Biomedical subjects

C M Epstein

Publications and source records attributed to C M Epstein.

At least 19 recordsLinked to original sources

PubMed1999

Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy.

OBJECTIVE: To determine possible sites of therapeutic action of vagus nerve stimulation (VNS), by correlating acute VNS-induced regional cerebral blood flow (rCBF) alterations and chronic therapeutic responses. BACKGROUND: We previously found that VNS acutely induces rCBF alterations at sites that receive vagal afferents and higher-order projections, including dorsal medulla, somatosensory cortex (contralateral to stimulation), thalamus and cerebellum bilaterally, and several limbic structures (including hippocampus and amygdala bilaterally). METHODS: VNS-induced rCBF changes were measured by subtracting resting rCBF from rCBF during VNS, using [O-15]water and PET, immediately before ongoing VNS began, in 11 partial epilepsy patients. T-statistical mapping established relative rCBF increases and decreases for each patient. Percent changes in frequency of complex partial seizures (with or without secondary generalization) during three months of VNS compared with pre-VNS baseline, and T-thresholded rCBF changes (for each of the 25 regions of previously observed significant CBF change), were rank ordered across patients. Spearman rank correlation coefficients assessed associations of seizure-frequency change and t-thresholded rCBF change. RESULTS: Seizure-frequency changes ranged from 71% decrease to 12% increase during VNS. Only the right and left thalami showed significant associations of rCBF change with seizure-frequency change. Increased right and left thalamic CBF correlated with decreased seizures (p < 0.001). CONCLUSIONS: Increased thalamic synaptic activities probably mediate some antiseizure effects of VNS. Future studies should examine neurotransmitter-receptor alterations in reticular and specific thalamic nuclei during VNS.

Adult↗

PubMed1999

Localization and characterization of speech arrest during transcranial magnetic stimulation.

OBJECTIVE: To determine the anatomic and physiologic localization of speech arrest induced by repetitive transcranial magnetic stimulation (rTMS), and to examine the relationship of speech arrest to language function. METHODS: Ten normal, right-handed volunteers were tested in a battery of language tasks during rTMS. Four underwent mapping of speech arrest on a 1 cm grid over the left frontal region. Compound motor action potentials from the right face and hand were mapped onto the same grid. Mean positions for speech arrest and muscle activation were identified in two subjects on 3-dimensional MRI. RESULTS: All subjects had lateralized arrest of spontaneous speech and reading aloud during rTMS over the left posterior-inferior frontal region. Writing, comprehension, repetition, naming, oral praxis, and singing were relatively spared (P < .05). Stimulation on the right during singing abolished melody in two subjects, but minimally affected speech production. The area of speech arrest overlay the caudal portion of the left precentral gyrus, congruous with the region where stimulation produced movement of the right face. CONCLUSIONS: The site of magnetic speech arrest appears to be the facial motor cortex. Its characteristics differ from those of classic aphasias, and include a prominent dissociation among different types of speech output.

Adult↗

PubMed1999

Role of the posterior parietal cortex in updating reaching movements to a visual target.

The exact role of posterior parietal cortex (PPC) in visually directed reaching is unknown. We propose that, by building an internal representation of instantaneous hand location, PPC computes a dynamic motor error used by motor centers to correct the ongoing trajectory. With unseen right hands, five subjects pointed to visual targets that either remained stationary or moved during saccadic eye movements. Transcranial magnetic stimulation (TMS) was applied over the left PPC during target presentation. Stimulation disrupted path corrections that normally occur in response to target jumps, but had no effect on those directed at stationary targets. Furthermore, left-hand movement corrections were not blocked, ruling out visual or oculomotor effects of stimulation.

Humans↗

PubMed1998

Repetitive transcranial magnetic stimulation activates specific regions in rat brain.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

Animals↗

PubMed1998

Alumina gel injections into the temporal lobe of rhesus monkeys cause complex partial seizures and morphological changes found in human temporal lobe epilepsy.

