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E Halgren

Publications and source records attributed to E Halgren.

At least 37 records · Page 2Linked to original sources

Divided attention-enhancing effects of AF102B and THA in aging monkeys.

The effects of cholinergic drugs proposed for treatment of cognitive impairment in normal aging and dementia on divided attention have been little studied in non-human primates. We tested the hypothesis that cholinergic drugs improve spatial divided attention in primates via a computer task requiring simultaneous tracking of two visual targets in three young and two aged healthy bonnet macaques. Task accuracy (number of correct responses) and reaction time (RT) were measured 2 h after administration of either the m1 agonist +/- -cis-2-methyl-spiro(1,3-oxathiolane-5,3')quinuclidine (AF102B; 0.1-2.1 mg/kg IM) or the cholinesterase inhibitor 9-amino-1,2,3,4-tetrahydroamino-acridine (THA; 0.5-2.0 mg/kg orally). Accuracy increased for four of five monkeys at appropriate doses of one or both cholinomimetics, accompanied in two monkeys by a drop in RT. Responses were less uniform to THA than to AF102B. For the five-monkey group at Best dose, accuracy increased 34% (THA) or 43% (AF102B) above baseline (P<0.05 for both drugs), respectively, with no significant change in RT and with minimal untoward effects. Cholinotherapy may improve divided attention in young and aged healthy primates.

Aging↗

Face-selective spectral changes in the human fusiform gyrus.

OBJECTIVE: To characterize ventral occipitotemporal and prefrontal EEG during cognitive processing. METHODS: Depth probes were implanted for seizure localization in 16 pharmaco-resistant epileptics. Probes penetrated from middle temporal through fusiform to lingual gyrus, and from inferior frontal to anterior cingulate gyrus. Event-related potentials (ERPs) and event-related spectral power (ERSP) were calculated during delayed recognition for faces or words. RESULTS: Face stimuli evoked a broadband fusiform ERSP increase from 5 to 45 Hz at 150-210 ms after stimulus onset. This ERSP increase was immediately followed by an ERSP decrease in the same region from 300 to 1000 ms. Both the early increased ERSP and the late decreased ERSP, were greater for faces than words. Simultaneous with the late temporal ERSP decrease, the prefrontal depth EEG displayed a low frequency (5-12 Hz) ERSP increase to face and word stimuli. CONCLUSION: Early temporal ERSP increases occur at a time when the fusiform gyrus is thought to contribute to face processing. This increase is also reflected in spectral analysis of the ERP, but the late temporal ERSP decrease and frontal ERSP increase are not. Thus, intracranial recordings in humans demonstrate event-related fluctuations in EEG spectral power with clear anatomical, temporal and cognitive specificity.

Brain↗

Intracranial ERPs in humans during a lateralized visual oddball task: I. Occipital and peri-Rolandic recordings.

OBJECTIVES: This study investigated the relative participation of each cerebral hemisphere during a lateralized task that can be performed by a single hemisphere. This first of two articles focuses on recordings from visual and motor cortices. METHODS: Intracranial event-related potentials (ERPs) were recorded from occipital and/or peri-Rolandic sites in 8 patients with intractable epilepsy while they performed a lateralized visual oddball task. RESULTS: As expected, lateralized visual (N150, P200, N250) and motor (N/P400, N/P550) ERP effects were found for occipital and peri-Rolandic recordings, respectively. These reflect an advantage for direct over indirect sensory/motor pathways. More surprisingly, some occipital recordings were paradoxically larger in amplitude for indirect than for direct visual stimulus lateralization, and other occipital sites were sensitive to motor response factors. Likewise, one peri-Rolandic site exhibited a slow wave component that was sensitive to visual sensory factors. There was also pervasive bilaterally-symmetric ERP activity as reflected by P3-like and slow wave-like components. CONCLUSIONS: These findings argue against a hemispheric independence model of information processing. With the exception of initial stimulus input and final response output pathway effects, the processing in this simple task engages both hemispheres in a roughly symmetrical fashion, even though a single hemisphere may be adequate for task performance.

Brain Mapping↗

Intracranial ERPs in humans during a lateralized visual oddball task: II. Temporal, parietal, and frontal recordings.

