3D 7Li magnetic resonance imaging of brain lithium distribution in bipolar disorder.
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ABSTRACT:
SUBMITTER: Smith FE
PROVIDER: S-EPMC5955212 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A link between negative life stress and the onset of mood episodes in bipolar disorder (BD) has been established, but processes underlying such a link remain unclear. Growing evidence suggests that stress can negatively affect reward processing and related neurobiological substrates, indicating that a dysregulated reward system may provide a partial explanation. The aim of this study was to test the impact of stress on reward-related neural functioning in BD.Thirteen euthymic or mildly depressed individuals with BD and 15 controls performed a Monetary Incentive Delay (MID) task while undergoing functional magnetic resonance imaging during no-stress and stress (negative psychosocial stressor involving poor performance feedback and threat of monetary deductions) conditions.In hypothesis-driven region-of-interest analyses, a significant group-by-condition interaction emerged in the amygdala during reward anticipation. Relative to controls, while anticipating a potential reward, subjects with BD were characterized by amygdalar hyperactivation in the no-stress condition but hypoactivation during stress. Moreover, relative to controls, subjects with BD had significantly larger amygdala volumes. After controlling for structural differences, the effects of stress on amygdalar function remained, whereas groups no longer differed during the no-stress condition. During reward consumption, a group-by-condition interaction emerged in the putamen due to increased putamen activation in response to rewards in participants with BD during stress, but an opposite pattern in controls.Overall, findings highlight possible impairments in using reward-predicting cues to adaptively engage in goal-directed actions in BD, combined with stress-induced hypersensitivity to reward consumption. Potential clinical implications are discussed.
| S-EPMC5234857 | biostudies-other
Project description:BACKGROUND:Increased activity of the habenula has been implicated in the etiology of major depressive disorder (MDD), in which reductions in habenula volume are present after death. We conducted the first magnetic resonance imaging analysis of habenula volume in MDD and bipolar disorder (BD). METHODS:High-resolution images (resolution approximately .4 mm(3)) were acquired with a 3T scanner, and a pulse sequence was optimized for tissue contrast resolution. The habenula was manually segmented by one rater blind to diagnosis. Seventy-four healthy control subjects (HC) were compared with both medicated (lithium/divalproex, n = 15) and unmedicated, depressed BD (n = 22) patients; unmedicated, depressed MDD patients (n = 28); and unmedicated MDD patients in remission (n = 32). RESULTS:The unmedicated BD patients displayed significantly smaller absolute (p < .01) and normalized (p < .05) habenula volumes than the HC subjects. In post hoc assessments analyzing men and women separately, the currently-depressed women with MDD had smaller absolute (p < .05) habenula volumes than the HC women. None of the other psychiatric groups differed significantly from the HC group. CONCLUSIONS:We provide further evidence for the involvement of the habenula in affective illness but suggest that a reduction in volume might be more pronounced in unmedicated, depressed BD subjects and female currently depressed MDD subjects. The habenula plays major roles in the long-term modification of monoamine transmission and behavioral responses to stress and in the suppression of dopamine cell activity after the absence of an expected reward. A reduction in habenula volume might thus have functional consequences that contribute to the risk for developing affective disease.
| S-EPMC3030670 | biostudies-literature
Project description:BACKGROUND:Bipolar Disorder (BD) cannot be reliably distinguished from Major Depressive Disorder (MDD) until the first manic or hypomanic episode. Consequently, many patients with BD are treated with antidepressants without mood stabilizers, a strategy that is often ineffective and carries a risk of inducing a manic episode. We previously reported reduced cortical thickness in right precuneus, right caudal middle-frontal cortex and left inferior parietal cortex in BD compared with MDD. METHODS:This study extends our previous work by performing individual level classification of BD or MDD in an expanded, currently unmedicated, cohort using gray matter volume (GMV) based on Magnetic Resonance Imaging and a Support Vector Machine. All patients were in a Major Depressive Episode and a leave-two-out analysis was performed. RESULTS:Nineteen out of 26 BD subjects and 20 out of 26 MDD subjects were correctly identified, for a combined accuracy of 75%. The three brain regions contributing to the classification were higher GMV in bilateral supramarginal gyrus and occipital cortex indicating MDD, and higher GMV in right dorsolateral prefrontal cortex indicating BD. LIMITATIONS:This analysis included scans performed with two different headcoils and scan sequences, which limited the interpretability of results in an independent cohort analysis. CONCLUSIONS:Our results add to previously published data which suggest that regional gray matter volume should be investigated further as a clinical diagnostic tool to predict BD before the appearance of a manic or hypomanic episode.
