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Research Square May 2024Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal syndrome for Parkinson's disease (PD) and related -synucleinopathies. We conducted a...
Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal syndrome for Parkinson's disease (PD) and related -synucleinopathies. We conducted a longitudinal imaging study of network changes in iRBD and their relationship to phenoconversion. Expression levels for the PD-related motor and cognitive networks (PDRP and PDCP) were measured at baseline, 2 and 4 years, along with dopamine transporter (DAT) binding. PDRP and PDCP expression increased over time, with higher values in the former network. While abnormal functional connections were identified initially within the PDRP, others bridging the two networks appeared later. A model based on the rates of PDRP progression and putamen dopamine loss predicted phenoconversion within 1.2 years in individuals with iRBD. In aggregate, the data suggest that maladaptive reorganization of brain networks takes place in iRBD years before phenoconversion. Network expression and DAT binding measures can be used together to assess phenoconversion risk in these individuals.
PubMed: 38853923
DOI: 10.21203/rs.3.rs-4427198/v1 -
Journal of Psychopharmacology (Oxford,... Jun 2024A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective...
BACKGROUND
A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective treatments.
AIMS
This study aimed to investigate the relationships of two proposed main pathophysiology of schizophrenia, altered prefrontal-striatal connectivity and the dopamine system, with cognitive impairment and their interactions.
METHODS
Thirty-three patients with schizophrenia and 27 healthy controls (HCs) who are right-handed and matched for age and sex were recruited. We evaluated their cognition, functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC)/middle frontal gyrus (MiFG) and striatum, and the availability of striatal dopamine transporter (DAT) using a cognitive battery investigating attention, memory, and executive function, resting-state functional magnetic resonance imaging with group independent component analysis and single-photon emission computed tomography with 99mTc-TRODAT.
RESULTS
Patients with schizophrenia exhibited poorer cognitive performance, reduced FC between DLPFC/MiFG and the caudate nucleus (CN) or putamen, decreased DAT availability in the left CN, and decreased right-left DAT asymmetry in the CN compared to HCs. In patients with schizophrenia, altered imaging markers are associated with cognitive impairments, especially the relationship between DLPFC/MiFG-putamen FC and attention and between DAT asymmetry in the CN and executive function.
CONCLUSIONS
This study is the first to demonstrate how prefrontal-striatal hypoconnectivity and altered striatal DAT markers are associated with different domains of cognitive impairment in schizophrenia. More research is needed to evaluate their complex relationships and potential therapeutic implications.
Topics: Humans; Male; Female; Schizophrenia; Adult; Cognitive Dysfunction; Magnetic Resonance Imaging; Tomography, Emission-Computed, Single-Photon; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Dopamine; Prefrontal Cortex; Dorsolateral Prefrontal Cortex; Case-Control Studies; Middle Aged; Executive Function; Neuropsychological Tests; Young Adult
PubMed: 38853592
DOI: 10.1177/02698811241257877 -
Modern Pathology : An Official Journal... Jun 2024Multiple system atrophy (MSA) is a neurodegenerative disorder with variable disease course and distinct constellations of clinical (cerebellar [MSA-C] or parkinsonism...
