Decreased activation of the anterior cingulate in bipolar patients: an fMRI study

BACKGROUND: Previous neuroimaging investigations of patients with bipolar disorder have reported abnormalities of the frontal subcortical network. The role of the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) in bipolar disorder are not clear, although both regions have been shown to be components of a neural network which plays a critical role in the completion of tasks requiring self-monitoring and inhibition, functions often noted to be altered in bipolar patients. fMRI studies have helped clarify the role of specific subdivisions of the ACC and the DLPFC during the performance of cognitive challenges, including the Stroop color word test. To date, studies that have examined ACC function in bipolar patients have not differentiated subregions within this area, nor have they examined changes in these subregions in relation with DLPFC activation. METHODS: To help clarify the specific roles of these regions in bipolar patients, we examined stable patients and control subjects during performance of the Stroop test using BOLD fMRI techniques. We hypothesized that bipolar patients would demonstrate reduced activation of two subdivisions of the ACC (AAA and VOA), as well as altered activation of the DLPFC, during the interference condition. RESULTS: Results indicate that relative to controls, bipolar patients demonstrated significantly reduced signal intensity within the right AAA subdivision (p=0.011), which accompanied an increase in the DLPFC (p=0.049) during the task. LIMITATIONS: The study sample was somewhat small (11 patients, 10 controls) which limits the generalizability of the study findings, however, the patient sample consisted of well-diagnosed, stable, chronic individuals with bipolar disorder and the sample size provided enough power to detect between-group differences. CONCLUSIONS: These findings suggest differential processing strategies of bipolar patients and support the theory of altered frontal systems in these patients during the performance of cognitive tasks.     

Verbal fluency dysfunction in euthymic bipolar patients: a controlled study

OBJECTIVE: To study the executive functioning in euthymic bipolar patients in comparison to healthy controls and to examine the relationship between neuropsychological deficits and clinical variables. METHODS: Twenty-five euthymic bipolar patients and 31 controls underwent a battery of executive tasks including mental flexibility, inhibitory control and verbal fluency tests. RESULTS: There were no significant differences between bipolar patients and controls in relation to mental flexibility and inhibitory control. However, patients performed worse than controls on verbal fluency tests. Poor performances on the Stroop Test and the Hayling and Brixton Tests--part A were associated to lifetime occurrence of psychotic symptoms, prior number of episodes, and previous hospitalizations. CONCLUSIONS: In our study, only verbal fluency tests differentiated bipolar euthymic patients from healthy controls. Patients who showed deficits in information processing speed and inhibitory control had more episodes and hospitalizations and lifetime occurrence of psychotic symptoms.     

Investigation into activation of dysfunctional schemas in euthymic bipolar disorder following positive mood induction

OBJECTIVES.?There are dysfunctional cognitions that may be characteristic of bipolar disorder (BD), and which may be mood-state dependent. However, it has been found that such cognitions may be resilient to minor positive mood increase. The aim of this study is to investigate whether positive mood-induction procedure has the effect of altering the availability of dysfunctional schemas in a group of individuals with BD. DESIGN.?The sentence completion task was designed to assess the content of dysfunctional schemas: it was modified for use with positive mood-induction procedure in the current study so that more dysfunctional schematic models would lead to completion of sentence stems by negative constructs, whereas functional schematic models led to completion of sentence stems by positive constructs. METHODS.?Using the modified sentence completion task, 30 participants with remitted bipolar I disorder were compared with 30 individuals with no history of affective disorder. Results.?At baseline the bipolar group inserted significantly more dysfunctional completions than the control group. Following mood induction, the number of dysfunctional completions was reduced for both groups. The bipolar group still inserted significantly more dysfunctional completions relating to autonomy than the control group following mood induction. However, no significant group by time interactions were identified. CONCLUSIONS.?As predicted, participants' reports of dysfunctional attitudes reduced following the mood-induction procedure, although no difference was identified between the groups in terms of the size of this reduction. The bipolar group continued to insert significantly more dysfunctional completions for the factor of autonomy, suggesting that this group has more access to autonomy schemas, regardless of change in mood. This finding may have implications in terms of focus of therapy and relapse prevention work.     

