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Biomedical subjects

Patricia T Michie

Publications and source records attributed to Patricia T Michie.

17 recordsLinked to original sources

Components of task-set reconfiguration: differential effects of 'switch-to' and 'switch-away' cues.

Preparation for a switch in task was manipulated using two types of switch cues: 'switch-away' from the previous task-set and 'switch-to' a different task-set. Increasing cue-stimulus interval resulted in a reduction in reaction time switch cost for switch-to trials only. Cue-locked difference waveforms for both switch-to and switch-away trials showed a large, broad differential positivity, relative to repeat waveforms. However, the later part of the differential positivity was significantly reduced on switch-away trials. A differential positivity then emerged after stimulus onset for switch-away trials only. This suggests that, with a long cue-stimulus interval, the new task-set was implemented before stimulus onset for switch-to trials, whereas on switch-away trials this process was delayed until after stimulus onset leading to increased switch cost. These results demonstrate dissociable effects of switching away from the current task-set and switching to the upcoming task-set and support the interpretation that the differential positivity observed for switch-to trials reflects processes associated with anticipatory task-set reconfiguration.

Adolescent↗

Switching between univalent task-sets in schizophrenia: ERP evidence of an anticipatory task-set reconfiguration deficit.

OBJECTIVE: The present study used behavioral and event-related potential (ERP) indices of task-switching to examine whether schizophrenia patients have a specific deficit in anticipatory task-set reconfiguration. METHODS: Participants switched between univalent tasks in an alternating runs paradigms with blocked response-stimulus interval (RSI) manipulation (150, 300, 600, and 1200ms). Nineteen high functioning people with schizophrenia were compared to controls that were matched for age, gender, education and premorbid IQ estimate. RESULTS: Schizophrenia patients had overall increased RT, but no increase in corrected RT switch cost. In the schizophrenia group, ERPs showed reduced activation of the differential positivity in anticipation of switch trial at the optimal 600ms RSI and reduced activation of the frontal post-stimulus switch negativity at both 600 and 1200ms RSI compared to the control group. CONCLUSIONS: Despite no behavioral differences in task switching performance, anticipatory and stimulus-triggered ERP indices of task-switching suggest group differences in processing of switch and repeat trials, especially at longer RSI conditions that for control participants provide opportunity for anticipatory activation of task-set reconfiguration processes. SIGNIFICANCE: These results are compatible with impaired implementation of endogenously driven processes in schizophrenia and greater reliance on external task cues, especially at long preparation intervals.

Adult↗

ERPs dissociate the effects of switching task sets and task cues.

Recent studies have suggested that reaction time (RT) costs associated with switching tasks do not reflect an endogenous control process of task set reconfiguration [Logan, G. D., Bundesen, C., 2003. Clever Homunculus: Is There an Endogenous Act of Control in the Explicit Task-Cuing Procedure? J. Exp. Psychol. Hum. Percept. Perform. 29 (3), 575-599]. Participants randomly switched between two simple tasks. Task was cued 600 ms prior to stimulus presentation using either a color or shape cue. A significant RT task switch cost was found when controlling for either a repeat or switch in cue category. In comparison, a switch in cue category had no effect on RT, even when examined across a cumulative distribution. Electrophysiological data revealed early cue processing effects within the first 300 ms after cue onset. However, replicating previous findings, an increased parietal positivity was found for task switch relative to task repeat trials that emerged prior to stimulus onset. This suggests that task set reconfiguration processes are activated when switching between tasks and supports the usefulness of task-switching paradigms in investigating cognitive control processes.

Adolescent↗

Preliminary investigation of gene expression profiles in peripheral blood lymphocytes in schizophrenia.

Schizophrenia is a heterogenous disorder that is phenomenologically characterised by a combination of negative, positive, and cognitive symptoms with variable expression in the course of illness. Here, we investigated differential gene expression in relation to age to address the heterogeneity of this disorder We used 6000 gene cDNA microarrays to generate gene expression profiles from peripheral blood lymphocytes from 14 individuals with schizophrenia and 14 non-psychiatric controls. Genes showing altered expression were identified and 18 genes with brain-related functions were altered, 4 of which, endothelial differentiation gene 2 (Edg-2), ezrin-radixin-moesin phosphoprotein 50 (EBP50), Myc-associated zinc finger protein (MAZ) and Tumor Necrosis Factor Receptor 2 (TNFR2), were confirmed by relative real-time PCR. Dendrograms were constructed using genes that showed significantly different expression (p<0.05) between groups based on median split of age dividing the matched pairs into distinct subclasses. Our findings suggest that distinct gene expression profiles in peripheral blood lymphocytes associated with schizophrenia phenotypes may provide a first step towards the biological classification of schizophrenia subtypes. The validity of this approach may lead to better methods of defining this enigmatic disease.

