Biomedical subjects

John A Sweeney

Publications and source records attributed to John A Sweeney.

At least 19 recordsLinked to original sources

PubMed2007

Spatial working memory deficits in autism.

Previous studies have reported working memory deficits in autism, but this finding has been inconsistent. One possibility is that deficits in this domain may be present only when working memory load exceeds some limited capacity. High-functioning individuals with autism performed the CANTAB computerized test of spatial working memory. Individuals with autism made more errors than a matched group of typically developing controls on this task, and were less likely to consistently use a specific organized search strategy to complete the task. Overall, these results demonstrate reduced spatial working memory abilities in autism, and extend previous findings by demonstrating that these deficits are significant when tasks impose heavier demands on working memory.

Adolescent↗

PubMed2006

Affective neural circuitry during facial emotion processing in pediatric bipolar disorder.

BACKGROUND: Facial emotions are central to human interaction. Identifying pathophysiology in affect processing circuitry that supports the ability to assess facial emotions might facilitate understanding of affect regulation in pediatric bipolar disorder. METHODS: Ten euthymic, unmedicated pediatric bipolar patients and 10 healthy control subjects matched for age, gender, race, socioeconomic status, and IQ were scanned with functional magnetic resonance imaging. Angry, happy, and neutral faces were presented in 30-sec blocks, with a 20-sec rest period between blocks. Subjects were asked to press a button when each face appeared, to ensure that attention was maintained on-task. RESULTS: In bipolar patients, in response to both angry and happy faces relative to neutral faces, we observed reduced activation of right rostral ventrolateral prefrontal cortex together with increased activity in right pregenual anterior cingulate, amygdala, and paralimbic cortex. Bipolar patients also showed reduced activation of visual areas in occipital cortex together with greater activation in higher-order visual perceptual areas, including superior temporal sulcus and fusiform gyrus with angry faces and posterior parietal cortex with happy faces. CONCLUSIONS: Findings document a disturbance in affective neurocircuitry in pediatric bipolar disorder. Reduced activation in ventrolateral prefrontal cortex might reflect diminished top-down control that leads to the observed exaggerated activation in amygdala and paralimbic areas. Changes in occipital areas might represent an effort to gate sensory input when affective responses to the faces could not be successfully modulated. Disturbances in affect processing circuitry could contribute to emotional dysregulation and social cognitive difficulties in bipolar youth.

Adolescent↗

PubMed2006

Biological risk factors in pediatric bipolar disorder.

BACKGROUND: The current study attempted to determine whether neurodevelopmental and acquired brain abnormalities are more common in pediatric bipolar disorder (PBD). METHODS: The study sample consisted of 98 subjects with a mean age of 11.5 +/- 3.3 years comprising three demographically matched groups: healthy controls (HC, n = 28), subjects with bipolar disorder - Type I (PBD, n = 37), and bipolar disorder - Type I combined with attention deficit hyperactivity disorder (PBD+ADHD, n = 33). Family history of PBD was determined using the Family History Screen. Additional measures were administered to assess the history on perinatal risk, development milestones, serious physical illnesses, and head injury. RESULTS: Logistic regression showed that that family history and perinatal risk factors predicted the diagnosis of PBD. PBD diagnosis was 15 times higher among those with a family history of BD. Second, for every additional perinatal risk factor such as prenatal exposure to drugs or birth complications, the risk of having a PBD diagnosis increased more than six-fold. CONCLUSIONS: Having a positive familial history of BD in a first degree relative and perinatal insults may elevate the risk for developing PBD. Presence of these risk factors, especially in the context of clinical signs of affect dysregulation, should alert clinicians to screen for PBD.

Adolescent↗

PubMed2006

Cognitive processes in the development of TOL performance.

Components of executive function continue to develop through adolescence. There is limited knowledge of how these cognitive components impact complex cognitive function requiring their integration. This study examines the development of response planning, a complex cognitive function, and the contributions of selected cognitive processes, including speed of processing, response inhibition, and working memory to its development. We tested 100 healthy 8-30 year old individuals with a computerized version to the Tower of London (TOL) task and cognitive oculomotor tests including the visually guided saccade, oculomotor delayed response, and antisaccade tasks. Speed of processing, response inhibition, working memory, and TOL performance all demonstrated maturation in adolescence. While all processes were correlated with the development of TOL performance, antisaccade performance showed the strongest association indicating an important role for response inhibition in planning. These results indicate that the development of converging cognitive processes in adolescence, including response inhibition and working memory, support response planning and may serve as a model for the development of performance in other complex problem solving tasks.

