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E Halgren

Publications and source records attributed to E Halgren.

At least 19 recordsLinked to original sources

Studies of working memory using 18FDG-positron emission tomography in normal controls and subjects with epilepsy.

We have studied three groups of subjects with a working memory paradigm, using 18FDG-PET. Controls show the greatest increase on uptake in dorsolateral prefrontal cortex, basal forebrain and angular gyrus. A group of subjects with focal frontal epilepsy did not show increases compared to a control task of attention. Primary generalized epilepsy subjects show the greatest changes in angular gyrus, dorsal temporal, medial frontal and parietal regions. Factor and regression analyses extend these observations and show reliance of both patient groups on the medial and inferior temporal lobe. We propose that the normal network of working memory is disrupted by these two forms of epilepsy and different networks are accessed. Declarative memory may be used as a compensatory system, which results in decreased performance.

Adult

Primary or working memory in frontal lobe epilepsy: An 18FDG-PET study of dysfunctional zones.

INTRODUCTION: We previously demonstrated that patients with frontal lobe epilepsy show deficits on a visual working memory paradigm and that this paradigm produces increased 18FDG uptake in the dorsolateral prefrontal cortex (DPFC), premotor cortex, angular and supramarginal gyri, basal forebrain, and ventral frontal poles of normal subjects when compared with a control task. We hypothesized that subjects with frontal lobe epilepsy would have impaired frontal activation during this task. METHODS: One resting and two activated images were obtained with 18FDG-PET in 15 subjects and 14 controls. One was a delayed (DMS) and one an immediate (IMS) match to sample paradigm. Discriminant and factor analyses were used to analyze the data, supplemented by selected t tests. RESULTS: No differences in glucose uptake were found between the DMS and IMS in the epilepsy subjects, in distinct contrast to controls. A comparison between controls and epilepsy subjects showed differences both ipsilateral and contralateral to the epileptic focus in the frontal regions involved in the task, with small changes in nonfrontal, task-related regions as well. The task itself brought out or highly exaggerated differences seen at rest. There was weak evidence that other frontal and temporal regions were attempting to compensate for the DPFC deficit. CONCLUSION: A unilateral epileptic focus is capable of suppressing function along a large task-related circuit ipsilateral and contralateral to the focus. Peripheral cortical regions compensate poorly for the area of dysfunction.

Adult

Visual working memory in primary generalized epilepsy: an 18FDG-PET study.

It is generally believed that patients with primary generalized epilepsy have normal cognition and neuroimaging studies. We have previously shown that patients with juvenile myoclonic epilepsy (JME) have impaired visual working memory. In this study we examined relative regional changes in 18FDG uptake during a visual working memory paradigm in patients with JME. At rest, there were regional decreases in relative glucose uptake compared to controls. Unlike control subjects, increased activity in the dorsolateral prefrontal cortex was not found during the working memory task. Other regions with increased uptake in controls, such as premotor cortex and basal frontal cortex, also showed no increases, whereas medical temporal structures appeared to play a role in JME but not in control subjects' task performance. The data suggest that JME, a type of primary generalized epilepsy, may suffer from cortical disorganization that affects both the epileptogenic potential and frontal lobe cognitive functioning.

Adult

Intracerebral potentials to rare target and distractor auditory and visual stimuli. I. Superior temporal plane and parietal lobe.