Adolescent↗

Auditory sensory memory and the aging brain: A mismatch negativity study.

The mismatch negativity (MMN) component of the auditory event-related potential has been used in the past to study between group differences in the accuracy and retention of information in auditory sensory memory (ASM). The MMN is elicited by infrequent 'deviant' tones that differ from a repeating 'standard' tone. In the present study, the type of deviant and the time interval between tones (stimulus-onset asynchrony: SOA) were manipulated in a study of normal aging. MMN responses of an elderly (mean age = 69) and a young group (mean age = 21) to both a duration and a frequency deviant tone were measured at a short (450 ms) and long (3 s) SOA. A smaller and later MMN (recorded at Fz) was observed in the elderly relative to the young group across SOA and Deviant conditions. The results are consistent with an age-related deficit in the encoding of sound properties in ASM. However, analysis of the MMN reversal at the mastoids provides some support for the proposal that the elderly have an additional deficit related to the retention of information in ASM.

Acoustic Stimulation↗

Auditory hallucinations in schizophrenia: intrusive thoughts and forgotten memories.

INTRODUCTION: This paper presents a new cognitive model of auditory hallucinations in schizophrenia. We suggest that auditory hallucinations are auditory representations derived from the unintentional activation of memories and other irrelevant current mental associations. Our model proposes that a combination of deficits in intentional inhibition and contextual memory is critical to the experience of auditory hallucinations. The failure in intentional inhibition produces unwanted and uncontrollable mental events which are not recognised because they have lost the contextual cues that would normally facilitate recognition. METHODS: This article amalgamates recently published data and presents a reanalysis of the findings on 43 patients with a diagnosis of schizophrenia (Badcock, Waters, Maybery, & Michie, 2005; Waters, Badcock, Maybery, & Michie, 2003a; Waters, Maybery, Badcock, & Michie, 2004a). Relative risk was also estimated to determine whether the combination of deficits increases the risk of having auditory hallucinations. RESULTS: Almost 90% of patients currently experiencing auditory hallucinations showed the predicted combination of deficits on both inhibition and context memory, compared to only a third of patients without hallucinations. In addition, the results showed that those patients with the specified cognitive deficits were at an especially increased risk of having auditory hallucinations relative to patients without the deficits. CONCLUSIONS: The results of our investigations strongly support the role of intentional inhibition and context memory in auditory hallucinations. Critical consideration of the findings also suggests that additional cognitive processes might be important for the expression of this symptom.

Cognition↗

A multivariate electrophysiological endophenotype, from a unitary cohort, shows greater research utility than any single feature in the Western Australian family study of schizophrenia.

BACKGROUND: Previous studies have found several electrophysiological endophenotypes that each co-varies individually with schizophrenia. This study extends these investigations to compare and contrast four electrophysiological endophenotype, mismatch negativity, P50, P300, and antisaccades, and analyze their covariance on the basis of a single cohort tested with all paradigms. We report a multivariate endophenotype that is maximally associated with diagnosis and evaluate this new endophenotype with respect to its application to genetic analysis. METHODS: Group differences and covariance were analyzed for probands (n = 60), family members (n = 53), and control subjects (n = 44). Associations between individual endophenotypes and diagnostic groups, as well as between the multivariate endophenotype and diagnostic groups, were investigated with logistic regression. RESULTS: Results from all four individual endophenotypes replicated previous findings of deficits in the proband group. The P50 and P300 endophenotypes similarly replicated significant deficits in the family member group, whereas mismatch negativity and antisaccade measures showed a trend. There was minimal correlation between the different endophenotypes. A logistic regression model based on all four features significantly represented the diagnostic grouping (chi(2) = 32.7; p < .001), with 80% accuracy in predicting group membership. CONCLUSIONS: A multivariate endophenotype, based on a weighted combination of electrophysiological features, provides greater diagnostic classification power than any single endophenotype.

Acoustic Stimulation↗

Genetic evidence for a distinct subtype of schizophrenia characterized by pervasive cognitive deficit.

