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Michael C Stevens

Publications and source records attributed to Michael C Stevens.

11 recordsLinked to original sources

Functional neural circuits for mental timekeeping.

Theories of mental timekeeping suggest frontostriatal networks may mediate performance of tasks requiring precise timing. We assessed whether frontostriatal networks are functionally integrated during the performance of timing tasks. Functional magnetic resonance imaging (fMRI) data from 31 healthy adults were collected during performance of several different types of discrete interval timing tasks. Independent component analysis (ICA) was used to examine functional connectivity within frontostriatal circuits. ICA identifies groups of spatially discrete brain regions sharing similar patterns of hemodynamic signal change over time. The results confirm the existence of a frontostriatal neural timing circuit that includes anterior cingulate gyrus, supplementary motor area, bilateral anterior insula, bilateral putamen/globus pallidus, bilateral thalamus, and right superior temporal gyrus and supramarginal gyrus. Several other distinct neural circuits were identified that may represent the neurobiological substrates of different information processing stages of mental timekeeping. Small areas of right cerebellum were engaged in several of these circuits, suggesting that cerebellar function may be important in, but not the primary substrate of, the mental timing tasks used in this experiment. These findings are discussed within the context of current biological and information processing models of neural timekeeping.

Acoustic Stimulation↗

The hemodynamics of oddball processing during single-tone and two-tone target detection tasks.

Event-related potential (ERP) studies have shown that the neural systems engaged during performance of oddball tasks are sensitive to contextual manipulations, such as the number of stimulus classes. Some ERP components (i.e., N1) are modulated by the number of stimulus types, while others (i.e., P3) are not greatly affected. However, little is known about how these contextual manipulations affect the hemodynamics underlying oddball processing. The purpose of this study was to examine the hemodynamic correlates of target stimulus processing in single-tone (targets alone) and two-tone (targets and standard tones) auditory oddball tasks. The primary hypothesis was that processing of salient stimuli in both contextual conditions would engage the same spatially distributed cortical and subcortical networks observed in previous oddball fMRI studies. Results were consistent with this hypothesis and suggest that the brain engages many potentially useful brain regions during salient stimulus processing despite the low probability that said regions are necessary for task performance, which likely reflects a form of "adaptive reflexive processing". Results were also consistent with ERP data that shows that the N1 is larger for single-tone tasks by showing greater amplitude of hemodynamic response for single-tone targets, relative to two-tone targets, in bilateral temporal cortex and bilateral inferior lateral frontal cortex. The results are discussed as they relate to the understanding of neurocognitive function pertaining to contextual manipulations in general, and orienting processes in particular.

Acoustic Stimulation↗

Low-dose estradiol alters brain activity.

Although several studies have examined the effects of estrogen replacement therapy (ERT) on neural activity associated with tasks of learning and memory, no study has examined such effects on a sustained attention task. This study examined the effect of low-dose estrogen replacement therapy on hemodynamic activity elicited by a visual three-stimulus oddball task recorded using event-related functional magnetic resonance imaging (fMRI). Participants included 16 women between the ages of 73 and 84 who were part of a randomized controlled double-blind study to evaluate the effect of an ultralow dose micronized estradiol on bone. No significant differences in behavioral performance were found with ERT. However, there was evidence that ERT group participants had both reductions and increases in the amplitude of hemodynamic response in a variety of subcortical and cortical brain regions. These included regions involved in perception and attention such as the occipital and parietal lobes, motor cortex, anterior cingulate and prefrontal cortex. These findings suggest that estrogen may facilitate the efficiency of brain function during the performance of sustained attention tasks in post-menopausal elderly women.

Aged↗

Abnormal hemodynamics in schizophrenia during an auditory oddball task.

BACKGROUND: Schizophrenia is a heterogeneous disorder characterized by diffuse brain abnormalities that affect many facets of cognitive function. One replicated finding in schizophrenia is abnormalities in the neural systems associated with processing salient stimuli in the context of oddball tasks. This deficit in the processing of salience stimuli might be related to abnormalities in orienting, attention, and memory processes. METHODS: Behavioral responses and functional magnetic resonance imaging data were collected while 18 patients with schizophrenia and 18 matched healthy control subjects performed a three-stimulus auditory oddball task. RESULTS: Target detection by healthy participants was associated with significant activation in all 38 regions of interest embracing distributed cortical and subcortical systems. Similar reproducibility was observed in healthy participants for processing novel stimuli. Schizophrenia patients, relative to control subjects, showed diffuse cortical and subcortical hypofunctioning during target detection and novelty processing, including bilateral frontal, temporal, and parietal cortices and amygdala, thalamus, and cerebellum. CONCLUSIONS: These data replicate and extend imaging studies of target detection in schizophrenia and present new insights regarding novelty processing in the disorder. The results are consistent with the hypothesis that schizophrenia is characterized by a widespread pathologic process affecting many cerebral areas, including cortical, subcortical, and cerebellar circuits.