A pilot study of positive mood induction in euthymic bipolar subjects compared with healthy controls

BACKGROUND: Demonstrating differences between euthymic bipolar subjects and healthy controls in response to positive (happy) mood induction may help elucidate how mania evolves. This pilot study evaluates the Go task in a reward paradigm as a method for inducing a happy mood state and compares the response of euthymic bipolar subjects and healthy controls. METHOD: The Sense of Hyperpositive Self Scale, the Tellegen positive and negative adjectives, the Global-Local task and a visual analogue scale for measuring positive affect were administered to 15 euthymic bipolar subjects and 19 age-and-sex-matched healthy control subjects before and after they had performed the Go task in a reward paradigm. RESULTS: Significant differences were found between subjects and controls on several measures at each time-point but there were no differences across the groups across time except for the visual analogue scales, where subjects had a more sustained duration in self-reported happiness compared with controls. CONCLUSIONS: This pilot study has shown that a positive affect can be induced in bipolar subjects and controls which can be demonstrated by changes in scores on several tasks. However, only the visual analogue scales showed a significant difference between cases and controls over time. Such tests may prove valuable in furthering understanding about the evolution of manic mood states.     

Cortical activation to indoor versus outdoor scenes: an fMRI study

Prior studies identify two cortical areas, posterior parahippocampal cortex and retrosplenial cortex, that preferentially activate to images of real-world scenes compared to images of other meaningful visual stimuli such as objects and faces. Behavioral and computational studies suggest that sub-categories of real-world scenes differ in their visual and semantic properties. It is presently unknown whether the cortical areas that have been implicated in scene analysis similarly activate differentially to behaviorally relevant scene sub-categories. To examine this issue, we directly compared cortical activation to indoor and outdoor scenes in an fMRI study with a large number of non-repeated images in each condition. Activation in posterior parahippocampal cortex, including parahippocampal place area, was significantly greater for indoor than outdoor scenes. In contrast, no such difference was observed in retrosplenial cortex, though this region preferentially activated to scenes over faces. These findings suggest differences in function in these two areas. The results are consistent with the view that posterior parahippocampal cortex is functional in processing local space.     

Reduced long distance gamma (28-48 Hz) coherence in euthymic patients with bipolar disorder

Background

EEG coherence represents the brain's functional connectivity. Synchronous neural gamma oscillations are critical for cortico-cortical communication and large-scale integration of distributed sets of neurons. We investigated long distance gamma (28-48 Hz) coherence in bipolar disorder.

Methods

Sensory evoked coherence (EC) and event related coherence (ERC) values for the gamma frequency band during simple light stimulation and visual odd-ball paradigm was assessed in 20 drug-free euthymic bipolar patients in comparison to healthy controls. Groups were compared for the coherence values of the left (F₃-T₃, F₃-TP₇, F₃-P₃, F₃-O₁) and right (F₄-T₄, F₄-TP₈, F₄-P₄, F₄-O₂) intra-hemispheric electrode pairs by means of a repeated measure analysis of variance (ANOVA) and t-tests.

Results

Patients showed significantly lower gamma coherence values in response to target stimuli than the healthy controls between left and right fronto-temporal, as well as between frontal and temporo-parietal electrode pairs. Coherence values for the non-target stimuli were significantly lower in the patients than the healthy controls between frontal and temporo-parietal regions on both right and left sides. EP coherence values did not differ significantly between the groups.

Limitations

A relatively small sample size is the major limitation of the study.

Conclusions

Bipolar patients present disturbance in functional long-range connectivity between the frontal and temporal as well as temporo-parietal brain structures during a cognitive paradigm requiring attention and immediate recall. The location of the connectivity disturbance corresponds to the underlying neurobiology of executive function, memory and attention impairments in bipolar disorder and raises the question of whether gamma coherence reduction may be a candidate biomarker for bipolar disorder.     

