Atypical cortical language organization in epilepsy patients: evidence for divergent hemispheric dominance for receptive and expressive language function.

The central goal of presurgical language mapping is to identify brain regions that subserve cortical language function to minimize postsurgical language deficits. Presurgical language mapping in patients with epilepsy presents a key challenge because of the atypical pattern of hemispheric language dominance found in this population, with higher incidences of bilateral and right-biased language dominance than typical. In this prospective study, we combine magnetoencephalography with a panel of tasks designed to separately assess receptive and expressive function to provide a sensitive measure of language function in 15 candidates for resective surgery. We report the following: 4 of 15 patients (27%) showed left hemisphere dominance across all tasks, 4 of 15 patients (27%) showed right hemisphere dominance across all tasks, and 7 of 15 (46%) showed discordant language dominance, with right-dominant receptive and left-dominant expressive language. All patients with discordant language dominance showed this right-receptive and left-expressive pattern. Results provide further evidence supporting the importance of using a panel of tasks to assess separable aspects of language function. The clinical relevance of the findings is discussed, especially about current clinical operative measures for assessing language dominance, which use single hemisphere procedure (intracarotid amobarbital procedure and awake intraoperative stimulation) for determining language laterality.

Rethinking clinical language mapping approaches: discordant receptive and expressive hemispheric language dominance in epilepsy surgery candidates.

Neuroimaging studies have shed light on cortical language organization, with findings implicating the left and right temporal lobes in speech processing converging to a left-dominant pattern. Findings highlight the fact that the state of theoretical language knowledge is ahead of current clinical language mapping methods, motivating a rethinking of these approaches. The authors used magnetoencephalography and multiple tasks in seven candidates for resective epilepsy surgery to investigate language organization. The authors scanned 12 control subjects to investigate the time course of bilateral receptive speech processes. Laterality indices were calculated for left and right hemisphere late fields ∼150 to 400 milliseconds. The authors report that (1) in healthy adults, speech processes activated superior temporal regions bilaterally converging to a left-dominant pattern, (2) in four of six patients, this was reversed, with bilateral processing converging to a right-dominant pattern, and (3) in three of four of these patients, receptive and expressive language processes were laterally discordant. Results provide evidence that receptive and expressive language may have divergent hemispheric dominance. Right-sided receptive language dominance in epilepsy patients emphasizes the need to assess both receptive and expressive language. Findings indicate that it is critical to use multiple tasks tapping separable aspects of language function to provide sensitive and specific estimates of language localization in surgical patients.

Magnetic source imaging of cortical dysfunction in amyotrophic lateral sclerosis.

OBJECTIVE: The goal was to determine whether magnetic source imaging could identify a signature for cortical involvement in patients with amyotrophic lateral sclerosis (ALS), and to determine whether the method might provide insight into functional abnormalities associated with the disease process. DESIGN: Spontaneous brain activity recordings from whole-head 148-channel magnetoencephalography (MEG) were employed to look for localized dipolar sources of focal delta-theta (1-7 Hz) discharges in patients with ALS without dementia. Localized slow wave dipoles were mapped and counted by anatomic brain region, defined by MRI, and correlated against the revised ALS functional rating scale (a functional measure of ALS disability). In a substudy, defects in cortical activations mediating purposeful movement were investigated in an ALS patient with probable motor apraxia of an upper limb. RESULTS: MEG revealed localized slow wave dipole sources in 7/7 ALS patients, including two recently diagnosed patients (0/8 age-similar controls). Systematic brain mapping of dipole source generators was possible in all seven ALS patients. The slow wave bursts were being generated from frontal, temporal, and parietal cortices, but not from occipital areas. The density of slow wave dipoles in cingulate gyrus correlated with the severity of upper-extremity disability as judged by the functional ALS measure. Further magnetic source imaging in the substudy patient with unilateral limb apraxia revealed abnormal central processing of purposeful movement with absent M2 in the contralateral secondary motor areas generating slow waves. CONCLUSIONS: This exploratory study documents widespread cortical dysfunction in patients with ALS, including those with recent onset of their disease. MEG is likely to be a powerful new tool for researching the contribution of cortical dysfunction to the motor disability that characterizes the disease process.

High-resolution magnetoencephalographic functional mapping of the cortical network mediating intentional movement.

Magnetoencephalography (MEG) is a sensitive technique that can detect and map cortical electrophysiologic activations with high spatial (mm) and temporal (msecs) resolutions. We used 148-channel whole-head MEG to record the activation sequence for the somatosensory and motor cortical network during cued hand movements in a healthy 39-yr-old subject. The complex sequence and topography of cortical activations were superimposed onto the subject's brain magnetic resonance images. Frontal premotor and supplementary motor and cingulate areas activated well before the primary motor area and again repetitively from 200 msecs onward with activations alternating repeatedly between frontal and parietal areas. The network's very close functional integration of supplementary motor areas suggests how brain injury that is localized to these regions, but not to the primary motor area itself, can disrupt integrity of movement, and why preservation of functional integrity of some areas traditionally viewed as extramotor may be necessary for recovery from neurologic disability.

Magnetoencephalogram recording from secondary motor areas during imagined movements.

This study determined whether the activity of the secondary motor cortex (M2) could be recorded during imagined movements (IM) of the right and left hand using magnetoencephalography (MEG). Results during IM were compared with a somatosensory trial during a passive tactile stimulation in one subject. During the somatosensory trial, dipoles were detected in somatosensory (SS) and motor primary (M1) areas, scoring 94.4-98.4% for SS, 1.6-5.6% for M1 and 0% for M2. During the IM trial, dipoles were detected in SS, M1 and M2 areas, scoring 61.1-68.8% for SS, 2.6-9.3% for M1 and 28.6-29.6% for M2. These data support the hypothesis that M2 areas are activated during imagined hand movements. This study aims for the development of a diagnosis test for patients with motor deficits by evaluating the whole somatomotor network with specific interest in M2 areas.

Magnetoencephalogram recording from secondary motor areas during imagined movements

Este estudo determina se a atividade motora secundária cortical (M2) pode ser gravada durante simulação interna do movimento (IM) das mãos direita e esquerda utilizando-se magnetencefalografia (MEG). Os resultados da simulação dos movimentos estudados foram comparados com um ensaio somato-sensorial com estimulação tactil passiva em um sujeito. Durante o ensaio somato-sensorial dipolos foram detectados em áreas somato-sensoriais (SS) e motoras primarias (MI) tendo como score 94,4-98,4% para SS, 1,6-5,6% para M1 e 0% para M2. Durante o ensaio de simulação dos movimentos também foram detectados dipolos em SS 61,1-68,8%, M1 2,6-9,3% e M2 28,6-29,6%. Estes dados evidenciam a hipótese de que as áreas M2 são ativadas durante a simulação dos movimentos das mãos. Este estudo sugere o desenvolvimento de um teste diagnóstico para pacientes com deficites motores, que avalie a rede somatomotora com interesse específico nas áreas M2.

Using magnetoencephalography to study patterns of brain magnetic activity in Alzheimer's disease.

The use of magnetoencephalography to study neurophysiologic abnormalities associated with Alzheimer's disease is reviewed. The most consistent observation is that Alzheimer's disease patients exhibit an increase in focal slow-wave activity that covaried with cognitive performance. It is still unclear whether generation of focal slow-wave activity precedes or is a consequence of Alzheimer's disease-related neuropathology. Also reviewed is the use of magnetoencephalography to identify early functional changes preceding the diagnosis of dementia. Magnetoencephalography detected neurophysiologic abnormalities associated with cognitive deficits before the diagnosis of mild cognitive impairment. This is supported by evidence presented suggesting that some patients with subjective cognitive complaints, without evidence of dementia, show an increase in focal slow-wave generators. Further research is needed to determine whether the outstanding spatial and temporal resolution of the magnetoencephalography technique could complement other neuroimaging techniques in identifying neurophysiologic abnormalities preceding the diagnosis of Alzheimer's disease and mild cognitive impairment.

Relationship of lumen diameter to type and degree of arterial remodeling at sites of expanding wall or plaque thickness in human carotid artery.

BACKGROUND: Arterial remodeling exhibits a bidirectional capacity. Whether lumen size affects remodeling response to lesion change is unknown. METHODS: Prospective study by duplex ultrasonography over 2 years in 61 subjects with coronary artery disease. Direction and magnitude of vessel remodeling are calculated for internal carotid, bifurcation, and common carotid artery segments. RESULTS: A linear trend is discernible between lumen diameter and direction and magnitude of remodeling at sites of expanding intima-media thickness (IMT) or plaque. Rate of lesion change varied inversely with lesion thickness with an inflection between rates for low-dimension IMT and plaque. CONCLUSIONS: Dilatation versus shrinkage in the remodeling response to expanding lesions appears related to lumen size. IMT and plaque exhibit independent biologies.

Integration and added value of the modern noninvasive vascular laboratory in vascular diseases management.

BACKGROUND AND PURPOSE: Today's vascular laboratory technology offers broad applications throughout vascular medicine. We explore the diagnostic work-up and management of selected peripheral vascular diseases by benchmarking the institutional mix of invasive and noninvasive technology utilization and associated cost burdens. METHODS: Specialized diagnostic studies for prevention of stroke and pulmonary embolism, and diagnosis and management of femoral pseudoaneurysm were reviewed for our 355-physician clinic and hospital practice. The proportions and costs for invasive and noninvasive diagnostic procedures were tabulated for carotid stenosis, deep venous thrombosis (DVT), and iatrogenic femoral pseudoaneurysm. Current technology utilization mix cost burdens were compared to projected cost burdens for hypothetical equivalent medical value (i.e., the same total test volume) in the theoretical absence of noninvasive laboratory services. RESULTS: The technology utilization mix was dominated by noninvasive duplex ultrasonography for all 3 vascular disease workups. The technology utilization mix benchmarks were 92% noninvasive for carotid stenosis, 98% noninvasive for DVT, and 100% noninvasive for pseudoaneurysm. Under hypothetical constant test volume normalized to utilization level for the 2-year period, the maximal range in cost burdens between current reliance on noninvasive diagnoses versus projected 100% reliance on invasive procedures for the 3 vascular applications is approximately $6 million. CONCLUSION: Benchmark indices reveal near total adoption of noninvasive technology for vascular diagnostic workups at our center. The benefits to institutions of benchmarking their technology utilization mix and costs are discussed in relation to identifying potential for cost-containment from modifying technology utilization practices.