http://hdl.handle.net/10027/7338 Tue, 21 May 2013 15:48:43 GMT 2013-05-21T15:48:43Z http://hdl.handle.net/10027/8402 Salience of working-memory maintenance and manipulation deficits in schizophrenia Hill, S. K.; Griffin, G. B.; Miura, T. Kazuto; Herbener, E. S.; Sweeney, J. A. Background. Encoding and maintenance of information in working memory, followed by internal manipulation of that information for planning adaptive behavior, are two key components of working-memory systems. Both processes have been reported to be impaired in schizophrenia, but few studies have directly compared the relative severity of these abnormalities, or the degree to which manipulation deficits might be secondary to alterations in maintenance processes. Method. Clinically stable schizophrenia patients (n=25) and a demographically similar healthy comparison group (n=24) were administered a verbal span task with three levels of working-memory load. Maintenance was assessed using sequential position questions. Manipulation processes were assessed by requiring comparison of the relative sequential position of test items, which entailed simultaneous serial search strategies regarding item order. Results. Both groups showed reduced accuracy and increased reaction time for manipulation compared with maintenance processing. There were significant patient impairments across working-memory loads. There was no differential deficit in manipulation processing, and effect sizes of relative deficit in the patient group were higher for maintenance than manipulation processing. Conclusions. The strong correlation for maintenance and manipulation deficits suggest that impairments in the ability to internally manipulate information stored in working-memory systems are not greater than alterations in the encoding and maintaining of information in working memory and that disturbances in maintenance processing may contribute to deficits in higher-order working-memory operations. © 2010 by Cambridge University Press, Psychological Medicine DOI: 10.1017/S003329171000019X Fri, 01 Jan 2010 06:00:00 GMT http://hdl.handle.net/10027/8402 2010-01-01T06:00:00Z http://hdl.handle.net/10027/7752 Fronto-limbic Dysfunction in Mania Pre-Treatment and Persistent Amygdala Over-activity Post-Treatment in Pediatric Bipolar Disorder Passarotti, Alessandra M.; Sweeney, John A.; Pavuluri, Mani N. Rationale. Neural deficits at the interface of affect and cognition may improve with pharmacotherapy in pediatric bipolar disorder (PBD). Objectives. We examined lamotrigine treatment impact on the neural interface of working memory and affect in PBD. Methods. Un-medicated, acutely-ill, patients with mania and hypomania (n=17) and healthy controls (HC; n=13) (mean age = 13.36 ± 2.55) performed an affective 2-back fMRI task with blocks of angry vs neutral faces (i.e., angry face condition) or happy vs neutral faces (i.e., happy face condition) before treatment and at follow-up, after 8-week treatment with second generation antipsychotics (SGAs) followed by 6 weeks of lamotrigine monotherapy. Results. At baseline, for the angry face condition, PBD, relative to HC, showed reduced activation in left ventrolateral prefrontal cortex (VLPFC) and right caudate; for the happy face condition, they showed increased activation in bilateral PFC, and right amygdala and middle temporal gyrus. Post treatment, PBD showed greater activation in right amygdala relative to HC, for both conditions. Patients, relative to HC, exhibited greater changes over time in right VLPFC and amygdala, left subgenual anterior cingulated cortex (ACC) and left caudate for the angry face condition, and in right middle temporal gyrus for the happy face condition. Conclusions. Pharmacotherapy resulted in symptom improvement and normalization of higher cortical emotional and cognitive regions in patients relative to HC, suggesting that VLPFC dysfunction may be state-specific in PBD. Amygdala was overactive in PBD, relative to HC, regardless of reduction in manic symptoms, and may be a trait marker of PBD. Post print version of article may differ from published version. The original publication is available at www.springerlink.com; DOI: 10.1007/s00213-011-2243-2. Thu, 10 Mar 2011 06:00:00 GMT http://hdl.handle.net/10027/7752 2011-03-10T06:00:00Z http://hdl.handle.net/10027/7362 Emotion Processing Influences Working Memory Circuits in Pediatric Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder Passarotti, Alessandra M.; Sweeney, John A.; Pavuluri, Mani N. Objective. We examined how working memory circuits are affected by face emotion processing in pediatric bipolar disorder (PBD) and attention-deficit hyperactivity disorder (ADHD). Methods. Twenty-three patients with bipolar disorder, 14 patients with ADHD and 19 healthy controls (HC) (mean age = 13.36 ± 2.55) underwent an affective 2-back fMRI task with blocks of happy, angry and neutral faces. Results. For angry vs neutral faces PBD patients, relative to ADHD patients, exhibited increased activation in subgenual anterior cingulate cortex (ACC) and orbitofrontal cortex, and reduced activation in dorsolateral prefrontal cortex (DLPFC) and premotor cortex. Also, relative to HC the PBD group showed no increased activation and reduced activation at the junction of DLPFC and ventrolateral prefrontal cortex (VLPFC). Relative to HC the ADHD patients exhibited greater activation in DLPFC and reduced activation in ventral and medial PFC, pregenual ACC, striatum and temporo-parietal regions. For happy vs neutral faces, relative to ADHD the PBD group exhibited greater activation in bilateral caudate, and increased activation relative to HC in DLPFC, striatal and parietal regions, an no reduced activation. The ADHD group, compared to HC, showed no reduced activation and increased activation in regions that were under-active for the angry vs neutral face condition. Conclusions. Relative to the ADHD group the PBD group exhibited greater deployment of the emotion processing circuitry and reduced deployment of working memory circuitry. Commonalities across PBD and ADHD patients, relative to HC, entailed cortico-subcortical activity that is reduced under negative emotional challenge, and increased under positive emotional challenge. Post print version of article may differ from published version. The definitive version is available through Elsevier at DOI: 10.1016/j.jaac.2010.07.009 Fri, 01 Oct 2010 05:00:00 GMT http://hdl.handle.net/10027/7362 2010-10-01T05:00:00Z