Martin Kaltenhäuser

Temporo-spatial analysis of cortical activation by phasic innocuous and noxious cold stimuli - a magnetoencephalographic study

&NA; Clinical findings and recent non‐invasive functional imaging studies pinpoint the insular cortex as the crucial brain area involved in cold sensation. By contrast, the role of primary (SI) and secondary (SII) somatosensory cortices in central processing of cold is controversial. So far, temporal activation patterns of cortical areas involved in cold processing have not been examined. Using magnetoencephalography, we studied, in seven healthy subjects, the temporo‐spatial dynamics of brain processes evoked by innocuous and noxious cold stimulation as compared to tactile stimuli. For this purpose, a newly designed and magnetically silent cold‐stimulator was employed. In separate runs, cold and painful cold stimuli were delivered to the dorsum of the right hand. Tactile afferents were stimulated by pneumatic tactile stimulation. Following innocuous cold stimulation (&Dgr;T=5±0.3°C in 50±2 ms), magnetic source imaging revealed an exclusive activation of the contra‐ and ipsilateral posterior insular cortex. The mean peak latencies were 194.3±38.1 and 241.0±31.7 ms for the response in the ipsi‐ and contralateral insular cortex, respectively. Based on the measurement of onset latencies, the estimated conduction velocity of peripheral nerve fibres mediating cold fell in the range of A&dgr;‐fibres (7.4±0.8 m/s). Noxious cold stimulation (&Dgr;T=35±5°C in 70±12 ms) initially activated the contra‐ and ipsilateral insular cortices in the same latency ranges as innocuous cold stimuli. Additionally, we found an activation of the contra‐ and ipsilateral SII areas (peak latencies 304±22.7 and 310.1±19.4 ms, respectively) and a variable activation of the cingulate cortex. Notably, neither cold‐ nor painful cold stimulation produced an activation of SI. By contrast, the evoked cortical responses following tactile stimulation could be located to the contralateral SI cortex and bilateral SII. In conclusion, this study strongly corroborates the posterior insular cortex as the primary somatosensory area for cortical processing of cold sensation. Furthermore, it supports the role of SII and the cingulate cortex in mediating freeze‐pain. Therefore, these results suggest different processing of cold, freeze‐pain and touch in the human brain.

Cortical activity associated with auditory hallucinations.

Auditory hallucinations are one the most enigmatic and hampering symptoms associated with schizophrenia. Non-invasive functional imaging techniques have begun to delineate the underlying neuronal basis. We investigated the spontaneous magnetoencephalographic activity in a 33-year-old male schizophrenic patient and compared the results to those obtained from 13 healthy controls. Despite current neuroleptic medication (clozapine) the patient was still suffering from auditory hallucinations. Using the dipole density method, we were able to demonstrate an increase of fast MEG activity (12.5–30 Hz) in the left auditory cortex associated with hallucinations. This activity was absent in healthy controls. We conclude that an increase in fast MEG activity in the auditory cortex is a neurophysiologic correlate for auditory hallucinations in schizophrenia.

Epilepsy surgery, resection volume and MSI localization in lesional frontal lobe epilepsy.

To verify whether interictal noninvasive information detected by magnetoencephalography (MEG) recordings can contribute to localize focal epileptic activity relevant for seizure generation in lesional frontal lobe epilepsy, magnetic source imaging (MSI) localizations of epileptic discharges were compared to the extent of neurosurgical resection and postoperative outcome. Preoperative MEG spike localizations were displayed in postoperative magnetic resonance imaging (MRI) scans to check whether dipole sites were located within the resection cavity. Moreover, MEG localizations were compared with results of prolonged video-EEG monitoring and, in three cases, with invasive EEG recordings. Our results in five cases with lesional frontal lobe epilepsy showed that good surgical outcome could be achieved in those patients where the majority of MEG spike localizations were located within the resected brain volume.

