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NeuroImage. Clinical 2024Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice.
OBJECTIVE
We performed a systematic review and meta-analysis on the use of QSM in MS.
METHODS
Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively.
RESULTS
After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions.
CONCLUSIONS
We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Gray Matter; Brain
PubMed: 38582068
DOI: 10.1016/j.nicl.2024.103598 -
International Journal of Developmental... Jun 2024Grey matter, a crucial component of the brain, has been found altered in generalized anxiety disorder (GAD) of several voxel-based morphometry studies. The conclusive... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Grey matter, a crucial component of the brain, has been found altered in generalized anxiety disorder (GAD) of several voxel-based morphometry studies. The conclusive and consistent grey matter alterations in GAD have not been confirmed.
METHOD
Eleven voxel-based morphometry studies of GAD patients were included in the current systematic review and meta-analysis. The linear model of anxiety severity scores was applied to explore the relationship of grey matter alterations and anxiety severity. The subgroup analysis of adult GAD and adolescent GAD was also performed.
RESULTS
Significantly modest grey matter alterations in the left superior temporal gyrus of patients with GAD were found. The anxiety severity score was significantly correlated with grey matter alterations in the right insula, lenticular nucleus, putamen and striatum. The subgroup analysis of adult GAD and adolescent GAD all failed to show significant grey matter alterations. However, in the adult GAD subgroup, anxiety severity score was significantly correlated with grey matter alterations in the right insula.
CONCLUSION
GAD might have the modest grey matter alterations in the left superior temporal gyrus. Anxiety severity might be related to the grey matter alterations in the limbic regions, such as the right insula, lenticular nucleus, putamen and striatum. This kind of correlation might be related to the effects of adult GAD. Future studies with adequate sample sizes and sophisticated GAD categories will be needed.
Topics: Humans; Gray Matter; Anxiety Disorders; Magnetic Resonance Imaging; Brain; Adult; Image Processing, Computer-Assisted; Adolescent
PubMed: 38638086
DOI: 10.1002/jdn.10330 -
Brain and Behavior Dec 2023Posttraumatic stress disorder (PTSD) is a complex and heterogeneous mental health condition that can develop after exposure to a traumatic event. Clinical trials have... (Review)
Review
BACKGROUND
Posttraumatic stress disorder (PTSD) is a complex and heterogeneous mental health condition that can develop after exposure to a traumatic event. Clinical trials have used alternative pharmacological agents to treat PTSD, but their associated neural correlates remain unclear. The present systematic review aims to summarize the changes in brain function associated with the use of these alternative pharmacological agents in PTSD.
METHODS
Clinical trials using functional magnetic resonance imaging, either at rest or during the performance of tasks, were included if they compared the effects of alternative pharmacological agents between PTSD patients and either trauma-exposed controls or never-exposed healthy controls.
RESULTS
Sixteen studies were included, of which 11 used intranasal oxytocin, 2 used hydrocortisone, and 3 used delta-9-tetrahydrocannabinol (THC). Oxytocin administration was associated with the normalization of functional connectivity between the ventromedial prefrontal cortex and amygdala as well as enhanced the function of brain regions specifically involved in emotion processing (e.g., amygdala), working memory (e.g., dorsolateral prefrontal cortex), and reward (e.g., putamen). Hydrocortisone did not influence brain function at rest or during the performance of an autobiographical memory task, whereas THC was associated with the reduction of the amygdala and increased medial prefrontal cortex activation.
CONCLUSIONS
This systematic review identified preliminary evidence for normalizing brain function after the use of alternative pharmacological agents. Importantly, sex-specific differences were noted, in particular when using oxytocin, that will require further investigation.
