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MedRxiv : the Preprint Server For... Apr 2024Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has...
OBJECTIVE
Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has been thought of as a disorder of the basal ganglia, but newer results in idiopathic dystonia and lesion-induced dystonia in adults point to broader motor network dysfunction spanning the basal ganglia, cerebellum, premotor cortex, sensorimotor, and frontoparietal regions. It is unclear whether a similar network is shared between different etiologies of pediatric lesion-induced dystonia.
METHODS
Three cohorts of pediatric patients with lesion-induced dystonia were identified. The lesion etiologies included hypoxia, kernicterus, and stroke versus comparison subjects with acquired lesions not associated with dystonia. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with dystonia.
RESULTS
Multivariate lesion-symptom mapping showed that lesions of the putamen (stroke: r = 0.50, p <0.01; hypoxia, r = 0.64, p <0.001) and globus pallidus (kernicterus, r = 0.61, p <0.01) were associated with dystonia. Lesion network mapping using normative connectome data from healthy children demonstrated that these regional findings occurred within a common brain-wide network that involves the basal ganglia, anterior and medial cerebellum, and cortical regions that overlap the cingulo-opercular and somato-cognitive-action networks.
INTERPRETATION
We interpret these findings as novel evidence for a unified dystonia brain network that involves the somato-cognitive-action network, which is involved in higher order coordination of movement. Elucidation of this network gives insight into the functional origins of dystonia and provides novel targets to investigate for therapeutic intervention.
PubMed: 38645071
DOI: 10.1101/2024.04.06.24305421 -
Molecular Psychiatry Dec 2023Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs....
Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.
Topics: Humans; Schizophrenia; Depressive Disorder, Major; Bipolar Disorder; Female; Male; Magnetic Resonance Imaging; Adult; Neuroimaging; Brain; Autism Spectrum Disorder; Middle Aged; Mental Disorders; Organ Size
PubMed: 37537281
DOI: 10.1038/s41380-023-02141-9 -
Molecular Psychiatry Feb 2024Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited....
Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited. In this study, we capitalized on a large sample of patients to examine the neural correlates of PmD in depression. This study included 820 healthy participants and 699 patients with remitted (n = 402) or current (n = 297) depression. Patients were further categorized as having psychomotor retardation, agitation, or no PmD. We compared resting-state functional connectivity (ROI-to-ROI) between nodes of the cerebral motor network between the groups, including primary motor cortex, supplementary motor area, sensory cortex, superior parietal lobe, caudate, putamen, pallidum, thalamus, and cerebellum. Additionally, we examined network topology of the motor network using graph theory. Among the currently depressed 55% had PmD (15% agitation, 29% retardation, and 11% concurrent agitation and retardation), while 16% of the remitted patients had PmD (8% retardation and 8% agitation). When compared with controls, currently depressed patients with PmD showed higher thalamo-cortical and pallido-cortical connectivity, but no network topology alterations. Currently depressed patients with retardation only had higher thalamo-cortical connectivity, while those with agitation had predominant higher pallido-cortical connectivity. Currently depressed patients without PmD showed higher thalamo-cortical, pallido-cortical, and cortico-cortical connectivity, as well as altered network topology compared to healthy controls. Remitted patients with PmD showed no differences in single connections but altered network topology, while remitted patients without PmD did not differ from healthy controls in any measure. We found evidence for compensatory increased cortico-cortical resting-state functional connectivity that may prevent psychomotor disturbance in current depression, but may perturb network topology. Agitation and retardation show specific connectivity signatures. Motor network topology is slightly altered in remitted patients arguing for persistent changes in depression. These alterations in functional connectivity may be addressed with non-invasive brain stimulation.
Topics: Humans; Female; Male; Adult; Depressive Disorder, Major; Magnetic Resonance Imaging; Middle Aged; Psychomotor Disorders; Psychomotor Agitation; Brain; Depression; Neural Pathways; Motor Cortex; Brain Mapping; Nerve Net
PubMed: 38036604
DOI: 10.1038/s41380-023-02327-1 -
Schizophrenia Bulletin Sep 2023Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique...