Lobar localization information in epilepsy patients: MEG—A useful tool in routine presurgical diagnosis

Epilepsy surgery is an established therapy for pharmacoresistant focal epilepsy. This study investigated the contribution of routinely used magnetoencepahlography (MEG) in addition to long term video-EEG-monitoring in presurgical evaluation. The distribution of localization results to anatomical lobes was compared with special focus to MEG spike localization results in cases without or with ambiguous EEG findings. A total of 105 consecutive patients with intractable focal epilepsy and epilepsy surgery after investigation by video-EEG-monitoring and MEG were included. The percentages of monolobar results were analysed and compared, especially with respect to the resection lobe. Postoperative outcome was used for further validation. No spikes were recorded on MEG in 30% (32 of 105). In cases with a diagnostic finding by the respective method, MEG localized in 82% (60 of 73 patients) within one anatomical lobe. Ictal EEG localized within one lobe in 72% (66 of 92 patients), interictal EEG in 60% (59 of 98 patients). In 25 of 105 patients (24%) no clear localization within one lobe was found either in interictal or in ictal EEG. In 11 of these cases MEG localized within the resection lobe. Six patients of these became seizure free, the other five had at least 50% reduction of their seizure rate 1 year after surgery. In summary MEG is a useful tool in the routine workup for epilepsy surgery contributing information to focus hypothesis in addition to video-EEG.

Localization analysis of neuronal activities in benign rolandic epilepsy using magnetoencephalography

Benign epilepsy of childhood with rolandic spikes (BECRS) is an electroclinical syndrome characterized by partial sensorimotor seizures with centrotemporal spikes. We report a detailed localization analysis of spontaneous magnetic brain activities in seven BECRS patients using magnetoencephalography (MEG). All patients had BECRS diagnosis with typical seizures and electroencephalographic findings and five patients had minor psychomotor deficits. MEG was recorded over both parieto-temporal regions using a 2x37-channel biomagnetic system. The collected data were digitally bandpass-filtered (2-6, 14-30, or 1-70 Hz) to analyze slow- and fast-wave magnetic activities and rolandic spikes. Slow-wave activity was increased in four hemispheres of three patients. Increased fast-wave activity was found in all five patients with minor neuropsychological deficits. The presence of increased fast-wave magnetic brain activity appeared to cause functional anomalies in the higher brain function processes. In the spike analysis, the dipoles of rolandic spikes which constantly manifested anterior positivity in direction were concentrated in the superior rolandic region in four cases and the inferior rolandic region in three cases. The localizations of increased slow- and fast-wave activities were identical with those of the spikes. The seizure profiles were frequently characterized by the spike locations. Source localizations of the focal brain activities and rolandic spikes by MEG will contribute to the different diagnosis and pathophysiological elucidation of BECRS.

Persistent idiopathic facial pain exists independent of somatosensory input from the painful region: findings from quantitative sensory functions and somatotopy of the primary somatosensory cortex.

&NA; In 14 patients with unilateral persistent idiopathic facial pain (PIFP), classified according to the criteria of the International Headache Society, and 16 age‐matched control subjects sensory functions were examined on the face by quantitative sensory testing (QST). Additionally, the somatotopy of the primary somatosensory cortex (SI) to tactile input from the pain area was evaluated by means of magnetoencephalography. Previously reported abnormalities in PIFP as a dishabituation of the R2 component of the blink reflex and psychiatric disturbances were co‐evaluated. Psychiatric evaluation included a Structured Clinical Interview for axis‐I DSM IV disorders (SCID‐I) and employment of the SCL‐90‐R and a depression scale (ADS). Thresholds to touch, pin prick, warm, cold, heat and pressure pain as well as the pain ratings to single and repetitive (perceptual wind up) painful pin prick stimuli did not indicate a significant sensory deficit or hyperactivity in the pain area when compared with the asymptomatic side nor when compared with the values of healthy control subjects. QST results were not significantly altered in patients (n=4) that showed an abnormal dishabituation of the R2 component of the blink reflex. The interhemispheric difference in distance between the cortical representation of the lip and the index finger did not differ between patients and control subjects. Psychiatric evaluation did not disclose significant abnormalities at a group level. It is concluded that PIFP is maintained by mechanisms which do not involve somatosensory processing of stimuli from the pain area.

Alteration of the somatosensory cortical map in peripheral mononeuropathy due to carpal tunnel syndrome.

