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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 (WM) were immuno-stained with the disease-associated 5G4 anti-αSyn antibody. Following digital scanning and image processing, total 5G4-immunoreactive pathology (i.e., neuronal, neuritic, and glial) and GCIs were optically dissected for inclusion size and density measurement then evaluated applying a novel computer-based method using ImageJ. GCI size varied between cases and brain regions (p < 0.0001) 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 significantly higher density of all αSyn pathology in the cerebellar WM (p = 0.049). Some region-specific morphological 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 three distinct groups based on region-specific morphological 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 morphological variables between brain regions and cases highlight i) the importance of computer-based approaches to detect features not considered in the routine diagnostic practice, and ii) 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 -
Journal of Nuclear Medicine Technology Jun 2024Ethnic differences exist among patients with Parkinson disease (PD). PD is more common in the White than the African American population. This study aimed to explore...
Ethnic differences exist among patients with Parkinson disease (PD). PD is more common in the White than the African American population. This study aimed to explore whether differences exist in [I]ioflupane binding, which reflects dopamine transporter binding, between African American and White individuals. Medical charts were reviewed for patients who underwent [I]ioflupane SPECT imaging as part of routine practice in a single academic medical center. All images were visually graded as showing normal or abnormal presynaptic dopaminergic function (normal or abnormal scan status). Quantitative [I]ioflupane uptake as measured by the specific binding ratios in the right and left striata and their subregions (caudate nucleus and anterior and posterior putamen) and by bilateral putamen-to-caudate ratios were compared between African American and White patients using multiple linear regression adjusted for age, sex, and abnormal scan status. Additional models included an ethnicity-by-abnormal-scan-status interaction term to determine whether abnormal scan status was modulated by ethnicity effect. The percentage of patients with abnormal scan status was comparable between African American and White patients. Compared with White patients ( = 173), African American patients ( = 82) had statistically significantly higher uptake as measured by specific binding ratios in the right and left striata and some of their subregions (right and left caudate nuclei and right posterior putamen). Ethnicity-by-abnormal-scan-status interactions were not statistically supported for any models. We observed differences in [I]ioflupane binding between African American and White patients independent of presynaptic dopaminergic dysfunction status. Future studies are needed to examine whether and how ethnicity affects dopamine transporter binding activities and its clinical relevance.
Topics: Humans; Nortropanes; Male; Female; Black or African American; White People; Tomography, Emission-Computed, Single-Photon; Aged; Middle Aged; Neostriatum; Corpus Striatum; Parkinson Disease; Retrospective Studies
PubMed: 38839126
DOI: 10.2967/jnmt.123.265806 -
Cortex; a Journal Devoted To the Study... May 2024How to fairly allocate goods is a key issue of social decision-making. Extensive research demonstrates that people do not selfishly maximize their own benefits, but...
How to fairly allocate goods is a key issue of social decision-making. Extensive research demonstrates that people do not selfishly maximize their own benefits, but instead also consider how others are affected. However, most accounts of the psychological processes underlying fairness-related behavior implicitly assume that assessments of fairness are somewhat stable. In this paper, we present results of a novel task, the Re-Allocation Game, in which two players receive an allocation determined by the computer and, on half of the trials, one player has the subsequent possibility to change this allocation. Importantly, prior to the receipt of the allocation, players were shown either their respective financial situations, their respective performance on a previous simple task, or random information, while being scanned using functional neuroimaging. As expected, our results demonstrate when given the opportunity, participants allocated on average almost half the money to anonymous others. However, our findings further show that participants used the provided information in a dynamic manner, revealing the underlying principle based on which people re-allocate money - namely based on merit, need, or equality - switches dynamically. On the neural level, we identified activity in the right and left dorsolateral prefrontal cortices related to context-independent inequity and context-dependent fairness information respectively when viewing the computer-generated allocations. At the same time, activity in the temporoparietal and precuneus represented these different types of fairness-related information in adjacent and partially overlapping clusters. Finally, we observed that the activity pattern in the precuneus and putamen was most clearly related to participants' subsequent re-allocation decisions. Together, our findings suggest that participants judge an allocation as fair or unfair using a network associated with cognitive control and theory-of-mind, while dynamically switching between what might constitute a fair allocation in a particular context.
PubMed: 38838559
DOI: 10.1016/j.cortex.2024.03.015