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Biomedical subjects

E Halgren

Publications and source records attributed to E Halgren.

At least 19 recordsLinked to original sources

The value of multichannel MEG and EEG in the presurgical evaluation of 70 epilepsy patients.

OBJECTIVE: To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery. METHODS: Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers. RESULTS: MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients). CONCLUSION: Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.

Adolescent↗

Top-down facilitation of visual recognition.

Cortical analysis related to visual object recognition is traditionally thought to propagate serially along a bottom-up hierarchy of ventral areas. Recent proposals gradually promote the role of top-down processing in recognition, but how such facilitation is triggered remains a puzzle. We tested a specific model, proposing that low spatial frequencies facilitate visual object recognition by initiating top-down processes projected from orbitofrontal to visual cortex. The present study combined magnetoencephalography, which has superior temporal resolution, functional magnetic resonance imaging, and a behavioral task that yields successful recognition with stimulus repetitions. Object recognition elicited differential activity that developed in the left orbitofrontal cortex 50 ms earlier than it did in recognition-related areas in the temporal cortex. This early orbitofrontal activity was directly modulated by the presence of low spatial frequencies in the image. Taken together, the dynamics we revealed provide strong support for the proposal of how top-down facilitation of object recognition is initiated, and our observations are used to derive predictions for future research.

Cerebral Cortex↗

3T phased array MRI improves the presurgical evaluation in focal epilepsies: a prospective study.

BACKGROUND: Although detection of concordant lesions on MRI significantly improves postsurgical outcomes in focal epilepsy (FE), many conventional MR studies remain negative. The authors evaluated the role of phased array surface coil studies performed at 3 Tesla (3T PA MRI). METHODS: Forty patients with medically intractable focal epilepsies were prospectively imaged with 3T PA-MRI including high matrix TSE T2, fluid attenuated inversion recovery, and magnetization prepared rapid gradient echo. All patients were considered candidates for epilepsy surgery. 3T PA-MRIs were reviewed by a neuroradiologist experienced in epilepsy imaging with access to clinical information. Findings were compared to reports of prior standard 1.5T MRI epilepsy studies performed at tertiary care centers. RESULTS: Experienced, unblinded review of 3T PA-MRI studies yielded additional diagnostic information in 48% (19/40) compared to routine clinical reads at 1.5T. In 37.5% (15/40), this additional information motivated a change in clinical management. In the subgroup of patients with prior 1.5T MRIs interpreted as normal, 3T PA-MRI resulted in the detection of a new lesion in 65% (15/23). In the subgroup of 15 patients with known lesions, 3T PA-MRI better defined the lesion in 33% (5/15). CONCLUSION: Phased array surface coil studies performed at 3 Tesla read by an experienced unblinded neuroradiologist can improve the presurgical evaluation of patients with focal epilepsy when compared to routine clinical 1.5T studies read at tertiary care centers.

Adolescent↗

How can intracranial recordings assist MEG source localization?

MEG/EEG are the only non-invasive methods to instantaneously and directly measure the currents underlying cerebral information processing, but their ability to localize those currents is limited. Source localization from MEG is always uncertain, unless the signal is already known to be coming exclusively from a single focal source, or a few highly separated focal sources. Furthermore, since many cerebral currents produce little or no MEG signal, even accurate localization of the MEG sources may provide a very incomplete map of brain activation. Intracranial EEG (iEEG) can unambiguously localize sources, using steep voltage gradients, doubly-inverting gradients, traverses of the source structure from multiple directions, and/or spatial arrays of microelectrodes. These recordings show that except for a few milliseconds after the first cortical sensory response, multiple overlapping sources are active. For the commonly-studied cognitive potential components, N400 and P3b, iEEG demonstrates distributed sources in multiple lobes with similar time-courses. These data, as well as basic cortical neurophysiology from animal studies, do not support the common assumptions that the MEG generating sources are focal, and/or independent. Although focal hemodynamic activation is often described, this may be an artefact of the usual data analysis schemes. In summary, MEG source localization depends on prior assumptions of unknown accuracy, and MEG is insensitive to much cerebral activity. MEG publications should explicitly acknowledge these limitations. If possible, reference should be made to more certain knowledge, which in some cases includes iEEG.

Animals↗

Head position in the MEG helmet affects the sensitivity to anterior sources.

Current MEG instruments derive the whole-head coverage by utilizing a helmet-shaped opening at the bottom of the dewar. These helmets, however, are quite a bit larger than most people's heads so subjects commonly lean against the back wall of the helmet in order to maintain a steady position. In such cases the anterior brain sources may be too distant to be picked up by the sensors reliably. Potential "invisibility" of the frontal and anterior temporal sources may be particularly troublesome for the studies of cognition and language, as they are subserved significantly by these areas. We examined the sensitivity of the distributed anatomically-constrained MEG (aMEG) approach to the head position ("front" vs. "back") secured within a helmet with custom-tailored bite-bars during a lexical decision task. The anterior head position indeed resulted in much greater sensitivity to language-related activity in frontal and anterior temporal locations. These results emphasize the need to adjust the head position in the helmet in order to maximize the "visibility" of the sources in the anterior brain regions in cognitive and language tasks.

