Wade M. Mueller

Functional magnetic resonance imaging of complex human movements

Functional magnetic resonance imaging (FMRI) is a new, noninvasive imaging tool thought to measure changes related to regional cerebral blood flow (rCBF). Previous FMRI studies have demonstrated functional changes within the primary cerebral cortex in response to simple activation tasks, but it is unknown whether FMRI can also detect changes within the nonprimary cortex in response to complex mental activities. We therefore scanned six right-handed healthy subjects while they performed self-paced simple and complex finger movements with the right and left hands. Some subjects also performed the tasks at a fixed rate (2 Hz) or imagined performing the complex task. Functional changes occurred (1) in the contralateral primary motor cortex during simple, self-paced movements; (2) in the contralateral (and occasionally ipsilateral) primary motor cortex, the supplementary motor area (SMA), the premotor cortex of both hemispheres, and the contralateral somatosensory cortex during complex, self-paced movements; (3) with less intensity during paced movements, presumably due to the slower movement rates associated with the paced (relative to self-paced) condition; and (4) in the SMA and, to a lesser degree, the premotor cortex during imagined complex movements. These preliminary results are consistent with hierarchical models of voluntary motor control.

Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy

Objective: To perform an open-label, long-term efficacy and safety/tolerability study of vagus nerve stimulation (VNS) of 454 patients with refractory epilepsy. Methods: Subjects were enrolled from five clinical trials of VNS between 1988 and 1995 after undergoing an implantation of a pulse generator in the chest and a left cervical vagus nerve-stimulating lead coil. Patients were assessed at 6-month intervals until device approval. Seizure frequencies, medication treatment, and adverse events (AEs) were recorded and entered into a database. Results: A total of 454 patients were implanted, and 440 patients yielded assessable data. A ≥50% seizure reduction postimplantation occurred in 36.8% of patients at 1 year, in 43.2% at 2 years, and in 42.7% at 3 years. Median seizure reductions compared with baseline were 35% at 1 year, 44.3% at 2 years, and 44.1% at 3 years. Most common AEs postimplantation at 1 year were hoarseness (28%) and paraesthesias (12%), at 2 years were hoarseness (19.8%) and headache (4.5%), and at 3 years was shortness of breath (3.2%). Continuation rates were 96.7% at 1 year, 84.7% at 2 years, and 72.1% at 3 years. Conclusion: Long-term, open-label vagus nerve stimulation (VNS) provided seizure reduction similar to or greater than acute studies, for median reductions and for those reaching a ≥50% seizure reduction. VNS remained safe and well tolerated, with nearly three-quarters of the patients choosing to continue therapy.

Functional Magnetic Resonance Imaging Mapping of the Motor Cortex in Patients with Cerebral Tumors

OBJECTIVE The purpose of this study was to determine the usefulness of functional magnetic resonance imaging (FMRI) to map cerebral functions in patients with frontal or parietal tumors. METHODS Charts and images of patients with cerebral tumors or vascular malformations who underwent FMRI with an echoplanar technique were reviewed. The FMRI maps of motor (11 patients), tactile sensory (12 patients), and language tasks (4 patients) were obtained. The location of the FMRI activation and the positive responses to intraoperative cortical stimulation were compared. The reliability of the paradigms for mapping the rolandic cortex was evaluated. RESULTS Rolandic cortex was activated by tactile tasks in all 12 patients and by motor tasks in 10 of 11 patients. Language tasks elicited activation in each of the four patients. Activation was obtained within edematous brain and adjacent to tumors. FMRI in three cases with intraoperative electrocortical mapping results showed activation for a language, tactile, or motor task within the same gyrus in which stimulation elicited a related motor, sensory, or language function. In patients with > 2 cm between the margin of the tumor, as revealed by magnetic resonance imaging, and the activation, no decline in motor function occurred from surgical resection. CONCLUSIONS FMRI of tactile, motor, and language tasks is feasible in patients with cerebral tumors. FMRI shows promise as a means of determining the risk of a postoperative motor deficit from surgical resection of frontal or parietal tumors.

Use of preoperative functional neuroimaging to predict language deficits from epilepsy surgery

Background: Left anterior temporal lobectomy (L-ATL) may be complicated by confrontation naming deficits. Objective: To determine whether preoperative fMRI predicts such deficits in patients with epilepsy undergoing L-ATL. Methods: Twenty-four patients with L-ATL underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language dominance, and pre- and postoperative neuropsychological testing. fMRI laterality indexes (LIs), reflecting the interhemispheric difference between activated volumes in left and right homologous regions of interest, were calculated for each patient. Relationships between the fMRI LI, Wada language dominance, and naming outcome were examined. Results: Both the fMRI LI (p < 0.001) and the Wada test (p < 0.05) were predictive of naming outcome. fMRI showed 100% sensitivity and 73% specificity in predicting significant naming decline. Both fMRI and the Wada test were more predictive than age at seizure onset or preoperative naming performance. Conclusions: Preoperative fMRI predicted naming decline in patients undergoing left anterior temporal lobectomy surgery.

Use of preoperative functional MRI to predict verbal memory decline after temporal lobe epilepsy surgery.

Purpose: Verbal memory decline is a frequent complication of left anterior temporal lobectomy (L‐ATL). The goal of this study was to determine whether preoperative language mapping using functional magnetic resonance imaging (fMRI) is useful for predicting which patients are likely to experience verbal memory decline after L‐ATL.