| S-EPMC5805651 | biostudies-literature
Project description:Amplified MRI (aMRI) is a promising new technique that can visualize pulsatile brain tissue motion by amplifying sub-voxel motion in cine MRI data, but it lacks the ability to quantify the sub-voxel motion field in physical units. Here, we introduce a novel post-processing algorithm called 3D quantitative amplified MRI (3D q-aMRI). This algorithm enables the visualization and quantification of pulsatile brain motion. 3D q-aMRI was validated and optimized on a 3D digital phantom and was applied in vivo on healthy volunteers for its ability to accurately measure brain parenchyma and CSF voxel displacement. Simulation results show that 3D q-aMRI can accurately quantify sub-voxel motions in the order of 0.01 of a voxel size. The algorithm hyperparameters were optimized and tested on in vivo data. The repeatability and reproducibility of 3D q-aMRI were shown on six healthy volunteers. The voxel displacement field extracted by 3D q-aMRI is highly correlated with the displacement measurements estimated by phase contrast (PC) MRI. In addition, the voxel displacement profile through the cerebral aqueduct resembled the CSF flow profile reported in previous literature. Differences in brain motion was observed in patients with dementia compared with age-matched healthy controls. In summary, 3D q-aMRI is a promising new technique that can both visualize and quantify pulsatile brain motion. Its ability to accurately quantify sub-voxel motion in physical units holds potential for the assessment of pulsatile brain motion as well as the indirect assessment of CSF homeostasis. While further research is warranted, 3D q-aMRI may provide important diagnostic information for neurological disorders such as Alzheimer's disease.
| S-EPMC11352018 | biostudies-literature
Project description:BackgroundBipolar disorder (BPD) is a common mood disorder that is often goes misdiagnosed or undiagnosed. Recently, machine learning techniques have been combined with neuroimaging methods to aid in the diagnosis of BPD. However, most studies have focused on the construction of classifiers based on single-modality MRI. Hence, in this study, we aimed to construct a support vector machine (SVM) model using a combination of structural and functional MRI, which could be used to accurately identify patients with BPD.MethodsIn total, 44 patients with BPD and 36 healthy controls were enrolled in the study. Clinical evaluation and MRI scans were performed for each subject. Next, image pre-processing, VBM and ReHo analyses were performed. The ReHo values of each subject in the clusters showing significant differences were extracted. Further, LASSO approach was recruited to screen features. Based on selected features, the SVM model was established, and discriminant analysis was performed.ResultsAfter using the two-sample t-test with multiple comparisons, a total of 8 clusters were extracted from the data (VBM = 6; ReHo = 2). Next, we used both VBM and ReHo data to construct the new SVM classifier, which could effectively identify patients with BPD at an accuracy of 87.5% (95%CI: 72.5-95.3%), sensitivity of 86.4% (95%CI: 64.0-96.4%), and specificity of 88.9% (95%CI: 63.9-98.0%) in the test data (p = 0.0022).ConclusionsA combination of structural and functional MRI can be of added value in the construction of SVM classifiers to aid in the accurate identification of BPD in the clinic.
| S-EPMC7542439 | biostudies-literature
Project description:BackgroundBipolar disorder is one of the most severe mental disorders. Its chronic course is associated with high rates of morbidity and mortality, a high risk of suicide and poor social and occupational outcomes. Despite the great advances over the last decades in understanding mental disorders, the mechanisms underlying bipolar disorder at the neural network level still remain elusive. This has severe consequences for clinical practice, for instance by inadequate diagnoses or delayed treatments. The German research consortium BipoLife aims to shed light on the mechanisms underlying bipolar disorders. It was established in 2015 and incorporates ten university hospitals across Germany. Its research projects focus in particular on individuals at high risk of bipolar disorder, young patients in the early stages of the disease and patients with an unstable highly relapsing course and/or with acute suicidal ideation.MethodsFunctional and structural magnetic resonance imaging (MRI) data was acquired across nine sites within three different studies. Obtaining neuroimaging data in a multicenter setting requires among others the harmonization of the acquisition protocol, the standardization of paradigms and the implementation of regular quality control procedures. The present article outlines the MRI imaging protocols, the acquisition parameters, the imaging paradigms, the neuroimaging quality assessment procedures and the number of recruited subjects.DiscussionThe careful implementation of a MRI study protocol as well as the adherence to well-defined quality assessment procedures is one key benchmark in the evaluation of the overall quality of large-scale multicenter imaging studies. This article contributes to the BipoLife project by outlining the rationale and the design of the MRI study protocol. It helps to set the necessary standards for follow-up analyses and provides the technical details for an in-depth understanding of follow-up publications.