Multiple system atrophy (MSA) is a neurodegenerative disorder with variable disease course and distinct constellations of clinical (cerebellar [MSA-C] or parkinsonism [MSA-P]) and pathological phenotypes, suggestive of distinct α-synuclein (αSyn) strains. Neuropathologically, MSA is characterized by the accumulation of αSyn in oligodendrocytic glial cytoplasmic inclusions (GCI). Using a novel computer-based method, this study quantified the size of GCIs, density of all αSyn pathology, density of only the GCIs, and number of GCIs in MSA cases (n = 20). The putamen and cerebellar white matter were immunostained with the disease-associated 5G4 anti-αSyn antibody. Following digital scanning and image processing, total 5G4-immunoreactive pathology (ie, neuronal, neuritic, and glial) and GCIs were optically dissected for inclusion size and density measurement and then evaluated applying a novel computer-based method using ImageJ. GCI size varied between cases and brain regions (P < .0001), and heterogeneity in the density of all αSyn pathology including the density and number of GCIs were observed between regions and across cases, where MSA-C cases had a significantly higher density of all αSyn pathology in the cerebellar white matter (P = .049). Some region-specific morphologic variables inversely correlated with the age of onset and death, suggestive of an underlying aging-related cellular mechanism. Unsupervised K-means cluster analysis classified MSA cases into 3 distinct groups based on region-specific morphologic variables. In conclusion, we developed a novel computer-based method that is easily accessible, providing a first step to developing artificial intelligence-based evaluation strategies for large scale comparative studies. Our observations on the variability of morphologic variables between brain regions and cases highlight (1) the importance of computer-based approaches to detect features not considered in the routine diagnostic practice, and (2) novel aspects for the identification of previously unrecognized MSA subtypes that do not necessarily reflect the current clinical classification of MSA-C or MSA-P.
PubMed: 38852813
DOI: 10.1016/j.modpat.2024.100533 -
BMC Psychiatry Jun 2024Theoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to...
BACKGROUND
Theoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to identify the specific brain regions of the DMN that is impaired in patients with BD.
METHODS
A total of 56 patients with BD and 71 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Three commonly used functional indices, i.e., fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC), were utilized to identify the brain region showing abnormal spontaneous brain activity in patients with BD. Then, this region served as the seed region for resting-state functional connectivity (rsFC) analysis.
RESULTS
Compared to the HC group, the BD group showed reduced fALFF, ReHo, and DC values in the left precuneus. Moreover, patients exhibited decreased rsFCs within the left precuneus and between the left precuneus and the medial prefrontal cortex. Additionally, there was diminished negative connectivity between the left precuneus and the left putamen, extending to the left insula (putamen/insula). The abnormalities in DMN functional connectivity were confirmed through various analysis strategies.
CONCLUSIONS
Our findings provide convergent evidence for the abnormalities in the DMN, particularly located in the left precuneus. Decreased functional connectivity within the DMN and the reduced anticorrelation between the DMN and the salience network are found in patients with BD. These findings suggest that the DMN is a key aspect for understanding the neural basis of BD, and the altered functional patterns of DMN may be a potential candidate biomarker for diagnosis of BD.
Topics: Humans; Bipolar Disorder; Magnetic Resonance Imaging; Female; Male; Adult; Default Mode Network; Nerve Net; Parietal Lobe; Connectome; Prefrontal Cortex; Case-Control Studies; Young Adult; Middle Aged; Brain; Brain Mapping
PubMed: 38849793
DOI: 10.1186/s12888-024-05869-y -
NeuroImage Aug 2024Humans constantly make predictions and such predictions allow us to prepare for future events. Yet, such benefits may come with drawbacks as premature predictions may...
Humans constantly make predictions and such predictions allow us to prepare for future events. Yet, such benefits may come with drawbacks as premature predictions may potentially bias subsequent judgments. Here we examined how prediction influences our perceptual decisions and subsequent confidence judgments, on scenarios where the predictions were arbitrary and independent of the identity of the upcoming stimuli. We defined them as invalid and non-informative predictions. Behavioral results showed that, such non-informative predictions biased perceptual decisions in favor of the predicted choice, and such prediction-induced perceptual bias further increased the metacognitive efficiency. The functional MRI results showed that activities in the medial prefrontal cortex (mPFC) and subgenual anterior cingulate cortex (sgACC) encoded the response consistency between predictions and perceptual decisions. Activity in mPFC predicted the strength of this congruency bias across individuals. Moreover, the parametric encoding of confidence in putamen was modulated by prediction-choice consistency, such that activity in putamen was negatively correlated with confidence rating after inconsistent responses. These findings suggest that predictions, while made arbitrarily, orchestrate the neural representations of choice and confidence judgment.