Topics: Female; Humans; Male; Brain; Emotions; Hydrocortisone; Magnetic Resonance Imaging; Oxytocin; Stress Disorders, Post-Traumatic; Clinical Trials as Topic
PubMed: 37864378
DOI: 10.1002/brb3.3292 -
International Journal of Molecular... Apr 2022(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a... (Review)
Review
(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, PsycInfo, and ProQuest was performed. Only cross-sectional studies using H MRS techniques in participants with SAD and healthy controls (HCs) were selected. (3) Results: The search generated eight studies. The results indicated regional abnormalities in the 'fear neurocircuitry' in patients with SAD. The implicated regions included the anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), insula, occipital cortex (OC), as well as the subcortical regions, including the thalamus, caudate, and the putamen. (4) Conclusions: The evidence derived from eight studies suggests that possible pathophysiological mechanisms of SAD include impairments in the integrity and function of neurons and glial cells, including disturbances in energy metabolism, maintenance of phospholipid membranes, dysregulations of second messenger systems, and excitatory/inhibitory neurocircuitry. Conducting more cross-sectional studies with larger sample sizes is warranted given the limited evidence in this area of research.
Topics: Brain; Cross-Sectional Studies; Humans; Magnetic Resonance Imaging; Phobia, Social; Proton Magnetic Resonance Spectroscopy; Protons
PubMed: 35563145
DOI: 10.3390/ijms23094754 -
Journal of Personalized Medicine Jul 2023COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a... (Review)
Review
COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer OR structural OR ROI OR whole-brain OR hippocamp* OR amygd* OR "deep gray matter" OR "cortical thickness" OR caudate OR striatum OR accumbens OR putamen OR "regions of interest" OR subcortical)) OR (COVID-19 AND brain AND (voxel[ti] OR VBM[ti] OR magnetic[ti] OR resonance[ti] OR imaging[ti] OR neuroimaging[ti] OR neuroimage[ti] OR positron[ti] OR photon*[ti] OR PET[ti] OR SPET[ti] OR SPECT[ti] OR spectroscop*[ti] OR MRS[ti])), which produced 486 records and two additional records from other sources, of which 36 were found to be eligible. Alterations were identified and described and plotted against the ordinary PTSD imaging findings. Common elements were hypometabolism in the insula and caudate nucleus, reduced hippocampal volumes, and subarachnoid hemorrhages, while white matter hyperintensities were widespread in both PTSD and post-COVID-19 brain infection. The comparison partly supported our initial hypothesis. These data may contribute to further investigation of the effects of long COVID on brain structure and function.
PubMed: 37511753
DOI: 10.3390/jpm13071140 -
Progress in Neuro-psychopharmacology &... Mar 2022Abnormalities in spontaneous brain activity, measured with resting-state functional magnetic resonance imaging (rs-fMRI), may be key biomarkers for bipolar disorders....
OBJECTIVE
Abnormalities in spontaneous brain activity, measured with resting-state functional magnetic resonance imaging (rs-fMRI), may be key biomarkers for bipolar disorders. This systematic review compares rs-fMRI findings in people experiencing a bipolar depressive or (hypo)manic episode to bipolar euthymia and/or healthy participants.
METHODS
Medline, Web of Science and Embase were searched up until April 2021. Studies without control group, or including minors, neurological co-morbidities or mixed episodes, were excluded. Qualitative synthesis was used to report results and risk of bias was assessed using the National Heart, Lung and Blood Institute tool for case-control studies.
RESULTS
Seventy-one studies were included (3167 bipolar depressed/706 (hypo)manic). In bipolar depression, studies demonstrated default-mode (DMN) and frontoparietal network (FPN) dysfunction, altered baseline activity in the precuneus, insula, striatum, cingulate, frontal and temporal cortex, and disturbed regional homogeneity in parietal, temporal and pericentral areas. Functional connectivity was altered in thalamocortical circuits and between the cingulate cortex and precuneus. In (hypo)mania, studies reported altered functional connectivity in the amygdala, frontal and cingulate cortex. Finally, rs-fMRI disturbances in the insula and putamen correlate with depressive symptoms, cerebellar resting-state alterations could evolve with disease progression and altered amygdala connectivity might mediate lithium effects.
CONCLUSIONS
Our results suggest DMN and FPN dysfunction in bipolar depression, whereas local rs-fMRI alterations might differentiate mood states. Future studies should consider controlling rs-fMRI findings for potential clinical confounding factors such as medication. Considerable heterogeneity of methodology between studies limits conclusions. Standardised clinical reporting and consistent analysis approaches would increase coherence in this promising field.
