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 Children's 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 (Student's 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 (Student's 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.

Magnetoencephalographic recordings demonstrate attentional modulation of mismatch-related neural activity in human auditory cortex.

It is widely agreed that the negative brain potential elicited at 150-200 ms by a deviant, less intense sound in a repetitive series can be modulated by attention. To investigate whether this modulation represents a genuine attention effect on the mismatch negativity (MMN) arising from auditory cortex or attention-related activity from another brain region, we recorded both the MMN and the mismatch magnetic field (MMF) elicited by such deviants in a dichotic listening task. Deviant tones in the attended ear elicited a sizable MMF that was well modeled as a dipolar source in auditory cortex. Both the MMN and MMF to unattended-ear deviants were highly attenuated. These findings support the view that the MMN/MMF elicited in auditory cortex by intensity deviants, and thus the underlying feature-analysis and mismatch-detection processes, are not strongly automatic but rather can be gated or suppressed if attention is strongly focused elsewhere.

Magnetic source imaging of abnormal low-frequency magnetic activity in presurgical evaluations of epilepsy.

PURPOSE: Regional cortical dysfunction associated with epileptogenic activity was predicted from interictal localized abnormal low frequency neuromagnetic activity (ALFMA) using Magnetic Source Imaging (MSI). ALFMA can be detected in patients who show no interictal spikes. METHODS: A large array biomagnetometer was used in a blinded, rapid screening protocol. The MSI procedure required no alteration in epileptic medications. MSI results were compared with the presumed epileptogenic region as determined by a consensus of standard techniques, which included MR and electroclinical monitoring. RESULTS: One or more sites of localized abnormality were detected by MSI ALFMA in 29 of the 33 epileptic patients. ALFMA mapped with MSI showed a 48.5% specificity with respect to the presumed epileptogenic region. MSI ALFMA was in agreement with the final consensus as often as was ictal noninvasive video EEG monitoring, and was exceeded in specificity overall only by invasive ictal video EEG monitoring, which was required for conventional localization in 21 of the 33 patients tested with MSI. CONCLUSIONS: ALFMA measurements with MSI may augment the array of noninvasive methods used for reaching a consensus for epilepsy surgery.

Potential contribution of bilateral magnetic source imaging to the evaluation of epilepsy surgery candidates.

The current procedures that are used to evaluate candidates for epilepsy surgery are time-consuming, costly, and often invasive. Magnetic source imaging (MSI), the combination of magnetoencephalography and anatomic imaging modalities, has shown promise as an efficient noninvasive means of localizing and characterizing seizure sources for possible resection. However, MSI has been limited by the inability to conduct simultaneous bilateral monitoring. In this study, a newly developed dual-magnetometer system was employed to record bilaterally the interictal activity in 30 candidates for epilepsy surgery. A standard monitoring protocol that included concurrent electroencephalographic recording and required a 2- to 3-hour examination period for each patient was developed. As a first step in a series of studies, the resultant MSI indications were compared with the information available from standard magnetic resonance imaging and concurrent electroencephalographic results. In 83% of the cases, this MSI protocol provided new information about the location of interictal epileptic activity that could be directive for subsequent patient care. Based on these results, it seems that MSI may become a cost-effective early step in epilepsy surgery evaluation. To continue the development on this basis, a study intended to validate the accuracy of MSI indicated by comparison with invasive electroencephalography has been initiated.

Presurgical localization of functional cortex using magnetic source imaging.

The boundaries of somatosensory cortex were localized noninvasively by means of a large-array biomagnetometer in six patients with mass lesions in or near eloquent cortex. The results were used by neurosurgeons and neurologists in preoperative planning and for reference in the operating room. The magnetic source imaging (MSI) localizations from somatosensory evoked potentials were used to predict the pattern of phase reversals measurable intraoperatively on the cortical surface, providing a quantitative comparison between the two measures. The magnetic localizations were found to be predictive in all six cases, with the two sets of localizations falling within an 8-mm distance on average. Somatosensory localizations using MSI offer accuracy in localizing somatosensory cortex stereotactically and in depicting its relationship to lesions. Such data are valuable preoperatively in assessing the risks associated with a proposed surgical procedure and for optimizing subsequent minimum-risk surgical strategy.

Magnetoencephalography and magnetic source imaging. Capabilities and limitations.

The advent of large-array superconducting biomagnetometer systems, including sophisticated operating and data processing electronics, has enabled practical patient studies evaluating the potential contribution of magnetoencephalography to clinical medicine. The superimposition of sources localized magnetically onto anatomic images, referred to as magnetic source imaging, has allowed physicians to conduct this evaluation in the content of their customary medical practice. This article summarizes the basic technology of magnetoencephalography and magnetic source imaging and includes brief descriptions of the various applications that are being studied with these new sensor systems, some of which are discussed in subsequent articles.

Intracranial neurosurgery guided by functional imaging.