Event-related potentials were recorded from 537 sites in the superior temporal plane and parietal lobe of 41 patients. Depth electrodes were implanted to localize seizure origin prior to surgical treatment. Subjects received an auditory discrimination task with target and non-target rare stimuli ("standard oddball paradigm"). In some cases, the target, distracting and frequent tones were completely balanced across blocks for pitch and volume. Variants included an analogous visual discrimination task, or auditory tasks where the rare target event was the omission of a tone, or the repetition of a tone within a series of alternating tones. In some subjects, the same auditory stimuli were delivered but the patient ignored them while reading. Three general response patterns could be distinguished on the basis of their wave forms, latencies and task correlates. First, potentials apparently related to rarity per se, as opposed to differences in sensory characteristics, or in habituation, were observed in the posterior superior temporal plane, beginning with a large positivity superimposed on early components. This positivity peaked at 150 msec after stimulus onset and inverted in sites superior to the Sylvian fissure. Subsequent components could be large, focal and/or inverting in polarity, and usually included a positivity at 230 msec and a negativity at 330 msec. All components in this area were specific to the auditory modality. Second, in the posterior cingulate and supramarginal gyri, a sharp triphasic negative-positive-negative wave form with peaks at about 210-300-400 msec was observed. This wave form was of relatively small amplitude and diffuse, and seldom inverted in polarity. It was multimodal but most prominent to auditory stimuli, appeared to remain when the stimuli were ignored, and was not apparent to repeated words and faces. Third, a broad, often monophasic, wave form peaking at about 380 msec was observed in the superior parietal lobe, similar to that which has been recorded in the hippocampus. This wave form could be of large amplitude, often highly focal, and could invert over short distances. It was equal to visual and auditory stimuli and was also evoked by repeating words and faces. The early endogenous activity in auditory cortex may embody activity that is antecedent to the other patterns in multimodal association cortex. The "triphasic" pattern may embody a diffuse non-specific orienting response that is also reflected in the scalp P3a. The later broad pattern may embody the cognitive closure that is also reflected in the scalp P3b or late positive component.

Acoustic Stimulation

Intracerebral potentials to rare target and distractor auditory and visual stimuli. II. Medial, lateral and posterior temporal lobe.

Event-related potentials were recorded from 1221 sites in the medial, lateral and posterior aspects of the temporal lobe in 39 patients. Depth electrodes were implanted for about 4 days in order to localize seizure origin prior to surgical treatment. Subjects received an auditory discrimination task with target and non-target rare stimuli. In some cases, the target, distracting and frequent tones were completely balanced across blocks for pitch and volume. Some subjects also received an analogous visual discrimination task, or auditory tasks in which the rare target event was the omission of a tone, or the repetition of a tone within a series of alternating tones. In some subjects, the same auditory stimuli were delivered but the patient ignored them while reading. A complex field was recorded, indicating multiple components with overlapping time-courses, task correlates and generators. Two general patterns could be distinguished on the basis of their waveforms, latencies and task correlates. In the temporal pole and some middle temporal, posterior parahippocampal and fusiform gyrus sites, a sharp triphasic negative-positive-negative waveform with peaks at about 220-320-420 msec was usually observed. This wave was of relatively small amplitude and diffuse, and seldom inverted in polarity. It was multimodal but most prominent to auditory stimuli, appeared to remain when the stimuli were ignored, and was not apparent to repeated words and faces. A second broad, often monophasic, waveform peaking at about 380 msec was generated in the hippocampus, a limited region of the superior temporal sulcus, and (by inference) in the anterobasal temporal lobe (possible rhinal cortex). This waveform was of large amplitude, often highly focal, and could invert over short distances. It was equal to visual and auditory stimuli, was greatly diminished when the stimuli were ignored, and was also evoked by repeating words and faces. Preceding this waveform was a non-modality-specific negativity, possibly generated in rhinal cortex, and a visual-specific negativity in inferotemporal cortex. The early triphasic pattern may embody a diffuse non-specific orienting response that is also reflected in the scalp P3a. The late monophasic pattern may embody the cognitive closure that is also reflected in the scalp P3b or late positive component.

Acoustic Stimulation

Intracerebral potentials to rare target and distractor auditory and visual stimuli. III. Frontal cortex.