BACKGROUND
Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique called quantitative susceptibility mapping (QSM) to study these regions in psychosis. QSM quantifies magnetic susceptibility in the brain, which is associated with iron concentrations. Since iron is a cofactor in dopamine pathways and co-localizes with inhibitory neurons, differences in QSM could reflect changes in these processes.
METHODS
We scanned 83 patients with first-episode psychosis and 64 healthy subjects. We reassessed 22 patients and 21 control subjects after 3 months. Mean susceptibility was measured in 6 deep-brain nuclei. Using linear mixed models, we analyzed the effect of case-control differences, region, age, gender, volume, framewise displacement (FD), treatment duration, dose, laterality, session, and psychotic symptoms on QSM.
RESULTS
Patients showed a significant susceptibility reduction in the putamen and globus pallidus externa (GPe). Patients also showed a significant R2* reduction in GPe. Age, gender, FD, session, group, and region are significant predictor variables for QSM. Dose, treatment duration, and volume were not predictor variables of QSM.
CONCLUSIONS
Reduction in QSM and R2* suggests a decreased iron concentration in the GPe of patients. Susceptibility reduction in putamen cannot be associated with iron changes. Since changes observed in putamen and GPe were not associated with symptoms, dose, and treatment duration, we hypothesize that susceptibility may be a trait marker rather than a state marker, but this must be verified with long-term studies.
Topics: Humans; Dopamine; Brain; Brain Mapping; Magnetic Resonance Imaging; Iron; Psychotic Disorders
PubMed: 37030007
DOI: 10.1093/schbul/sbad041 -
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 -
Head & Face Medicine Jun 2023This study compares the observation efficiency of brain gray matter nuclei of patients with early-stage Parkinson's disease among various Magnetic Resonance Imaging...
PURPOSE
This study compares the observation efficiency of brain gray matter nuclei of patients with early-stage Parkinson's disease among various Magnetic Resonance Imaging techniques, which include susceptibility weighted imaging (SWI), quantitative susceptibility imaging (QSM), diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Based on the findings, this study suggests an efficient combination of scanning techniques for brain gray matter nuclei observation, aiming to provide an opportunity to advance the understanding of clinical diagnosis of early-stage Parkinson's disease.
METHODS
Forty examinees, including twenty patients who were clinically diagnosed with early Parkinson's disease with a course of 0.5-6 years (PD group) and twenty healthy controls (HC group), underwent head MRI examination. Philips 3.0T (tesla) MR machine was used to measure the imaging indexes of gray matter nuclei in patients with early Parkinson's disease. SWI, QSM, DTI and DKI were used for diagnosis. SPSS (Statistical Product and Service Solutions) 21.0 was used for data analysis.
RESULTS
When SWI was used, fifteen PD patients and six healthy volunteers were diagnosed correctly. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic coincidence rate about the diagnosis of nigrosome-1 on imaging were 75.0%, 30.0%, 51.7%, 54.5% and 52.5% respectively. By contrast, when QSM was used, 19 PD patients and 11 healthy volunteers were diagnosed correctly. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic coincidence rate about the diagnosis of Nigrosome-one on imaging were 95.0%, 55.0%, 67.9%, 91.7% and 75.0% respectively. The mean kurtosis (MK) value within both the substantia nigra and thalamus, together with the mean diffusivity (MD) within both the substantia nigra and the head of caudate nucleus in PD group was greater than that of HC group. The susceptibility values within the substantia nigra, red nucleus, head of caudate nucleus and putamen of PD group was greater than that of HC group. The MD value in substantia nigra reveals the optimal diagnostic efficiency to distinguish the HC group and the PD group, followed by the MK value in substantia nigra. Specifically, the maximum area under ROC curve (AUC) of the MD value was 0.823, the sensitivity 70.0%, the specificity 85.0%, and the diagnostic threshold 0.414. The area under ROC curve (AUC) of the MK value was 0.695, the sensitivity 95.0%, the specificity 50.0%, and the diagnostic threshold was 0.667. Both of them were statistically significant.
CONCLUSIONS
In the early diagnosis of Parkinson's disease, QSM is more efficient than SWI in observing nigrosome-1 in substantia nigra. In the early diagnosis of Parkinson's disease, MD and MK values of substantia nigra in DKI parameters have higher diagnostic efficiency. The combined scanning of DKI and QSM has the highest diagnostic efficiency and provides imaging basis for clinical diagnosis of early Parkinson's disease.
Topics: Humans; Diffusion Tensor Imaging; Gray Matter; Parkinson Disease; Magnetic Resonance Imaging; Healthy Volunteers
PubMed: 37386479
DOI: 10.1186/s13005-023-00371-4 -
Frontiers in Psychiatry 2024Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a...
INTRODUCTION
Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a brain-based model is lacking. In adult samples, current models highlight deficient serotonin release as a potential suicide biomarker, and in particular, involvement of serotonergic dysfunction in relation to the putamen and suicidal behavior. Less is known about associations among striatal regions and relative suicidal risk across development. The current study examined putamen connectivity in depressed adolescents with (AT) and without history of a suicide attempt (NAT), specifically using resting-state functional magnetic resonance imaging (fMRI) to evaluate patterns in resting-state functional connectivity (RSFC). We hypothesized the AT group would exhibit lower striatal RSFC compared to the NAT group, and lower striatal RSFC would associate with greater suicidal ideation severity and/or lethality of attempt.
METHODS
We examined whole-brain RSFC of six putamen regions in 17 adolescents with depression and NAT (M [SD] = 16.4[0.3], 41% male) and 13 with AT (M [SD] = 16.2[0.3], 31% male).
RESULTS
Only the dorsal rostral striatum showed a statistically significant bilateral between-group difference in RSFC with the superior frontal gyrus and supplementary motor area, with higher RSFC in the group without a suicide attempt compared to those with attempt history (voxel-wise <.001, cluster-wise <.01). No significant associations were found between any putamen RSFC patterns and suicidal ideation severity or lethality of attempts among those who had attempted.
DISCUSSION
The results align with recent adult literature and have interesting theoretical and clinical implications. A possible interpretation of the results is a mismatch of the serotonin transport to putamen and to the supplementary motor area and the resulting reduced functional connectivity between the two areas in adolescents with attempt history. The obtained results can be used to enhance the diathesis-stress model and the Emotional paiN and social Disconnect (END) model of adolescent suicidality by adding the putamen. We also speculate that connectivity between putamen and the supplementary motor area may in the future be used as a valuable biomarker of treatment efficacy and possibly prediction of treatment outcome.
PubMed: 38903634
DOI: 10.3389/fpsyt.2024.1364271 -
NPJ Parkinson's Disease Feb 2024Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons. Exercise has been reported to slow the clinical progression of PD. We evaluated...
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons. Exercise has been reported to slow the clinical progression of PD. We evaluated the dopaminergic system of patients with mild and early PD before and after a six-month program of intense exercise. Using F-FE-PE2I PET imaging, we measured dopamine transporter (DAT) availability in the striatum and substantia nigra. Using NM-MRI, we evaluated the neuromelanin content in the substantia nigra. Exercise reversed the expected decrease in DAT availability into a significant increase in both the substantia nigra and putamen. Exercise also reversed the expected decrease in neuromelanin concentration in the substantia nigra into a significant increase. These findings suggest improved functionality in the remaining dopaminergic neurons after exercise. Further research is needed to validate our findings and to pinpoint the source of any true neuromodulatory and neuroprotective effects of exercise in PD in large clinical trials.
PubMed: 38336768
DOI: 10.1038/s41531-024-00641-1 -
Research Square Aug 2023Studies exploring the brain correlates of behavioural symptoms in the frontotemporal dementia spectrum (FTD) have mainly searched for linear correlations with single...
