Publications by authors named "Kamyar Keramatian"

17 Publications

  • Page 1 of 1

New Developments in the Use of Atypical Antipsychotics in the Treatment of Bipolar Disorder: a Systematic Review of Recent Randomized Controlled Trials.

Curr Psychiatry Rep 2021 May 8;23(7):39. Epub 2021 May 8.

Department of Psychiatry, Detwiller Pavilion, University of British Columbia, 2255 Wesbrook mall, Vancouver, BC, V6T 2A1, Canada.

Purpose Of Review: Atypical antipsychotics are increasingly used in the treatment of bipolar disorder (BD). This systematic review provides an overview of recently published randomized controlled trials (RCTs) on the efficacy and safety of atypical antipsychotics in BD.

Recent Findings: Several studies supported efficacy of quetiapine monotherapy in acute bipolar I (BDI) and bipolar II (BDII) depression. Moreover, quetiapine adjunctive therapy showed superior efficacy to placebo in treatment-resistant bipolar depression. Cariprazine 1.5 mg was effective in treating bipolar I depression. Aripiprazole 400 mg IM once monthly was effective in preventing manic episodes with minimal metabolic effects. In youth with BD, lurasidone was effective and well-tolerated for acute depression while asenapine showed efficacy in treating acute manic and mixed episodes. Recently published RCTs generally support the efficacy of atypical antipsychotics in different phases of BD. Future studies should focus on understudied populations including pediatric BD and geriatric BD and BDII, as well as a focus on cognitive functioning and quality of life measures.
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http://dx.doi.org/10.1007/s11920-021-01252-wDOI Listing
May 2021

Response to Commentary on "Grey Matter Abnormalities in First Episode Mania: A Systematic Review and Meta-analysis of Voxel-Based Morphometry Studies".

Bipolar Disord 2021 May 3. Epub 2021 May 3.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

We appreciate the comments by Sheng and colleagues on our manuscript titled "Grey matter abnormalities in first-episode mania: A systematic review and meta-analysis of voxel-based morphometry studies " and would like to take this opportunity to clarify our methodology and share the findings of additional analyses we have performed.
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http://dx.doi.org/10.1111/bdi.13091DOI Listing
May 2021

Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression: A Randomized Clinical Trial.

JAMA Netw Open 2021 Mar 1;4(3):e210963. Epub 2021 Mar 1.

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

Importance: Major depressive episodes in bipolar disorder are common and debilitating. Repetitive transcranial magnetic stimulation is well established in the treatment of major depressive disorder, and the intermittent theta burst stimulation (iTBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, iTBS has not been adequately studied in bipolar disorder and, therefore, its efficacy is uncertain.

Objective: To determine whether iTBS to the left dorsolateral prefrontal cortex (LDLPFC) is safe and efficacious in the treatment of acute bipolar depression.

Design, Setting, And Participants: This study was a double-blind, 4-week, randomized clinical trial of iTBS targeting the LDLPFC. Two Canadian academic centers recruited patients between 2016 and 2020. Adults with bipolar disorder type I or type II experiencing an acute major depressive episode were eligible if they had not benefited from a first-line treatment for acute bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments and were currently treated with a mood stabilizer, an atypical antipsychotic, or their combination. Seventy-one participants were assessed for eligibility, and 37 were randomized to daily sham iTBS or active iTBS using a random number sequence, stratified according to current pharmacotherapy. Data analysis was performed from April to September 2020.

Interventions: Four weeks of daily active iTBS (120% resting motor threshold) or sham iTBS to the LDLPFC. Nonresponders were eligible for 4 weeks of open-label iTBS.

Main Outcomes And Measures: The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. Secondary outcomes included clinical response, remission, and treatment-emergent mania or hypomania.