Evoked potentials (EPs) were recorded from 991 frontal and peri-rolandic sites (106 electrodes) in 36 patients during an auditory discrimination task with target and non-target (distractor) rare stimuli. Variants of this task explored the effects of attention, dishabituation and stimulus characteristics (including modality). Rare stimuli evoked a widespread triphasic waveform with negative, positive and negative peaks at about 210, 280 and 390 msec, respectively. This waveform was identified with the scalp EP complex termed the N2a/P3a/slow wave and associated with orienting. It was evoked by rare target and distractor auditory and visual stimuli, as well as by rare stimulus repetitions or omissions. Across most frontal trajectories, N2a/P3a/SW amplitudes changed only slowly with distance. However, large (120 microV) P3as with steep voltage gradients were observed laterally, especially near the inferior frontal sulcus, and clear inversions of the P3a were noted in the orbito-frontal and the anterior cingulate cortices. The frontal P3a was earlier to distractor than to target stimuli, but only in some sites and with a latency difference much smaller than that observed at the scalp. Frontal P3a latencies were significantly shorter than those recorded simultaneously at the scalp and often were also shorter than P3a latency in the parietal or temporal lobes. In summary, this study demonstrates an early P3a-like activity that polarity inverts over short distances in the medial frontal lobe, and that it has a significantly shorter latency than similar potentials recorded in the temporal and parietal cortices.

Acoustic Stimulation

Auditory and visual sensory representations in human prefrontal cortex as revealed by stimulus-evoked spike-wave complexes.

Multimodal sensory properties of the prefrontal cortex have been extensively studied in monkeys, while little is known of such functions in humans. We report electrophysiological evidence for auditory and visual representations in the dorsolateral prefrontal cortex, as inferred from intracerebral 'depth' recordings of focal, sensory-evoked spike-wave complexes (SWC) in an epileptic patient. In addition to clinical monitoring, the patient participated in behavioural evoked potential studies involving auditory and visual discrimination tasks. Inspection of evoked potential recordings from different medial-to-lateral prefrontal sites revealed overlapping, but non-identical topographies of evoked SWC for the two sensory modalities. The maximal activity of sensory-evoked SWC was located 7 mm more medially for visual than for auditory stimuli, and occurred later for visual presentations (mean = 117 ms following stimulus onset) than for auditory ones (mean = 87 ms). Effects of sensory habituation were seen. Evoked SWC were less likely to occur following repeated presentations of an unchanging tone than when tones alternated in pitch, or when a tone followed an omission in stimulus presentation. Visual hemifield effects were found, with greater prefrontal responsiveness to presentations in the contralateral visual hemifield. These results are consistent with electrophysiological findings in animals indicating overlapping auditory and visual representations in the dorsolateral prefrontal cortex.

Adult

An 18FDG-PET study of cortical activation during a short-term visual memory task in humans.

Studies of subhuman primates and man have shown that the prefrontal cortex is important for spatial working memory. We have used 18fluorodeoxyglucose positron emission tomography (18FDG-PET) to study a non-spatial, abstract visual memory task of in man. Using a regions-of-interest approach with discriminant analysis of the relative regional cerebral metabolic rate of glucose consumption (rCMRGlc), we found that changes in dorsal prefrontal, premotor/motor frontal and posterior cingulate areas differentiated the primary memory task from the control task. Less robust increases in glucose uptake were observed in lateral parietal cortex, while some subcortical and limbic regions showed decreases. This is the first activation study with a non-spatial, visual task. These results complement previous studies in that they substantiate the role of the prefrontal cortex in the mediation of cross-temporal contingencies of behavior, and point to a role of the premotor region in this mediation as well.

Adult

Influence of cholinesterase inhibitors on cortical slow-wave activity in aging nonhuman primate.