Topics: Humans; Male; Magnetic Resonance Imaging; Female; Metacognition; Young Adult; Adult; Prefrontal Cortex; Brain Mapping; Judgment; Gyrus Cinguli; Choice Behavior
PubMed: 38848980
DOI: 10.1016/j.neuroimage.2024.120670 -
Behavioural Brain Research Jun 2024Parkinson's is the most common neurodegenerative disease after Alzheimer's. Motor findings in Parkinson's occur as a result of the degeneration of dopaminergic neurons... (Review)
Review
Parkinson's is the most common neurodegenerative disease after Alzheimer's. Motor findings in Parkinson's occur as a result of the degeneration of dopaminergic neurons starting in the substantia nigra pars compacta and ending in the putamen and caudate nucleus. Loss of neurons and the formation of inclusions called Lewy bodies in existing neurons are characteristic histopathological findings of Parkinson's. The disease primarily impairs the functional capacity of the person with cardinal findings such as tremor, bradykinesia, etc., as a result of the loss of dopaminergic neurons in the substantia nigra. Experimental animal models of Parkinson's have been used extensively in recent years to investigate the pathology of this disease. These models are generally based on systemic or local(intracerebral) administration of neurotoxins, which can replicate many features of Parkinson's mammals. The development of transgenic models in recent years has allowed us to learn more about the modeling of Parkinson's. Applying animal modeling, which shows the most human-like effects in studies, is extremely important. It has been demonstrated that oxidative stress increases in many neurodegenerative diseases such as Parkinson's and various age-related degenerative diseases in humans and that neurons are sensitive to it. In cases where oxidative stress increases and antioxidant systems are inadequate, natural molecules such as flavonoids and polyphenols can be used as a new antioxidant treatment to reduce neuronal reactive oxygen species and improve the neurodegenerative process. Therefore, in this article, we examined experimental animal modeling in Parkinson's disease and the effect of green chemistry approaches on Parkinson's disease.
PubMed: 38844056
DOI: 10.1016/j.bbr.2024.115092 -
Journal of Psychiatric Research May 2024Bipolar Disorder (BPD) and Schizophrenia (SCZ) are complex psychiatric disorders with shared symptomatology and genetic risk factors. Understanding the molecular...
Bipolar Disorder (BPD) and Schizophrenia (SCZ) are complex psychiatric disorders with shared symptomatology and genetic risk factors. Understanding the molecular mechanisms underlying these disorders is crucial for refining diagnostic criteria and guiding targeted treatments. In this study, publicly available RNA-seq data from post-mortem samples of the basal ganglia's striatum were analyzed using an integrative computational approach to identify differentially expressed (DE) transcripts associated with SCZ and BPD. The analysis aimed to reveal both shared and distinct genes and long non-coding RNAs (lncRNAs) and to construct competitive endogenous RNA (ceRNA) networks within the striatum. Furthermore, the functional implications of these identified transcripts are explored, alongside their presence in established databases such as BipEx and SCHEMA. A significant outcome of our analysis was the identification of 21 DEmRNAs and 1 DElncRNA shared between BPD and SCZ across the Caudate, Putamen, and Nucleus Accumbens. Another noteworthy finding was the identification of Hub nodes within the ceRNA networks that were linked to major psychosis. Particularly, MED19, HNRNPC, MAGED4B, KDM5A, GOLGA7, CHASERR, hsa-miR-4778-3p, hsa-miR-4739, and hsa-miR-4685-5p emerged as potential biomarkers. These findings shed light on the common and unique molecular signatures underlying BPD and SCZ, offering significant potential for the advancement of diagnostic and therapeutic strategies tailored to these psychiatric disorders.
PubMed: 38843579
DOI: 10.1016/j.jpsychires.2024.05.050 -
Journal of Behavioral Addictions Jun 2024Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive...
BACKGROUND
Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive whether ED is accompanied by similar brain alterations as seen in substance use disorders. Therefore, we investigated brain alterations in individuals with ED and inactive control participants.