BACKGROUND
Studies exploring the brain correlates of behavioural symptoms in the frontotemporal dementia spectrum (FTD) have mainly searched for linear correlations with single modality neuroimaging data, either structural magnetic resonance imaging (MRI) or fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). We aimed at studying the two imaging modalities in combination to identify nonlinear co-occurring patterns of atrophy and hypometabolism related to behavioural symptoms.
METHODS
We analysed data from 93 FTD patients who underwent T1-weighted MRI, FDG-PET imaging, and neuropsychological assessment including the Neuropsychiatric Inventory, Frontal Systems Behaviour Scale, and Neurobehavioral Rating Scale. We used a data-driven approach to identify the principal components underlying behavioural variability, then related the identified components to brain variability using a newly developed method fusing maps of grey matter volume and FDG metabolism.
RESULTS
A component representing apathy, executive dysfunction, and emotional withdrawal was associated with atrophy in bilateral anterior insula and putamen, and with hypometabolism in the right prefrontal cortex. Another component representing the disinhibition versus depression/mutism continuum was associated with atrophy in the right striatum and ventromedial prefrontal cortex for disinhibition, and hypometabolism in the left fronto-opercular region and sensorimotor cortices for depression/mutism. A component representing psychosis was associated with hypometabolism in the prefrontal cortex and hypermetabolism in auditory and visual cortices.
DISCUSSION
Behavioural symptoms in FTD are associated with atrophy and altered metabolism of specific brain regions, especially located in the frontal lobes, in a hierarchical way: apathy and disinhibition are mostly associated with grey matter atrophy, whereas psychotic symptoms are mostly associated with hyper-/hypo-metabolism.
PubMed: 37674710
DOI: 10.21203/rs.3.rs-3271530/v1 -
Frontiers in Neurology 2023The extensive clinical variations observed in Parkinson's disease (PD) pose challenges in early diagnosis and treatment initiation. However, genetic research in PD has...
INTRODUCTION
The extensive clinical variations observed in Parkinson's disease (PD) pose challenges in early diagnosis and treatment initiation. However, genetic research in PD has significantly transformed the clinical approach to its treatment. Moreover, researchers have adopted a subtyping strategy based on homogeneous clinical symptoms to improve clinical diagnosis and treatment approaches. We conducted a study to explore clinical characteristics in genetic PD groups with motor symptom subtyping.
METHODS
Data was driven from the Parkinson's Progression Markers Initiative (PPMI) database. The sporadic PD (sPD) group and the genetic PD group including patients with leucine-rich kinase 2 () or glucosylceramidase β () mutations were analyzed. Motor subtyping was performed using Movement Disorder Society-Unified Parkinson's disease rating scale (MDS-UPDRS) scores. I-123 FP-CIT SPECT scans were used to calculate specific binding ratios (SBRs) in the caudate and putamen. Clinical symptoms of each group were also compared.
RESULTS
MDS-UPDRS III scores were lower in the group, compared with the and sPD group ( < 0.001), but no significant differences in striatal SBRs. The putaminal SBR value of the group was higher than the sPD group ( < 0.05). Within the group, we observed lower SBR values in the postural instability/gait difficulty (PIGD) subtype group compared to the tremor-dominant (TD) subtype group ( < 0.05). The TD subtype group exhibited superior putaminal SBRs compared to the TD subtype sPD group ( < 0.05). The TD subtype group had better putaminal SBR values ( < 0.001) and MDS-UPDRS Part III scores ( < 0.05) compared to the TD sPD group.
DISCUSSIONS
Our subtyping approach offers valuable insights into the clinical characteristics and progression of different genetic PD subtypes. To further validate and expand these findings, future research with larger groups and long-term follow-up data is needed. The subtyping strategy based on motor symptoms holds promise in enhancing the diagnosis and treatment of genetic PD.
PubMed: 37954645
DOI: 10.3389/fneur.2023.1276251