Adolescent↗

PubMed2006

Impact of neurocognitive function on academic difficulties in pediatric bipolar disorder: A clinical translation.

BACKGROUND: Previous research has demonstrated that academic and neuropsychological functions are compromised in pediatric bipolar disorder (PBD). Investigation of the degree to which neuropsychological deficits might contribute to those academic problems is needed to aid in the recognition and intervention for school achievement difficulties in PBD. METHODS: A sample of 55 children and adolescents with PBD with and without attention-deficit/hyperactivity disorder (ADHD) (PBD group, n = 28; PBD+ADHD group, n = 27) were tested with a computerized neurocognitive battery and standardized neuropsychological tests. Age range of subjects was 7-17 years, with the mean age of 11.97 (3.18) years. Parents completed a structured questionnaire on school and academic functioning. RESULTS: Logistic regression analyses indicated that executive function, attention, working memory, and verbal memory scores were poorer in those with a history of reading/writing difficulties. A separate logistic regression analysis found that attentional dysfunction predicted math difficulties. These relationships between neuropsychological function and academic difficulties were not different in those with PBD+ADHD than in those with PBD alone. CONCLUSIONS: In PBD neuropsychological deficits in the areas of attention, working memory, and organization/problem solving skills all contribute to academic difficulties. Early identification and intervention for these difficulties might help prevent lower academic achievement in PBD.

Adolescent↗

PubMed2006

Maturation of executive function in autism.

BACKGROUND: Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. METHODS: 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. CONCLUSIONS: These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.

Adolescent↗

PubMed2006

Functional magnetic resonance imaging studies of eye movements in first episode schizophrenia: smooth pursuit, visually guided saccades and the oculomotor delayed response task.

Schizophrenia patients show eye movement abnormalities that suggest dysfunction in neocortical control of the oculomotor system. Fifteen never-medicated, first episode schizophrenia patients and 24 matched healthy individuals performed eye movement tasks during functional magnetic resonance imaging studies. For both visually guided saccade and smooth pursuit paradigms, schizophrenia patients demonstrated reduced activation in sensorimotor areas supporting eye movement control, including the frontal eye fields, supplementary eye fields, and parietal and cingulate cortex. The same findings were observed for an oculomotor delayed response paradigm used to assess spatial working memory, during which schizophrenia patients also had reduced activity in dorsolateral prefrontal cortex. In contrast, only minimal group differences in activation were found during a manual motor task. These results suggest a system-level dysfunction of cortical sensorimotor regions supporting oculomotor function, as well as in areas of dorsolateral prefrontal cortex that support spatial working memory. These findings indicate that a generalized rather than localized pattern of neocortical dysfunction is present early in the course of schizophrenia and is related to deficits in the sensorimotor and cognitive control of eye movement activity.

Adolescent↗

PubMed2006

Risperidone in first-episode psychosis: a longitudinal, exploratory voxel-based morphometric study.

Previous studies have provided evidence supporting a neuroplastic effect of atypical antipsychotics. The present investigation explores the short-term effects of risperidone on brain parenchyma by performing voxel-based morphometry on baseline and 6-week follow-up MRI scans obtained from 15 neuroleptic-naïve individuals with first-episode psychosis treated with risperidone and 15 healthy controls. The risperidone-treated subjects demonstrated changes in grey matter and white matter in several brain regions, including superior temporal gyrus. No areas of change were found in controls. The results of this exploratory investigation support the possibility that risperidone has short-term effects on brain parenchyma in individuals with first-episode psychosis.

Adolescent↗

PubMed2006

Longitudinal studies of antisaccades in antipsychotic-naive first-episode schizophrenia.