Event related oscillations in euthymic patients with bipolar disorder

Bipolar disorder involves dysfunction in gamma amino butyric acid (GABA)/glutamatergic systems and neural circuits that regulate cognitive processing. Valproate, a mood stabilizing anticonvulsant, modulates GABA/glutamate and shows neuroprotective effect. Electroencephalographic oscillatory activity assessment is an alternative brain imaging technique with high time resolution. It presents integrative brain functioning. We aimed to assess the oscillatory responses of patients with bipolar disorder in euthymic state of bipolar disorder and the changes after treatment with valproate. Event related potentials to visual odd-ball paradigm in 10 euthymic medication free, bipolar patients were measured before and after 6 weeks of valproate monotherapy and compared with sex- and age-matched healthy controls. Delta frequency bands, as representative of signal detection and decision-making, were obtained by digital filtering. At baseline, patients showed higher delta responses to target stimuli in all but significantly left frontal channels in comparison to controls. After 6 weeks of treatment, delta responses decreased significantly in central frontal (Fz) (p: 0.028), left frontal (F3) (p: 0.028), left (T3) (p: 0.015), right anterior (T4) (p: 0.011), and left posterior temporal (T5) (p: 0.011) channels compared to baseline and became no different to the controls, which did not differ between two assessments. The findings point to a diffuse increase in low frequency electrical activity which was prominent in the left frontal location in euthymic patients with bipolar disorder. Reduction of the electrical activity of the left frontal and bilateral anterior temporal areas with treatment may be through modulation of glutamatergic and GABAergic mechanisms and indicative of valproate's neuroprotective effect.     

Neuropsychological correlates of homocysteine levels in euthymic bipolar patients

BACKGROUND: We have previously reported that homocysteine levels are elevated in euthymic bipolar patients with functional deterioration. The current study was designed to extend this finding by examining the relationship between neuropsychological functioning and homocysteine levels in euthymic bipolar patients. METHODS: Fifty-seven euthymic bipolar outpatients were assessed for serum levels of homocysteine, folic acid, and vitamin B-12 and administered a battery of neuropsychological tests. RESULTS: We found that male bipolar subjects showed higher average homocysteine levels than a comparison group of normal subjects, that poorer functioning on a task of executive function (Wisconsin Card Sort) was related to higher homocysteine levels, and that folic acid or vitamin B-12 levels did not significantly affect neuropsychological functioning. LIMITATIONS: These results, while suggesting some relationship between higher homocysteine levels, bipolar illness, and impairment in cognitive function do not establish any causative effects. CONCLUSIONS: The findings of this study confirm that in euthymic bipolar patients, higher homocysteine levels are associated with poorer performance in some neuropsychological tests. Treatment trials will be required before it will be known if the putative decrements in the executive function of bipolar patients can be reversed, or at least retarded, if homocysteine levels are reduced (as, for example, by dietary addition of B vitamin supplements).     

Experience of subjective symptoms in euthymic patients with bipolar disorder

Bipolar patients often experience subjective symptoms even if they do not have active psychotic symptoms in their euthymic state. Most studies about subjective symptoms are conducted in schizophrenia, and there are few studies involving bipolar patients. We examined the nature of the subjective symptoms of bipolar patients in their euthymic state, and we also compared it to that of schizophrenia and normal control. Thirty bipolar patients, 25 patients with schizophrenia, and 21 normal control subjects were included. Subjective symptoms were assessed using the Korean version of the Frankfurter Beschwerde Fragebogen (K-FBF) and the Symptom Check List 90-R (SCL90-R). Euthymic state was confirmed by assessing objective psychopathology with the Positive and Negative Syndrome scale of Schizophrenia (PANSS), the Young Mania Rating Scale (YMRS), and the Montgomery Asberg Depression Rating Scale (MADRS). K-FBF score was significantly higher in bipolar patients than in normal controls, but similar to that in schizophrenia patients (F=5.86, p=0.004, R2=2033.6). In contrast, SCL90-R scores did not differ significantly among the three groups. Euthymic bipolar patients experience subjective symptoms that are more confined to cognitive domain. This finding supports the hypothesis that subtle cognitive impairments persists in euthymic bipolar patients.     