Results: The trial was terminated for futility after 37 participants (23 women [62%]; mean [SD] age, 43.86 [13.87] years; age range, 20-68 years) were randomized, 19 to sham iTBS and 18 to active iTBS. There were no significant differences in Montgomery-Asberg Depression Rating Scale score changes (least squares mean difference between groups, -1.36 [95% CI, -8.92 to 6.19; P = .91] in favor of sham iTBS), and rates of clinical response were low in both the double-blind phase (3 of 19 participants [15.8%] in the sham iTBS group and 3 of 18 participants [16.7%] in the active iTBS group) and open-label phase (5 of 21 participants [23.8%]). One active iTBS participant had a treatment emergent hypomania, and a second episode occurred during open-label treatment.

Conclusions And Relevance: iTBS targeting the LDLPFC is not efficacious in the treatment of acute bipolar depression in patients receiving antimanic or mood stabilizing agents. Additional research is required to understand how transcranial magnetic stimulation treatment protocols differ in efficacy between unipolar and bipolar depression.

Trial Registration: ClinicalTrials.gov Identifier: NCT02749006.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955269PMC
March 2021

Cognitive subgroups in first episode bipolar I disorder: Relation to clinical and brain volumetric variables.

Acta Psychiatr Scand 2021 02 28;143(2):151-161. Epub 2020 Nov 28.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Objective: Distinct cognitive subgroups are seen in patients with long duration bipolar I disorder (BDI), possibly reflective of underlying pathophysiological differences. It is unknown whether such cognitive heterogeneity is present at illness onset. We applied latent class analysis (LCA) to cognitive test scores in first episode BDI patients. Exploratory analysis elucidated whether impaired subgroups were characterized by 'early neurodevelopmental' (low premorbid IQ and intracranial volume) versus 'later neurodevelopmental' (decline from premorbid to current IQ, changes in relative grey (GM)/white (WM) matter volumes) pathology.

Methods: Recently recovered first manic episode BDI patients (n = 91) and healthy controls (HC, n = 63) comprised the study sample. LCA identified subgroups based on processing speed, verbal memory, non-verbal memory, executive functioning, attention and working memory scores. Subgroups were compared amongst each other and HC on premorbid/current IQ, intracranial (ICV), total brain and regional volumes.

Results: Three cognitive subgroups emerged: (i) globally impaired (GI, n = 31), scoring 0.5-1 SD below demographically corrected norms across domains, (ii) selectively impaired (SI, n = 47), with predominant processing speed deficits and (iii) high performing (HP, n = 13), with above-average cognitive performance. GI patients showed a 'later neurodevelopmental' pattern, with normal ICV, significant decline from premorbid to current IQ, higher total GM and lower total WM (with respect to total brain volume) versus SI and HC (p = 0.003). GI patients had higher left frontal pole GM versus HC (p < 0.05, FWE corrected).

Conclusions: A globally impaired patient subgroup is identifiable in first episode BDI, possibly characterized by unique neurodevelopmental pathologic processes proximal to illness onset.
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http://dx.doi.org/10.1111/acps.13245DOI Listing
February 2021

Grey matter abnormalities in first-episode mania: A systematic review and meta-analysis of voxel-based morphometry studies.

Bipolar Disord 2020 Sep 22. Epub 2020 Sep 22.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Objectives: It has been proposed that different stages of bipolar disorder may be underpinned by distinct neurobiological substrates. However, structural neuroimaging studies in early stages of the illness are limited by small sample sizes yielding inconsistent findings. The purpose of this systematic review and meta-analysis, therefore, was to identify regional grey matter volume (GMV) changes that are consistently associated with first episode of mania (FEM).

Methods: Following PRISMA guidelines, we conducted a systematic search of the literature to identify Voxel-Based Morphometry (VBM) studies in FEM patients compared with healthy individuals. We then conducted a voxel-wise meta-analysis using Seed-based d-Mapping technique. Finally, we performed univariate meta-regression analyses to explore the potential effects of moderator variables including age, gender, and percentage of lithium users on GMV alterations.