Neurosurgery on eloquent cortex entails important risks of functional deficits complicating aggressive lesion resection. In this study, advanced biomagnetic functional imaging of somatosensory and motor cortex combined with surface rendered magnetic resonance imaging displays including vascular anatomy were used in conjunction with a new nonintrusive intraoperative guided instrumentation system to resect a tumor in eloquent cortex. Intraoperative verification of the accuracy of pre-operative motor localization demonstrated highly accurate results comparing direct stimulation and noninvasive presurgical mapping. The applicability of surface rendered combined functional and anatomic maps of cortex is directly evident on comparison of preoperative computer images and intraoperative pictures. This combination of new technologies has a significant potential for reduced risk and improved outcome in neurosurgery of eloquent cortex.

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.

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.

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.

Modulation of early sensory processing in human auditory cortex during auditory selective attention.

Neuromagnetic fields were recorded from human subjects as they listened selectively to sequences of rapidly presented tones in one ear while ignoring tones of a different pitch in the opposite ear. Tones in the attended ear evoked larger magnetic brain responses than did unattended tones in the latency ranges 20-50 msec and 80-130 msec poststimulus. Source localization techniques in conjunction with magnetic resonance imaging placed the neural generators of these early attention-sensitive brain responses in auditory cortex on the supratemporal plane. These data demonstrate that focused auditory attention in humans can selectively modulate sensory processing in auditory cortex beginning as early as 20 msec poststimulus, thereby providing strong evidence for an "early selection" mechanism of auditory attention that can regulate auditory input at or before the initial stages of cortical analysis.

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.

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.

Locating the central sulcus: comparison of MR anatomic and magnetoencephalographic functional methods.

PURPOSE: To compare MR anatomic and magnetoencephalographic (MEG) functional methods in locating the central sulcus. METHODS: Eleven healthy subjects and five patients with focal cerebral lesions were studied. The central sulcus was located anatomically with MR by two independent observers using axial vertex and sagittal (midline and lateral) images. Locations via the MEG functional method were based on detecting the somatosensory-evoked magnetic fields elicited by painless tactile stimuli. RESULTS: The axial method yielded the most consistent interrater results, with complete agreement in 76% of sections in both control subjects and patients. The intermethod discordance of the sagittal midline and lateral methods was 32% in control subjects and 33% in patients. The concordance of MR and MEG methods ranged from 55% to 84% in control subjects and 65% to 67% in patients. CONCLUSION: MR anatomic techniques can usually identify the central sulcus, but in the presence of anatomic distortion, the MEG functional method adds significant information.

Neuromagnetic mapping of brain function.

Magnetic source imaging, a technique that combines magnetoencephalography (MEG) and magnetic resonance (MR) imaging, was used to localize the somatosensory and auditory cortex in seven healthy subjects. Functional neuromagnetic data were obtained with a 37-channel biomagnetometer. Structural MR imaging data were obtained with a 1.5-T superconducting imager. Coordinates used in defining MEG and MR imaging space were reconciled to produce magnetic source images that displayed the putative locations of somatosensory and auditory activity in relation to brain anatomy. Sources of somatosensory activity were typically localized to the postcentral gyrus; sources of auditory activity were localized to the superior temporal plane. Extension of these results to patients with tumors (or other disorders) that distort normal brain anatomy has the potential to make noninvasive magnetic source imaging examinations clinically useful in guiding neurosurgical interventional procedures.

Noninvasive somatosensory homunculus mapping in humans by using a large-array biomagnetometer.

To validate the feasibility of precise noninvasive functional mapping in humans, a large-array biomagnetometer was used to map the somatosensory cortical locations corresponding to numerous distinct tactile sites on the fingers, hand, arm, and face in different subjects. Source localizations were calculated by using a single equivalent current dipole (ECD) model. Dipole localizations were transposed upon the corresponding subject's magnetic resonance image (MRI) to resolve the anatomic locus of the individual dipoles within a given subject. Biomagnetic measurements demonstrated that (i) there were distinct separations between the ECD locations representing discrete sites on the face and hand; (ii) the ECD localizations from facial sites clustered in a region inferior to ECD localizations from hand and digit sites; and (iii) there was clear spatial resolution of ECD locations representing closely spaced tactile sites on the hand and face. The ability of magnetoencephalography (MEG) to provide high-resolution spatial maps of the somatosensory system noninvasively in humans should make MEG a useful tool to define the normal or pathological organization of the human somatosensory system and should provide an approach to the rapid detection of neuroplasticity.

Transcranial Doppler ultrasound and magnetoencephalography in migraine.

Eighty subjects--30 migraineurs during the attack, 30 patients in the interictal period, and 20 healthy volunteers--were studied using two technologies for functional assessment: transcranial Doppler ultrasound and magnetoencephalography. Transcranial Doppler studies showed an increased mean flow velocity at rest (p less than 0.05) in the middle cerebral artery on the side of the headache and a decreased vasomotor response to CO 2 (p less than 0.001) on the same side compared to control subjects. Biomagnetic measurements of somatosensory evoked fields of 11 patients and 11 control subjects in this study did not demonstrate differences between migraineurs and the control group in current flow or latency measures. The data from this study tend to support the hypothesis of vascular disease as a primary underlying deficit in migraine.