Christopher C. Gallen

Noninvasive detection of cerebral plasticity in adult human somatosensory cortex

After upper limb deafferentation, adult macaques exhibit substantial reorganization of cortical somatosensory topography with enlargement of cortical areas responsive to facial stimuli. In the present study non-invasive magnetic source imaging technology has been used to map in detail the bilateral somatosensory homunculi in four neurologically normal controls and two upper arm amputees. Bilateral homuncular maps of normals and of the unaffected hemisphere of both amputees showed a wide hand area. The affected hemisphere of both amputees showed marked intrusion of facial representations into the digit and hand area consistent with the earlier observations in macaques. Our findings provide the first evidence of massive somatosensory plasticity in human adults and suggest a mechanism for post-amputation perceptual changes.

Noninvasive Presurgical Neuromagnetic Mapping of Somatosensory Cortex

Rapid presurgical neuromagnetic localization of the somatosensory cortex was performed successfully on five patients with a large-array biomagnetometer by a protocol called magnetic source imaging (MSI). Determination of the location of the central sulcus is important in assessing operative risk and determining the optimal operative approach to structural lesions in the vicinity of the motor strip. The use of magnetic resonance imaging anatomical methods and intraoperative visual identification can be imprecise, whereas invasive localization prolongs operative time, adds cost, and entails added risk. Until the recent development of large-array biomagnetometer systems, neuromagnetic localization of the central sulcus had been demonstrated in research but was so time consuming and laborious as to preclude routine clinical use. In this study, the validity of MSI localizations was confirmed intraoperatively by direct cortical recording of somatosensory evoked potentials and/or direct motor stimulation. Complete agreement was found between MSI and intraoperative mapping in locating the central sulcus. Objective confirmations considered together with the speed and reliability of the procedure and with the presurgical availability of the results suggests the potential utility of MSI for routine surgical planning.

Randomized Controlled Trial of Yogic Meditation Techniques for Patients With Obsessive-Compulsive Disorder

The objective of this study was to compare efficacy of two meditation protocols for treating patients with obsessive-compulsive disorder (OCD). Patients were randomized to two groups-matched for sex, age, and medication status-and blinded to the comparison protocol. They were told the trial would last for 12 months, unless one protocol proved to be more efficacious. If so, groups would merge, and the group that received the less efficacious treatment would also be afforded 12 months of the more effective one. The study was conducted at Childrens Hospital, San Diego, Calif. Patients were selected according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R) criteria and recruited by advertisements and referral. At baseline, Group 1 included 11 adults and 1 adolescent, and Group 2 included 10 adults. Group 1 employed a kundalini yoga meditation protocol and Group 2 employed the Relaxation Response plus Mindfulness Meditation technique. Baseline and 3-month interval testing was conducted using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Symptoms Checklist-90-Revised Obsessive Compulsive (SCL-90-R OC) and Global Severity Index (SCL-90-R GSI) scales, Profile of Moods scale (POMS), Perceived Stress Scale (PSS), and Purpose in Life (PIL) test. Seven adults in each group completed 3 months of therapy. At 3 months, Group 1 demonstrated greater improvements (Students independent groups t-test) on the Y-BOCS, SCL-90-R OC and GSI scales, and POMS, and greater but nonsignificant improvements on the PSS and PIL test. An intent-to-treat analysis (Y-BOCS) for the baseline and 3-month tests showed that only Group 1 improved. Within-group statistics (Students paired t-tests) showed that Group 1 significantly improved on all six scales, but Group 2 had no improvements. Groups were merged for an additional year using Group 1 techniques. At 15 months, the final group (N=11) improved 71%, 62%, 66%, 74%, 39%, and 23%, respectively, on the Y-BOCS, SCL-90-R OC, SCL-90-R GSI, POMS, PSS, and PIL; P<0.003 (analysis of variance). This study demonstrates that kundalini yoga techniques are effective in the treatment of OCD.

Intrasubject reliability and validity of somatosensory source localization using a large array biomagnetometer

Neuromagnetic fields were evoked by tactile stimuli and detected with a multi-channel biomagnetometer through 72 independent repetitive measurements on a single subject. Each measurement consisted of a somatosensory evoked response (N = 256 stimuli) using a single probe placement. These fields were then analyzed for source localization using an equivalent current dipole model and demonstrated highly reliable localizations. The 3 major neuromagnetic somatosensory response components peaking at 35, 65 and 110 msec all localized to the same area of cortex. The relative contributions of intrinsic brain activity, habituation, probe placement, and choice of fiduciary points for headframe determination were quantified. Intrinsic factors were found to constitute the major source of inter-measurement error. Sources localized by magnetic source imaging (MSI) appeared valid relative to neuroanatomical estimation of the central fissure on MRI. Non-invasive presurgical biomagnetic localization of somatosensory cortex produces reliable and valid functional localizations which can be of potential value in risk assessment and may provide a useful guide for invasive functional mapping.