Results: We identified 15 VBM studies and included 12 studies in the meta-analysis. Four studies found no regional differences in GM volumes while other 11 studies reported volume changes in frontal and temporal regions as well as anterior cingulate cortex (ACC), cerebellum and basal ganglia. The meta-analysis revealed a single cluster of GMV reduction in bilateral pregenual ACC in patients with FEM compared to healthy individuals (P < .001). The Egger's test showed no evidence of publication bias at peak voxel level (P = .447). Meta-regression analyses revealed no significant effects of moderators evaluated.

Conclusions: Structural brain changes are evident in the early stages of bipolar disorder. GMV reduction in bilateral pregenual ACC is the most consistent finding in VBM studies of FEM.
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http://dx.doi.org/10.1111/bdi.12995DOI Listing
September 2020

Preservation of Gray Matter Volume in Early Stage of Bipolar Disorder: A Case for Early Intervention: Préservation du volume de matière grise au stade précoce du trouble bipolaire: un cas pour intervention précoce.

Can J Psychiatry 2021 Feb 18;66(2):139-146. Epub 2020 May 18.

Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.

Objective: It has been proposed that different stages of the bipolar disorder might have distinct neurobiological changes. However, the evidence for this has not been consistent, as the studies in early stages of the illness are limited by small sample sizes. The purpose of this study was to investigate the gray matter volume changes in bipolar patients who recently recovered from their first episode of mania (FEM).

Methods: Using a whole-brain voxel-based analysis, we compared the regional gray matter volumes of 61 bipolar patients who have recovered from their FEM in the past 3 months with 43 age- and gender-matched healthy participants. We also performed a series of subgroup analyses to determine the effects of hospitalization during the FEM, history of depressive episodes, and exposure to lithium.

Results: No statistically significant difference was found between gray matter volumes of FEM patients and healthy participants, even at a more liberal threshold ( < 0.001, uncorrected for multiple comparisons). Voxel-based subgroup analyses did not reveal significant gray matter differences except for a trend toward decreased gray matter volume in left lateral occipital cortex ( < 0.001, uncorrected) in patients with a previous history of depression.

Conclusion: This study represents the largest structural neuroimaging investigation of FEM published to date. Early stage of bipolar disorder was not found to be associated with significant gray matter volume changes. Our findings suggest that there might be a window of opportunity for early intervention strategies to prevent or delay neuroprogression in bipolar disorder.
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http://dx.doi.org/10.1177/0706743720927827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918870PMC
February 2021

Treatment of Mixed Features in Bipolar Disorder: an Updated View.

Curr Psychiatry Rep 2020 02 6;22(3):15. Epub 2020 Feb 6.

Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada.

Purpose Of Review: Mixed presentations in bipolar disorder have long posed clinical and nosological challenges. The DSM-5 mixed features specifier was developed to provide a more flexible and clinically relevant definition of mixed presentations compared with narrowly defined DSM-IV mixed episodes. However, there is little guidance on treating such presentations. Here, we summarize the evidence for biological treatments of DSM-5 and similarly defined mixed features (MFs).

Recent Findings: The literature on treating MFs is almost exclusively based on post hoc analyses. Within this limited evidence base is preliminary positive data for aripiprazole, asenapine, cariprazine, olanzapine, risperidone, and ziprasidone in treating acute mania with MFs, and cariprazine, lurasidone, olanzapine, and ziprasidone for depressive symptoms in depression with MFs. Divalproex may also be efficacious for acute mania with MFs. The few extant maintenance studies suggest that divalproex and olanzapine may have long-term efficacy in those with index MFs or for the prevention of MFs, respectively. The existing evidence suggests that clinicians consider atypical antipsychotics and divalproex for treating acute mixed presentations. However, adequately powered treatment trials-and studies of maintenance and neurostimulation therapies-are needed. Additionally, data-driven techniques to identify relevant symptom clusters may help improve our conceptualization of mixed presentations.
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http://dx.doi.org/10.1007/s11920-020-1137-6DOI Listing
February 2020

Lithium vs valproate in the maintenance treatment of bipolar I disorder: A post- hoc analysis of a randomized double-blind placebo-controlled trial.