A novel phenotyping strategy in schizophrenia, targeting different neurocognitive domains, neurobehavioral features, and selected personality traits, has allowed us to identify a homogeneous familial subtype of the disease, characterized by pervasive neurocognitive deficit. Our genome scan data indicate that this subtype, which accounts for up to 50% of our sample, has a distinct genetic basis and explains linkage to chromosome 6p24 reported previously. If representative of other populations, the ratio of schizophrenia subtypes observed in our families could have a profound impact on sample heterogeneity and on the power of genetic studies to detect linkage and association. Our proposed abbreviated battery of tests should facilitate phenotype characterization for future genetic analyses and allow a focus on a crisply defined schizophrenia subtype, thus promoting a more informed search for susceptibility genes.

Attention↗

Auditory hallucinations: failure to inhibit irrelevant memories.

INTRODUCTION: The frequency of auditory hallucinations (AH) is associated with efficiency in inhibiting irrelevant memories, suggesting that the presence of AH may be related to the intrusion of strongly activated representations in memory. Therefore, we hypothesised that the inability to suppress irrelevant memories would be found only in patients currently experiencing AH. METHOD: Performance on a repeated, continuous recognition task was examined in 23 schizophrenia patients with AH present, 20 schizophrenia patients with AH absent, and 24 healthy controls. RESULTS: Patients with current AH made significantly more inappropriate responses (false alarms) to distractors seen on previous runs of the task than nonhallucinating patients. The ability to detect targets (hits) was significantly better in healthy controls than schizophrenia patients, however, there was no significant difference between the two patient subgroups. CONCLUSIONS: The findings confirm that the presence of AH involves a failure to suppress memories that are not relevant to ongoing reality. We propose that a combination of deficits in inhibition and (episodic) memory provides a useful model of AH, which can accommodate many of the characteristic features of the symptom and fits well with the neuroanatomical circuitry that is believed to underlie the occurrence of AH.

Journal Article↗

Electrophysiological correlates of anticipatory task-switching processes.

Recent studies show a differential switch-related positivity emerging before a switch trial and reflecting anticipatory task-set reconfiguration processes. In this study, the switch-related positivity was examined in a cued task-switching paradigm. Cue-stimulus and response-stimulus intervals were independently manipulated to dissociate between the effects of anticipatory preparation and passive dissipation of task-set interference. Reaction time switch cost declined with increasing cue-stimulus and response-stimulus intervals, suggesting a contribution from both active preparation and passive interference processes. In cue-related difference waveforms, a switch positivity peaked around 350-400 ms and is interpreted as reflecting differential activation of task-set reconfiguration. In stimulus-related difference waveforms, a switch-related negativity is believed to indicate the role of S-R priming and response interference in task-switching.

Adolescent↗

Context memory and binding in schizophrenia.

The current study aimed to provide evidence for the context-memory hypothesis, which proposes that schizophrenia is linked to a deficit in retrieving contextual information and in binding the different components of a memory together. A new task was developed in which memory for the content of events could be assessed in conjunction with memory for both source and temporal information. Forty-three patients with schizophrenia and 24 normal controls took part in the study. Patients were found to be less accurate in identifying the source and temporal context of events. Furthermore, whereas controls tended to identify correctly both source and temporal context of events, patients tended to have a more fractionated recollection of those events. The study provides support for the context-memory hypothesis by demonstrating that patients with schizophrenia show a fundamental deficit in binding contextual cues together to form a coherent representation of an event in memory.

Adult↗

Is the fusiform face area specialized for faces, individuation, or expert individuation?

Several brain imaging studies have identified a region of fusiform gyrus (FG) that responds more strongly to faces than common objects. The precise functional role of this fusiform face area (FFA) is, however, a matter of dispute. We sought to distinguish among three hypotheses concerning FFA function: face specificity, individuation, and expert individuation. According to the face-specificity hypothesis, the FFA is specialized for face processing. Alternatively, the FFA may be specialized for individuating visually similar items within a category (the individuation hypothesis) or for individuating within categories with which a person has expertise (the expert-individuation hypothesis). Our results from two experiments supported the face-specificity hypothesis. Greater FFA activation to faces than Lepidoptera, another homogeneous object class, occurred during both free viewing and individuation, with similar FFA activation to Lepidoptera and common objects (Experiment 1). Furthermore, during individuation of Lepidoptera, 83% of activated FG voxels were outside the face FG region and only 15% of face FG voxels were activated. This pattern of results suggests that distinct areas may individuate faces and Lepidoptera. In Experiment 2, we tested Lepidoptera experts using the same experimental design. Again, the results supported the face-specificity hypothesis. Activation to faces in the FFA was greater than to both Lepidoptera and objects with little overlap between FG areas activated by faces and Lepidoptera. Our results suggest that distinct populations of neurons in human FG may be tuned to the features needed to individuate the members of different object classes, as has been reported in monkey inferotemporal cortex, and that the FFA contains neurons tuned for individuating faces.