Adult↗

Cortical thickness in a case of congenital unilateral perisylvian syndrome.

In congenital perisylvian syndrome, there is polymicrogyric cortex distributed in variable extensions around the sylvian fissure. Unilateral cases usually present with congenital hemiparesis, while bilateral cases have pseudobulbar paralysis of the oropharingoglossal region. Both unilateral and bilateral cases have a high rate of epilepsy. Polymicrogyric cortex is characterized by too many small convolutions. Often there are no intervening sulci, and almost no white matter can be seen under them. On MRI they appear to have increased thickness. Bilateral and symmetric polimycrogiria can be hard to recognize on standard MRIs. Accurate and automated methods for measuring the thickness of cerebral cortex are available. They have mainly been used to study a variety of disorders with diminished cortical thickness. We studied a case of right perisylvian polymicrogyria, who presented in adult life with epilepsy and had a normal neurological exam. Fischl and Dale's automated cortical thickness analysis rendered a very clear picture of increased cortical thickness with values up to 9 mm in the affected areas (normal cortical thickness varies between 1 and 4.5 mm). The thickest areas were seen over grossly abnormal gyri on the reconstructed cerebral cortex. On MEG he presented a prominent and monotonous 9 Hz activity that was located within the limits of a thick gyrus. There was a significant difference of thickness between homologous hemispheric areas. To our surprise some areas of the left hemisphere also appeared to have increased thickness, raising the question of a bilateral asymmetric case.

Cerebral Cortex↗

Rapid distributed fronto-parieto-occipital processing stages during working memory in humans.

Cortical potentials were recorded from implanted electrodes during a difficult working memory task requiring rapid storage, modification and retrieval of multiple memoranda. Synchronous event-related potentials were generated in distributed occipital, parietal, Rolandic and prefrontal sites beginning approximately 130 ms after stimulus onset and continuing for >500 ms. Coherent phase-locked, event-related oscillations supported interaction between these dorsal stream structures throughout the task period. The Rolandic structures generated early as well as sustained potentials to sensory stimuli in the absence of movement. Activation peaks and phase lags between synaptic populations suggested that perceptual processing occurred exclusively in the visual association cortex from approximately 90 to 130 ms, with its results projected to fronto-parietal areas for interpretation from approximately 130 to 280 ms. The direction of interaction then appeared to reverse from approximately 300 to 400 ms, consistent with mental arithmetic being performed by fronto-parietal areas operating upon a visual scratch pad in the dorsolateral occipital cortex. A second reversal, from approximately 420 to 600 ms, may have represented an updating of memoranda stored in fronto-parietal sites. Lateralized perisylvian oscillations suggested an articulatory loop. Anterior cingulate activity was evoked by feedback signals indicating errors. These results indicate how a fronto-centro-parietal 'central executive' might interact with an occipital visual scratch pad, perisylvian articulatory loop and limbic monitor to implement the sequential stages of a complex mental operation.

Adolescent↗

Spatiotemporal maps of brain activity underlying word generation and their modification during repetition priming.

Spatiotemporal maps of brain activity based on magnetoencephalography were used to observe sequential stages in language processing and their modification during repetition priming. Subjects performed word-stem completion and produced either novel or repeated (primed) words across trials. Activation passes from primary visual cortex (activated at approximately 100 msec after word presentation), to left anteroventral occipital ( approximately 180 msec), to cortex in and near Wernicke's ( approximately 210 msec) and then Broca's ( approximately 370 msec) areas. In addition, a posteroventral temporal area is activated simultaneously with posterosuperior temporal cortex. This area shows an early ( approximately 200-245 msec) increase in activation to repeated word stems. In contrast, prefrontal and anterior temporal regions showed activity reductions to repeated word stems late ( approximately 365-500 msec) in processing. These results tend to support classical models of language and suggest that an effect of direct item repetition is to allow word-form processing to increase its contribution to task performance while concurrently allowing reductions in time-consuming frontal temporal processing.

Brain↗

Multiple microelectrode-recording system for human intracortical applications.

The human brain is dominated by the neocortex, a large folded surface, whose cellular and synaptic elements are arranged in layers. Since cortical structure is relatively constant across its surface, local information processing can be inferred from multiple laminar recordings of its electrical activity along a line perpendicular to its surface. Such recordings need to be spaced at least as close together as the cortical layers, and need to be wideband in order to sample both low frequency synaptic currents as well as high-frequency action potentials. Finally, any device used in the human brain must comply with strict safety standards. The current paper presents details of a system meeting these criteria, together with sample results obtained from epileptic subjects undergoing acute or chronic intracranial monitoring for definition of the epileptogenic region.