BACKGROUND: Prefrontal cortical dysfunctions, including disturbances in adaptive context-specific behavior, have been reported in neuropsychological and brain imaging studies of schizophrenia. Some data suggest that treatment with antipsychotic medications may ameliorate these deficits. METHOD: We investigated antisaccade performance in 39 antipsychotic-naive, first-episode schizophrenia patients who were re-evaluated 6 weeks after treatment initiation. A group of matched healthy subjects were examined at similar time-points. Patients and healthy individuals available for longer-term testing were re-assessed 26 and 52 weeks after initial testing. RESULTS: Before treatment, patients showed elevated rates of response suppression errors and prolonged latencies of correct antisaccades. Increased rates of antisaccade errors were associated with faster response latencies during a separate, visually guided saccade task, but only prior to treatment. Throughout the 1-year follow-up, patients progressively improved in their ability to voluntarily suppress context-inappropriate behavior. Although treatment assignment was by clinician choice, results of exploratory analyses revealed that patients treated with risperidone progressively planned and initiated correct antisaccades more quickly than patients receiving haloperidol. CONCLUSIONS: Deficits in the voluntary control of spatial attention are exaggerated during acute episodes of illness, but remain an enduring aspect of prefrontal dysfunction in schizophrenia even after treatment. During acute illness, speeded sensorimotor transformations may compound these deficits and contribute to the heightened distractibility associated with acute psychosis. Continued improvement in task performance throughout the 1-year follow-up suggests that partial normalization of prefrontal cognitive functions resulting from antipsychotic treatment may have a longer and more gradual time course than the reduction of acute psychotic symptoms.

Adolescent↗

PubMed2006

Adverse effects of risperidone on spatial working memory in first-episode schizophrenia.

CONTEXT: Working memory impairments are a central neurocognitive feature of schizophrenia. The nature of these impairments early in the course of illness and the impact of antipsychotic drug treatment on these deficits are not well understood. The oculomotor delayed response task is a translational spatial working memory paradigm used to characterize the neurophysiologic and neurochemical aspects of working memory in the primate brain. OBJECTIVE: To examine oculomotor delayed response task performance in patients with first-episode schizophrenia before and after antipsychotic drug treatment. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five antipsychotic drug-naive, acutely ill patients with first-episode schizophrenia performed an oculomotor delayed response task at baseline before any drug treatment and again after 6 weeks of risperidone treatment. Twenty-five matched healthy controls were studied in parallel. MAIN OUTCOME MEASURE: Accuracy for remembered spatial locations on an oculomotor delayed response task. RESULTS: Before treatment, patients demonstrated baseline impairment in the ability to maintain spatial location information in working memory at longer delay-period durations (8 seconds), when maintenance demands on working memory were greatest. After 6 weeks of risperidone treatment and significant clinical improvement, this pretreatment impairment worsened such that patients were uniformly impaired across all delay period durations (1-8 seconds). This occurred in the absence of any generalized adverse effect on oculomotor systems or significant extrapyramidal adverse effects. CONCLUSIONS: Deficits in the maintenance of spatial information in working memory are present early in the course of illness. Risperidone treatment exacerbated these deficits, perhaps by impairing the encoding of information into working memory. Studies with nonhuman primates performing oculomotor delayed response tasks suggest that the apparent adverse effect of risperidone might result from treatment-related changes in modulatory functions of prefrontal D1 receptor systems.

Acute Disease↗

PubMed2006

Brain basis of developmental change in visuospatial working memory.

Although brain changes associated with the acquisition of cognitive abilities in early childhood involve increasing localized specialization, little is known about the brain changes associated with the refinement of existing cognitive abilities that reach maturity in adolescence. The goal of this study was to investigate developmental changes in functional brain circuitry that support improvements in visuospatial working memory from childhood to adulthood. We tested thirty 8- to 47-year-olds in an oculomotor delayed response task. Developmental transitions in brain circuitry included both quantitative changes in the recruitment of necessary working memory regions and qualitative changes in the specific regions recruited into the functional working memory circuitry. Children recruited limited activation from core working memory regions (dorsal lateral prefrontal cortex [DLPFC] and parietal regions) and relied primarily on ventromedial regions (caudate nucleus and anterior insula). With adolescence emerged a more diffuse network (DLPFC, anterior cingulate, posterior parietal, anterior insula) that included the functional integration of premotor response preparation and execution circuitry. Finally, adults recruited the most specialized network of localized regions together with additional performance-enhancing regions, including left-lateralized DLPFC, ventrolateral prefrontal cortex, and supramarginal gyrus. These results suggest that the maturation of adult-level cognition involves a combination of increasing localization within necessary regions and their integration with performance-enhancing regions.

Adolescent↗

PubMed2006

Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients.