OBJECTIVE: We investigated the relative participation of each cerebral hemisphere during a lateralized task that can be performed by a single hemisphere. While our companion article ( Clarke et al. 1999) focused on visual and motor event-related potentials (ERPs) recorded from occipital and peri-Rolandic sites, the present article is concerned with ERP correlates of intermediate stages of information processing from remaining cerebral regions. METHODS: Intracranial ERPs were recorded from temporal, parietal and frontal lobe sites in 13 patients with intractable epilepsy while they performed a lateralized visual oddball task. RESULTS: Visually-responsive N2 and/or P3 effects were recorded from medial temporal and supramarginal sites that appear to reflect activity along ventral and dorsal visual streams, respectively. Likewise, certain prefrontal sites, that are probably involved in working memory, were also visually-responsive. The majority of sites exhibiting N2, P3 and/or slow wave components, however, were unaffected by lateralized visual field or response hand effects. Target-evoked P3-like components were most frequently recorded from medial temporal and prefrontal sites. Post-response slow wave components were pervasive, and polarity reversals were present in the insula/operculum region, apparently reflecting somatosensory activity from SII. CONCLUSIONS: The general absence of lateralized ERP effects despite lateralized stimulus input and response output suggests the importance of interhemispheric integration over hemispheric independence in the processing of this type of task.

Adult↗

Reduction of motoric agitation and restlessness by AF102B and tacrine in the macaque.

The cholinesterase inhibitor tacrine (THA) and the M1 muscarinic agonist AF102B (cevimeline), both reported to enhance cognition in animals and humans, were tested in 5 macaques for reduction of spontaneous, random movements. Monkeys were videotaped 1 hour after administration of normal saline vehicle, after low- and high-dose intramuscular AF102B, and after low- and high-dose oral THA. Two independent blind judges counted numbers of spontaneous movements made by each monkey over 12 consecutive 15-second segments for each drug condition. Both THA and AF102B reduced movement significantly at high doses without overt side effects, warranting further research on the agitation-reducing potential of cognition-enhancing cholinomimetic drugs.

Alzheimer Disease↗

Location of human face-selective cortex with respect to retinotopic areas.

Functional Magnetic Resonance Imaging (fMRI) was used to identify a small area in the human posterior fusiform gyrus that responds selectively to faces (PF). In the same subjects, phase-encoded rotating and expanding checkerboards were used with fMRI to identify the retinotopic visual areas V1, V2, V3, V3A, VP and V4v. PF was found to lie anterior to area V4v, with a small gap present between them. Further recordings in some of the same subjects used moving low-contrast rings to identify the visual motion area MT. PF was found to lie ventral to MT. In addition, preliminary evidence was found using fMRI for a small area that responded to inanimate objects but not to faces in the collateral sulcus medial to PF. The retinotopic visual areas and MT responded equally to faces, control randomized stimuli, and objects. Weakly face-selective responses were also found in ventrolateral occipitotemporal cortex anterior to V4v, as well as in the middle temporal gyrus anterior to MT. We conclude that the fusiform face area in humans lies in non-retinotopic visual association cortex of the ventral form-processing stream, in an area that may be roughly homologous in location to area TF or CITv in monkeys.

Adult↗

Generators of the late cognitive potentials in auditory and visual oddball tasks.

Recordings directly within the brain can establish local evoked potential generation without the ambiguities always associated with extracranial electromagnetic measures. Depth recordings have found that sensory stimuli activate primary cortex and then material-specific encoders. Sensory-specific areas remain active for long periods, but by about 200 ms are joined by activation in widespread brain systems. One system is related to the orientation of attention. It is centered in paralimbic and attentional frontoparietocingular cortex, and associated with the P3a. A second system associated with P3b envelopes cognitive contextual integration. It engages the ventral temporofrontal event-encoding cortices (inferotemporal, perirhinal, and ventrolateral prefrontal), association cortices (superior temporal sulcal and posterior parietal), and the hippocampus. Thus, even in simple tasks, activation is widespread but concentrated in particular multilobar systems. With this information, the late cognitive potentials can be used to monitor the probable location, timing and intensity of brain activation during cognitive tasks.

Brain↗

Effects of AF102B and tacrine on delayed match-to-sample in monkeys.

1. Object working memory, a function which declines in aging and dementia, was tested in young and aged pretrained monkeys using a delayed match-to-sample task. 2. During drug treatment, monkeys were given the m 1 muscarinic agonist AF102B (0.1-2.1 mg/kg i.m.), the cholinesterase inhibitor tacrine (0.5-2.0 mg/kg p.o.), or vehicle controls in a repeated measures design to assess putative cognitive enhancement. 3. Both agents improved task performance in both young and aged monkeys, AF102B yielding equivalent or greater, and less variable, improvement than tacrine. 4. AF102B may represent a low-toxicity alternative to tacrine for the treatment of age-related memory disorders.

Age Factors↗

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↗