Action Potentials↗

Timing and localization of movement-related spectral changes in the human peri-Rolandic cortex: intracranial recordings.

Event-related spectral power (ERSP) was measured from intracranial EEG and used to characterize the time-course and localization of the Rolandic mu rhythms in 12 patients during the delayed recognition of words or faces (DR) and the discrimination of simple lateralized visual targets (LVD). On each trial, the subject decided whether to make manual response (Go) or not (NoGo). ERSP increased on both Go and NoGo trials in peri-Rolandic regions of all subjects with a peak latency of approximately 330-ms poststimulus and duration of 260 ms during the DR task. The peak of this ERSP increase preceded movement by approximately 300 ms. All subjects produced a subsequent movement specific ERSP decrease of peri-Rolandic mu rhythms (starting approximately 90 ms before the average reaction time) with an peak latency of approximately 800 ms and duration of approximately 520 ms. The LVD task produced bilateral movement-selective readiness potentials and reproduced the movement-specific late ERSP decreases seen in the DR task (strongest from 7-24 Hz). Furthermore, the LVD task demonstrated that the late movement-related ERSP decrease is larger for the contralateral hand. However, the LVD task did not consistently reproduce the early ERSP increase seen in the DR task. Movement-related ERSP decreases were widespread, occurring in pre- and post-Rolandic as well as primary-motor, supplemental motor, and cingulate cortical regions. Other cortical areas including frontal, temporal, and occipital regions did not show movement-related ERSP changes. Peri-Rolandic ERSP decreases in mu rhythms correlate with the generation of a motor command. The early increases in mu may reflect a transient state of motor inhibition just prior to motor execution.

Brain Mapping↗

Spatiotemporal mapping of brain activity by integration of multiple imaging modalities.

Functional magnetic resonance imaging (fMRI) and positron emission tomography measure local changes in brain hemodynamics induced by cognitive or perceptual tasks. These measures have a uniformly high spatial resolution of millimeters or less, but poor temporal resolution (about 1s). Conversely, electroencephalography (EEG) and magnetoencephalography (MEG) measure instantaneously the current flows induced by synaptic activity, but the accurate localization of these current flows based on EEG and MEG data alone remains an unsolved problem. Recently, techniques have been developed that, in the context of brain anatomy visualized with structural MRI, use both hemodynamic and electromagnetic measures to arrive at estimates of brain activation with high spatial and temporal resolution. These methods range from simple juxtaposition to simultaneous integrated techniques. Their application has already led to advances in our understanding of the neural bases of perception, attention, memory and language. Further advances in multi-modality integration will require an improved understanding of the coupling between the physiological phenomena underlying the different signal modalities.

Animals↗

Early discrimination of coherent versus incoherent motion by multiunit and synaptic activity in human putative MT+.

A laminar probe was chronically implanted in human putative MT+. The area was specifically responsive to globally coherent visual motion, a crucial aspect of the perception of movement through space. The probe contained 23 microcontacts spaced every 175 microm in a linear array roughly perpendicular to the cortical surface. Current-source density (CSD) and multiunit activity (MUA) were recorded while viewing initially stationary random dot patterns that either moved incoherently or dilated from the central fixation. Onset of visual motion evoked large MUA/CSD activity, with coherent motion evoking earlier and faster-rising MUA/CSD activity than incoherent, in both superficial and deep pyramidal layers. The selective response, peaking at approximately 115 ms, was especially large in deep pyramids, providing evidence that information necessary for visual flow calculations is projected from MT+ at an early latency to distant structures. The early onset of differential MUA/CSD implies that the selectivity of this area does not depend on recurrent inhibition or other intrinsic circuitry to detect coherent motion. The initially greater increase of MUA to coherent stimuli was followed by a greater decrease beginning at approximately 133 ms, apparently because of recurrent inhibition. This resulted in the total MUA being greater to incoherent than coherent stimuli, whereas total rectified CSD was overall greater to coherent than to incoherent stimuli. However, MUA distinguished stationary from moving stimuli more strongly than did CSD. Thus, while estimates of total cell firing (MUA), and of total synaptic activity (CSD) generally correspond to previously reported BOLD results, they may differ in important details.