Aust N Z J Psychiatry 2020 03 17;54(3):298-307. Epub 2019 Dec 17.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Objective: Lithium and valproate are commonly used either in monotherapy or in combination with atypical antipsychotics in maintenance treatment of bipolar I disorder; however, their comparative efficacy is not well understood. This study aimed to compare the efficacy of valproate and lithium on mood stability either in monotherapy or in combination with atypical antipsychotics.

Methods: We performed a post hoc analysis using data from a 52-week randomized double-blind, placebo-controlled trial, that recruited 159 patients with recently remitted mania during treatment with lithium or valproate and adjunctive atypical antipsychotic therapy. Patients were randomized to discontinue adjunctive atypical antipsychotic at 0, 24 or 52 weeks.

Results: No significant differences in efficacy were observed between valproate and lithium (hazard ratio: 0.99; 95% confidence interval: [0.66, 1.48]) in time to any mood event. Valproate with 24 weeks of atypical antipsychotic was significantly superior to valproate monotherapy in preventing any mood relapse (hazard ratio: 0.46; 95% confidence interval: [0.22, 0.97]) while lithium with 24 weeks of atypical antipsychotic was superior to lithium monotherapy in preventing mania (hazard ratio: 0.27; 95% confidence interval: [0.09, 0.85]) but not depression.

Conclusion: Overall, this study did not find significant differences in efficacy between the two mood-stabilizing agents when used as monotherapy or in combination with atypical antipsychotics. However, study design and small sample size might have precluded from detecting an effect if true difference in efficacy existed. Further head-to-head investigations with stratified designs are needed to evaluate maintenance therapies.
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http://dx.doi.org/10.1177/0004867419894067DOI Listing
March 2020

Cannabidiol as a Treatment for Mood Disorders: A Systematic Review.

Can J Psychiatry 2020 04 13;65(4):213-227. Epub 2019 Dec 13.

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1177/0706743719895195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385425PMC
April 2020

Cariprazine in the treatment of Bipolar Disorder: A systematic review and meta-analysis.

Bipolar Disord 2020 06 19;22(4):360-371. Epub 2019 Nov 19.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Objectives: Cariprazine is a partial agonist at D2/D3 receptors that has been approved for the treatment of mania associated with bipolar disorder (BD). This meta-analysis aimed to assess the efficacy and tolerability of cariprazine in the treatment of BD.

Methods: Randomized controlled trials investigating the efficacy of cariprazine in BD were included. Of the 391 studies yielded by search, 7 were included. The PRISMA protocol was followed and a set of analyses involving random-effects model with restricted maximum-likelihood estimator were used to synthesize effect sizes.

Results: Cariprazine was associated with a moderate and significant reduction of manic symptoms based on YMRS change scores (SMD: -0.52; 95%CI: -0.82 to -0.21; P = .018). Cariprazine resulted in significantly higher remission (OR: 2.05; 95%CI: 1.61-2.61; P = .006) and response rates (OR: 2.31; 95%CI: 1.35-3.95; P = .021) for manic and mixed episodes compared with placebo. Both cariprazine 1.5 mg and 3 mg doses were associated with small but significant reduction in depressive symptoms assessed with MADRS scores (SMD: -0.26, 95%CI: -0.49 to -0.02; P = .040) (SMD: -0.21, 95%CI: -0.41 to -0.01; P = .045), respectively. Cariprazine was significantly associated with the development of adverse effects but not with dropouts due to these adverse effects, when compared to placebo.

Conclusion: Cariprazine appears to be safe and efficacious in the treatment of acute mania and mixed episodes associated with BD. Cariprazine at doses of 1.5-3 mg/day is efficacious in acute bipolar depression but the effect sizes were smaller. Controlled studies evaluating its efficacy for prophylaxis are needed.
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http://dx.doi.org/10.1111/bdi.12850DOI Listing
June 2020

Long-Acting Injectable Second-Generation/Atypical Antipsychotics for the Management of Bipolar Disorder: A Systematic Review.