The goal of the present study was to determine whether alumina gel injections into temporal lobe structures cause complex partial seizures (CPS) and pathological changes observed in human temporal lobe epilepsy. Rhesus monkeys with alumina gel injections in the amygdala, perirhinal and entorhinal cortices, or Ammon's horn and dentate gyrus all initially displayed focal pathological electroencephalographic (EEG) slowing limited to the site of injection. After clinical seizures developed, they also displayed widespread pathological EEG slowing over both hemispheres, interictal and ictal epileptiform EEG abnormalities limited to the mesial-inferior temporal lobe on the side of injection, and different degrees of spread to other ipsilateral and contralateral structures. Noninjected control and nonepileptic monkeys with injections into the middle and inferior temporal gyri displayed no hippocampal neuronal loss or mossy fiber sprouting. When alumina gel was injected into the amygdala, CPS began within 3-6 weeks and degeneration of neurons and gliosis occurred in the perirhinal cortex or the hippocampus, with consequent sprouting of mossy fibers in the dentate gyrus. Dispersion of the granule cell layer was also observed. Other monkeys with alumina gel in the perirhinal and entorhinal cortices developed CPS within 2-3 weeks after the injections and displayed mossy fiber sprouting only after 4 weeks after the injections. Alumina gel in Ammon's horn and the dentate gyrus also induced CPS, but mossy fiber sprouting was limited to sites immediately adjacent to the injection, probably because none survived more than 4 weeks after the injections. This nonhuman primate model of CPS displayed similar anatomical, behavioral, and EEG features as observed in human temporal lobe epilepsy and provides opportunities to analyze the chronological sequence of epileptogenesis and to test potential therapies.

Aluminum Oxide↗

PubMed1998

Transcranial magnetic stimulation: language function.

Studies of language using transcranial magnetic stimulation (TMS) have focused both on identification of language areas and on elucidation of function. TMS may result in either inhibition or facilitation of language processes and may operate directly at a presumptive site of language cortex or indirectly through intracortical networks. TMS has been used to create reversible "temporary lesions," similar to those produced by Wada tests and direct cortical electrical stimulation, in cerebral cortical areas subserving language function. Rapid-rate TMS over the left inferior frontal region blocks speech output in most subjects. However, the results are not those predicted from classic models of language organization. Speech arrest is obtained most easily over facial motor cortex, and true aphasia is rare, whereas right hemisphere or bilateral lateralization is unexpectedly prominent. A clinical role for these techniques is not yet fully established. Interfering with language comprehension and verbal memory is currently more difficult than blocking speech output, but numerous TMS studies have demonstrated facilitation of language-related tasks, including oral word association, story recall, digit span, and picture naming. Conversely, speech output also facilitates motor responses to TMS in the dominant hemisphere. Such new and often-unexpected findings may provide important insights into the organization of language.

Cerebral Cortex↗

PubMed1998

Magnetic stimulation of visual cortex: factors influencing the perception of phosphenes.

Using transcranial magnetic stimulation of occipital cortex, the authors studied the stimulus parameters that generate phosphenes in healthy volunteers. Single pulses or trains of stimuli readily elicited phosphenes in all subjects. The threshold current needed to elicit perception of phosphenes was essentially the same for stimulus trains from 250 msec to 2000 msec in length, but increased dramatically for trains of shorter duration. The effect of stimulus frequency was variable, with each subject having a distinctive "frequency tuning curve," but overall, the threshold current necessary to produce phosphenes decreased as frequency of stimulation increased. Using paired pulses, the perceptual threshold was flat for interstimulus intervals between 2 msec and 100 msec, but increased rapidly as the interstimulus interval was increased above 100 msec. Stimulation of sites lateral to the midline elicited phosphenes in the contralateral visual field. Phosphenes were dominant in the lower and peripheral aspects of the visual fields. The findings are discussed in relation to similar studies of electrical stimulation of somatosensory cortex.

Adult↗

PubMed1998

Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation.

PURPOSE: Left cervical vagus nerve stimulation (VNS) decreases complex partial seizures (CPS) by unknown mechanisms of action. We hypothesized that therapeutic VNS alters synaptic activities at vagal afferent terminations and in sites that receive polysynaptic projections from these medullary nuclei. METHODS: Ten patients with partial epilepsy underwent positron emission tomographic (PET) measurements of cerebral blood flow (BF) three times before and three times during VNS. Parameters for VNS were at high levels for 5 patients and at low levels for 5. Resting BF measurements were subtracted from measurements during VNS in each subject. Subtraction data were averaged in each of 2 groups of 5 patients. t Tests were applied to BF changes in brain regions that receive vagal afferents and projections (significant at p < 0.05, corrected for repeated measures). RESULTS: In both the low- and high-stimulation groups during VNS, brain BF was (a) increased in the rostral, dorsal-central medulla; (b) increased in the right postcentral gyrus, (c) increased bilaterally in the hypothalami, thalami, and insular cortices, and in cerebellar hemispheres inferiorly; and (d) decreased bilaterally in hippocampus, amygdala, and posterior cingulate gyri. The high-stimulation group had greater volumes of activation and deactivation sites. CONCLUSIONS: Our findings suggest that left cervical VNS acutely increases synaptic activity in structures directly innervated by central vagal structures and areas that process left-sided somatosensory information, but VNS also acutely alters synaptic activity in multiple limbic system structures bilaterally. These findings may reflect sites of therapeutic actions of VNS.

