Urs Ribary

Central motor loop oscillations in parkinsonian resting tremor revealed magnetoencephalography

A variety of clinical and experimental findings suggest that parkinsonian resting tremor results from the involuntary activation of a central mechanism normally used for the production of rapid voluntary alternating movements. However, such central motor loop oscillations have never been directly demonstrated in parkinsonian patients. Using magnetoencephalography, we recorded synchronized and tremor-related neuromagnetic activity over wide areas of the frontal and parietal cortex. The spatial and temporal organization of this activity was studied in seven patients suffering from early-stage idiopathic Parkinsons disease (PD). Single equivalent current dipole (ECD) analysis and fully three-dimensional distributed source solutions (magnetic field tomography, MFT) were used in this analysis. ECD and MFT solutions were superimposed on high-resolution MRI. The findings indicate that 3 to 6 Hz tremor in PD is accompanied by rhythmic subsequent electrical activation at the diencephalic level and in lateral premotor, somatomotor, and somatosensory cortex. Tremor-evoked magnetic activity can be attributed to source generators that were previously described for voluntary movements. The interference of such slow central motor loop oscillations with voluntary motor activity may therefore constitute a pathophysiologic link between tremor and bradykinesia in PD. NEUROLOGY 1996;46:1359-1370

Consciousness and the Brain

Abstract: The goal of this paper is to explore the basic assumption that large‐scale, temporal coincidence of specific and nonspecific thalamic activity generates the functional states that characterize human cognition.

Content and Context in Temporal Thalamocortical Binding

Given that sensory systems generate but a fractured representation of universals, the issue of perceptual unity has been approached by defining the mechanisms by which different sensory components are gathered into one global image. In recent years, this has been described as “binding,” and has been thought to be implemented by temporal conjunction (Bienenstock and von der Malsburg 1986, von der Malsburg 1981; Crick and Koch 1990; Llinas 1990).

The Interactive Use of Magnetoencephalography in Stereotactic Image-guided Neurosurgery

OBJECTIVE To expand the use of magnetoencephalography (MEG) functional mapping in the operating room as well as preoperatively, a method of integrating the MEG sensorimotor mapping information into a stereotactic database, using computed tomographic scans, magnetic resonance imaging scans, and digital angiography, was developed. The combination of functional mapping and the stereotactic technique allows simultaneous viewing of the spatial relationship between the MEG-derived functional mapping, the radiological/structural anatomic characteristics, and the pathological abnormality. METHODS MEG data were collected using a MAGNES II Biomagnetometer and were incorporated into the COMPASS frame-based and REGULUS frameless stereotactic systems. The transformation process, by calculating a translational vector and a rotation matrix, integrates functional and anatomic information that is then directly available intraoperatively in the stereotactic database. This procedure was employed in 10 patients undergoing computer-assisted stereotactic volumetric resections for lesions involving the sensorimotor cortex. The principles of coregistration and coordinate transformation are reviewed in the context of preoperative functional mapping. We introduce innovations to apply these techniques to intraoperative stereotactic systems. RESULTS Tests of the accuracy of the intraoperative integration of functional information in patients and calibration phantoms indicated close agreement with earlier preoperative methods. The intraoperative availability of functional information was a significant aid to the surgeon because it provided more accurate information on the location of functional tissue than could be derived solely by radiological criteria. CONCLUSION The real-time availability of functional mapping information in an interactive fashion can reduce surgical risk and minimize functional morbidity. Within the ever-expanding realm of functional mapping and image-guided neurosurgery, further progress and integration of these methods is critical for resection of lesions involving eloquent cortex.

Long-term sleep disturbances in children: A cause of neuronal loss

Short-term sleep loss is known to cause temporary difficulties in cognition, behaviour and health but the effects of persistent sleep deprivation on brain development have received little or no attention. Yet, severe sleep disorders that last for years are common in children especially when they have neurodevelopmental disabilities. There is increasing evidence that chronic sleep loss can lead to neuronal and cognitive loss in children although this is generally unrecognized by the medical profession and the public. Without the restorative functions of sleep due to total sleep deprivation, death is inevitable within a few weeks. Chronic sleep disturbances at any age deprive children of healthy environmental exposure which is a prerequisite for cognitive growth more so during critical developmental periods. Sleep loss adversely effects pineal melatonin production which causes disturbance of circadian physiology of cells, organs, neurochemicals, neuroprotective and other metabolic functions. Through various mechanisms sleep loss causes widespread deterioration of neuronal functions, memory and learning, gene expression, neurogenesis and numerous other changes which cause decline in cognition, behaviour and health. When these changes are long-standing, excessive cellular stress develops which may result in widespread neuronal loss. In this review, for the first time, recent research advances obtained from various fields of sleep medicine are integrated in order to show that untreated chronic sleep disorders may lead to impaired brain development, neuronal damage and permanent loss of developmental potentials. Further research is urgently needed because these findings have major implications for the treatment of sleep disorders.