| S-EPMC8595454 | biostudies-literature
Project description:Lithium has been a drug for bipolar disorders (BD) for over 70 years; however, its usage has been limited by its narrow therapeutic window (between 0.6 and 1.2 mM). Understanding the cellular distribution of lithium ions (Li+) in patient cells will offer deep insight into this limitation, but selective imaging of Li+ in living cells under biomedically relevant concentration ranges has not been achieved. Herein, we report in vitro selection and development of a Li+-specific DNAzyme fluorescent sensor with >100-fold selectivity over other biorelevant metal ions. This sensor allows comparative Li+ visualization in HeLa cells, human neuronal progenitor cells (NPCs), and neurons derived from BD patients and healthy controls. Strikingly, we detected enhanced accumulation of Li+ in cells derived from BD patients compared with healthy controls in differentiated neurons but not NPCs. These results establish the DNAzyme-based sensor as a novel platform for biomedical research into BD and related areas using lithium drugs.
| S-EPMC8614110 | biostudies-literature
Project description:19F-magnetic resonance imaging (MRI) is a promising technique that may allow us to measure the concentration of exogenous fluorinated imaging probes quantitatively in vivo. Here, we describe the synthesis and characterisation of a novel geminal bisphosphonate (19F-BP) that contains chemically-equivalent fluorine atoms that show a single and narrow 19F resonance and a bisphosphonate group that may be used for labelling inorganic materials based in calcium phosphates and metal oxides. The potential of 19F-BP to provide contrast was analysed in vitro and in vivo using 19F-MRI. In vitro studies demonstrated the potential of 19F-BP as an MRI contrast agent in the millimolar concentration range with signal-to-noise ratios (SNR) comparable to previously reported fluorinated probes. The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of 19F-BP, showing uptake in the liver and in the bladder/urinary system areas. However, bone uptake was not observed. In addition, 19F-BP showed undesirable toxicity effects in mice that prevent further studies with this compound at the required concentrations for MRI contrast. This study highlights the importance of developing 19F MRI probes with the highest signal intensity achievable.
| S-EPMC4834630 | biostudies-literature
Project description:BackgroundImpaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects.MethodsOne-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters.ResultsThe BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition.ConclusionsThese results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment.
| S-EPMC5821068 | biostudies-literature
Project description:BackgroundPerformance during cognitive control functional magnetic resonance imaging (fMRI) tasks are associated with frontal lobe hypoactivation in patients with bipolar disorder, even while euthymic. Here, we study the structural underpinnings for this functional abnormality simultaneously with brain activation data.MethodsIn a sample of ninety adults (45 with inter-episode Bipolar I disorder and 45 healthy controls), we explored whether abnormal functional activation patterns in bipolar euthymic subjects during a Go-NoGo fMRI task are associated with regional deficits in cortical gray matter thickness in the same regions. Cross-sectional differences in fMRI activation were used to form a-priori hypotheses for region-of-interest cortical gray matter thickness analyses. fMRI BOLD to structural magnetic resonance imaging (sMRI) thickness correlations were conducted across the sample and within patients and controls separately.ResultsDuring response inhibition (NoGo minus Go), bipolar subjects showed significant hypoactivation and reduced thickness in the inferior frontal cortex (IFC), superior frontal gyrus and cingulate compared to controls. Cingulate hypoactivation corresponded with reduced regional thickness. A significant activation by disease state interaction was observed with thickness in left prefrontal areas.ConclusionsReduced cingulate fMRI activation is associated with reduced cortical thickness. In the left frontal lobe, a thinner cortex was associated with increased fMRI activation in patients, but showed a reverse trend in controls. These findings suggest that reduced activation in the IFC and cingulate during a response inhibition task may have an underlying structural etiology, which may explain task-related functional hypoactivation that persists even when patients are euthymic.
| S-EPMC5157843 | biostudies-literature