Adult↗

PubMed1998

Presentation of narcolepsy after 40.

To advance understanding of the clinical spectra of narcolepsy, we retrospectively reviewed the histories and clinical and polysomnographic features of 41 consecutive patients in whom this diagnosis was established in our center over 3 years. A total of 51% presented after the age of 40 years. Among the older patients, three subpopulations were noted: 1) narcolepsy/cataplexy with presentation delayed because of mild disease severity or misdiagnosis; 2) narcolepsy/cataplexy with diagnosis delayed until late-life expression of cataplexy; and 3) narcolepsy lacking cataplexy with later-life onset of excessive daytime sleepiness. Clinical, polysomnographic, and multiple sleep latency test assessments of rapid eye movement sleep dyscontrol and sleepiness were unrelated to age. This analysis identified older patients lacking cataplexy as the least severely affected narcoleptic subgroup. Narcolepsy, a continuum of phenotypes and severities that masks its recognition, should be considered in the differential diagnosis of sleepiness or transient loss of muscle tone in older patients.

Adult↗

PubMed1997

Mapping transcranial magnetic stimulation (TMS) fields in vivo with MRI.

Transcranial magnetic stimulation (TMS) is a non-invasive technique for investigating brain function that uses pulsed magnetic fields created by special coils to induce localized neuronal depolarization. Despite the technique's expanding application, the exact magnetic field produced by TMS coils have never been directly measured in human subjects. Using a standard 1.5T MR scanner and TMS coils constructed from non magnetic materials, we have obtained 3D maps of the magnetic field created by TMS coils in human volunteers. Further, we mapped the combined field of two coils and demonstrated that combinations of coils might be used to focus the magnetic field to achieve improved stimulation patterns and, perhaps, reach areas out of reach of single coils.

Brain↗

PubMed1996

Temporal lobe epilepsy and performance on the Wisconsin Card Sorting Test.

The replicability of previous evidence for differential performance between left and right temporal lobe epileptic patients on the Wisconsin Card Sorting Test (WCST) was evaluated in a new sample of candidates for focal resection. Many subjects obtained high scores on indices of perseveration, which are commonly thought to reflect frontal dysfunction, but there were no differences in performance between patients with language-dominant and nondominant temporal foci. The findings confirm existing evidence that performance decrements on the WCST can be associated with epileptic foci and focal lesions in nonfrontal brain lesions.

Adult↗

PubMed1996

Magnetic coil suppression of extrafoveal visual perception using disappearance targets.

We used magnetic brain stimulation with a butterfly coil over the occipital lobes to study extrafoveal visual field effects in six subjects. The visual test pattern was a grid of asterisks around a central fixation point, and the target was the disappearance of one asterisk for a single frame of the video monitor. Using single magnetic pulses at stimulator outputs of 55-95%, we noted robust interference effects at latencies < or = 100 ms, peaking at approximately 50-90 ms. Suppression of visual perception occurred with both transverse and sagittal alignments of the coil. When the coil was moved laterally over either occipital lobe, perception of target disappearance was consistently suppressed in the contralateral visual field. Movement of the coil rostrally produced consistent suppression in the lower and middle field, but preferential suppression of the upper field could not be obtained. This altitudinal asymmetry may be correlated with the anatomy of the occipital lobe in relation to the scalp surface.

Attention↗

PubMed1996

Magnetic coil suppression of visual perception at an extracalcarine site.

Perception of extrafoveal visual targets can be suppressed by magnetic stimulation over the occipital lobes, but the site of interference for this and similar phenomena has not been well defined. We modified a previously used technique to determine the locus of magnetic activation. Using butterfly stimulus coils of different sizes and electric field profiles, we determined a scalp position of minimum threshold and a level of stimulator output that produced 50% error rates for each coil. Intersection of the corresponding electric field profiles in air and in a saline model head was similar and identified superficial occipital cortex rather than the primary visual area as the site of perceptual suppression. Less direct analyses involving the distribution of induced electric fields produced the same conclusion. These results suggest specific hypotheses about the effects of magnetic stimulation on visual physiology.

Attention↗

PubMed1996

Focal paresthesias with cervical magnetic stimulation.