Magnetoencephalographic mapping: Basis of a new functional risk profile in the selection of patients with cortical brain lesions

OBJECTIVE Surgical management of cortical lesions adjacent to or within the eloquent cerebral cortex requires a critical risk: benefit analysis of the procedure before intervention. This study introduced a measure of surgical risk, based on preoperative magnetoencephalographic (MEG) sensory and motor mapping, and tested its value in predicting surgical morbidity. METHODS Forty patients (21 men and 19 women; mean age, 36.5 yr) with cortical lesions (12 arteriovenous malformations and 28 tumors) in the vicinity of the sensorimotor cortex were classified into high-, medium-, or low-risk categories by using the MEG-defined functional risk profile (FRP). This was based on the minimal distance between the lesion margin and the sensory and motor MEG sources, superimposed on a magnetic resonance imaging scan. Case management decisions were based on the MEG mapping-derived FRP in combination with biopsy pathological findings, radiographic findings, and anatomic characteristics of the lesion. A recently developed protocol was used to transform MEG source locations into the stereotactic coordinate system. This procedure provided intraoperative access to MEG data in combination with stereotactic anatomic data displays routinely available on-line during surgery. RESULTS It was determined that 11 patients diagnosed as having gliomas had high FRPs. The margin of the lesion was less than 4 mm from the nearest MEG dipole or involved the central sulcus directly. A nonoperative approach was used for six patients of this group, based on the MEG mapping-derived FRP. In the group with arteriovenous malformations, 6 of 12 patients with high or medium FRPs underwent nonoperative therapy. The remaining 28 patients, whose lesions showed satisfactory FRPs, underwent uneventful lesion resection, without postoperative neurological deficits. CONCLUSION Our results suggest that MEG mapping-derived FRPs can serve as powerful tools for use in presurgical planning and during surgery.

Words without Mind

A woman (LR), unconscious for 20 years, spontaneously produces infrequent, isolated words unrelated to any environmental context. Fluorodeoxy-glucose-positron emission tomography (FDG-PET) imaging coregistered with magnetic resonance imaging (MRI) revealed a mean brain metabolism equivalent to deep anesthesia. Nevertheless, PET imaging demonstrated islands of modestly higher metabolism that included Brocas and Wernickes areas. Functional brain imaging with magnetoencephalographic (MEG) imaging, a technique providing a temporal resolution of better than 1 msec, identified preserved dynamic patterns of spontaneous and evoked brain activity in response to sensory stimulation. Specifically, we examined spontaneous gamma-band activity (near 40 Hz) and its reset or modification during early auditory processing, a measure that correlates with human perception of sensory stimuli (Joliot, Ribary, & Llins, 1994). Evidence of abnormal and incomplete gamma-band responses appeared in the left hemisphere only in response to auditory or somatosensory stimulation. MEG single-dipole reconstructions localized to the auditory cortex in the left hemisphere and overlapped with metabolically active regions identified by FDG-PET. The observation demonstrates that isolated neuronal groups may express well-defined fragments of activity in a severely damaged, unconscious brain. The motor fixed-action pattern character of her expressed words supports the notion of brain modularity in word generation.

Rostrocaudal Scan in Human Brain: A Global Characteristic of the 40-Hz Response During Sensory Input

Cortical oscillatory activity in the 40-Hz range has been observed in man during cognitive tasks and following sensory stimulation, as analyzed by electroencephalographic (EEG) and magnetoencephalographic (MEG) means (Galambos et al., 1981; Maekelae and Hari,1987; Sheer, 1989; Weinberg et al., 1988). Such oscillatory activity is not unique to man but has been seen in many mammalian forms during attentive states (Bouyer et al, 1987) and during physiological stimulation of the olfactory (Bressler and Freeman, 1980) or the visual systems (Eckhorn et al., 1988; Gray and Singer, 1989). However, these 40-Hz activity recording were restricted to localized brain areas and on occasion to small cell groups, to include a few cortical columns. Even in those studies where EEG and MEG recordings were attained, data analysis was restricted to a single time slice at the maximum positive or negative peak of an averaged evoked response. Nevertheless, these studies indicate that 40-Hz coherent neuronal activity large enough to be detected from the scalp is generated during cognitive tasks (cf. Sheer, 1989).

Neuropsychiatric thalamocortical dysrhythmia: surgical implications

Clearly, more clinical experience must be amassed to define in detail the possibilities of this surgical approach in disabling neuropsychiatric disorders. We propose, however, that the evidence for benign and efficient surgical intervention against the neuropsychiatric TCD syndrome is already compelling. The potential appearance of strong postoperative reactive manifestations requires a close association between surgery and psychotherapy, with the latter providing support for the integration of the new situation as well as the resolution of old unresolved issues.

Thalamocortical dysrhythmia I. Functional and imaging aspects

Thalamic and cortical neurons are richly and reciprocally interconnected and support recurrent functional loops in the intact brain, but the role of this circuitry is still poorly understood. Here, we present evidence—from cellular and from functional neuroimaging in control and clinical domains—that thalamocortical resonance is not only a prerequisite for normal cognition, but that its perturbation, in a dynamic sense (e.g. a dysrhythmia) can underlie a variety of neurological and psychiatric disorders.