Acoustic Stimulation↗

An adaptive reflexive processing model of neurocognitive function: supporting evidence from a large scale (n = 100) fMRI study of an auditory oddball task.

Recent hemodynamic imaging studies have shown that processing of low probability task-relevant target stimuli (i.e., oddballs) and low probability task-irrelevant novel stimuli elicit widespread activity in diverse, spatially distributed cortical and subcortical systems. The nature of this distributed response supports the model that processing of salient and novel stimuli engages many brain regions regardless of whether said regions were necessary for task performance. However, these latter neuroimaging studies largely employed small sample sizes and fixed-effect analyses, limiting the characterization and inference of the results. The present study addressed these issues by collecting a large sample size (n = 100) and employed random effects statistical models. Analyses were also conducted to determine the inter-subject reliability of the hemodynamic response and the effects of gender and age on target detection and novelty processing. Group data demonstrated highly significant activation in all 34 specified regions of interest for target detection and all 24 specified regions of interest for processing of novel stimuli. Neither age nor gender systematically influenced the results. These data are discussed within the context of a model that proposes that the mammalian brain has evolved to adopt a strategy of engaging distributed neuronal systems when processing salient stimuli despite the low probability that many of these brain regions are required for successful task performance. This process may be termed 'adaptive reflexive processing.' The implications of these results for interpreting functional MRI studies are discussed.

Adolescent↗

Hemispheric differences in hemodynamics elicited by auditory oddball stimuli.

Evidence from neuroimaging studies suggests that the right hemisphere of the human brain might be more specialized for attention than the left hemisphere. However, differences between right and left hemisphere in the magnitude of hemodynamic activity (i.e., 'functional asymmetry') rarely have been explicitly examined in previous neuroimaging studies of attention. This study used a new voxel-based comparison method to examine hemispheric differences in the amplitude of the hemodynamic response in response to infrequent target, infrequent novel, and frequent standard stimuli during an event-related fMRI auditory oddball task in 100 healthy adult participants. Processing of low probability task-relevant target stimuli, or 'oddballs', and low probability task-irrelevant novel stimuli is believed to engage in orienting and attentional processes. It was hypothesized that greater right-hemisphere activation compared to left would be observed to infrequent target and novel stimuli. Consistent with predictions, greater right hemisphere than left frontal, temporal, and parietal lobe activity was observed for target detection and novelty processing. Moreover, asymmetry effects did not differ with respect to age or gender of the participants. The results (1) support the proposal that the right hemisphere is differentially engaged in processing salient stimuli and (2) demonstrate the successful use of a new voxel-based laterality analysis technique for fMRI data.

Acoustic Stimulation↗

fMRI in an oddball task: effects of target-to-target interval.

The amplitude of the P3 event-related potential (ERP) elicited by task-relevant target ("oddball") stimuli has been shown to vary in proportion to the length of time between targets. Here we use functional magnetic resonance imaging (fMRI) to identify neural systems modulated by target interval in a large sample of healthy adults (n=100) during performance of an auditory oddball task that included both target and novel stimuli. A positive relationship was found between target interval and hemodynamic activity in the anterior cingulate and in bilateral lateral prefrontal cortex, temporal-parietal junction, postcentral gryi, thalamus, and cerebellum. This modulation likely represents updating of the working memory template for the target stimuli. There was no such effect of novel interval, suggesting that neuronal modulation may only occur for task-relevant stimuli, possibly in the service of strategic resource allocation processes.

Adolescent↗

The effect of short-term estradiol therapy on cognitive function in older men receiving hormonal suppression therapy for prostate cancer.