Adult↗

Effects of guanfacine on three forms of distraction in the aging macaque.

alpha-2 adrenoceptor agonists, such as clonidine and guanfacine, enhance attention in aged animals. According to one theory, alpha-2 receptor agonists improve attention by decreasing distractibility to task-irrelevant stimuli. In two healthy aging bonnet macaques, we investigated the effects of low-(0.001 mg/kg) and high-dose (0.05 mg/kg) acute intramuscular guanfacine versus saline control on accuracy (number of trials correct) in three tasks requiring attention: delayed matching-to-sample, one-target visual tracking (test of focused attention) and two-target visual tracking (test of divided attention). Each task employed distracting stimuli in a different paradigmatic context. One monkey responded to guanfacine at both doses with significant rises in accuracy on all three tasks. The second monkey showed significant accuracy improvement for high-dose guanfacine only. No sedation was observed. These results suggest that guanfacine improves attention and reduces distractibility in multiple task contexts in healthy aging primates.

Adrenergic alpha-Agonists↗

Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity.

Functional magnetic resonance imaging (fMRI) can provide maps of brain activation with millimeter spatial resolution but is limited in its temporal resolution to the order of seconds. Here, we describe a technique that combines structural and functional MRI with magnetoencephalography (MEG) to obtain spatiotemporal maps of human brain activity with millisecond temporal resolution. This new technique was used to obtain dynamic statistical parametric maps of cortical activity during semantic processing of visually presented words. An initial wave of activity was found to spread rapidly from occipital visual cortex to temporal, parietal, and frontal areas within 185 ms, with a high degree of temporal overlap between different areas. Repetition effects were observed in many of the same areas following this initial wave of activation, providing evidence for the involvement of feedback mechanisms in repetition priming.

Brain↗

Cognitive response profile of the human fusiform face area as determined by MEG.

Activation in or near the fusiform gyrus was estimated to faces and control stimuli. Activation peaked at 165 ms and was strongest to digitized photographs of human faces, regardless of whether they were presented in color or grayscale, suggesting that face- and color-specific areas are functionally separate. Schematic sketche evoked approximately 30% less activation than did face photographs. Scrambling the locations of facial features reduced the response by approximately 25% in either hemisphere, suggesting that configurational versus analytic processing is not lateralized at this latency. Animal faces evoked approximately 50% less activity, and common objects, animal bodies or sensory controls evoked approximately 80% less activity than human faces. The (small) responses evoked by meaningless control images were stronger when they included surfaces and shading, suggesting that the fusiform gyrus may use these features in constructing its face-specific response. Putative fusiform activation was not significantly related to stimulus repetition, gender or emotional expression. A midline occipital source significantly distinguished between faces and control images as early as 110 ms, but was more sensitive to sensory qualities. This source significantly distinguished happy and sad faces from those with neutral expressions. We conclude that the fusiform gyrus may selectively encode faces at 165 ms, transforming sensory input for further processing.

Adult↗

Alcohol effects on movement-related potentials: a measure of impulsivity?

OBJECTIVE: To assess the effects of acute alcohol intoxication on lateralized readiness potential (LRP), a central measure of movement-related brain activity, and the potential association of such effects with personality measures. METHOD: Male volunteers (N = 12) alternated responding hands during a "go/no go" verbal recognition task across all four sessions of the balanced placebo design in which beverage content (either juice only or a vodka and juice mixture that raised the average blood alcohol concentration to 0.045%) was crossed with instructions as to beverage content. RESULTS: Whereas the instructions had no effect on behavioral (response accuracy and reaction time) and physiological (LRP) measures, alcohol decreased reaction times adjusted for psychometer speed. As expected, large LRPs were recorded on "go" trials and were not affected by the beverage. However, the "no go" words that did not require and did not evoke motor responses, also evoked significant LRPs under alcohol but not placebo. Since only trials with correct responses and correct abstentions from responses were included in the averages, the motor preparation was not completed and was terminated before the motor response on "no go" trials. Similarly, there was a decrease in spectral power of the movement-related mu-rhythm on "no go" trials under alcohol. CONCLUSIONS: Alcohol may result in disinhibition such that the "response execution" process is activated based on very preliminary stimulus evaluation. This alcohol-induced brain activity signaling premature motor preparation exhibited correlation trends with personality traits related to impulsivity, hyperactivity and antisocial tendencies, thus concurring with other evidence that indicates commonalities between alcoholism and impulsivity, disinhibition and antisocial behaviors. The LRP on "no go" trials could potentially be used as a psychological index of the impulsiveness induced by alcohol intoxication.

Adult↗

Early widespread cortical distribution of coherent fusiform face selective activity.

Intracranial EEG was analyzed from 16 pharmaco-resistant epilepsy patients. Subjects participated in memory tasks for faces and/or words. Face-selective coherence increases were found between the fusiform gyrus and temporal, parietal, and frontal cortices at 160-230 ms poststimulus onset. Word stimuli elicited weak or negligible response at the same latency. Phase lag increased monotonically with distance from the fusiform region. The slope was consistent with conduction velocities of myelinated cortico-cortical pathways. These results suggest that the contribution of the fusiform gyrus to face processing at around 200 ms poststimulus onset is rapidly projected to widespread cortical regions.

Cerebral Cortex↗