Ksenija Marinkovic

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.

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.

Spatiotemporal Dynamics of Modality-Specific and Supramodal Word Processing

The ability of written and spoken words to access the same semantic meaning provides a test case for the multimodal convergence of information from sensory to associative areas. Using anatomically constrained magnetoencephalography (aMEG), the present study investigated the stages of word comprehension in real time in the auditory and visual modalities, as subjects participated in a semantic judgment task. Activity spread from the primary sensory areas along the respective ventral processing streams and converged in anterior temporal and inferior prefrontal regions, primarily on the left at around 400 ms. Comparison of response patterns during repetition priming between the two modalities suggest that they are initiated by modality-specific memory systems, but that they are eventually elaborated mainly in supramodal areas.

Alcohol: Effects on Neurobehavioral Functions and the Brain

Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction.

N400-like Magnetoencephalography Responses Modulated by Semantic Context, Word Frequency, and Lexical Class in Sentences

Words have been found to elicit a negative potential at the scalp peaking at approximately 400 ms that is strongly modulated by semantic context. The current study used whole-head magnetoencephalography (MEG) as male subjects read sentences ending with semantically congruous or incongruous words. Compared with congruous words, sentence-terminal incongruous words consistently evoked a large magnetic field over the left hemisphere, peaking at approximately 450 ms. Source modeling at this latency with conventional equivalent current dipoles (ECDs) placed the N400 m generator in or near the left superior temporal sulcus. A distributed solution constrained to the cortical surface suggested a sequence of differential activation, beginning in Wernickes area at approximately 250 ms, spreading to anterior temporal sites at approximately 270 ms, to Brocas area by approximately 300 ms, to dorsolateral prefrontal cortices by approximately 320 ms, and to anterior orbital and frontopolar cortices by approximately 370 ms. Differential activity was exclusively left-sided until >370 ms, and then involved right anterior temporal and orbital cortices. At the peak of the N400 m, activation in the left hemisphere was estimated to be widespread in the anterior temporal, perisylvian, orbital, frontopolar, and dorsolateral prefrontal cortices. In the right hemisphere, the orbital, as well as, weakly, the right anterior temporal cortices were activated. Similar but weaker field patterns were evoked by intermediate words in the sentences, especially to low-frequency words occurring in early sentence positions where there is little preceding context. The locations of the N400 m sources identified with the distributed solution correspond well with those previously demonstrated with direct intracranial recordings, and suggested by functional magnetic resonance imaging (fMRI). These results help identify a distributed cortical network that supports online semantic processing.

Spatio-temporal stages in face and word processing. 1. Depth recorded potentials in the human occipital and parietal lobes

Abstract 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. A N310-N430-P630 sequence to words and faces was largest and polarity-inverted in the hippocampal formation and amygdala, but was also probably locally-generated in many sites including the lingual g, lateral occipitotemporal cortex, middle and superior temporal g, temporal pole, supramarginal g, and posterior cingulate g. The P660 had the same distribution as has been noted for the P3b to rare target simple auditory and visual stimuli in ‘oddball’ tasks, with inversions in the hippocampus. In several sites, the N310 and N430 were smaller to repeated faces, and the P630 was larger. Putative information-processing functions were tentatively assigned to successive EP components based upon their cognitive correlates, as well as the functions and connections of their generating structures. For the N75-P105, this putative function is simple feature detection in primary visual cortex (V1 and V2). The N130-P180-N240 may embody structural face encoding in posterobasal inferotemporal cortex (homologous to V4?), with the results being spread widely to inferotemporal, multimodal and paralimbic cortices. For words, similar visual-form encoding (in fusiform g) or visual-phonemic encoding (in angular g) may occur between 150 and 280 ms. During the N310, faces and words may be multiply encoded for form and identity (inferotemporal), emotional (amygdala), recent declarative mnestic (hippocampal formation), and semantic (supramarginal and superior temporal sulcal supramodal cortices) characteristics. These multiple characteristics may be contextually integrated across inferotemporal, supramodal association, and limbic cortices during the N430, with cognitive closure following in the P630. In sum, visual information arrives at area 17 by about 75 ms, and is structurally-encoded in occipito-temporal cortex during the next 110 ms. By 150–200 ms after stimulus onset, activation has spread to parietal, lateral temporal, and limbic cortices, all of which continue to participate with the more posterior areas for the next 500 ms of event-encoding. Thus, face and word processing is serial in the sense that it can be divided into successive temporal stages, but highly parallel in that (after the initial stages where visual primitives are extracted) multiple anatomical areas with distinct perceptual, mnestic and emotional functions are engaged simultaneously. Consequently, declarative memory and emotional encoding can participate in early stages of perceptual, as well as later stages of cognitive integration. Conversely, occipitotemporal cortex is involved both early in processing (immediately after V1), as well as later, in the N430. That is, most stages of face and word processing appear to take advantage of the rich ‘upstream’ and ‘downstream’ anatomical connections in the ventral visual processing stream to link the more strictly perceptual networks with semantic, emotional, and mnestic networks.

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. Hum. Brain Mapping 7:29–37, 1999.

Responses of Human Anterior Cingulate Cortex Microdomains to Error Detection, Conflict Monitoring, Stimulus-Response Mapping, Familiarity, and Orienting

Human anterior cingulate cortex (ACC) activity modulation has been observed in numerous tasks, consistent with a wide variety of functions. However, previous recordings have not had sufficient spatial resolution to determine whether microdomains (approximately one to two columns) are involved in multiple tasks, how activity is distributed across cortical layers, or indeed whether modulation reflected neuronal excitation, inhibition, or both. In this study, linear arrays of 24 microelectrodes were used to estimate population synaptic currents and neuronal firing in different layers of ACC during simple/choice reaction time, delayed word recognition, rhyming, auditory oddball, and cued conditional letter-discrimination tasks. Responses to all tasks, with differential responses to errors, familiarity, difficulty, and orienting, were recorded in single microdomains. The strongest responses occurred ∼300-800 ms after stimulus onset and were usually a current source with inhibited firing, strongly suggesting active inhibition in superficial layers during the behavioral response period. This was usually followed by a sink from ∼800 to 1400 ms, consistent with postresponse rebound activation. Transient phase locking of task-related theta activity in superficial cingulate layers suggested extended interactions with medial and lateral frontal and temporal sites. These data suggest that each anterior cingulate microdomain participates in a multilobar cortical network after behavioral responses in a variety of tasks.

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 (Brocas 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 Brocas area, to cognitive integration in ventro-lateral prefrontal, and to response organization in premotor cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Frontal White Matter and Cingulum Diffusion Tensor Imaging Deficits in Alcoholism

BACKGROUND Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity. METHODS Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans. RESULTS Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only. CONCLUSIONS The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism.