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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 -
Journal of Parkinson's Disease 2021The hallmark of Parkinson's disease is depletion of dopamine in the basal ganglia. Models of Parkinson's disease include dopamine as a contributor to disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The hallmark of Parkinson's disease is depletion of dopamine in the basal ganglia. Models of Parkinson's disease include dopamine as a contributor to disease progression. However, intraneuronal levels of dopamine have not been reported.
OBJECTIVE
Meta-analytic methods were utilized to determine intracellular dopamine levels in Parkinson's disease.
METHODS
A systematic review of the literature and frequentist meta-analyses were performed. Dopamine levels were scaled for cell and axon numbers as well as VMAT2 protein levels.
RESULTS
Reduced tissue dopamine, dopaminergic cell bodies and VMAT2 protein were confirmed. The ratio of Parkinson's to normal brain intracellular dopamine scaled for either cell or axon number, each with VMAT2 level in the caudate ranged from 1.49 to 1.87 (p = 0.51 and p = 0.12, respectively) and in the putamen from 0.75 to 4.61 (p = 0.40 and 0.001, respectively).
CONCLUSION
Free, intracellular dopamine levels are not reduced in Parkinson's disease compared to normals to a similar degree as are total tissue concentrations, supporting the relevance of modulating VMAT2, neuromelanin and/or dopamine synthesis as rational neuroprotective strategies.
Topics: Basal Ganglia; Dopamine; Dopaminergic Neurons; Humans; Parkinson Disease; Putamen
PubMed: 34024786
DOI: 10.3233/JPD-212715 -
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 -
Journal of Alzheimer's Disease : JAD 2022Affecting nearly half of the patients with Alzheimer's disease (AD), apathy is associated with higher morbidity and reduced quality of life. Basal ganglia and cortical... (Meta-Analysis)
Meta-Analysis
Cerebral Volumetric Correlates of Apathy in Alzheimer's Disease and Cognitively Normal Older Adults: Meta-Analysis, Label-Based Review, and Study of an Independent Cohort.
BACKGROUND
Affecting nearly half of the patients with Alzheimer's disease (AD), apathy is associated with higher morbidity and reduced quality of life. Basal ganglia and cortical atrophy have been implicated in apathy. However, the findings have varied across studies and left unclear whether subdomains of apathy may involve distinct neuroanatomical correlates.
OBJECTIVE
To identify neuroanatomical correlates of AD-associated apathy.
METHODS
We performed a meta-analysis and label-based review of the literature. Further, following published routines of voxel-based morphometry, we aimed to confirm the findings in an independent cohort of 19 patients with AD/mild cognitive impairment and 25 healthy controls assessed with the Apathy Evaluation Scale.
RESULTS
Meta-analysis of 167 AD and 56 healthy controls showed convergence toward smaller basal ganglia gray matter volume (GMV) in apathy. Label-based review showed anterior cingulate, putamen, insula, inferior frontal gyrus (IFG) and middle temporal gyrus (MTG) atrophy in AD apathy. In the independent cohort, with small-volume-correction, right putamen and MTG showed GMVs in negative correlation with Apathy Evaluation Scale total, behavioral, and emotional scores, and right IFG with emotional score (p < 0.05 family-wise error (FWE)-corrected), controlling for age, education, intracranial volume, and depression. With the Mini-Mental State Examination scores included as an additional covariate, the correlation of right putamen GMV with behavioral and emotional score, right MTG GMV with total and emotional score, and right IFG GMV with emotional score were significant.
CONCLUSION
The findings implicate putamen, MTG and IFG atrophy in AD associated apathy, potentially independent of cognitive impairment and depression, and suggest potentially distinct volumetric correlates of apathy.
Topics: Aged; Alzheimer Disease; Apathy; Atrophy; Basal Ganglia; Brain; Cognitive Dysfunction; Cohort Studies; Gray Matter; Gyrus Cinguli; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Prefrontal Cortex
PubMed: 34924392
DOI: 10.3233/JAD-215316 -
Frontiers in Psychiatry 2022Obsessive-compulsive disorder (OCD) is characterized by recurrent distressing thoughts and repetitive behaviors, or mental rituals performed to reduce anxiety. Recent...
INTRODUCTION
Obsessive-compulsive disorder (OCD) is characterized by recurrent distressing thoughts and repetitive behaviors, or mental rituals performed to reduce anxiety. Recent neurobiological techniques have been particularly convincing in suggesting that cortico-striatal-thalamic-cortico (CSTC) circuits, including orbitofrontal cortex (OFC) and striatum regions (caudate nucleus and putamen), are responsible for mediation of OCD symptoms. However, it is still unclear how these regions are affected by OCD treatments in adult patients. To address this yet open question, we conducted a systematic review of all studies examining neurobiological changes before and after first-line psychological OCD treatment, i.e., cognitive-behavioral therapy (CBT).
METHODS
Studies were included if they were conducted in adults with OCD and they assessed the neurobiological effects of CBT before and after treatment. Two databases were searched: PsycINFO and PubMed for the time frame up to May 2022.
RESULTS
We obtained 26 pre-post CBT treatment studies performed using different neurobiological techniques, namely functional magnetic resonance imaging (fMRI), Positron emission tomography (PET), regional cerebral blood flow (rCBF), 5-HT concentration, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), Electroencephalography (EEG). Neurobiological data show the following after CBT intervention: (i) reduced activations in OFC across fMRI, EEG, and rCBF; (ii) decreased activity in striatum regions across fMRI, rCBF, PET, and MRI; (iii) increased activations in cerebellum (CER) across fMRI and MRI; (iv) enhanced neurochemical concentrations in MRS studies in OFC, anterior cingulate cortex (ACC) and striatum regions. Most of these neurobiological changes are also accompanied by an improvement in symptom severity as assessed by a reduction in the Y-BOCS scores.
CONCLUSION
Cognitive-behavioral therapy seems to be able to restructure, modify, and transform the neurobiological component of OCD, in addition to the clinical symptoms. Nevertheless, further studies are necessary to frame the OCD spectrum in a dimensional way.
PubMed: 36569616
DOI: 10.3389/fpsyt.2022.1063116 -
AJNR. American Journal of Neuroradiology Aug 2016Polyglutamine expansion spinocerebellar ataxias are autosomal dominant slowly progressive neurodegenerative diseases with no current treatment. MR imaging is the...
BACKGROUND AND PURPOSE
Polyglutamine expansion spinocerebellar ataxias are autosomal dominant slowly progressive neurodegenerative diseases with no current treatment. MR imaging is the best-studied surrogate biomarker candidate for polyglutamine expansion spinocerebellar ataxias, though with conflicting results. We aimed to review quantitative central nervous system MR imaging technique findings in patients with polyglutamine expansion spinocerebellar ataxias and correlations with well-established clinical and molecular disease markers.
MATERIALS AND METHODS
We searched MEDLINE, LILACS, and Cochrane data bases of clinical trials between January 1995 and January 2016, for quantitative MR imaging volumetric approaches, MR spectroscopy, diffusion tensor imaging, or other quantitative techniques, comparing patients with polyglutamine expansion spinocerebellar ataxias (SCAs) with controls. Pertinent details for each study regarding participants, imaging methods, and results were extracted.
RESULTS
After reviewing the 706 results, 18 studies were suitable for inclusion: 2 studies in SCA1, 1 in SCA2, 15 in SCA3, 1 in SCA7, 1 in SCA1 and SCA6 presymptomatic carriers, and none in SCA17 and dentatorubropallidoluysian atrophy. Cerebellar hemispheres and vermis, whole brain stem, midbrain, pons, medulla oblongata, cervical spine, striatum, and thalamus presented significant atrophy in SCA3. The caudate, putamen and whole brain stem presented similar sensitivity to change compared with ataxia scales after 2 years of follow-up in a single prospective study in SCA3. MR spectroscopy and DTI showed abnormalities only in cross-sectional studies in SCA3. Results from single studies in other polyglutamine expansion spinocerebellar ataxias should be replicated in different cohorts.
CONCLUSIONS
Additional cross-sectional and prospective volumetric analysis, MR spectroscopy, and DTI studies are necessary in polyglutamine expansion spinocerebellar ataxias. The properties of preclinical disease biomarkers (presymptomatic) of MR imaging should be targeted in future studies.
Topics: Adult; Female; Humans; Male; Neuroimaging; Spinocerebellar Ataxias
PubMed: 27173364
DOI: 10.3174/ajnr.A4760 -
Frontiers in Neuroscience 2023Neuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study...