METHODS
In this cross-sectional neuroimaging investigation, 29 individuals with ED as assessed with the Exercise Dependence Scale (EDS) and 28 inactive control participants (max one hour exercising per week) underwent structural and functional resting-state magnetic resonance imaging (MRI). Group differences were explored using voxel-based morphometry and functional connectivity analyses. Analyses were restricted to the striatum, amygdala, and inferior frontal gyrus (IFG). Exploratory analyses tested whether relationships between brain structure and function were differently related to EDS subscales among groups.
RESULTS
No structural differences were found between the two groups. However, right IFG and bilateral putamen volumes were differently related to the EDS subscales "time" and "tolerance", respectively, between the two groups. Resting-state functional connectivity was increased from right IFG to right superior parietal lobule in individuals with ED compared to inactive control participants. Furthermore, functional connectivity of the angular gyrus to the left IFG and bilateral caudate showed divergent relationships to the EDS subscale "tolerance" among groups.
DISCUSSION
The findings suggest that ED may be accompanied by alterations in cognition-related brain structures, but also functional changes that may drive compulsive habitual behaviour. Further prospective studies are needed to disentangle beneficial and detrimental brain effects of ED.
Topics: Humans; Male; Magnetic Resonance Imaging; Adult; Cross-Sectional Studies; Female; Exercise; Brain; Young Adult; Multimodal Imaging; Behavior, Addictive; Neuroimaging
PubMed: 38842943
DOI: 10.1556/2006.2024.00028 -
Journal of Neurology Jun 2024Parkinson's disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease...
BACKGROUND
Parkinson's disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease progression remain largely unknown.
METHODS
In this retrospective cohort study, we enrolled 113 patients who underwent F-FP-CIT PET scan twice. Given the negative exponential progression pattern of dopamine loss in PD, we applied the natural logarithm to the specific binding ratio (SBR) of two consecutive F-FP-CIT PET scans and conducted linear mixed model to calculate individual slope to define the progression rate of nigrostriatal degeneration. We investigated the clinical and dopamine transporter (DAT) availability patterns associated with the progression rate of dopamine depletion in each striatal sub-region.
RESULTS
More symmetric parkinsonism, the presence of dyslipidemia, lower K-MMSE total score, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the caudate nucleus. More symmetric parkinsonism and lower anteroposterior gradient of the mean putaminal SBR were associated with faster depletion of dopamine in the anterior putamen. Older age at onset, more symmetric parkinsonism, the presence of dyslipidemia, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the posterior putamen. Lower striatal mean SBR predicted the development of LID, while lower mean SBR in the caudate nuclei predicted the development of dementia.
DISCUSSION
Our results suggest that the evaluation of baseline clinical features and patterns of DAT availability can predict the progression of PD and its prognosis.
PubMed: 38839638
DOI: 10.1007/s00415-024-12477-z -
Journal of UOEH 2024A woman in her 30s who was being treated for a mental illness with several psychotropic drugs was admitted to the hospital after being found in a state of...
A woman in her 30s who was being treated for a mental illness with several psychotropic drugs was admitted to the hospital after being found in a state of unconsciousness and respiratory arrest at home. She was pronounced dead 12 hours after she was discovered. Her autopsy revealed symmetrical hemorrhagic necrosis in the putamen on both sides of her cerebrum. Although many drugs were detected in her blood, all of those other than dextromethorphan (DXM) were within or below the therapeutic range. Her blood DXM was 1.73 μg/ml at admission and 1.61 μg/ml at autopsy, which were within the toxic range or coma-to-death range. The cause of death was diagnosed as DXM poisoning. DXM can cause hallucinations and euphoria if taken in excess, but since it is available as an over-the-counter drug at general pharmacies, an increasing number of young people are overdosing on it, mistakenly believing it to be a safe drug with few side effects. We believe that further social measures against DXM are necessary in Japan, such as disseminating correct knowledge in society and regulating over-the-counter sales.
Topics: Humans; Dextromethorphan; Female; Autopsy; Adult; Fatal Outcome
PubMed: 38839290
DOI: 10.7888/juoeh.46.221