Lesion-induced pseudo-dominance at functional magnetic resonance imaging: implications for preoperative assessments

OBJECTIVE:To illustrate how lesion-induced neurovascular uncoupling at functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance opposite the side of a lesion preoperatively. METHODS:We retrospectively reviewed preoperative fMRI mapping data from 50 patients with focal brain abnormalities to establish patterns of hemispheric dominance of language, speech, visual, or motor system functions. Abnormalities included gliomas (31 patients), arteriovenous malformations (AVMs) (11 patients), other congenital lesions (4 patients), encephalomalacia (3 patients), and tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric dominance was compared with actual hemispheric dominance as verified by electrocortical stimulation, Wada testing, postoperative and posttreatment deficits, and/or lesion-induced deficits. fMRI activation maps were generated with cross-correlation (P < 0.001) or t test (P < 0.001) analysis. RESULTS:In 50 patients, a total of 85 functional areas were within 5 mm of the edge of a potentially resectable lesion. In 23 of these areas (27%), reduced fMRI signal in perilesional eloquent cortex in conjunction with preserved or increased signal in homologous contralateral brain areas revealed functional dominance opposite the side of the lesion. This suggested possible lesion-induced transhemispheric cortical reorganization to homologous brain regions (homotopic reorganization). In seven patients, however, the fMRI data were inconsistent with other methods of functional localization. In two patients with left inferior frontal gyrus gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI incorrectly suggested strong right hemispheric speech dominance. In two patients with lateral precentral gyrus region gliomas and one patient with a left central sulcus AVM, the fMRI pattern incorrectly suggested primary corticobulbar motor dominance contralateral to the side of the lesion. In a patient with a right superior frontal gyrus AVM, fMRI revealed pronounced left dominant supplementary motor area activity in response to a bilateral complex motor task, but right superior frontal gyrus perilesional hemorrhage and edema subsequently caused left upper-extremity plegia. Pathophysiological factors that might have caused neurovascular uncoupling and facilitated pseudo-dominance at fMRI in these patients included direct tumor infiltration, neovascularity, cerebrovascular inflammation, and AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient), probable (2 patients), or possible (13 patients) but unproven lesion-induced homotopic cortical reorganization. CONCLUSION:Lesion-induced neurovascular uncoupling causing reduced fMRI signal in perilesional eloquent cortex, in conjunction with normal or increased activity in homologous brain regions, may simulate hemispheric dominance and lesion-induced homotopic cortical reorganization.

Functional magnetic resonance imaging of somatosensory stimulation

Functional magnetic resonance imaging (FMRI) has detected changes in regional cerebral blood flow and volume in response to motor movements, visual stimuli, and auditory stimuli in each of their respective primary cortices. This experiment was conducted to determine whether signal changes in the somatosensory cortex secondary to tactile stimulation could be demonstrated. The palm of the right hand was periodically stimulated while the subject was undergoing echo-planar imaging with a 1.5-T magnetic resonance scanner equipped with local gradient and radio frequency coils. Sagittal and coronal images of 10- to 15-mm slice thickness were selected to include the postcentral gyrus and surrounding regions. Temporally correlated signal changes of 1% to 5% occurred in the peri-rolandic region in each of six subjects. The time course of signal changes was comparable to that found in other primary sensory and motor cortices. The results provide preliminary evidence of the sensitivity of FMRI to activation of the somatosensory cortex with tactile stimulation and support FMRI as a promising noninvasive technique for study of the functional organization and integrity of the cerebrum.

Side of seizure focus predicts left medial temporal lobe activation during verbal encoding

Objective: Functional MRI (FMRI) was used to investigate the effect of medial temporal lobe (MTL) pathology on activation of language encoding areas in patients with temporal lobe epilepsy (TLE). Methods: Whole-brain FMRI was obtained. Twenty-eight patients with either left TLE(LTLE) or right TLE (RTLE) performed a semantic decision task alternating with an auditory perceptual task. Results: Activation of language areas in the frontal and parietal lobes was similar in both groups, with no group differences in the total number of active voxels. However, the RTLE group showed much stronger activation of the left MTL, including the hippocampus, parahippocampal gyrus, and collateral sulcus, than did the LTLE group. Conclusions: Activation of the left MTL during semantic encoding discriminates patients with RTLE and LTLE. This FMRI technique may potentially be of use in determining memory lateralization and for predicting the side of seizure focus in TLE.

Memory outcome after left anterior temporal lobectomy in patients with expected and reversed Wada memory asymmetry scores.

Summary:  Purpose: The ideal candidate for anterior temporal lobectomy surgery shows a Wada memory asymmetry (WMA) score characterized by better memory performance in the hemisphere contralateral to the seizure focus relative to the ipsilateral (surgical) hemisphere. However, some surgical candidates show a reversed WMA or better Wada memory performance in the hemisphere of surgical interest relative to the hemisphere contralateral to the seizure focus. To date, no data are available contrasting memory and seizure outcome for these two Wada groups. The present study compared memory and seizure outcome after left anterior temporal lobectomy (L‐ATL) in patients showing expected and reversed WMA scores, and also examined the relationship of the individual hemisphere Wada memory scores for predicting verbal memory outcome after L‐ATL.

A comparison of two fMRI methods for predicting verbal memory decline after left temporal lobectomy: language lateralization versus hippocampal activation asymmetry.

Purpose:  Language lateralization measured by preoperative functional magnetic resonance imaging (fMRI) was shown recently to be predictive of verbal memory outcome in patients undergoing left anterior temporal lobe (L‐ATL) resection. The aim of this study was to determine whether language lateralization or functional lateralization in the hippocampus is a better predictor of outcome in this setting.