Topics: Amygdala; Biomarkers; Bipolar Disorder; Brain; Default Mode Network; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Mania; Neostriatum; Parietal Lobe; Temporal Lobe
PubMed: 34736998
DOI: 10.1016/j.pnpbp.2021.110465 -
Frontiers in Neurology 2018Around 30% Parkinson's disease (PD) patients develop impulse control disorders (ICDs) to D dopamine agonists and, to a lesser extent, levodopa. We aim to investigate...
Around 30% Parkinson's disease (PD) patients develop impulse control disorders (ICDs) to D dopamine agonists and, to a lesser extent, levodopa. We aim to investigate striatal dopaminergic function in PD patients with and without ICD. PubMed, Science Direct, EBSCO, and ISI Web of Science databases were searched (from inception to March 7, 2018) to identify PET or SPECT studies reporting striatal dopaminergic function in PD patients with ICD (ICD+) compared to those without ICD (ICD-). Studies which included drug naïve patients, explored non-pharmacological procedures (e.g., deep brain stimulation), and those using brain blood perfusion or non-dopaminergic markers were excluded. Standardized mean difference (SDM) was used and random-effect models were applied. Separate meta-analyses were performed for dopamine transporter level, dopamine release, and dopamine receptors availability in the putamen, caudate, dorsal, and ventral striatum. A total of 238 studies were title and abstract screened, of which 19 full-texts were assessed. Nine studies (ICD+: = 117; ICD-: = 175 patients) were included in the analysis. ICD+ showed a significant reduction of dopamine transporter binding in the putamen (SDM = -0.46; 95% CI: -0.80, -0.11; = 2.61; = 0.009), caudate (SDM = -0.38; 95% CI: -0.73, -0.04; = 2.18; = 0.03) and dorsal striatum (SDM = -0.45; 95% CI: -0.77, -0.13; = 2.76; = 0.006), and increased dopamine release to reward-related stimuli/gambling tasks in the ventral striatum (SDM = -1.04; 95% CI: -1.73, -0.35; = 2.95; = 0.003). Dopamine receptors availability did not differ between groups. Heterogeneity was low for dopamine transporter in the dorsal striatum ( = 0%), putamen ( = 0%) and caudate ( = 0%), and pre-synaptic dopamine release in the dorsal ( = 0%) and ventral striatum ( = 0%); heterogeneity was high for dopamine transporter levels in the ventral striatum ( = 80%), and for dopamine receptors availability in the ventral ( = 89%) and dorsal ( = 86%) striatum, putamen ( = 93%), and caudate ( = 71%). ICD+ patients show lower dopaminergic transporter levels in the dorsal striatum and increased dopamine release in the ventral striatum when engaged in reward-related stimuli/gambling tasks. This dopaminergic imbalance might represent a biological substrate for ICD in PD. Adequately powered longitudinal studies with drug naïve patients are needed to understand whether these changes may represent biomarkers of premorbid vulnerability to ICD.
PubMed: 30568628
DOI: 10.3389/fneur.2018.01018 -
Sleep Medicine Reviews Aug 2021Sleep disturbances are commonly reported in patients with chronic liver disease (CLD). Changes in quality of sleep in patients with CLD could be related to multiple... (Meta-Analysis)
Meta-Analysis Review
Sleep disturbances are commonly reported in patients with chronic liver disease (CLD). Changes in quality of sleep in patients with CLD could be related to multiple factors viz., elevated levels of tryptophan, histamine, and increased turnover of dopamine in caudate-putamen and cingulate cortex. Also, iron metabolism disturbances are reported in patients with CLD. These changes may result in restless legs syndrome (RLS) that worsens sleep-quality. There have been reports suggesting an increased prevalence of RLS among patients with CLD. Literature was searched in PubMed, EMBASE, and Google Scholar. A total of twenty-two relevant articles were found. Out of these, nine studies have assessed the prevalence of RLS among patients with chronic liver disease or cirrhosis in the clinical population. Population prevalence reported from various studies was used to calculate odds ratio. Having included studies using various methods for diagnosis (clinical as well as questionnaires) pooled odds-ratio for the RLS was 8.62. It remains unaffected by study-method, gender, age, and geographical-area. However, studies using clinical diagnosis for RLS had lower odds compared to questionnaire based diagnosis. Studies varied with regards to diagnostic methods, age, gender, etiology, and severity of liver dysfunction. The severity and etiology of CLD and biochemical correlate of CLD were not found to be associated with RLS. Possible pathophysiological mechanisms are discussed for the occurrence of RLS in this population. In conclusion, the prevalence of RLS is higher among patients with CLD, however, the correlates are unknown.
