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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.)

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., (Copyright © 2017 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.)

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.

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.

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.

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.

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.

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.

New perspectives in neurorehabilitation suggest that behavioral treatments of movement disorders may modify the functional organization of central somatosensory neural networks. On the basis of the assumption that use-dependent reorganization in these networks contributes to the fundamental abnormalities seen in focal dystonia, we treated 10 affected musicians and measured the concomitant somatosensory changes by using whole-head magnetoencephalography. We found that effective treatment, using the method of sensory motor retuning, leads to alterations in the functional organization of the somatosensory cortex. Specifically, before treatment, somatosensory relationships of the individual fingers differ between the affected and unaffected hands, whereas after treatment, finger representations contralateral to the dystonic side become more similar to the less-affected side. Further, somatosensory finger representations are ordered more according to homuncular principles after treatment. In addition, the observed physiologic changes correlated with behavioral data. These results confirm that plastic changes in parallel with emergent neurological dysfunction may be reversed by context-specific, intensive training-based remediation.

Background and Purpose: Patients with Alzheimer disease (AD) have more low-frequency activity on conventional EEG and increased focal magnetoencephalographic (MEG) dipole density (DD) in delta and theta bands. This activity concurs with atrophy and reduced metabolic and perfusion rates, particularly in temporoparietal structures. The relationship between functional and structural measures and their conjoined capability to improve the diagnosis of AD were assessed in this study., Methods: Whole-head MEG recordings were obtained in 15 patients in whom the diagnosis of AD had been made and in 16 healthy control subjects during a resting condition. MR imaging volumetric data were also obtained; these included global cerebral, temporal lobe, and hippocampal volumes., Results: DD in the delta and theta bands was enhanced in the AD group compared with the healthy control subjects. Slow-wave activity differed significantly between the groups in the temporoparietal regions of both hemispheres. Left hippocampal volume was correlated with left temporal and parietal delta DD and left temporal theta DD. A combination of left hippocampal volume and left temporal theta DD enabled correct classification in 87.1% of the patients with AD or control subjects., Conclusion: Results support the predominant role of temporoparietal hypofunction as defined by DD and hippocampal structural deficits shown on MR images in patients with AD. A multidisciplinary perspective of different techniques may improve our understanding of the disease and our diagnostic abilities.

Background: Patients suffering from Alzheimer's disease exhibit more activity in the conventional electroencephalographic delta and theta bands. This activity concurs with atrophy and reduced metabolic and perfusion rates, particularly in temporoparietal structures., Methods: Whole-head magnetoencephalographic recordings were obtained from 15 patients diagnosed with Alzheimer's disease and 19 healthy control subjects during a resting condition. The generators of focal magnetic slow waves were located employing a single moving dipole model., Results: Dipole density in the delta and theta bands was enhanced in the Alzheimer's disease group compared with healthy control subjects. Slow-wave activity differed significantly between groups in temporoparietal regions of both hemispheres. Right temporoparietal slow-wave activity covaried with cognitive performance, whereas left temporal delta activity varied with a functional status scale., Conclusions: Our results support the predominant role of the temporoparietal areas in the diagnosis of Alzheimer's disease. Magnetoencephalography and the source analysis of focal slow activity in particular provide interesting and potentially clinically useful tools to assess functional modifications of patients' brain and to evaluate its relationship with the cognitive status.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.