Age-related dedifferentiation of learning systems: an fMRI study of implicit and explicit learning

Abundant research finds that in young adults explicit learning (EL) is more dependent on the medial temporal lobes (MTL) whereas implicit learning (IL) is more dependent on the striatum. Using fMRI, we investigated age differences in each task and whether this differentiation is preserved in older adults. Results indicated that, while young recruited the MTL for EL and striatum for IL, both activations were significantly reduced in older adults. Additionally, results indicated that older adults recruited the MTL for IL, and this activation was significantly greater in older compared with young adults. A significant Task × Age interaction was found in both regions—with young preferentially recruiting the MTL for EL and striatum for IL, and older adults showing no preferential recruit for either task. Finally, young adults demonstrated significant negative correlations between activity in the striatum and MTL during both the EL and IL tasks. These correlations were attenuated in older adults. Taken together results support dedifferentiation in aging across memory systems.     

Brain activation disturbance for target detection in patients with mild cognitive impairment: an fMRI study

Functional brain imaging in mild cognitive impairment (MCI) reveals differences in activation of task-relevant brain areas between patients and age-matched healthy controls. However, some studies reported hyperactivation and others hypoactivation in MCI compared with controls. The inconsistencies may be explained by compensatory mechanisms due to high complexity of the applied tasks. The oddball task is a simple paradigm that is known to activate a widespread network in the brain, involving attentional and monitoring mechanisms. In the present study, we examined amnestic or amnestic multidomain MCI patients (n = 12) and healthy controls (n = 13) in an auditory oddball task. Participants had to respond to infrequent targets and inhibit response to infrequent novel-nontarget stimuli. Lower stimulus related activation was found in MCI patients compared with healthy controls in parts of the middle temporal gyrus, the temporal pole, regions along the superior temporal sulcus, in the left cuneus, the left supramarginal gyrus, the anterior cingulated cortex and in the left inferior and middle frontal gyrus. Activation for oddball stimuli is assumed to reflect an automatic reflexive engagement of many brain regions in response to potentially important changes in the environment as well as cognitive control to monitor responses. The mechanisms of attention and cognitive control may be severely impaired in MCI and thus, underlie the cognitive deficits of this clinical group.     

A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder

BACKGROUND: A number of studies have reported evidence of cognitive deficits in euthymic bipolar patients. Qualitative reviews of the literature have indicated impairments in executive functions and declarative memory are most consistently reported. However, not all primary studies conducted to date have had sufficient power to detect statistically significant differences and there have been few attempts to quantify the magnitude of impairments. This review aims to combine data from available studies to identify the profile of neuropsychological deficits in euthymic bipolar patients and quantify their magnitude. METHOD: Systematic literature review and meta-analysis. RESULTS: Large effect sizes (d>or=0.8) were noted for aspects of executive function (category fluency, mental manipulation) and verbal learning. Medium effect sizes (0.5相似文献   

Verbal episodic memory deficits in remitted bipolar patients: A combined behavioural and fMRI study

Background

Episodic memory deficits affect the majority of patients with bipolar disorder (BD).

Aims

The study investigates episodic memory performance through different approaches, including behavioural measures, physiological parameters, and the underlying functional activation patterns with functional neuroimaging (fMRI).

Methods

26 Remitted BD patients and a matched group of healthy controls underwent a verbal episodic memory test together with monitored autonomic response, psychopathological ratings and functional magnetic resonance imaging (fMRI) during the verbal episodic memory test.

Results

Compared to healthy controls, BD patients performed significantly worse during the episodic memory task. The results further indicate that verbal episodic memory deficits in BD are associated with abnormal functional activity patterns in frontal, occipital and limbic regions, and an increase in stress parameters.

Limitations

We aimed to minimise sample heterogeneity by setting clear criteria for remission, based on the scores of a depression (BDI II) and mania scale (BRMAS) and on the DSM IV criteria. However, our patients were not symptom-free and scored higher on BDI II scores than the control group.