Substantial evidence has now accumulated suggesting that the cognitive decrements characteristic of Alzheimer's disease and, to a lesser degree, of normal aging, may result, at least in part, from degenerative changes in the cholinergic system innervating archi- and neocortices. This evidence for cholinergic degeneration in AD has provided the key rationale for many recent clinical trials utilizing cholinergic agents for the purpose of palliating cognitive loss. The basal forebrain cholinergic system plays an important function in electrocortical activation associated with behavioral arousal and cognitive functions. We recorded electrocortical changes from nonhuman primates following administration of potentially clinically useful cholinergic agonists as well as an antagonist. The cholinesterase inhibitors tacrine (THA) and, to a lesser extent, physostigmine (PHYSO) and amodiaquine (AMDQ), caused an upward shift in the frequency of the resting electrocortical activity, although scopolamine significantly slowed the activity below baseline levels. We believe these findings support the concept that the cholinergic system may play an important role in cognitive processes associated with cortical activation.

Aging

Role of inhibition in memory retrieval by hippocampal area CA3.

A network model with some general properties of hippocampal area CA3, and the results of its simulation on a massively parallel processor, are described. This network performs the tasks of recent declarative memory including recovery of complete traces from partial cues and recognition of familiarity. Immediate recurrent inhibition is essential for providing sensitivity to small cues while preventing spurious recall. Tonic inhibition seems to set the retrieval speed/accuracy trade-off. Delayed inhibition resets hippocampal activity. The behavior under excessive or deficient inhibition resembles that of amnesics with lesions in brainstem areas known to modulate hippocampal inhibition. The rate of recall and dynamics of inhibition by the model are similar to those inferred to occur in the human hippocampus from unit and evoked potential recordings. The model suggests a mechanism whereby the hippocampus can control its own plasticity. These simulations demonstrate that the retrieval mechanism in several hippocampal models is feasible and that the theta rhythm and the cognitive evoked potentials may be generated by synaptic events modulating network parameters.

Cognition

Spatio-temporal stages in face and word processing. I. Depth-recorded potentials in the human occipital, temporal and parietal lobes [corrected].

Evoked potentials (EPs) were used to help identify the timing, location, and intensity of the information-processing stages applied to faces and words in humans. EP generators were localized using intracranial recordings in 33 patients with depth electrodes implanted in order to direct surgical treatment of drug-resistant epilepsy. While awaiting spontaneous seizure onset, the patients gave their fully informed consent to perform cognitive tasks. Depth recordings were obtained from 1198 sites in the occipital, temporal and parietal cortices, and in the limbic system (amygdala, hippocampal formation and posterior cingulate gyrus). Twenty-three patients received a declarative memory recognition task in which faces of previously unfamiliar young adults without verbalizable distinguishing features were exposed for 300 ms every 3 s; 25 patients received an analogous task using words. For component identification, some patients also received simple auditory (21 patients) or visual (12 patients) discrimination tasks. Eight successive EP stages preceding the behavioral response (at about 600 ms) could be distinguished by latency, and each of 14 anatomical structures was found to participate in 2-8 of these stages. The earliest response, an N75-P105, focal in the most medial and posterior of the leads implanted in the occipital lobe (lingual g), was probably generated in visual cortical areas 17 and 18. These components were not visible in response to words, presumably because words were presented foveally. A focal evoked alpha rhythm to both words and faces was also noted in the lingual g. This was followed by an N130-P180-N240 focal and polarity-inverting in the basal occipitotemporal cortex (fusiform g, probably areas 19 and 37). In most cases, the P180 was evoked only by faces, and not by words, letters or symbols. Although largest in the fusiform g this sequence of potentials (especially the N240) was also observed in the supramarginal g, posterior superior and middle temporal g, posterior cingulate g, and posterior hippocampal formation. The N130, but not later components of this complex, was observed in the anterior hippocampus and amygdala. Faces only also evoked longer-latency potentials up to 600 ms in the right fusiform g. Words only evoked a series of potentials beginning at 190 ms and extending to 600 ms in the fusiform g and near the angular g (especially left). Both words and faces evoked a N150-P200-PN260 in the lingual g, and posterior inferior and middle temporal g.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Spatio-temporal stages in face and word processing. 2. Depth-recorded potentials in the human frontal and Rolandic cortices.