CNS Drugs 2019 05;33(5):431-456

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Background: Non-adherence to medications is a major determinant of poor outcome in bipolar disorder. Second-generation long-acting injectable (LAI) antipsychotics help ensure medication adherence which in turn can lead to more favourable outcomes. However, the role of these medications in bipolar disorder is not well established.

Objective: We sought to review available evidence relating to the efficacy and safety of using second-generation LAI antipsychotics in bipolar disorder.

Methods: PRISMA guidelines were followed to systematically review all clinical studies that reported on the efficacy and safety of second-generation LAI antipsychotics in patients with bipolar disorder. We searched Ovid Medline, PsycINFO, and Cochrane Central Register of Controlled Trials from inception to November 2018.

Results: Of 459 identified citations, 53 studies were fully evaluated and 37 met our inclusion criteria. Overall, second-generation LAI antipsychotics were found to be well tolerated and effective for treatment of manic symptoms and preventing mood recurrences in adults with bipolar disorder. However, we found disparity in the evidence available for individual agents. While several randomized controlled trials (RCTs) reported on the use of risperidone LAI in bipolar disorder, we found only one RCT on the use of aripiprazole LAI, and none for use of paliperidone palmitate or olanzapine pamoate (evidence for the former is limited to one observational study and one case series, and for the latter to a single case report). Studies in children and adolescents were restricted to case reports and small open-label studies.

Conclusion: Second-generation LAI antipsychotics, particularly risperidone and aripiprazole LAI, may be a safe and effective alternative to oral medications in the management of bipolar disorder.
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http://dx.doi.org/10.1007/s40263-019-00629-zDOI Listing
May 2019

Structural brain changes in first episode mania with and without psychosis: Data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

World J Biol Psychiatry 2018 8;19(sup2):S30-S40. Epub 2016 Dec 8.

a Department of Psychiatry , University of British Columbia , Vancouver , BC , Canada.

Objectives: The neurobiological underpinnings of bipolar I disorder are not yet understood. Previous structural neuroimaging studies of bipolar disorder have produced rather conflicting results. We hypothesise that clinical sub-phenotypes of bipolar I disorder defined by their psychotic symptoms, especially those with mood-incongruent psychotic features, may have more extensive structural brain abnormalities.

Methods: We investigated structural brain alterations in patients with first-episode mania (n = 55) with mood-congruent (n = 16) and mood-incongruent (n = 32) psychotic features, as well as those without psychotic symptoms (n = 7), relative to healthy subjects (n = 56).

Results: Total intracranial volume was significantly reduced in patients with mood-incongruent psychosis compared to healthy subjects while cerebrospinal fluid (CSF) volume was significantly increased. Patients with mood-congruent psychosis showed significant reduction in total white matter volume and significant CSF volume increase. Patients with psychosis had significant volume reduction in anterior cingulate and medial prefrontal cortices. Relative to mood-congruent psychotic features, mood-incongruent psychotic features were associated with volume reduction in the left middle temporal gyrus, right inferior parietal gyrus, right fusiform gyrus, left middle orbitofrontal gyrus and cerebellum.

Conclusions: While preliminary, our findings suggest that the presence and type of psychosis in first-episode mania may be phenotypic markers of underlying biological variants of bipolar disorder.
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http://dx.doi.org/10.1080/15622975.2016.1249950DOI Listing
May 2019

Neuroprogression and episode recurrence in bipolar I disorder: A study of gray matter volume changes in first-episode mania and association with clinical outcome.

Bipolar Disord 2016 09;18(6):511-519

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Objectives: Bipolar I disorder (BD-I) is associated with gray matter volume (GMV) alterations in neural regions important for emotional regulation. Reductions found in patients with multiple episodes are not seen at illness onset, suggesting that changes occur with illness progression, although no prospective studies to date have examined this. In the present study, we assessed GMV at baseline and one year following a first manic episode, examining the impact of episode recurrence on the trajectory of change.