OBJECTIVE: A systematic evaluation of neuropsychological functioning in individuals with pediatric bipolar disorder is necessary to clarify the types of cognitive deficits that are associated with acutely ill and euthymic phases of the disorder and the effects of medication on these deficits. METHOD: Unmedicated (N=28) and medicated (N=28) pediatric bipolar patients and healthy individuals (N=28) (mean age=11.74 years, SD=2.99) completed cognitive testing. Groups were matched on age, sex, race, parental socioeconomic status, general intelligence, and single-word reading ability. A computerized neurocognitive battery and standardized neuropsychological tests were administered to assess attention, executive function, working memory, verbal memory, visual memory, visuospatial perception, and motor skills. RESULTS: Subjects with pediatric bipolar disorder, regardless of medication and illness status, showed impairments in the domains of attention, executive functioning, working memory, and verbal learning compared to healthy individuals. Also, bipolar subjects with comorbid attention deficit hyperactivity disorder (ADHD) performed worse on tasks assessing attention and executive function than patients with bipolar disorder alone. CONCLUSIONS: The absence of differences in the deficits of neurocognitive profiles between acutely ill unmedicated patients and euthymic medicated patients suggests that these impairments are trait-like characteristics of pediatric bipolar disorder. The cognitive deficits found in individuals with pediatric bipolar disorder suggest significant involvement of frontal lobe systems supporting working memory and mesial temporal lobe systems supporting verbal memory, regardless of ADHD comorbidity.

Adolescent↗

PubMed2005

Genetically predisposed offspring with schizotypal features: an ultra high-risk group for schizophrenia?

Biomarkers proposed in the schizophrenia diathesis have included neurocognitive deficits in domains such as working memory that implicate prefrontal systems. However, the relationship between these biomarkers and psychopathological markers such as schizotypy has not been systematically assessed, particularly in adolescent offspring of schizophrenia patients. Convergence between these markers may identify individuals at especially high risk for schizophrenia. In the current study the authors assessed whether functional deficits in working memory assessed using the oculomotor delayed response task (ODR) and executive function assessed using the Wisconsin Card Sort task (WCST), and structural deficits in prefrontal cortex, in the adolescent offspring of patients were predictive of schizotypy. Schizotypal offspring made more perseverative errors on the WCST (p<.002) and showed age-related deficits on the ODR task (p<.02) compared to their non-schizotypal counterparts or healthy controls. Reduced gray matter concentration in prefrontal cortex (p<.001) was also associated with schizotypy. Schizotypy in offspring of schizophrenia patients appears to be highly associated with known biomarkers of the illness such as executive function impairment and reductions in cortical gray matter. Furthermore, schizotypy appears to interact with development leading to greater impairment in working memory in schizotypal offspring closer to the typical age of onset of schizophrenia than non-schizotypal offspring. Thus, clinical and neurocognitive biomarkers of the illness appear to be highly interrelated in this sample of at-risk offspring. We propose that schizotypy may define a hyper vulnerable sub-sample among individuals genetically predisposed to schizophrenia and that future studies that attempt to assess risk may benefit from such a convergent approach.

Adolescent↗

PubMed2005

Premorbid indicators and risk for schizophrenia: a selective review and update.

Prospective studies of young relatives at risk for schizophrenia (high-risk studies, HR) can shed light on premorbid precursors of schizophrenia. Early HR studies pointed to a wide prevalence of schizophrenia spectrum psychopathology among young relatives at increased genetic risk. Recent studies suggest that young HR relatives have neurobehavioral deficits and structural, physiological, and neurochemical brain abnormalities that may date back to childhood or earlier. In this paper, we provide a selected overview of the lessons and limitations of early "first generation" studies and the beginning insights from recent "second generation" studies. We also provide an interim summary of data from the ongoing studies of young relatives at risk for schizophrenia in Pittsburgh. Collectively, such data may help us to predict the eventual emergence of schizophrenia, and schizophrenia spectrum or non-spectrum psychopathology.

Adolescent↗

PubMed2005

Oculomotor studies of cerebellar function in autism.

