oscillatory dynamics, indicating some reorganization capacity in schizophrenia. Demonstrating a generalization of such task training effects to spontaneous oscillations at rest would not only enrich understanding of this neuroplastic potential but inform the interpretation of spontaneous gamma oscillations in the service of normal cognitive function. In the present study, neuromagnetic resting-state oscillatory brain activity and cognitive performance were assessed before and after training in 61 schizophrenia patients, who were randomly assigned to 4 weeks of neuroplasticity-oriented targeted cognitive training or treatment as usual (TAU). Gamma power of 40-90 Hz increased after training, but not after TAU, in a frontoparietal network. Across two types of training, this increase was related to improved cognitive test performance. These results indicate that abnormal oscillatory dynamics in schizophrenia patients manifested in spontaneous gamma activity can be changed with neuroplasticity-oriented training parallel to cognitive performance., (© 2018 Society for Psychophysiological Research.)

Post-Traumatic Stress Disorder (PTSD) has been linked to deviations in lateralized frontal functional oscillatory activity. This is possibly because left and right DLPFC have differential roles in regulating both memory and stress response, which are both dysfunctional in PTSD. However, previous results are heterogeneous, and could be attributable to individual symptom clusters, traumatic or aggressive life events, early life stress, or the interaction of these factors. In a large sample of active combatants (N=401), we regressed these factors on frontal electroencephalography (EEG) asymmetry across 5 frequency bands (delta: 2-4Hz; theta: 4-8Hz; alpha: 8-12Hz; beta: 12-24Hz; gamma: 24-48Hz). Negative cognition and mood was associated with stronger relative left delta and theta band power. Traumatic life events showed stronger right alpha and beta band power. Traumatic life events in interaction with hyperarousal predicted stronger relative right left-right imbalance (theta, alpha, and beta bands), whereas childhood adversity, in interaction with negative cognition and mood, predicted stronger relative left left-right imbalance (delta, theta, alpha and beta bands). The contribution of lateralized DLPFC dysfunction to PTSD is thus dependent on the individual complexities of subsymptom clusters and life history, and future studies need to take these factors into account., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Dysfunctional emotion processing has been discussed as a contributing factor to functional neurological symptoms (FNS) in the context of conversion disorder, and refers to blunted recognition and the expression of one's own feelings. However, the emotion processing components characteristic for FNS and/or relevant for conversion remain to be specified. With this goal, the present study targeted the initial, automatic discrimination of emotionally salient stimuli., Methods: The magnetoencephalogram (MEG) was monitored in 21 patients with functional weakness and/or sensory disturbance subtypes of FNS and 21 healthy comparison participants (HC) while they passively watched 600 emotionally arousing, pleasant, unpleasant or neutral stimuli in a rapid serial visual presentation (RSVP) design. Neuromagnetic activity was analyzed 110-330ms following picture onset in source space for prior defined posterior and central regions of interest., Results: As early as 110ms and across presentation interval, posterior neural activity modulation by picture category was similar in both groups, despite smaller initial (110-150ms) overall and posterior power in patients with FNS. The initial activity modulation by picture category was also evident in the left sensorimotor area in patients with FNS, but not significant in HC., Conclusions: Similar activity modulation by emotional picture category in patients with FNS and HC suggests that the fast, automatic detection of emotional salience is unchanged in patients with FNS, but involves an emotion-processing network spanning posterior and sensorimotor areas., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cognitive interference control is disrupted in schizophrenia (SZ). Neuroimaging studies relate interference control to 4-7 Hz (theta) neural activity in a network spanning prefrontal, anterior cingulate (ACC), and parietal cortices. The mechanism of communication in this network and how it is disrupted in schizophrenia are unclear. Behavioral performance and EEG theta oscillations were examined in a Stroop color-word interference task in 17 healthy controls (HC) and 14 SZ patients. Color-word incongruence induced less theta power increase in SZ than in HC around 400 ms and 600-900 ms after word onset in ACC, left middle frontal gyrus (MFG), and inferior parietal regions. Coupling of ACC theta phase to MFG gamma amplitude, indexing interregional communication, was weaker in SZ than in HC. Results suggest ACC-MFG theta power modulation as a mechanism of interference control that supports executive function and is disrupted in schizophrenia., (© 2014 Society for Psychophysiological Research.)

