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Biomedical subjects

J J McDonald

Publications and source records attributed to J J McDonald.

At least 19 recordsLinked to original sources

Effects of spatial congruity on audio-visual multimodal integration.

Spatial constraints on multisensory integration of auditory (A) and visual (V) stimuli were investigated in humans using behavioral and electrophysiological measures. The aim was to find out whether cross-modal interactions between A and V stimuli depend on their spatial congruity, as has been found for multisensory neurons in animal studies (Stein & Meredith, 1993). Randomized sequences of unimodal (A or V) and simultaneous bimodal (AV) stimuli were presented to right- or left-field locations while subjects made speeded responses to infrequent targets of greater intensity that occurred in either or both modalities. Behavioral responses to the bimodal stimuli were faster and more accurate than to the unimodal stimuli for both same-location and different-location AV pairings. The neural basis of this cross-modal facilitation was studied by comparing event-related potentials (ERPs) to the bimodal AV stimuli with the summed ERPs to the unimodal A and V stimuli. These comparisons revealed neural interactions localized to the ventral occipito-temporal cortex (at 190 msec) and to the superior temporal cortical areas (at 260 msec) for both same- and different-location AV pairings. In contrast, ERP interactions that differed according to spatial congruity included a phase and amplitude modulation of visual-evoked activity localized to the ventral occipito-temporal cortex at 100-400 msec and an amplitude modulation of activity localized to the superior temporal region at 260-280 msec. These results demonstrate overlapping but distinctive patterns of multisensory integration for spatially congruent and incongruent AV stimuli.

Acoustic Stimulation↗

An analysis of audio-visual crossmodal integration by means of event-related potential (ERP) recordings.

Crossmodal integration was studied in humans by presenting random sequences of auditory (brief noise bursts), visual (flashes), and audiovisual (simultaneous noise bursts and flashes) stimuli from a central location at irregular intervals between 600 and 800 ms. The subjects' task was to press a button to infrequent and unpredictable (P=0.15) target stimuli that could be either a more intense noise burst, a brighter flash, or a combination of the two. In accordance with previous studies, behavioral data showed that bimodal target stimuli were responded to much faster and were identified more accurately than the unimodal target stimuli. The neural basis of this crossmodal interaction was investigated by subtracting the ERPs to the auditory (A) and the visual (V) stimuli alone from the ERP to the combined audiovisual (AV) stimuli (i.e. interaction=AV-(A+V)). Using this approach, we replicated previous reports of both early (at around 40 ms) and late (after 100 ms) ERP interaction effects. However, it appears that the very early interaction effects can be largely accounted for by an anticipatory ERP that precedes both the unimodal and bimodal stimuli. In calculating the ERP interaction this slow shift is subtracted twice, resulting in an apparent shift of the opposite polarity that may be confounded with actual crossmodal interactions.

Acoustic Stimulation↗

Transient spatial attention modulates distinct components of the auditory ERP.

We recorded ERPs to pairs of externally presented tones, T1 and T2, in the absence of attentional cues to determine whether attention is momentarily sustained at the location of a behaviourally relevant sound, and what effect this focusing of attention might have on the neural response to target stimuli. ERPs to T2 were more negative when the preceding T1 was presented on the same side of fixation than when T1 was presented on the opposite side of fixation. This negative difference consisted of an early, parietal phase and a later, frontocentral phase. These results confirm and extend previously reported effects of transient spatial attention on auditory ERPs, and they demonstrate that transient spatial attention has a distinct and robust effect on the early stages of stimulus processing in the auditory system.

Acoustic Stimulation↗

Electrophysiological evidence for the "missing link" in crossmodal attention.

Orienting attention involuntarily to the location of a sensory event influences responses to subsequent stimuli that appear in different modalities with one possible exception: orienting attention involuntarily to a sudden light sometimes fails to affect responses to subsequent sounds (e.g., Spence & Driver, 1997). Here we investigated the effects of involuntary attention to a brief flash on the processing of subsequent sounds in a design that eliminates stimulus-response compatibility effects and criterion shifts as confounding factors. In addition, the neural processes mediating crossmodal attention were studied by recording event-related brain potentials. Our data show that orienting attention to the location of a spatially nonpredictive visual cue modulates behavioural and neural responses to subsequent auditory targets when the stimulus onset asynchrony is short (between 100 and 300 ms). These findings are consistent with the hypothesis that involuntary shifts of attention are controlled by supramodal brain mechanisms rather than by modality-specific ones.

Adolescent↗

Involuntary orienting to sound improves visual perception.