Effects of alcohol on the EEG in Asian men with genetic variations of ALDH2

Approximately 50% of Asians experience a facial flush following alcohol ingestion. These individuals have an inactive form of mitochondrial aldehyde dehydrogenase (ALDH) encoded by the ALDH2*2 allele. This study matched 15 flushing and 15 nonflushing Asian men on demographics and drinking histories. The 30 subjects were genotyped for ALDH2 and were evaluated both before and following placebo and 0.75 ml/kg alcohol. The two groups did not differ significantly on blood alcohol concentrations after drinking, but did differ in electroencephalographic (EEG) response on the falling phase of the blood alcohol curve. Nonflushing subjects displayed significant increases in slow-alpha EEG activity (7.5-9.0 Hz) at 90 and 150 min post-alcohol consumption, compared to flushing subjects who did not show characteristic increases in this frequency band at these timepoints. These data suggest flushers, those with at least one ALDH2*2 allele, have less of slow-alpha wave EEG response to alcohol than nonflushers with ALDH2*1/2*1 genotype.

Utilization of multichannel magnetoencephalography in the guidance of ablative seizure surgery

Abstract Magnetoencephalography (MEG) was used to evaluate 50 seizure surgery candidates. Interictal spikes were recorded in 42 cases. Of 20 cases with other data suggesting a convexity (lateral neocortical) focus, MEG spikes were recorded from 19. In 17, MEG and electrographic data were localized to the same region. Invasive studies were or could have been avoided in 11 cases based on MEG and other noninvasive data. MEG spike data were present in 14 of 18 cases with anteromesial temporal foci, being localized to the same lobe as electrographic data in 11. MEG was not of value in surgical planning of cases with orbitofrontal foci, or depth nonlocalized seizures. Twenty-seven patients with MEG epileptiform data have had postoperative follow-up. Fourteen of 19 with electrographic and MEG data localized to the same region are seizure-free. Four of eight with spatial discordance of MEG and electrographic data are seizure-free. Preliminary conclusions are as follows: When MEG and electrographic data are localized to the same region, seizure-free surgical outcome is more likely. In convexity cases with MEG and noninvasive electrographic data localized to the same region, preoperative invasive studies may be unnecessary.

Magnetic Source Imaging of Abnormal Low-Frequency Magnetic Activity in Presurgical Evaluations of Epilepsy

Summary: Purpose: Regional cortical dysfunction associated with epileptogenic activity was predicted from interic‐tal localized abnormal low frequency neuromagnetic activity (ALFMA) using Magnetic Source Imaging (MSI). ALFMA can be detected in patients who show no interictal spikes.

Role of Multichannel Magnetoencephalography in the Evaluation of Ablative Seizure Surgery Candidates

Magnetic source imaging (MSI) was performed on 30 ablative epilepsy surgery candidates. The technique involved high resolution multiplanar MRI images with lipid fiducials attached to the patients head to define a head-based 3D coordinate space. Magnetoencephalography (MEG) was performed after digitizing the same fiducial points. A 37-channel magnetometer obtained data at two to five sites over each hemisphere. MEG epileptiform data were obtained with and without EEG triggering. A single equivalent current dipole model was used to determine orientation and location of a dipole generator whose surface isocontour map most closely fits the measured dipolar data for each event. The MEG data were then transformed to MRI images for source localization. In five of seven cases with ictal anterior temporal lobe foci, MSI data were localized to the same temporal lobe but did not provide additional spatial data. In 10 of 11 cases with convexity foci, MSI provided additional spatial localizing data. MSI did not verify depth electrode localization in one anterior temporal-orbital frontal and three orbitofrontal cases. In seven of eight cases in which depth EEG recordings were nonlocalizing, MSI provided insufficient localizing data. MSI appears to provide additional spatial localizing data in most cases with a convexity epileptic focus.

Multichannel Magnetoencephalography in Ablative Seizure Surgery Outside the Anteromesial Temporal Lobe

Magnetoencephalography (MEG) was used to evaluate 40 candidates for seizure surgery thought to have foci outside the anteromesial temporal lobe. Of 29 cases with electrographic data suggesting a convexity focus, MEG spikes were recorded from 28. In 21, MEG and electrographic data were localized to the same area. Invasive studies were, or could have been, avoided in 13 cases based on MEG and other noninvasive data. MEG was not localizing value in 4 orbitofrontal or 7-depth-nonlocalized cases. Seventeen patients with MEG epileptiform data have had postoperative follow-up. Eight of 13 with electrographic and MEG data localized to the same area are seizure free. None of 4 with spatial discordance of MEG electrographic data are seizure free.

Multichannel Magnetoencephalographic Mapping of Sensorimotor Cortex for Epilepsy Surgery

Preliminary reports have shown a close correlation between the anatomic location of evoked magnetic somatosensory fields and intraoperative evoked somatosensory potentials in patients with mass lesions. We have performed magnetic source imaging (MSI) of sensory and motor (MER) evoked responses or fields on 4 patients with frontal convexity epileptic foci. The method involves (1) graphic overlaying of magnetoencephalography evoked field data and three-dimensional (3D) phase contrast magnetic resonance angiographic data on 3D MRI surface cortical renderings, and (2) correlating these data with intraoperative stimulation-mapped sensory and/or motor responses and local cortical venous anatomy. Our initial results indicate that the location of MSI evoked sensory data correlates closely with the results of intraoperative stimulation mapping. MSI MERs have tended to show a less discrete spatial topography, involving areas of cortex extending beyond the motor strip.