Deficits in social cognition including facial affect recognition and their detrimental effects on functional outcome are well established in schizophrenia. Structured training can have substantial effects on social cognitive measures including facial affect recognition. Elucidating training effects on cortical mechanisms involved in facial affect recognition may identify causes of dysfunctional facial affect recognition in schizophrenia and foster remediation strategies. In the present study, 57 schizophrenia patients were randomly assigned to (a) computer-based facial affect training that focused on affect discrimination and working memory in 20 daily 1-hour sessions, (b) similarly intense, targeted cognitive training on auditory-verbal discrimination and working memory, or (c) treatment as usual. Neuromagnetic activity was measured before and after training during a dynamic facial affect recognition task (5 s videos showing human faces gradually changing from neutral to fear or to happy expressions). Effects on 10-13 Hz (alpha) power during the transition from neutral to emotional expressions were assessed via MEG based on previous findings that alpha power increase is related to facial affect recognition and is smaller in schizophrenia than in healthy subjects. Targeted affect training improved overt performance on the training tasks. Moreover, alpha power increase during the dynamic facial affect recognition task was larger after affect training than after treatment-as-usual, though similar to that after targeted perceptual-cognitive training, indicating somewhat nonspecific benefits. Alpha power modulation was unrelated to general neuropsychological test performance, which improved in all groups. Results suggest that specific neural processes supporting facial affect recognition, evident in oscillatory phenomena, are modifiable. This should be considered when developing remediation strategies targeting social cognition in schizophrenia.

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a non-invasive therapy for the treatment of neurological disorders such as depression, schizophrenia, tinnitus, and epilepsy. Complex interdependencies between stimulus duration, frequency and intensity obscure the exact effects of rTMS stimulation on neural activity in the cortex, making evaluation of and comparison between rTMS studies difficult. To explain the influence of rTMS on neural activity (e.g. in the motor cortex), we use a neuronal network model. The results demonstrate that the model adequately explains experimentally observed short term effects of rTMS on the band power in common frequency bands used in electroencephalography (EEG). We show that the equivalent local field potential (eLFP) band power depends on stimulation intensity rather than on stimulation frequency. Additionally, our model resolves contradictions in experiments.

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.

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., (Copyright © 2011 Society for Psychophysiological Research.)

Allocating electromagnetic auditory responses to active regions in the human auditory cortex can be difficult because of high interindividual variability of the relevant structures. Location and orientation of the primary auditory cortex (Heschl's Gyrus) and the temporal plane vary with individual features such as age, gender, handedness, or between healthy subjects and patients with a psychiatric disorder (e.g., schizophrenia). Here, we propose a reference coordinate system that considers the individual MRI-based position, orientation and length of the primary auditory cortex to account for interindividual variability. Transformation of the M50 dipole localizations in this new HG-(Heschl's-Gyrus)-coordinate system, accomplished for 10 healthy subjects and 10 schizophrenia patients, confirmed group difference more precisely than other registration methods. We suggest to use the HG-coordinate system for localization of functional measures and evaluation of brain activity differences between groups or measurement conditions., (Copyright 2010 Elsevier B.V. All rights reserved.)

It has been found in numerous electroencephalographic (EEG) studies that a negative potential arises following an erroneous response (so-called Error-Related Negativity, ERN). This typical component of the EEG has, however, proven more difficult to identify when transferring analogous paradigms to magnetoencephalography (MEG). The aim of this study was to devise and apply a paradigm to elicit erroneous responses and using MEG to measure both the error-related evoked brain activity (mERN) as well as accompanying induced oscillatory activity. Results clearly demonstrate that it is possible to measure the mERN and to identify cortical sources associated with it. Using distributed source modeling, it is possible to identify the mERN in source space and corroborate EEG findings, with the mERN generated in the anterior cingulate cortex (ACC). This supports notions regarding the role of the ACC in error monitoring and cognitive control of motor behavior. Furthermore, changes in induced oscillatory activity were observed in the theta and beta bands. This extends previous studies, which show that evoked theta activity could underlie the generation of the ERN., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

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 (<200 ms) of emotional stimuli without substantially affecting activity modulation by stimulus arousal value, (2) diminish later attention allocation processes (>300 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., (Copyright 2009 Elsevier B.V. All rights reserved.)

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.