Methods: A total of 41 recently remitted first manic episode patients with BD-I and 25 healthy subjects (HS) underwent 3T magnetic resonance imaging at baseline and one year later. Using voxel-based morphometry, we compared GMV change between HS, patients who experienced a recurrence of a mood episode (BD ), and patients in sustained remission (BD ).

Results: The GMV change from baseline to one year did not differ significantly between HS and the full BD-I group or BD and HS. However, the BD group had greater GMV loss than HS in left frontal and bilateral temporal regions, and BD patients involving bilateral frontal, temporal and left parietal regions.

Conclusions: GMV change early in the course of BD-I is associated with clinical outcome, such that neuroprogression found in patients who experience a recurrence of a mood episode is not seen in those with sustained remission. These findings have important implications for the treatment of BD-I as they suggest that prevention of recurrence might minimize neuroprogression of the disease, possibly requiring a multipronged early intervention approach to achieve this goal.
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http://dx.doi.org/10.1111/bdi.12437DOI Listing
September 2016

Improved modulation of rostrolateral prefrontal cortex using real-time fMRI training and meta-cognitive awareness.

Neuroimage 2011 Apr 13;55(3):1298-305. Epub 2010 Dec 13.

Department of Psychology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Recent real-time fMRI (rt-fMRI) training studies have demonstrated that subjects can achieve improved control over localized brain regions by using real-time feedback about the level of fMRI signal in these regions. It has remained unknown, however, whether subjects can gain control over anterior prefrontal cortex (PFC) regions that support some of the most complex forms of human thought. In this study, we used rt-fMRI training to examine whether subjects can learn to regulate the rostrolateral prefrontal cortex (RLPFC), or the lateral part of the anterior PFC, by using a meta-cognitive awareness strategy. We show that individuals can achieve improved regulation over the level of fMRI signal in their RLPFC by turning attention towards or away from their own thoughts. The ability to achieve improved modulation was contingent on observing veridical real-time feedback about the level of RLPFC activity during training; a sham-feedback control group demonstrated no improvement in modulation ability and neither did control subjects who received no rt-fMRI feedback but underwent otherwise identical training. Prior to training, meta-cognitive awareness was associated with recruitment of anterior PFC subregions, including both RLPFC and medial PFC, as well as a number of other midline and posterior cortical regions. Following training, however, regulation improvement was specific to RLPFC and was not observed in other frontal, midline, or parietal cortical regions. These results demonstrate the feasibility of acquiring control over high-level prefrontal regions through rt-fMRI training and offer a novel view into the correspondence between observable neuroscientific measures and highly subjective mental states.
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http://dx.doi.org/10.1016/j.neuroimage.2010.12.016DOI Listing
April 2011

Prefrontal organization of cognitive control according to levels of abstraction.

Brain Res 2009 Aug 6;1286:94-105. Epub 2009 Jun 6.

Department of Psychology, University of British Columbia, Vancouver, BC, Canada V6T 1Z4.

The prefrontal cortex (PFC) plays a crucial role in cognitive control and higher mental functions by maintaining working memory representations of currently relevant information, thereby inducing a mindset that facilitates the processing of such information. Using fMRI, we examined how the human PFC implements mindsets for information at varying levels of abstraction. Subjects solved anagrams grouped into three kinds of blocks (concrete, moderately abstract, and highly abstract) according to the degree of abstraction of their solutions. Mindsets were induced by cuing subjects at the beginning of every block as to the degree of abstraction of solutions they should look for. Different levels of abstraction were matched for accuracy and reaction time, allowing us to examine the effects of varying abstraction in the absence of variations in cognitive complexity. Mindsets for concrete, moderately abstract, and highly abstract information were associated with stronger relative recruitment of ventrolateral, dorsolateral, and rostrolateral PFC regions, respectively, suggesting a functional topography whereby increasingly anterior regions are preferentially associated with representations of increasing abstraction. Rather than being a structural property of the neurons in different prefrontal subregions, this relative specialization may reflect one of the principles according to which lateral PFC adaptively codes and organizes task-relevant information.
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http://dx.doi.org/10.1016/j.brainres.2009.05.096DOI Listing
August 2009

Localizing the rostrolateral prefrontal cortex at the individual level.