Subjects undergoing cervical magnetic stimulation with an appropriate coil report focal hand paresthesias in a dermatomal distribution, but the physiologic accuracy of such subjective experiences has been uncertain. In six subjects, we used a butterfly-shaped magnetic coil to stimulate positions on the back of the neck at 1-cm intervals, constant output, and random order, while the subject-estimated location and intensity of paresthesias and sensory nerve action potentials (SNAPs) were recorded from the thumb or index finger. Three subjects each also had recording of finger accelerometry or compound motor action potentials (CMAPs) in the hand and forearm. We found a consistent correlation between subjective paresthesias and SNAPs but an appropriate anatomic divergence between paresthesias and accelerometry or CMAPs. Focal paresthesias from cervical magnetic stimulation are reliable and anatomically accurate, strengthening the hypothesis that other magnetic sensory phenomena are valid as well.

Action Potentials↗

PubMed1996

Optimum stimulus parameters for lateralized suppression of speech with magnetic brain stimulation.

Rapid-rate transcranial magnetic brain stimulation produces lateralized suppression of speech output over the frontal lobe, consistent with cerebral dominance for language. But the sensitivity of magnetic speech localization has been limited, and reports are imprecise concerning the amount of discomfort involved. Using a focal magnetic coil, we evaluated the effectiveness and pain of stimulation at different intensities, orientations, and repetition rates (2 to 32 Hz) in six normal volunteers. We obtained complete and clearly lateralized speech arrest in all subjects. The best ratio of efficacy to pain occurred using slower repetition rates of 4 to 8 Hz with a horizontal alignment of the induced electric field. Lower stimulation frequency also allowed clearer distinction between speech arrest and dysarthria from tonic contraction of cranial muscles. The relative comfort and safety of stimulation at 4 Hz should allow more widespread use of magnetic speech localization in clinical and research applications.

Adult↗

PubMed1996

Evaluation of 1H magnetic resonance spectroscopic imaging as a diagnostic tool for the lateralization of epileptogenic seizure foci.

The purpose of this study was to assess whether a visual examination of 1H spectroscopic images could correctly lateralize patients with intractable temporal lobe epilepsy. 20 patients with intractable temporal lobe epilepsy and 10 volunteers were included in this study. Spectroscopic images were analysed using a protocol based on visual inspection. Images of the metabolites N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate were obtained from a transverse plane oriented along the sylvian fissure. Images from each individual were evaluated independently by six reviewers. Results of the lateralization procedure obtained from the visual examinations were compared with those obtained from quantitative analysis of the spectra and with those obtained by magnetic resonance imaging (MRI), positron emission tomography (PET), neuropsychological examinations, and electroencephalographic (EEG) recordings. NAA images were found to be the most effective, amongst metabolite images, in lateralizing the epileptogenic lobe. Using the site selected for resection as the definition of the correct lateralization, 70% of the patients who underwent temporal lobectomy were correctly lateralized by the majority of the examiners using the visual inspection protocol. Based on the results of this study it is concluded that visual examination of 1H spectroscopic images is potentially valid in lateralizing patients with intractable temporal lobe seizures. Confidence in the visual interpretation increased as the difference in NAA signal intensity between the temporal lobes increased. The threshold above which the majority of the examiners correctly lateralized the patients was approximately 15% in NAA signal loss in the ipsilateral lobe.

Adolescent↗

PubMed1995

Clozapine-induced EEG abnormalities and clinical response to clozapine.

The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures. BPRS scores improved significantly in the group of patients who developed abnormal EEGs but not in the group who did not. Findings are consistent with previous reports of a high incidence of clozapine-induced EEG abnormalities and a positive association between these abnormalities and clinical improvement.

Adult↗

PubMed1995

Abnormalities in posturography and estimations of visual vertical and horizontal in multiple sclerosis.

Twenty-seven patients with mild multiple sclerosis were tested with the dynamic posturography protocol used in the NeuroCom Equitest procedure. The purpose of this study was to determine if the standard test procedure elicited a pattern of responses that would suggest the possibility of multiple sclerosis during differential diagnosis of a patient with dysequilibrium. In addition, the patients' ability to align a light bar to vertical and horizontal was tested with the head erect and with the head tilted 45 degrees to the right and left shoulder. There was a pattern of abnormality in the Equitest motor coordination tests. Only one patient produced normal scores in both the latency and adaptation tests. No pattern of error was noted in the sensory organization tests. In the visual alignment tests, only 3 of the 27 patients tested produced values that were within normal limits for the three different head positions. Visual alignment and the motor coordination tests are not specific for multiple sclerosis, but poor performance probably indicates a disruption of the integration of visual, vestibular, and somatosensory information. Although patients with early multiple sclerosis and patients with purely vestibular disorders often have similar complaints, they have quite different profiles of abnormalities in posturography testing.

Diagnosis, Differential↗