Functional recovery in response to a brain lesion, such as a stroke, can even occur years after the incident and may be accelerated by effective rehabilitation strategies. In eleven chronic aphasia patients, we administered a short-term intensive language training to improve language functions and to induce cortical reorganization under rigorously controlled conditions. Overt naming performance was assessed during functional magnetic resonance imaging (fMRI) prior to and immediately after the language training. Regions of interest (ROIs) for statistical analyses were constituted by areas with individually determined abnormally high densities of slow wave generators (identified by magnetoencephalography prior to the language intervention) that clustered mainly in left perilesional areas. Three additional individually defined regions served to control for the specificity of the results for the selected respective target region: the homologue area of the individual patient's lesion, the mirror image of the delta ROI in the right hemisphere and left hemispheric regions that did not produce a significant amount of slow wave activity. Treatment-induced changes of fMRI brain activation were highly correlated with improved naming of the trained pictures, but selectively within the pre-training dysfunctional perilesional brain areas. Our results suggest that remodeling of cortical functions is possible even years after a stroke. The behavioral gain seems to be mediated by brain regions that had been partially deprived from input after the initial stroke. We therefore provide first time direct evidence for the importance of treatment-induced functional reintegration of perilesional areas in a heterogeneous sample of chronic aphasia patients.

Background: Repeated traumatic experiences, e.g. torture and war, lead to functional and structural cerebral changes, which should be detectable in cortical dynamics. Abnormal slow waves produced within circumscribed brain regions during a resting state have been associated with lesioned neural circuitry in neurological disorders and more recently also in mental illness., Methods: Using magnetoencephalographic (MEG-based) source imaging, we mapped abnormal distributions of generators of slow waves in 97 survivors of torture and war with posttraumatic stress disorder (PTSD) in comparison to 97 controls., Results: PTSD patients showed elevated production of focally generated slow waves (1-4 Hz), particularly in left temporal brain regions, with peak activities in the region of the insula. Furthermore, differential slow wave activity in right frontal areas was found in PTSD patients compared to controls., Conclusion: The insula, as a site of multimodal convergence, could play a key role in understanding the pathophysiology of PTSD, possibly accounting for what has been called posttraumatic alexithymia, i.e., reduced ability to identify, express and regulate emotional responses to reminders of traumatic events. Differences in activity in right frontal areas may indicate a dysfunctional PFC, which may lead to diminished extinction of conditioned fear and reduced inhibition of the amygdala.

Background: Slow waves in the delta (0.5-4 Hz) frequency range are indications of normal activity in sleep. In neurological disorders, focal electric and magnetic slow wave activity is generated in the vicinity of structural brain lesions. Initial studies, including our own, suggest that the distribution of the focal concentration of generators of slow waves (dipole density in the delta frequency band) also distinguishes patients with psychiatric disorders such as schizophrenia, affective disorders, and posttraumatic stress disorder., Methods: The present study examined the distribution of focal slow wave activity (ASWA: abnormal slow wave activity) in 116 healthy subjects, 76 inpatients with schizophrenic or schizoaffective diagnoses and 42 inpatients with affective (ICD-10: F3) or neurotic/reactive (F4) diagnoses using a newly refined measure of dipole density. Based on 5-min resting magnetoencephalogram (MEG), sources of activity in the 1-4 Hz frequency band were determined by equivalent dipole fitting in anatomically defined cortical regions., Results: Compared to healthy subjects the schizophrenia sample was characterized by significantly more intense slow wave activity, with maxima in frontal and central areas. In contrast, affective disorder patients exhibited less slow wave generators mainly in frontal and central regions when compared to healthy subjects and schizophrenia patients. In both samples, frontal ASWA were related to affective symptoms., Conclusion: In schizophrenic patients, the regions of ASWA correspond to those identified for gray matter loss. This suggests that ASWA might be evaluated as a measure of altered neuronal network architecture and communication, which may mediate psychopathological signs.

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.

Children with attention deficit hyperactivity disorder have difficulties with tasks that require response inhibition. We measured electroencephalographic data of nonmedicated children with attention deficit hyperactivity disorder and control children in two conditions: (a) a neutral condition without a self-regulation strategy and (b) a condition that involved the making of if-then plans (i.e. 'If situation X is encountered, then I will perform the goal-directed behavior Y'). If-then plans improved response inhibition and increased the P300 in children with attention deficit hyperactivity disorder compared with the neutral condition. The present results encourage the application of self-regulation using if-then plans in addition or as an alternative to common medical therapy.