To perceive real-world objects and events, we need to integrate several stimulus features belonging to different sensory modalities. Although the neural mechanisms and behavioural consequences of intersensory integration have been extensively studied, the processes that enable us to pay attention to multimodal objects are still poorly understood. An important question is whether a stimulus in one sensory modality automatically attracts attention to spatially coincident stimuli that appear subsequently in other modalities, thereby enhancing their perceptual salience. The occurrence of an irrelevant sound does facilitate motor responses to a subsequent light appearing nearby. However, because participants in previous studies made speeded responses rather than psychophysical judgements, it remains unclear whether involuntary auditory attention actually affects the perceptibility of visual stimuli as opposed to postperceptual decision and response processes. Here we provide psychophysical evidence that a sudden sound improves the detectability of a subsequent flash appearing at the same location. These data show that the involuntary orienting of attention to sound enhances early perceptual processing of visual stimuli.

Adult↗

Involuntary listening aids seeing: evidence from human electrophysiology.

It is well known that sensory events of one modality can influence judgments of sensory events in other modalities. For example, people respond more quickly to a target appearing at the location of a previous cue than to a target appearing at another location, even when the two stimuli are from different modalities. Such cross-modal interactions suggest that involuntary spatial attention mechanisms are not entirely modality-specific. In the present study, event-related brain potentials (ERPs) were recorded to elucidate the neural basis and timing of involuntary, cross-modal spatial attention effects. We found that orienting spatial attention to an irrelevant sound modulates the ERP to a subsequent visual target over modality-specific, extrastriate visual cortex, but only after the initial stages of sensory processing are completed. These findings are consistent with the proposal that involuntary spatial attention orienting to auditory and visual stimuli involves shared, or at least linked, brain mechanisms.

Acoustic Stimulation↗

On asymmetries in cross-modal spatial attention orienting.

In a previous study, Ward (1994) reported that spatially uninformative visual cues orient auditory attention but that spatially uninformative auditory cues fail to orient visual attention. This cross-modal asymmetry is consistent with other intersensory perceptual phenomena that are dominated by the visual modality (e.g., ventriloquism). However, Spence and Driver (1997) found exactly the opposite asymmetry under different experimental conditions and with a different task. In spite of the several differences between the two studies, Spence and Driver (see also Driver & Spence, 1998) argued that Ward's findings might have arisen from response-priming effects, and that the cross-modal asymmetry they themselves reported, in which auditory cues affect responses to visual targets but not vice versa, is in fact the correct result. The present study investigated cross-modal interactions in stimulus-driven spatial attention orienting under Ward's complex cue environment conditions using an experimental procedure that eliminates response-priming artifacts. The results demonstrate that the cross-modal asymmetry reported by Ward (1994) does occur when the cue environment is complex. We argue that strategic effects in cross-modal stimulus-driven orienting of attention are responsible for the opposite asymmetries found by Ward and by Spence and Driver (1997).

Adolescent↗

Reduced P300 responses in criminal psychopaths during a visual oddball task.

BACKGROUND: Clinicians have long recognized that psychopaths show deficits in cognitive function, but there have been few experimental studies exploring these deficits. We present here the first in a series of event-related potential (ERP) experiments designed to elucidate and characterize the neural correlates of cognitive processes of psychopaths. METHODS: We recorded ERPs from a topographic array from 11 psychopathic and 10 nonpsychopathic prison inmates, assessed with the Hare Psychopathy Checklist-Revised, during performance of a visual oddball task. ERPs to target (25% of trials) and nontarget (75% of trials) visual stimuli were analyzed. RESULTS: Consistent with previous research, there were no group differences in the latency or amplitude of the ERPs for the nontarget stimuli. For nonpsychopaths, the P300 amplitude was larger when elicited by the target stimuli than when elicited by the nontarget stimuli. In contrast, psychopaths failed to show reliable P300 amplitude differences between the target and nontarget conditions. Psychopaths had a smaller amplitude P300 to target stimuli than did nonpsychopaths. In addition, the amplitude of the P300 was less lateralized in psychopaths than in nonpsychopaths. Psychopaths also had a larger centrofrontal negative wave (N550) during the target condition than did nonpsychopaths. CONCLUSIONS: The results of this study indicate that there are substantial differences between psychopaths and others in the processing of even simple cognitive tasks and provide support for information processing models of psychopathy.

Adult↗

Forensic aspects of sexual harassment.

Sexual harassment law presents a complex set of issues not only for lawyers but also for psychiatrists in their roles both as evaluators and clinicians. Judge Reinhardt of the US Court of Appeals for the 9th Circuit, summed up these complexities: "We tend these days, far more than in earlier times, to find our friends, lovers, and even mates in the workplace. We ... often discover that our interests and values are closer to those of our colleagues or fellow employees than to those of people we meet in connection with other activities. In short, increased proximity breeds increased volitional sexual activity." On the other hand, he notes that Title VII "entitles individuals to a workplace that is free from the evil of sexual intimidation or repression. It is frequently difficult to reconcile the two competing values." He goes on to ask, "When does a healthy constructive interest in romance become sexual harassment? To what extent is pursuit of a co-worker proper but of a subordinate forbidden? Is wooing or courting a thing of the past? Must a suitor cease his attentions at the first sign of disinterest or resistance? Must there be an express agreement before the person seeking romance may even hold the hand of the subject of his affection? Is it now verboten to steal a kiss? In the workplace? Everywhere? Under all circumstances or only some? Has the art of romantic persuasion lost its charm? Questions relating to love and sex are among the most difficult for society to answer." The US Supreme Court has stressed the need for common sense in evaluating cases of sexual harassment. Perhaps psychiatrists can play a sobering role in developing answers to these questions.