BACKGROUND
Neuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.
METHODS
Eight databases were systematically searched for literature from inception to October 2022 with the keywords "Functional dyspepsia" and "Neuroimaging." Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.
RESULTS
A total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.
CONCLUSION
The current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.
PubMed: 37250423
DOI: 10.3389/fnins.2023.1174287 -
PloS One 2020Iron is involved in many processes in the brain including, myelin generation, mitochondrial function, synthesis of ATP and DNA and the cycling of neurotransmitters....
Iron is involved in many processes in the brain including, myelin generation, mitochondrial function, synthesis of ATP and DNA and the cycling of neurotransmitters. Disruption of normal iron homeostasis can result in iron accumulation in the brain, which in turn can partake in interactions which amplify oxidative damage. The development of MRI techniques for quantifying brain iron has allowed for the characterisation of the impact that brain iron has on cognition and neurodegeneration. This review uses a systematic approach to collate and evaluate the current literature which explores the relationship between brain iron and cognition. The following databases were searched in keeping with a predetermined inclusion criterion: Embase Ovid, PubMed and PsychInfo (from inception to 31st March 2020). The included studies were assessed for study characteristics and quality and their results were extracted and summarised. This review identified 41 human studies of varying design, which statistically assessed the relationship between brain iron and cognition. The most consistently reported interactions were in the Caudate nuclei, where increasing iron correlated poorer memory and general cognitive performance in adulthood. There were also consistent reports of a correlation between increased Hippocampal and Thalamic iron and poorer memory performance, as well as, between iron in the Putamen and Globus Pallidus and general cognition. We conclude that there is consistent evidence that brain iron is detrimental to cognitive health, however, more longitudinal studies will be required to fully understand this relationship and to determine whether iron occurs as a primary cause or secondary effect of cognitive decline.
Topics: Adult; Aged; Aged, 80 and over; Brain; Child; Cognition; Female; Humans; Iron; Male; Middle Aged
PubMed: 33057378
DOI: 10.1371/journal.pone.0240697 -
Biological Psychiatry Oct 2014Psychostimulant medication, most commonly the catecholamine agonist methylphenidate, is the most effective treatment for attention-deficit/hyperactivity disorder (ADHD).... (Review)
Review
BACKGROUND
Psychostimulant medication, most commonly the catecholamine agonist methylphenidate, is the most effective treatment for attention-deficit/hyperactivity disorder (ADHD). However, relatively little is known on the mechanisms of action. Acute effects on brain function can elucidate underlying neurocognitive effects. We tested methylphenidate effects relative to placebo in functional magnetic resonance imaging (fMRI) during three disorder-relevant tasks in medication-naïve ADHD adolescents. In addition, we conducted a systematic review and meta-analysis of the fMRI findings of acute stimulant effects on ADHD brain function.
METHODS
The fMRI study compared 20 adolescents with ADHD under either placebo or methylphenidate in a randomized controlled trial while performing stop, working memory, and time discrimination tasks. The meta-analysis was conducted searching PubMed, ScienceDirect, Web of Knowledge, Google Scholar, and Scopus databases. Peak coordinates of clusters of significant effects of stimulant medication relative to placebo or off medication were extracted for each study.
RESULTS
The fMRI analysis showed that methylphenidate significantly enhanced activation in bilateral inferior frontal cortex (IFC)/insula during inhibition and time discrimination but had no effect on working memory networks. The meta-analysis, including 14 fMRI datasets and 212 children with ADHD, showed that stimulants most consistently enhanced right IFC/insula activation, which also remained for a subgroup analysis of methylphenidate effects alone. A more lenient threshold also revealed increased putamen activation.
CONCLUSIONS
Psychostimulants most consistently increase right IFC/insula activation, which are key areas of cognitive control and also the most replicated neurocognitive dysfunction in ADHD. These neurocognitive effects may underlie their positive clinical effects.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Child; Deep Brain Stimulation; Female; Humans; Image Processing, Computer-Assisted; Inhibition, Psychological; Magnetic Resonance Imaging; Male; Meta-Analysis as Topic; Methylphenidate; Neuropsychological Tests; Oxygen; Randomized Controlled Trials as Topic
PubMed: 24314347
DOI: 10.1016/j.biopsych.2013.10.016