Conclusions

The results are of interest for the treatment of cognitive symptoms in BD patients, as persistent cognitive impairment may hamper full rehabilitation.     

Navigation ability dependent neural activation in the human brain: an fMRI study

Visual-spatial navigation in familiar and unfamiliar environments is an essential requirement of daily life. Animal studies indicated the importance of the hippocampus for navigation. Neuroimaging studies demonstrated gender difference or strategies dependent difference of neural substrates for navigation. Using functional magnetic resonance imaging, we measured brain activity related to navigation in four groups of normal volunteers: good navigators (males and females) and poor navigators (males and females). In a whole group analysis, task related activity was noted in the hippocampus, parahippocampal gyrus, posterior cingulate cortex, precuneus, parietal association areas, and the visual association areas. In group comparisons, good navigators showed a stronger activation in the medial temporal area and precuneus than poor navigators. There was neither sex effect nor interaction effect between sex and navigation ability. The activity in the left medial temporal areas was positively correlated with task performance, whereas activity in the right parietal area was negatively correlated with task performance. Furthermore, the activity in the bilateral medial temporal areas was positively correlated with scores reflecting preferred navigation strategies, whereas activity in the bilateral superior parietal lobules was negatively correlated with them. Our data suggest that different brain activities related to navigation should reflect navigation skill and strategies.     

颞叶癫痫患者语言相关功能区的fMRI研究

目的：通过功能磁共振成像（fMRI）检查,了解颞叶癫痫（TLE）患者语言相关功能区的分布,初步探讨影响其不典型分布的因素,评价fMRI对癫痫患者进行无创语言功能定位检查的临床可操作性。方法：健康对照组和成人发病的左、右一侧性TLE患者组各6例,均为右利手。所有受试者进行动词产生任务fMRI检查,以按键记录受试者的反应。使用统计参数图2（statisticalparametricmap-ping2,SPM2）对fMRI的图像进行个体和组分析。结果：所有受试者顺利完成任务,fMRI的结果显示左侧组较对照组有明显差异,语言激活出现不典型化表现,优势侧有向右侧转移的趋势,其偏侧化指数（1ateralityindex,LI）与病程呈相对的负相关。结论：左侧TLE患者的语言功能区出现不典型分布,偏侧化程度可能与病程有关。fMRI检查评价语言功能相关区结果基本可靠,受试者耐受性好,具有一定的临床可操作性。     

Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives

BACKGROUND: Previous work suggests that impairments in executive function and verbal memory in particular may persist in euthymic bipolar patients and serve as an indicator of genetic risk (endophenotype). METHOD: A systematic review of the literature was undertaken. Effects sizes were extracted from selected papers and pooled using meta-analytical techniques. RESULTS: In bipolar patients, large effect sizes (d>0.8) were noted for executive functions (working memory, executive control, fluency) and verbal memory. Medium effect sizes (0.5相似文献   

Increased left prefrontal activation in patients with unipolar depression: an event-related, parametric, performance-controlled fMRI study

BACKGROUND: Executive deficits associated with frontal lobe dysfunction are prominent in depression. We applied a newly developed WM task to investigate the neural correlates of executive processes with functional magnetic resonance imaging (fMRI) at comparable performance levels analyzing correct trials only. METHODS: We studied 12 partially remitted, medicated inpatients meeting DSM-IV criteria for major depressive disorder and 17 healthy controls. We used a parametric version of a delayed match-to-sample WM task requiring manipulation of verbal material during a delay period in an event-related fMRI design. RESULTS: Depressed patients were generally slower and load-dependently less accurate than healthy controls. Patients showed significantly more activation of left dorsolateral prefrontal cortex with highest cognitive load. Additionally, they showed higher activation in ventromedial prefrontal cortex during the control condition. LIMITATIONS: The fact that patients were taking different antidepressant drugs could limit the explanatory power of the present results. CONCLUSIONS: Increased lateral prefrontal activation despite comparably successful performance - when only correct trials were analyzed - in patients with depression can be interpreted as evidence for compensatory recruitment of prefrontal cortical resources.