Deficient phonological skills are considered to be a core problem in developmental dyslexia. Children with dyslexia often demonstrate poorer performance than non-impaired readers when categorizing speech-sounds. Using the automatic mismatch response, we show that in contrast to this deficit at the behavioural level, neurophysiological responding in dyslexic children indicates their ability to automatically discriminate syllables. Therefore, the phonological deficit is unlikely to be caused by a temporal deficit or by a noisy functional organization in the respective representational cortex. We obtained measures of reading, spelling and categorical speech-perception from 58 dyslexic children and 21 control children. The children also participated in magnetoencephalographic measurements while being stimulated acoustically with the syllables /ba/ and /da/ in an oddball paradigm. Mismatch field (MMF) amplitudes between standard and deviant stimuli were obtained. Dyslexic children performed more poorly than control children on all test measures. However, the groups did not differ in MMF amplitude or latency. No correlations were found between MMF amplitudes and behavioural performance. These results were obtained with a large sample size and thus speak robustly against a general deficit in auditory discrimination in dyslexia. These results are compatible with the idea that decoding difficulties occur later in the processing stream where access to the phonological lexicon is attempted.

We used the 40-Hz auditory steady-state response (SSR) to compare for the first time tonotopic frequency representations in the region of primary auditory cortex (PAC) between subjects with chronic tinnitus and hearing impairment and normal hearing controls. Frequency representations were measured in normal hearing (n=17) and tinnitus (n=28) subjects using eight carrier frequencies between 384 and 6561 Hz, each amplitude modulated (AM) at 40-Hz on trials of 3 min duration under passive attention. In normal hearing subjects, frequency gradients were observed in the medial-lateral, anterior-posterior, and inferior-superior axes, which were consistent with the orientation of Heschl's gyrus and with functional organization revealed by fMRI investigations. The frequency representation in the right hemisphere was approximately 5 mm anterior and approximately 7 mm lateral to that in the left hemisphere, corroborating with MEG measurements hemispheric asymmetries reported by cytoarchitectonic studies of the PAC and by MRI morphometry. In the left hemisphere, frequency gradients were inflected near 2 kHz in normal hearing subjects. These SSR frequency gradients were attenuated in both hemispheres in tinnitus subjects. Dipole power was also elevated in tinnitus, suggesting that more neurons were entrained synchronously by the AM envelope. These findings are consistent with animal experiments reporting altered tonotopy and changes in the response properties of auditory cortical neurons after hearing loss induced by noise exposure. Degraded frequency representations in tinnitus may reflect a loss of intracortical inhibition in deafferented frequency regions of the PAC after hearing injury.

From a neuroscience perspective, little is known about the long-term effect of torture. Dissociative experiences and posttraumatic stress disorder are often the results of this experience. We examined psychological dissociation within a group of 23 torture victims and report its manifestations within neural networks in the human brain. In particular, we observed that dissociative experiences are associated with slow abnormal brain waves generated in left ventrolateral frontal cortex. Given that focal slow waves often result from depriving neural networks of major input, the present results may indicate decoupling of frontal affective processors from left cortical language areas. This interpretation is consistent with the fact that disturbed access to structured verbal memory concerning traumatic events is a core feature of the dissociative experience.

There still is a need for devices that allow reproducible stimulation of skin areas of the human body. We constructed a stimulation system and tested it by using brief pneumatic stimulation to the right thumb of nine healthy volunteers. BOLD-signals in response to tactile stimulation with frequencies of 1, 3 and 5 Hz were measured using a 3T MRI scanner. The stimulation device consists of synthetic membranes connected to plastic tubes capable of carrying compressed air, and an electronic component, which controls the on- and off-switching of an electromagnetic valve. The valve near the MR-scanner did not lower the image quality. Primary somatosensory activation contralateral to the stimulation site was reliably detected in response to a stimulus magnitude of 3.5 bar in all volunteers. 1 Hz stimulation resulted in higher maximal percentage BOLD-signal changes. Our device is an easy-to-construct, low-cost and portable tool suitable for research and clinical environments. It permits passive non-painful stimulation relevant for clinical assessments and is also compatible with magnetoencephalography (MEG) and electroencephalography (EEG). In basic and clinical research, this device therefore contributes to meaningful comparisons between results obtained with different techniques.

Background: The aim of this study was to investigate brain responses triggered by different wordclasses in dyslexic and control children. The majority of dyslexic children have difficulties to phonologically assemble a word from sublexical parts following grapheme-to-phoneme correspondences. Therefore, we hypothesised that dyslexic children should mainly differ from controls processing low frequent words that are unfamiliar to the reader., Methods: We presented different wordclasses (high and low frequent words, pseudowords) in a rapid serial visual word (RSVP) design and performed wavelet analysis on the evoked activity., Results: Dyslexic children had lower evoked power amplitudes and a higher spectral frequency for low frequent words compared to control children. No group differences were found for high frequent words and pseudowords. Control children had higher evoked power amplitudes and a lower spectral frequency for low frequent words compared to high frequent words and pseudowords. This pattern was not present in the dyslexic group., Conclusion: Dyslexic children differed from control children only in their brain responses to low frequent words while showing no modulated brain activity in response to the three word types. This might support the hypothesis that dyslexic children are selectively impaired reading words that require sublexical processing. However, the lacking differences between word types raise the question if dyslexic children were able to process the words presented in rapid serial fashion in an adequate way. Therefore the present results should only be interpreted as evidence for a specific sublexical processing deficit with caution.