OBJECTIVES: To determine the effect of estrogen (E) alone (without the influence of testosterone (T)) on cognitive function in older men, using 17-beta micronized estradiol versus placebo in older men rendered hypogonadal (low T and E) by treatment for prostate cancer. DESIGN: Short-term double-blind, randomized, controlled trial. SETTING: An outpatient General Clinical Research Center. PARTICIPANTS: Twenty-seven community-dwelling men aged 65 and older receiving neoadjuvant or established therapy with luteinizing-hormone releasing-hormone agonists for treatment of prostate cancer enrolled in a short-term randomized, controlled trial of 17-beta micronized estradiol versus placebo on the effect on biochemical markers of bone turnover. MEASUREMENTS: Hormone levels, including E, T, and sex hormone-binding globulin; standardized neurocognitive tests, including measures of sustained attention, executive function, and memory; and questionnaires to assess subjects' perception of cognitive deficits and symptoms of depression. RESULTS: There were no significant differences between patients receiving E or placebo on 15 of 17 neurocognitive measures and no significant differences in self-reported cognitive deficits or number of depressive symptoms. CONCLUSION: Although studies have suggested that E replacement therapy may improve cognitive function, most notably memory performance in postmenopausal woman, there was no evidence in the present study that the addition of short-term E therapy was more beneficial than placebo in tests of cognitive performance in hypogonadal men.

Aged↗

Executive-cognitive functioning in the development of antisocial personality disorder.

The present study examined the association of cognitive-executive abilities to two risk factors for alcoholism, i.e., antisocial behaviors and a family history (FH+) of alcohol dependence. A sample of 91 right-handed, non-substance-dependent, young male adults recruited from the community were classified into three groups: (1) a control group of n=32 men with no history of DSM-III-R childhood conduct disorder (CD) or antisocial personality disorder (ASPD); (2) n=25 men who met criteria for a DSM-III-R childhood CD diagnosis, but did not meet diagnostic criteria for ASPD (i.e., CD/ASPD-); and (3) n=34 men who met DSM-III-R criteria for ASPD. They were further divided into those with and without a positive family history of alcoholism. A two-way (Antisocial Profile (3)x Family History of Alcoholism (2)) ANOVA was used to compare several neuropsychological measures of executive-cognitive functioning (ECF) ability. Verbal abstraction ability was found to be significantly lower in ASPD subjects compared with controls and CD-only subjects, inversely related to antisocial behavior severity (as measured by symptom count). CD-only and control subjects' abstraction ability were statistically indistinguishable. FH+ was associated with increased errors in planning performance on the Porteus Maze Test and diminished performance on Luria's simple alternate-tapping motor tasks. The effect was more pronounced when inhibition of prepotent motor planning was required. Results are consistent with previous work examining ECF ability in antisocial samples that find subtle differences in ECF ability compared to controls. The findings suggest that normal versus abnormal behavioral outcome for children with conduct problems may be influenced by cognitive ability profile, perhaps because of varying maturational processes.

Adult↗

The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development.

The National Institute of Mental Health initiated the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) program to evaluate the effectiveness of antipsychotic drugs in typical settings and populations so that the study results will be maximally useful in routine clinical situations. The CATIE schizophrenia trial blends features of efficacy studies and large, simple trials to create a pragmatic trial that will provide extensive information about antipsychotic drug effectiveness over at least 18 months. The protocol allows for subjects who receive a study drug that is not effective to receive subsequent treatments within the context of the study. Medication dosages are adjusted within a defined range according to clinical judgment. The primary outcome is all-cause treatment discontinuation because it represents an important clinical endpoint that reflects both clinician and patient judgments about efficacy and tolerability. Secondary outcomes include symptoms, side effects, neurocognitive functioning, and cost-effectiveness. Approximately 50 clinical sites across the United States are seeking to enroll a total of 1,500 persons with schizophrenia. Phase 1 is a double-blinded randomized clinical trial comparing treatment with the second generation antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone to perphenazine, a midpotency first generation antipsychotic. If the initially assigned medication is not effective, subjects may choose one of the following phase 2 trials: (1) randomization to open-label clozapine or a double-blinded second generation drug that was available but not assigned in phase 1; or (2) double-blinded randomization to ziprasidone or another second generation drug that was available but not assigned in phase 1. If the phase 2 study drug is discontinued, subjects may enter phase 3, in which clinicians help subjects select an open-label treatment based on individuals' experiences in phases 1 and 2.

Adolescent↗