Topics: Humans; Liver Diseases; Prevalence; Restless Legs Syndrome; Sleep Wake Disorders; Surveys and Questionnaires
PubMed: 33836477
DOI: 10.1016/j.smrv.2021.101463 -
Brain Research Aug 2020The progressive changes of brain structure in patients with Parkinson's disease (PD) remain controversial. To identify this controversy, a systematic review and... (Meta-Analysis)
Meta-Analysis
The progressive changes of brain structure in patients with Parkinson's disease (PD) remain controversial. To identify this controversy, a systematic review and meta-analysis of longitudinal magnetic resonance imaging studies in brain volume was performed. The percentage of volume change over time between patients with PD and healthy subjects of each brain region of interest was obtained. In total, 11 studies, comprising 833 cases (463 patients with PD and 370 healthy control subjects), were included for systematic review and meta-analysis. Ten brain regions were involved. Patients with PD in comparison with healthy controls showed significant progressive reductions in whole gray matter and caudate, putamen, accumbens, and amygdala volumes. Significant whole-brain atrophy from PD was also associated with cognitive dysfunction. The annual percentage of volume loss was -1.04% in whole-brain volume with cognitive decline, -1.16% in whole-brain volume in PD compared to PD with cognitive decline, -0.29% for whole gray matter, -0.62% for caudate, -0.97% for putamen, -3.55% for amygdala, and -5.40% for accumbens in patients with PD versus control subjects. Overall, our findings suggest that PD is related to progressive, regional brain atrophy, mainly affecting gray matter. However, due to existing confounding factors, the limited number of included studies, significant heterogeneity, and defective study design, the results should be interpreted with caution. Further confirmation is required by more studies with strict design, large samples, and unified paradigm.
Topics: Brain; Disease Progression; Humans; Magnetic Resonance Imaging; Parkinson Disease
PubMed: 32330518
DOI: 10.1016/j.brainres.2020.146847 -
Reviews in Endocrine & Metabolic... Aug 2022Obesity is the second most common cause of preventable morbidity worldwide. Resting-state functional magnetic resonance imaging (fMRI) has been used extensively to... (Review)
Review
Obesity is the second most common cause of preventable morbidity worldwide. Resting-state functional magnetic resonance imaging (fMRI) has been used extensively to characterise altered communication between brain regions in individuals with obesity, though findings from this research have not yet been systematically evaluated within the context of prominent neurobiological frameworks. This systematic review aggregated resting-state fMRI findings in individuals with obesity and evaluated the contribution of these findings to current neurobiological models. Findings were considered in relation to a triadic model of problematic eating, outlining disrupted communication between reward, inhibitory, and homeostatic systems. We identified a pattern of consistently increased orbitofrontal and decreased insula cortex resting-state functional connectivity in individuals with obesity in comparison to healthy weight controls. BOLD signal amplitude was also increased in people with obesity across studies, predominantly confined to subcortical regions, including the hippocampus, amygdala, and putamen. We posit that altered orbitofrontal cortex connectivity may be indicative of a shift in the valuation of food-based rewards and that dysfunctional insula connectivity likely contributes to altered homeostatic signal processing. Homeostatic violation signals in obesity may be maintained despite satiety, thereby 'hijacking' the executive system and promoting further food intake. Moving forward, we provide a roadmap for more reliable resting-state and task-based functional connectivity experiments, which must be reconciled within a common framework if we are to uncover the interplay between psychological and biological factors within current theoretical frameworks.
Topics: Brain; Brain Mapping; Humans; Magnetic Resonance Imaging; Obesity; Reward
PubMed: 34159504
DOI: 10.1007/s11154-021-09665-x