Evoked potentials (EPs) were recorded directly from 650 frontal and peri-Rolandic sites in 26 subjects during face and/or word recognition, as well as during control tasks (simple auditory and visual discrimination). Electrodes were implanted in order to localize epileptogenic foci resistant to medication, and thus direct their surgical removal. While awaiting spontaneous seizure onset, the patients gave informed consent to perform cognitive tasks during intracerebral EEG recording. The earliest potentials appeared to be related to sensory stimulation, were prominent in lateral prefrontal cortex, and occurred at peak latencies of about 150 and 190 ms. A small triphasic complex beginning slightly later (peak latencies about 200-285-350 ms) appeared to correspond to the scalp N2-P3a-slow wave, associated with non-specific orienting. Multiple components peaking from 280 to 900 ms, and apparently specific to words were occasionally recorded in the left inferior frontal g, pars triangularis (Broca's area). Components peaking at about 430 and 600 ms were recorded in all parts of the prefrontal cortex, but were largest (up to 180 microV) and frequently polarity-inverted in the ventro-lateral prefrontal cortex. These components appeared to represent the N4-P3b, which have been associated with contextual integration and cognitive closure. Finally, a late negativity (650-900 ms) was recorded in precentral and premotor cortices, probably corresponding to a peri-movement readiness potential. In summary, EP components related to early sensory processing were most prominent in lateral prefrontal, to orienting in medial limbic, to word-specific processing in Broca's area, to cognitive integration in ventro-lateral prefrontal, and to response organization in premotor cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Anatomical origin of déjà vu and vivid 'memories' in human temporal lobe epilepsy.

Jackson (Brain 1898; 21: 580-90) observed that seizures arising in the medial temporal lobe may result in a 'dreamy state', consisting of vivid memory-like hallucinations, and/or the sense of having previously lived through exactly the same situation (déjà vu). Penfield demonstrated that the dreamy state can sometimes be evoked by electrical stimulation of the lateral temporal neocortex, especially the superior temporal gyrus. Halgren et al. (Brain 1978; 101: 83-117) showed that the dreamy state can be evoked by stimulation of the hippocampal formation and amygdala and Gloor (Brain 1990; 113: 1673-94) has suggested that it is evoked by lateral stimulation only when the resulting after-discharge spreads medially. In order to resolve the relative importance of these areas, we considered the mental phenomena observed in epileptic patients with electrodes stereotaxically implanted into different brain areas for seizure localization prior to surgical treatment. Sixteen patients, all with seizures involving the temporal lobe, experienced the dreamy state either as a result of spontaneous seizures (nine dreamy states in six patients), or due to electrical stimulation (43 in 14) or to chemical activation (five in three). Déjà vu and hallucinations of scenes were often evoked by different stimulations of the same electrode in the same patient. As Jackson had also observed, the dreamy state could occur alone but was often associated with epigastric phenomena and fear, and followed by loss of contact and oro-alimentary automatisms, and then by simple gestural automatisms, all characteristic of partial seizures beginning in the medial temporal lobe. Furthermore, as also emphasized by Jackson, the dreamy state was seldom associated with sensory illusions. Stimulation of either the neocortex (15 occurrences), anterior hippocampus (17) or amygdala (10) could evoke a dreamy state. However, since fewer hippocampal and amygdala leads were stimulated than temporal neocortical, the proportion of medial temporal electrodes where dreamy states could be evoked was much higher than in the neocortex. Most responsive lateral temporal sites were located in the superior temporal gyrus, rather than the middle temporal gyrus which was significantly less responsive. In 85% of dreamy states evoked by medial temporal lobe stimulation, the discharge spread to the temporal neocortex; and in 53% of dreamy states evoked by lateral temporal stimulation, the discharge spread medially. Considering all dreamy states, the amygdala was involved (as the stimulated structure, or as the site of ictal- or after-discharge) in 73% of cases, the anterior hippocampus in 83% and the temporal neocortex in 88%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Localized brain metabolic response correlated with potentials evoked by words.