Neuroimage 2007 Jul 25;36(4):1387-96. Epub 2007 Apr 25.

Department of Psychology, University of British Columbia, Canada.

The functions of the rostrolateral prefrontal cortex (RLPFC) have recently become the target of multiple theories and empirical investigations. This region can be loosely defined as the lateral portion of Brodmann area (BA) 10. One of the challenges in testing theories about RLPFC functions is the difficulty in defining its boundaries when formulating predictions for its recruitment. Here we present a procedure that goes beyond the currently available anatomical definitions to attempt a functional localization of RLPFC. A combination of functional and anatomical criteria was employed, consistent with other localizer procedures. Functional localization was performed by comparing a relational condition involving relational matching to a control condition involving feature matching. It was expected that within an anatomically defined BA10 region, this procedure would produce functional activations in the lateral but not the medial subregions. The task was administered in the course of a single 13-min fMRI session. Results showed remarkable consistency, with all subjects activating RLPFC and activations consistently localized in the lateral part of BA10. These results demonstrate the practical feasibility of localizing RLPFC using a short procedure and a combination of functional and anatomical criteria. Such localization presents with a number of potential advantages for testing theories of RLPFC functions, including improved anatomical precision of experimental predictions, as well as the possibility of reduction in the rate of false-negative findings across studies. In addition, the results provide further support for the previously proposed functional dissociation between lateral and medial BA10.
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http://dx.doi.org/10.1016/j.neuroimage.2007.04.032DOI Listing
July 2007

Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury.

Clin Neurol Neurosurg 2006 Sep 13;108(6):539-42. Epub 2005 Oct 13.

Department of Neurosurgery, Isfahan University of Medical Sciences, Isfahan, Iran.

Objective: Traumatic brain injury is one of the major causes of death and disability among young people. Methylphenidate, a neural stimulant and protective drug, which has been mainly used for childhood attention deficit/hyperactivity disorder, has shown some benefits in late psychosocial problems in patients with traumatic brain injury. Its effect on arousal and consciousness has been also revealed in the sub-acute phase of traumatic brain injury. We studied its effect on the acute phase of moderate and severe traumatic brain injury (TBI) in relation to the length of ICU and hospital admission.

Patients And Methods: Severely and moderately TBI patients (according to inclusion and exclusion criteria) were randomized to treatment and control groups. The treatment group received methylphenidate 0.3mg/kg per dose PO BID by the second day of admission until the time of discharge, and the control group received a placebo. Admission information and daily Glasgow Coma Scale (GCS) were recorded. Medical, surgical, and discharge plans for patients were determined by the attending physician, blinded to the study.

Results: Forty patients with severe TBI (GCS = 5-8) and 40 moderately TBI patients (GCS = 9-12) were randomly divided into treatment and control groups on the day of admission. In the severely TBI patients, both hospital and ICU length of stay, on average, were shorter in the treatment group compared with the control group. In the moderately TBI patients while ICU stay was shorter in the treatment group, there was no significant reduction of the period of hospitalization.

Conclusion: There were no significant differences between the treatment and control groups in terms of age, sex, post resuscitation GCS, or brain CT scan findings, in either severely or moderately TBI patients. Methylphenidate was associated with reductions in ICU and hospital length of stay by 23% in severely TBI patients (P = 0.06 for ICU and P = 0.029 for hospital stay time). However, in the moderately TBI patients who received methylphenidate, there was 26% fall (P = 0.05) only in ICU length of stay.
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http://dx.doi.org/10.1016/j.clineuro.2005.09.003DOI Listing
September 2006