Animal studies show that following damage to inner-ear receptors, central representations of intact lesion-edge (LE) frequencies become enlarged (map reorganization). One theory of tinnitus holds that this process could be related to the tinnitus sensation. To test this hypothesis, neuromagnetic evoked fields of tinnitus participants with high-frequency hearing loss and normal hearing controls were measured, while subjects listened to monaurally presented LE or control (CO; an octave below LE) tones. The predictions made based on the map reorganization hypothesis of tinnitus were that neuronal responses to LE frequencies would be enhanced, and that source localizations for LE would be distorted. N1m equivalent dipole moments for LE were not supranormal in the tinnitus group, whereas responses to CO of tinnitus patients compared to controls were enlarged in the right hemisphere. This effect was positively associated with tinnitus-related distress. Abnormal source locations were found for generators activated by LE tones in the right hemisphere of the tinnitus group. This right-hemispheric map distortion was not associated with subjective variables of tinnitus. A positive correlation with tinnitus distress was found for the left hemisphere with more anterior sources being associated with enhanced distress. However, this result was independent of the frequency of the stimulus. Overall, the present study suggests that mechanisms of map reorganization, although present in the data, cannot satisfactorily explain the emergence of tinnitus and that differential hemispheric involvement must be considered.

Background: The present study was dedicated to investigate the influence of Methylphenidate (MPH) on cortical processing of children who were diagnosed with different subtypes of Attention Deficit Hyperactivity Disorder (ADHD). As all of the previous studies investigating power differences in different frequency bands have been using EEG, mostly with a relatively small number of electrodes our aim was to obtain new aspects using high density magnetoencephalography (MEG)., Methods: 35 children (6 female, 29 male) participated in this study. Mean age was 11.7 years (+/- 1.92 years). 17 children were diagnosed of having an Attention-Deficit/Hyperactivity Disorder of the combined type (ADHDcom, DSM IV code 314.01); the other 18 were diagnosed for ADHD of the predominantly inattentive type (ADHDin, DSM IV code 314.0). We measured the MEG during a 5 minute resting period with a 148-channel magnetometer system (MAGNES 2500 WH, 4D Neuroimaging, San Diego, USA). Power values were averaged for 5 bands: Delta (D, 1.5-3.5 Hz), Theta (T, 3.5-7.5 Hz), Alpha (A, 7.5-12.5 Hz), Beta (B, 12.5-25 Hz) and Global (GL, 1.5-25 Hz).). Additionally, attention was measured behaviourally using the D2 test of attention with and without medication., Results: The global power of the frequency band from 1.5 to 25 Hz increased with MPH. Relative Theta was found to be higher in the left hemisphere after administration of MPH than before. A positive correlation was found between D2 test improvement and MPH-induced power changes in the Theta band over the left frontal region. A linear regression was computed and confirmed that the larger the improvement in D2 test performance, the larger the increase in Theta after MPH application., Conclusion: Main effects induced by medication were found in frontal regions. Theta band activity increased over the left hemisphere after MPH application. This finding contradicts EEG results of several groups who found lower levels of Theta power after MPH application. As relative Theta correlates with D2 test improvement we conclude that MEG provide complementary and therefore important new insights to ADHD.

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 included 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 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.

Using neuromagnetic source imaging, we investigated tonotopic representation and direction sensitivity in the auditory cortex of humans (N = 15). For this purpose, source analysis was undertaken at every single sampling point during the presentation of a frequency-modulated tone (FM) sweeping slowly downward or upward across periods of 3 s duration. Stimuli were selected to target response properties of the central part of the primary auditory cortical field, which has been shown to exhibit sensitivity to distinct FM-sound features as compared to the ventral and dorsal part. Linear mixed-effects model statistics confirm tonotopic gradients in medial-lateral and anterior-posterior directions. The high resolution provided by this method revealed that the relationship between frequency and spatial location of the responding neural tissue is nonlinear. The idea that neurons specifically sensitive to the employed sound characteristics (slow, downward modulation) were activated is supported by the fact that the upward sweep of identical duration produced a different pattern of functional organisation.

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.