Histopathological, neuroimaging and genetic findings indicate cerebellar abnormalities in autism, but the extent of neurophysiological dysfunction associated with those findings has not been systematically examined. Suppression of intrusive saccades (square wave jerks) and the ability to sustain eccentric gaze, two phenomena requiring intact cerebellar function, were examined in 52 high-functioning individuals with autism and 52 age- and IQ-matched healthy subjects during visual fixation of static central and peripheral targets. Rates of intrusive saccades were not increased in autism during visual fixation, and foveopetal ocular drift was also not increased when subjects held an eccentric gaze. The absence of gross disturbances of visual fixation associated with cerebellar disease in individuals with autism, such as increased square wave jerk rates and foveopetal drift when holding eccentric gaze, indicates that the functional integrity of cerebellar--brainstem networks devoted to oculomotor control is preserved in autism despite reported anatomic variations. However, increased amplitude of intrusive saccades and reduced latency of target refixation after intrusive saccades were observed in individuals with autism, especially when subjects maintained fixation of remembered target locations without sensory guidance. The atypical metrics of intrusive saccades that were observed may be attributable to faulty functional connectivity in cortico-cerebellar networks.

Adolescent↗

PubMed2005

Functional neuroanatomy of anticipatory behavior: dissociation between sensory-driven and memory-driven systems.

The ability to anticipate predictable stimuli allows faster responses. The predictive saccade (PRED) task has been shown to quickly induce such anticipatory behavior in humans. In a PRED task subjects track a visual target jumping back and forth between fixed positions at a fixed time interval. During this task, saccade latencies drop from approximately 200 ms to <80 ms as subjects anticipate target appearance. This change in saccade latency indicates that subjects' behavior shifts from being sensory driven to being memory driven. We conducted functional magnetic resonance imaging studies with 10 healthy adults performing the PRED task using a standard block design. We compared the PRED task with a visually guided saccade (VGS) task using unpredictable targets matched for number, direction and amplitude of required saccades. Our results show greater activation during the PRED task in the prefrontal, pre-supplementary motor and anterior cingulate cortices, hippocampus, mediodorsal thalamus, striatum and cerebellum. The VGS task elicited greater activation in the cortical eye fields and occipital cortex. These results demonstrate the important dissociation between sensory and predictive neural control of similar saccadic eye movements. Anticipatory behavior induced by the PRED task required less sensory-related processing activity and was subserved by a distributed cortico-subcortical memory system including prefronto-striatal circuitry.

Adult↗

PubMed2005

Abnormalities in visually guided saccades suggest corticofugal dysregulation in never-treated schizophrenia.

BACKGROUND: Previous studies have reported intact visually guided saccades in schizophrenia, but these are limited by potential acute and long-term pharmacological treatment effects, small sample sizes, and a failure to follow patients over time. METHODS: Visually guided saccades were examined in 44 antipsychotic-naive patients experiencing their first episode of schizophrenia prior to treatment and again after 6, 26, and 52 weeks of antipsychotic treatment. Thirty-nine matched healthy individuals were followed over the same period. RESULTS: Before treatment, patients showed faster saccade latencies to unpredictable visual targets, suggesting reduced inhibitory regulation of brainstem saccade generators by neocortical attentional systems. Risperidone treatment reduced this deficit, suggesting a facilitation of attentional function, but haloperidol treatment did not. However, there was also a modest decline in saccade accuracy after risperidone treatment. The ability to sustain fixation of static central and peripheral targets was unimpaired before and after treatment. CONCLUSIONS: These findings provide evidence for impairments in neocortical attentional systems that cause reduced corticofugal regulation of brainstem systems in schizophrenia. This dysfunction appears to be minimized by the atypical antipsychotic risperidone but at the cost of a subtle reduction in saccade accuracy, possibly mediated via adverse effects on cerebellar vermis function.

Adult↗

PubMed2005

Effects of antipsychotic treatment on emotion perception deficits in first-episode schizophrenia.

OBJECTIVE: The authors evaluated emotion perception in acutely ill patients experiencing a first episode of schizophrenia. They also investigated the effects of antipsychotic medication on emotion perception. METHOD: Tests of the ability to perceive and discriminate emotional expressions from the Penn Computerized Neuropsychological Battery were given to 13 patients experiencing their first episode of schizophrenia. Patients were also assessed with the Positive and Negative Syndrome Scale. The patients were tested while they were unmedicated and again following clinical stabilization. Healthy individuals were evaluated over a similar time interval. RESULTS: Patients with first-episode schizophrenia demonstrated impairments in emotion perception before treatment and no significant improvement after treatment. Emotion perception deficits were correlated with negative symptoms after clinical stabilization. CONCLUSIONS: Deficits in emotion perception are present at illness onset in schizophrenia and show minimal response to effective antipsychotic treatment.

Antipsychotic Agents↗