Confidentiality↗

An event-related brain potential study of inhibition of return.

Event-related brain potentials (ERPs) were recorded during two spatial-cuing experiments using nonpredictive cues. Our primary goal was to determine the electrophysiological consequences of inhibition of return (IOR). At long (> 500 msec) cue-target intervals, subjects responded more slowly to targets that appeared at or near the cued location, relative to targets that appeared on the opposite side of fixation from the cue. This behavioral IOR effect was associated with cue-validity effects on several components of the target-elicited ERP waveforms. The earliest such effect was a smaller occipital P1 on valid-cue trials, which we interpret as a P1 reduction. The P2 component was also smaller on valid-cue trials, indicating that nonpredictive spatial cues influence multiple stages of information processing at long cue-target intervals. Both of these effects were observed when sensory interactions between cue and target were likely to be negligible, indicating that they were not caused by sensory refractoriness. A different effect of cue validity, the posterior negative difference, was found when sensory interactions were likely to be greatest, indicating that it could arise from sensory refractoriness.

Adult↗

Semantic and affective processing in psychopaths: an event-related potential (ERP) study.

We tested the hypothesis that psychopathy is associated with abnormal processing of semantic and affective verbal information. In Task 1, a lexical decision task, and in Task 2, a word identification task, participants responded faster to concrete than to abstract words. In Task 2, psychopaths made more errors identifying abstract words than concrete words. In Task 3, a word identification task, participants responded faster to positive than to negative words. In all three tasks, nonpsychopaths showed the expected event-related potential (ERP) differentiation between word stimuli, whereas psychopaths did not. In each task, the ERPs of the psychopaths included a large centrofrontal negative-going wave (N350); this wave was absent or very small in the nonpsychopaths. The interpretation and significance of these differences are discussed.

Adolescent↗

A mutation in human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC-55389A.

The hydroxyethylurea human immunodeficiency virus type 1 (HIV-1) protease inhibitors SC-55389A and SC-52151 were used to select drug-resistant variants in vitro. One clinical HIV-1 strain (89-959) and one laboratory HIV-1 strain (LAI) were passaged in peripheral blood mononuclear cells or CEMT4 cells in the presence of SC-55389A. Resistant isolates from both strains consistently had a mutation to serine for asparagine at amino acid 88 (N88S) in the protease gene either alone or in combination with a change to phenylalanine at position 10. The N88S mutation, recreated by oligonucleotide-mediated site-directed mutagenesis in HXB2, was sufficient to confer resistance to SC-55389A. In contrast, SC-52151-resistant variants selected from the monocytotropic strain SF162 had multiple substitutions in the protease gene (I11V, M461, F53L, A71V, and N88D), and the N88D mutation, re-created by oligonucleotide-mediated site-directed mutagenesis in HXB2, did not confer resistance to SC-52151. The potencies of L735,524 and Ro31-8959 were not reduced when these compounds were assayed against variants with either the N88S or N88D substitution. Position 88 is in a helix that lies behind the substrate binding pocket and may indirectly influence inhibitor binding through interactions with the amino acid at position 31. The selected mutations were persistent in the viral populations after more than 20 passages in the absence of drugs. Passaging of virus first in SC-55389A alone and then in combination with SC-52151 resulted in the accumulation of more mutations in the protease gene (L10F, D35E, D37M, I47V, 154L, A71V, V82I, and S88D) and in the selection of a variant that was cross-resistant to multiple protease inhibitors. These results indicate that a mutation in the HIV-1 protease at a position that is located outside of the substrate binding pocket confers resistance to a protease inhibitor and that mutations in the protease gene accumulate with increasing selection pressure and can persist in the absence of selection pressure.

Amino Acid Sequence↗

EEOC guidance on psychiatric disabilities: many problems, few workable solutions.

The EEOC recently issued "Enforcement Guidance" on psychiatric disabilities under the Americans with Disabilities Act. Although the Guidance provides clarification of a few issues involving mental disabilities under the ADA, in most respects the Guidance is problematic. For example, the Guidance suggests that the inability to get along with a supervisor or coworkers may constitute a disability under the ADA, that an employer may have to "accommodate" a disabled employee's misconduct, that an employer cannot require an employee to follow doctor's orders as a condition of employment, and that an employer may be obligated to modify work rules and procedures to accommodate a mentally disabled employee but is prohibited from explaining to coworkers why it is making such modifications. As the EEOC's Guidance exceeds or conflicts with the ADA in some respects and is largely unworkable in many respects, it remains to be seen how many courts will actually follow it.

Civil Rights↗