Substantial plasticity of the mature mammalian somatosensory cortex was demonstrated after deprivation of sensory input produced by amputation or somatosensory deafferentation. Following transection of the median nerve, adult owl and squirrel monkeys exhibit extensive reorganization in the cortical representation of the hand in areas 3b and 1. In the present study we investigated the possible effect of incomplete median nerve damage on sensory cortex somatotopy in a patient with unilateral carpal tunnel syndrome. We assessed interhemispheric differences of the hand representation in SI by means of magnetic source imaging. Additional intersubject data comparison was performed for specific results on the basis of available normal data from the literature and from own investigations in five healthy volunteers. Our results demonstrated a decreased extension of the cortical zone representing the injured median nerve and suggested invasion of the deprived area by cortical sectors receiving inputs from the little finger (supplied by the ulnar nerve) and from the dorsum of the thumb (innervated by the radial nerve). The study indicates topographic rearrangement of the hand representational zone in the human primary somatosensory cortex in a case of chronic median nerve injury.

A combined study of tumor-related brain lesions using MEG and proton MR spectroscopic imaging

The purpose of this study is to localize, in cases of brain tumors, pathological magnetic brain activities and to analyze metabolic alterations in functionally abnormal lesions using magnetoencephalography (MEG) and proton magnetic resonance spectroscopic imaging (1H MRSI). The study focused on 10 healthy volunteers and seven patients with common brain tumors, namely astrocytic tumor and meningioma. In spontaneous MEG, the pathological brain activities (slow, fast waves and spikes) were localized using a single equivalent dipole model. After the results of MEG and 1H MRSI were superimposed onto the corresponding MR images, the signal intensities of spectroscopically visible metabolites were analyzed in the regions where the dipoles of the pathological activities were concentrated. Increased slow wave activity was observed in four cases and fast wave or spike activity was significantly increased in one case. These pathological activities were localized in surrounding regions of the bulk of tumors, where mild reduction of N-acetyl aspartate (NAA) and slight accumulation of lactate (Lac) consistently existed. Preserved cortical areas, which are indicated by residual NAA, might be able to generate pathological magnetic activities under lactic acidosis. Such areas could be understood as a border zone between normal and seriously damaged brain tissue by tumors or associated brain edema. This combined technique with the different modalities gives insight into functional as well as metabolic aspects of pathological brain conditions.

MEG correlates of epileptic high gamma oscillations in invasive EEG

In patients with pharmacoresistant focal epilepsy, we demonstrate that magnetoencephalography (MEG) detects spike‐locked and spike‐independent epileptic high gamma oscillations (HGOs) using combined MEG and invasive electroencephalography (iEEG) from subdural macroelectrodes. Six patients, who underwent presurgical workup for epilepsy surgery with preoperative simultaneous MEG and subdural iEEG recordings, were investigated. HGOs in iEEG were detected automatically and served as triggers for averaging and localization of simultaneous MEG data. iEEG‐HGOs were detected in all patients and MEG‐HGOs in five patients. HGOs were highly associated with epileptic networks and correctly identified seizure‐onset zones in five (MEG) and six patients (iEEG). Minimum‐norm source analysis of MEG data yielded concordant localizations. Noninvasive analysis of HGOs may allow investigation of epileptic networks independent of spikes and seizures. Determination of sensitivity and specificity, as well as development of MEG‐HGO analysis without the need of iEEG should be addressed in a larger study.

Responses to silent Kanji reading of the native Japanese and German in task subtraction magnetoencephalography

The neuromagnetic activities evoked by semantic processing were localized by magnetoencephalography (MEG). We observed distinct time courses of the activities in native speaking Japanese subjects (Japanese speaker) and German subjects (German speaker) during silent reading of Japanese letters; Kanji and meaningless figures made by deforming the Arabian letters. There were significant differences in amplitude of the activities between Kanji and meaningless figure stimuli. The responses with meaningless figure stimuli were subtracted from those with Kanji stimuli to demonstrate the semantic responses. Earlier responses peaked at about 273.3+/-50. 8 and 245.0+/-23.8 ms (mean+/-S.D.) and were mainly located in the right fusiform gyrus (FuG) in the Japanese and German speakers, respectively. All the Japanese speakers constantly showed additional later responses in the left superior temporal gyrus (STG) and the supramarginal gyrus (SmG) at approximately 616.1+/-105.5 ms, whereas no further activity was observed in the German speakers who did not know the meaning of each Kanji. Because the later responses in the STG and SmG in the Japanese speakers were only observed in their dominant hemisphere, we believe the source of these responses to be part of the neural basis of Kanji semantic processing. The task subtraction MEG analysis could be a powerful method to discriminate distinct responses and visualize the neural networks involved in semantic processing.