Adolescent↗

Inhibition in schizophrenia: association with auditory hallucinations.

The study investigated whether auditory hallucinations (AH) in schizophrenia are linked to a deficit in inhibition. Two tasks assessing the intentional suppression of cognitive events-the Hayling Sentence Completion Test (HSCT) [Neuropsychologia 34 (1996) 263] and the Inhibition of Currently Irrelevant Memories Task (ICIM) [Nature Neuroscience 2 (1999) 677]-were administered to 42 patients with schizophrenia and 24 normal controls. Presence and severity of symptoms in the patient group were examined using the Positive and Negative Syndrome Scale (PANSS). Patients performed significantly worse on the measures of inhibition compared to controls. More importantly, among patients, significant positive correlations were obtained between an index of AH severity (defined as an increase in frequency of AH on PANSS) and the number of type A errors on the HSCT and errors in the last three runs of the ICIM. An increase in AH severity was, therefore, associated with increasingly impaired control of intentional inhibition. Furthermore, no significant correlations were found between these indices of inhibition and either negative, general or positive symptoms (excluding AH scores).

Adult↗

Functional neuroanatomy of auditory mismatch processing: an event-related fMRI study of duration-deviant oddballs.

This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a "no tone" condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophysiological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related "mismatch negativity" potential, a putative measure of auditory sensory memory.

Adult↗

Electrophysiological correlates of anticipatory and poststimulus components of task switching.

Task-switching paradigms can shed light on cognitive and neural processes underlying attentional control mechanisms. An alternating runs task-switching paradigm (R. D. Rogers & S. Monsell, 1995) is used to identify ERP components associated with anticipatory and poststimulus components of task-switching processes. Subjects alternated between two tasks in a predictable series (AABB). Reaction time (RT) switch cost reduced with increasing response-stimulus (R-S) interval and a residual switch cost remained at the longest R-S interval. A switch-related positivity (D-Pos) developed in the R-S interval. D-Pos was time-locked to response onset, peaked around 400 ms post-response onset, and was unaffected by task-set interference. A switch-related negativity (D-Neg) emerged after stimulus onset. D-Neg peaked earlier with increasing R-S interval and its amplitude and latency were affected by task-set interference. D-Pos and D-Neg were interpreted within current models of task-switching.

Adolescent↗

Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders.

BACKGROUND: One of the most consistent findings in schizophrenia research over the past decade is a reduction in the amplitude of an auditory event-related brain potential known as mismatch negativity (MMN), which is generated whenever a deviant sound occurs in a background of repetitive auditory stimulation. The reduced amplitude of MMN in schizophrenia was first observed for deviant sounds that differ in duration relative to background standard sounds, and similar findings have been observed for sounds that are deviant in frequency. The aim of this study was to determine whether first-degree relatives of schizophrenia patients show a similar reduction in MMN amplitude to duration deviants. METHODS: We measured MMN to duration increments (deviants 100 msec vs. standards 50 msec) in 22 medicated patients with a diagnosis in the schizophrenia spectrum, 17 individuals who were first-degree unaffected relatives of patients, and 21 healthy control subjects. RESULTS: Mismatch negativity amplitude was reduced in patients and relatives compared with control subjects. There were no significant differences between patients and relatives. In contrast, the subsequent positive component, P3a, was larger in relatives compared with patients. CONCLUSIONS: These findings suggest that a reduced MMN amplitude may be an endophenotype marker of the predisposition to schizophrenia.

Acoustic Stimulation↗

Motivations that maintain substance use among individuals with psychotic disorders.

This study quantitatively examined reasons for substance use among individuals with psychotic disorders and explored the relationship of these reasons to substance use problems and dependence. Sixty-nine people with psychotic disorders were interviewed using a battery of questionnaires called the Substance Use Scale for Psychosis (SUSP). Symptoms and medication side effects were also measured. A factor analysis revealed similar motives for substance use (mostly alcohol and cannabis use) as in the general population: "enhancement," "social motives," "coping with unpleasant affect," and "conformity and acceptance." A fifth factor, "relief of positive symptoms and side effects," demonstrated limited reliability. "Coping" and "enhancement" motives were found to lead to substance use problems and dependence. Mediator analysis indicated that worse symptoms lead to stronger motives for substance use, which in turn lead to stronger psychological dependence on that substance. These findings have the potential to inform effective treatment for substance use in psychosis.

Adaptation, Psychological↗