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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 -
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 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 -
Sleep Medicine Reviews Oct 2018The presence of polysomnography-confirmed REM sleep behavior disorder (RBD) is the stronger risk factor for having prodromal Parkinson disease (PD), followed by abnormal... (Meta-Analysis)
Meta-Analysis Review
The presence of polysomnography-confirmed REM sleep behavior disorder (RBD) is the stronger risk factor for having prodromal Parkinson disease (PD), followed by abnormal presynaptic dopaminergic radionuclide neuroimaging. Aim of the review is to conduct a meta-analysis of literature data regarding presynaptic dopaminergic neuroimaging in RBD. A literature search was conducted, resulting in 16 papers that met the inclusion criteria. Clinical and neuroimaging data were extracted. The studies are heterogeneous, especially for neuroimaging methodology. Two mathematical transformations were used to allow imaging data to be compared among studies. Tracer uptake progressively decreased from controls to idiopathic RBD and eventually PD patients with RBD at putamen level. Tracer uptake at caudate level overlapped between patients with idiopathic RBD and those with PD without RBD. These results support the hypothesis that idiopathic RBD patients are on the path to developing a synucleinopathy. The receiver operation characteristic analysis found good to excellent discrimination capability between all groups. Presynaptic dopaminergic neuroimaging may be a key feature in the stratification of subjects to be included in neuroprotective trials. However, literature data are heterogeneous. Multicentric, harmonized studies are needed to define the usefulness of presynaptic dopaminergic neuroimaging with the aim of testing neuroprotective trials for idiopathic RBD.
Topics: Dopamine; Humans; Neuroimaging; Parkinson Disease; Polysomnography; REM Sleep Behavior Disorder
PubMed: 29784534
DOI: 10.1016/j.smrv.2018.04.001 -
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 -
Frontiers in Psychiatry 2022Obesity is a multi-systemic disease with complex etiology. And consistent evidence indicated obesity or overweight subjects render brain structure changes. Increasing...
BACKGROUND
Obesity is a multi-systemic disease with complex etiology. And consistent evidence indicated obesity or overweight subjects render brain structure changes. Increasing evidence indicates these subjects have shown widespread structural brain gray matter volume (GMV) changes. However, results from other neuroimaging studies have been inconsistent. Consequently, the question remains whether body mass index (BMI), a gold standard to define obesity/overweight, is associated with brain structural changes.
METHODS
This study will apply an updated meta-analysis of voxel-based GMV studies to compare GMV changes in overweight and obese subjects. Online databases were used to build on relevant studies published before May 2022. The updated Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) explores GMV changes in individuals with overweight and obesity and further examines the correlation between GMV and obesity-related variables, specifically body mass index (BMI).
RESULTS
This research included fourteen studies and provided a whole-brain analysis of GMV distribution in overweight and obese individuals. It revealed lower GMV in brain regions, including the left putamen and right precentral gyrus, in individuals with overweight and obesity compared to lean controls. Further, meta-regression analyses revealed GMV in the left middle occipital gyrus was negatively correlated with the BMI of the whole sample.
CONCLUSION
GMV decreased was reported in reward circuit processing areas and sensorimotor processing areas of individuals with overweight and obesity diagnoses, suggesting an underlying structural basis for reward processing and sensorimotor processing dysregulation in overweight and obese subjects. Our results also suggest that GMV in occipital gyrus, a key region for food visual and gustatory encoding, is negatively associated with BMI. These results provide further evidence for the dysregulated reward circuit in individuals with overweight and obesity.
PubMed: 36226110
DOI: 10.3389/fpsyt.2022.955741 -
Biological Psychiatry. Cognitive... Jun 2018Patients with obsessive-compulsive disorder (OCD) experience aversive emotions in response to obsessions, motivating avoidance and compulsive behaviors. However, there... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with obsessive-compulsive disorder (OCD) experience aversive emotions in response to obsessions, motivating avoidance and compulsive behaviors. However, there is considerable ambiguity regarding the brain circuitry involved in emotional processing in OCD, especially whether activation is altered in the amygdala.
METHODS
We conducted a systematic literature review and performed a meta-analysis-seed-based d mapping-of 25 whole-brain neuroimaging studies (including 571 patients and 564 healthy control subjects) using functional magnetic resonance imaging or positron emission tomography, comparing brain activation of patients with OCD and healthy control subjects during presentation of emotionally valenced versus neutral stimuli. Meta-regressions were employed to investigate possible moderators.
RESULTS
Patients with OCD, compared with healthy control subjects, showed increased activation in the bilateral amygdala, right putamen, orbitofrontal cortex extending into the anterior cingulate and ventromedial prefrontal cortex, and middle temporal and left inferior occipital cortices during emotional processing. Right amygdala hyperactivation was most pronounced in unmedicated patients. Symptom severity was related to increased activation in the orbitofrontal and anterior cingulate cortices and precuneus. Greater comorbidity with mood and anxiety disorders was associated with higher activation in the right amygdala, putamen, and insula as well as with lower activation in the left amygdala and right ventromedial prefrontal cortex.
CONCLUSIONS
Patients with OCD show increased emotional processing-related activation in limbic, frontal, and temporal regions. Previous mixed evidence regarding the role of the amygdala in OCD has likely been influenced by patient characteristics (such as medication status) and low statistical power.
Topics: Amygdala; Brain; Compulsive Behavior; Emotions; Functional Neuroimaging; Humans; Magnetic Resonance Imaging; Obsessive-Compulsive Disorder
PubMed: 29550459
DOI: 10.1016/j.bpsc.2018.01.009