Evoked potentials (EPs) measure synaptic current flows that propagate from brain to scalp, Alternatively, positron emission tomography (PET) using fluoro-deoxyglucose (FDG) can measure the increased glucose metabolism supporting this synaptic activation. It is difficult to localize the brain activity-generating EPs from their scalp distribution, because activity originating in different regions tends to produce overlapping scalp topographies. In contrast, FDG-PET provides better spatial resolution for activity throughout the brain, but shows only the total metabolism integrated over a 30-min uptake period. We combined the temporal and psychological resolution of EPs with the spatial resolution of PET to help define when and where in the brain words are encoded for meaning.

Adult

Firing of human hippocampal units in relation to voluntary movements.

During certain movements (termed "type I," "instrumental," or "voluntary"), the rodent hippocampal EEG is dominated by regular 7-10 Hz waves. This "theta rhythm" is accompanied by increased firing of hippocampal interneurons and dentate gyrus granule cells. No obvious theta rhythm is present in comparable situations in humans or other primates. However, a widespread scalp negativity (the "readiness potential") starts approximately 1 second before spontaneous key presses at long intervals. The readiness potential has been recorded in the monkey hippocampus. In this study, action potentials were recorded in the human hippocampus in relation to various movements. During a broadly ranging interview including various movements and memory tests, hippocampal units were found that fired during movements of the tongue and/or hands. Only movements that required a high degree of effort were effective. Other hippocampal units appeared to be correlated with either the transitions between tasks or the interruptions within tasks. In a second experiment, hippocampal units were found to change their firing in the seconds preceding spontaneous key presses. These data indicate that, like the rodent hippocampus, human hippocampal neuronal activity is strongly influenced by movement.

Action Potentials

Memory dysfunction in epilepsy patients as a derangement of normal physiology.

Patients with CPS often display recent memory deficits. Typically, general intelligence, perceptual skills, language, remote memory, and primary memory are all normal. However, the ability to learn new combinations of cognitively complex material is deficient. This deficit may be specific for verbal material (e.g., as a difficulty with learning to recall a response word given an unrelated cue word), for nonverbal material (e.g., as a difficulty in drawing a complex figure from memory), or for both verbal and nonverbal material. Because these characteristics are typical of memory deficits after MTL damage, it is reasonable to suspect that these deficits in patients with epilepsy also reflect MTL damage. In many cases, MTL damage is apparent from neuroimaging studies, whereas seizure semiology suggests MTL onset. In these patients, the same pathology might be the cause of both the ictus and memory deficits. In other cases, memory impairment appears to be secondary to seizures. This suggestion is supported by cases where prolonged complex partial status resulted in a permanent global amnesia. Cases with shorter-lasting memory deficits were also presented. Neuropsychological testing revealed specific recent-memory deficits that cleared 2 weeks after a flurry of CPS and 24 hr after a single seizure. Depth recordings have demonstrated that MTL electrographic seizures can occur without subjective manifestations. When these are evoked by local electrical stimulation, a profound inability to learn new material may be observed during the afterdischarge. Similarly, artificially induced MTL spike-and-wave complexes interfere with the memory for simultaneously presented complex visual scenes. Recent evidence suggests that all of the above phenomena may reflect the engagement by epileptiform processes of the association-cortex (AC)-MTL circuits used in normal human memory. In recent memory tasks, cognitive evoked-potential components N4 and P3 are generated in the MTL and to a lesser degree in related AC regions. The N4/P3 are strongly modulated by familiarity in recent memory. This modulation is eliminated by anterior temporal lobectomy. The typical slow wave following spontaneous MTL interictal spikes has the same MTL voltage topography, and thus probably similar synaptic generators, as the cognitive P3 potential. Furthermore, MTL spike-and-wave complexes can be evoked in recent memory tasks at a fixed latency equal to that of the N4.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent