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BioRxiv : the Preprint Server For... Apr 2024Early psychosis (EP) is a critical period in the course of psychotic disorders during which the brain is thought to undergo rapid and significant functional and...
INTRODUCTION
Early psychosis (EP) is a critical period in the course of psychotic disorders during which the brain is thought to undergo rapid and significant functional and structural changes . Growing evidence suggests that the advent of psychotic disorders is early alterations in the brain's functional connectivity and structure, leading to aberrant neural network organization. The Human Connectome Project (HCP) is a global effort to map the human brain's connectivity in healthy and disease populations; within HCP, there is a specific dataset that focuses on the EP subjects (i.e., those within five years of the initial psychotic episode) (HCP-EP), which is the focus of our study. Given the critically important role of the midbrain function and structure in psychotic disorders (cite), and EP in particular (cite), we specifically focused on the midbrain macro- and micro-structural alterations and their association with clinical outcomes in HCP-EP.
METHODS
We examined macro- and micro-structural brain alterations in the HCP-EP sample (n=179: EP, n=123, Controls, n=56) as well as their associations with behavioral measures (i.e., symptoms severity) using a stepwise approach, incorporating a multimodal MRI analysis procedure. First, Deformation Based Morphometry (DBM) was carried out on the whole brain 3 Tesla T1w images to examine gross brain anatomy (i.e., seed-based and voxel-based volumes). Second, we extracted Fractional Anisotropy (FA), Axial Diffusivity (AD), and Mean Diffusivity (MD) indices from the Diffusion Tensor Imaging (DTI) data; a midbrain mask was created based on FreeSurfer v.6.0 atlas. Third, we employed Tract-Based Spatial Statistics (TBSS) to determine microstructural alterations in white matter tracts within the midbrain and broader regions. Finally, we conducted correlation analyses to examine associations between the DBM-, DTI- and TBSS-based outcomes and the Positive and Negative Syndrome Scale (PANSS) scores.
RESULTS
DBM analysis showed alterations in the hippocampus, midbrain, and caudate/putamen. A DTI voxel-based analysis shows midbrain reductions in FA and AD and increases in MD; meanwhile, the hippocampus shows an increase in FA and a decrease in AD and MD. Several key brain regions also show alterations in DTI indices (e.g., insula, caudate, prefrontal cortex). A seed-based analysis centered around a midbrain region of interest obtained from freesurfer segmentation confirms the voxel-based analysis of DTI indices. TBSS successfully captured structural differences within the midbrain and complementary alterations in other main white matter tracts, such as the corticospinal tract and cingulum, suggesting early altered brain connectivity in EP. Correlations between these quantities in the EP group and behavioral scores (i.e., PANSS and CAINS tests) were explored. It was found that midbrain volume noticeably correlates with the Cognitive score of PA and all DTI metrics. FA correlates with the several dimensions of the PANSS, while AD and MD do not show many associations with PANSS or CAINS.
CONCLUSIONS
Our findings contribute to understanding the midbrain-focused circuitry involvement in EP and complimentary alteration in EP. Our work provides a path for future investigations to inform specific brain-based biomarkers of EP and their relationships to clinical manifestations of the psychosis course.
PubMed: 38645197
DOI: 10.1101/2024.04.10.588901 -
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 -
CNS Neuroscience & Therapeutics Apr 2024Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor...
AIMS
Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism.
METHODS
Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups.
RESULTS
All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients.
CONCLUSION
Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.
Topics: Humans; Male; Female; Magnetic Resonance Imaging; Adult; Brain; Rest; Young Adult; Seizures; Middle Aged; Brain Mapping; Neural Pathways; Anticonvulsants; Adolescent; Motor Activity
PubMed: 38644561
DOI: 10.1111/cns.14672 -
NeuroImage. Clinical 2024Nigrostriatal microstructural integrity has been suggested as a biomarker for levodopa response in Parkinson's disease (PD), which is a strong predictor for motor...
BACKGROUND
Nigrostriatal microstructural integrity has been suggested as a biomarker for levodopa response in Parkinson's disease (PD), which is a strong predictor for motor response to deep brain stimulation (DBS) of the subthalamic nucleus (STN). This study aimed to explore the impact of microstructural integrity of the substantia nigra (SN), STN, and putamen on motor response to STN-DBS using diffusion microstructure imaging.
METHODS
Data was collected from 23 PD patients (mean age 63 ± 7, 6 females) who underwent STN-DBS, had preoperative 3 T diffusion magnetic resonance imaging including multishell diffusion-weighted MRI with b-values of 1000 and 2000 s/mm and records of motor improvement available.
RESULTS
The association between a poorer DBS-response and increased free interstitial fluid showed notable effect sizes (rho > |0.4|) in SN and STN, but not in putamen. However, this did not reach significance after Bonferroni correction and controlling for sex and age.
CONCLUSION
Microstructural integrity of SN and STN are potential biomarkers for the prediction of therapy efficacy following STN-DBS, but further studies are required to confirm these associations.
Topics: Humans; Deep Brain Stimulation; Subthalamic Nucleus; Female; Male; Parkinson Disease; Middle Aged; Substantia Nigra; Aged; Diffusion Magnetic Resonance Imaging; Treatment Outcome
PubMed: 38643635
DOI: 10.1016/j.nicl.2024.103607 -
Kardiologia Polska 2024The Pulmonary Embolism Severity Index (PESI) is a validated tool to predict 30-day all-cause mortality in patients with acute pulmonary embolism (PE) but includes only... (Observational Study)
Observational Study
BACKGROUND
The Pulmonary Embolism Severity Index (PESI) is a validated tool to predict 30-day all-cause mortality in patients with acute pulmonary embolism (PE) but includes only clinical variables.
AIMS
We aimed to determine the effectiveness of PESI extended with an echocardiographic parameter.
METHODS
This cross-sectional observational study included consecutive patients with acute PE diagnosed with computed tomography pulmonary angiography.
RESULTS
Of 117 subjects (57 men, 48.7%), at a median age of 69 (59-80) years, 16 patients died during the 30-day follow-up. Six modified models of PESI with an additional single echocardiographic parameter were created, which increased the predictive value of PESI (area under the curve [AUC] 0.8608): tricuspid annular plane systolic excursion (TAPSE) <18 mm, right ventricular (RV) free wall longitudinal strain (RVFWLS) >-23%, 60/60 sign, RV global longitudinal strain (RVGLS) >-16%, pulmonary ejection acceleration time (AcT) <67 ms, and thrombus in right heart cavities (AUC 0.8657 to 0.8976, respectively, all markers P <0.001). TAPSE, AcT, RVFWLS, and RVGLS showed significant correlations with the PESI score, but not a thrombus in the right heart cavity or the 60/60 sign. As PESI adjuncts, they independently predicted fatal outcomes: thrombus with hazard ratio (HR) 10.04 (95% confidence interval [CI], 2.81-37.12; P <0.001) and the 60/60 sign with HR 4.07 (95% CI, 1.27-12.81; P <0.001).
CONCLUSIONS
The quantitative echocardiographic parameters of RV systolic function and pulmonary artery blood flow are associated with the PESI score and thus increase its predictive value to a limited extent. PE- specific findings: a thrombus in the right heart cavity and the 60/60 sign are effective adjuncts to the PESI score.
Topics: Humans; Pulmonary Embolism; Male; Female; Aged; Middle Aged; Echocardiography; Aged, 80 and over; Severity of Illness Index; Cross-Sectional Studies; Acute Disease; Prognosis; Predictive Value of Tests
PubMed: 38638091
DOI: 10.33963/v.phj.100198 -
Communications Biology Apr 2024The amygdala nuclei modulate distributed neural circuits that most likely evolved to respond to environmental threats and opportunities. So far, the specific role of...
The amygdala nuclei modulate distributed neural circuits that most likely evolved to respond to environmental threats and opportunities. So far, the specific role of unique amygdala nuclei in the context processing of salient environmental cues lacks adequate characterization across neural systems and over time. Here, we present amygdala nuclei morphometry and behavioral findings from longitudinal population data (>1400 subjects, age range 40-69 years, sampled 2-3 years apart): the UK Biobank offers exceptionally rich phenotyping along with brain morphology scans. This allows us to quantify how 18 microanatomical amygdala subregions undergo plastic changes in tandem with coupled neural systems and delineating their associated phenome-wide profiles. In the context of population change, the basal, lateral, accessory basal, and paralaminar nuclei change in lockstep with the prefrontal cortex, a region that subserves planning and decision-making. The central, medial and cortical nuclei are structurally coupled with the insular and anterior-cingulate nodes of the salience network, in addition to the MT/V5, basal ganglia, and putamen, areas proposed to represent internal bodily states and mediate attention to environmental cues. The central nucleus and anterior amygdaloid area are longitudinally tied with the inferior parietal lobule, known for a role in bodily awareness and social attention. These population-level amygdala-brain plasticity regimes in turn are linked with unique collections of phenotypes, ranging from social status and employment to sleep habits and risk taking. The obtained structural plasticity findings motivate hypotheses about the specific functions of distinct amygdala nuclei in humans.
Topics: Humans; Adult; Middle Aged; Aged; Phenomics; Amygdala; Basal Ganglia; Prefrontal Cortex
PubMed: 38637627
DOI: 10.1038/s42003-024-06187-5 -
Biological Psychiatry Apr 2024Early adverse experiences are assumed to affect fundamental processes of reward learning and decision making. However, computational neuroimaging studies investigating...
BACKGROUND
Early adverse experiences are assumed to affect fundamental processes of reward learning and decision making. However, computational neuroimaging studies investigating these circuits in the context of adversity are sparse and limited to studies conducted in adolescent samples, leaving the long-term effects unexplored.
METHODS
Using data from a longitudinal birth cohort study (n = 156; 87 female), we investigated associations between adversities and computational markers of reward learning (i.e., expected value, prediction errors). At age 33 years, all participants completed a functional magnetic resonance imaging-based passive avoidance task. Psychopathology measures were collected at the time of functional magnetic resonance imaging investigation and during the COVID-19 pandemic. We applied a principal component analysis to capture common variations across 7 adversity measures. The resulting adversity factors (factor 1: postnatal psychosocial adversities and prenatal maternal smoking; factor 2: prenatal maternal stress and obstetric adversity; factor 3: lower maternal stimulation) were linked with psychopathology and neural responses in the core reward network using multiple regression analysis.
RESULTS
We found that the adversity dimension primarily informed by lower maternal stimulation was linked to lower expected value representation in the right putamen, right nucleus accumbens, and anterior cingulate cortex. Expected value encoding in the right nucleus accumbens further mediated the relationship between this adversity dimension and psychopathology and predicted higher withdrawn symptoms during the COVID-19 pandemic.
CONCLUSIONS
Our results suggested that early adverse experiences in caregiver context might have a long-term disruptive effect on reward learning in reward-related brain regions, which can be associated with suboptimal decision making and thereby may increase the vulnerability of developing psychopathology.
PubMed: 38636886
DOI: 10.1016/j.biopsych.2024.04.005 -
NeuroImage Jun 2024This systematic review investigates how prefrontal transcranial magnetic stimulation (TMS) immediately influences neuronal excitability based on oxygenation changes... (Review)
Review
This systematic review investigates how prefrontal transcranial magnetic stimulation (TMS) immediately influences neuronal excitability based on oxygenation changes measured by functional magnetic resonance imaging (fMRI) or functional near-infrared spectroscopy (fNIRS). A thorough understanding of TMS-induced excitability changes may enable clinicians to adjust TMS parameters and optimize treatment plans proactively. Five databases were searched for human studies evaluating brain excitability using concurrent TMS/fMRI or TMS/fNIRS. Thirty-seven studies (13 concurrent TMS/fNIRS studies, 24 concurrent TMS/fMRI studies) were included in a qualitative synthesis. Despite methodological inconsistencies, a distinct pattern of activated nodes in the frontoparietal central executive network, the cingulo-opercular salience network, and the default-mode network emerged. The activated nodes included the prefrontal cortex (particularly dorsolateral prefrontal cortex), insula cortex, striatal regions (especially caudate, putamen), anterior cingulate cortex, and thalamus. High-frequency repetitive TMS most consistently induced expected facilitatory effects in these brain regions. However, varied stimulation parameters (e.g., intensity, coil orientation, target sites) and the inter- and intra-individual variability of brain state contribute to the observed heterogeneity of target excitability and co-activated regions. Given the considerable methodological and individual variability across the limited evidence, conclusions should be drawn with caution.
Topics: Humans; Transcranial Magnetic Stimulation; Prefrontal Cortex; Magnetic Resonance Imaging; Spectroscopy, Near-Infrared; Oxygen; Brain Mapping; Brain
PubMed: 38636640
DOI: 10.1016/j.neuroimage.2024.120618 -
Journal of Biomedical Science Apr 2024Huntington's disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the...
BACKGROUND
Huntington's disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the cortex. Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply to brain regions in several neurological diseases, including HD, which could potentially trigger the process of neurodegeneration. In particular, it has been observed in cross-sectional human HD studies that vascular alterations are associated to impaired cerebral blood flow (CBF). To assess whether whole-brain changes in CBF are present and follow a pattern of progression, we investigated both resting-state brain perfusion and vascular reactivity longitudinally in the zQ175DN mouse model of HD.
METHODS
Using pseudo-continuous arterial spin labelling (pCASL) MRI in the zQ175DN model of HD and age-matched wild-type (WT) mice, we assessed whole-brain, resting-state perfusion at 3, 6 and 9 and 13 months of age, and assessed hypercapnia-induced cerebrovascular reactivity (CVR), at 4.5, 6, 9 and 15 months of age.
RESULTS
We found increased perfusion in cortical regions of zQ175DN HET mice at 3 months of age, and a reduction of this anomaly at 6 and 9 months, ages at which behavioural deficits have been reported. On the other hand, under hypercapnia, CBF was reduced in zQ175DN HET mice as compared to the WT: for multiple brain regions at 6 months of age, for only somatosensory and retrosplenial cortices at 9 months of age, and brain-wide by 15 months. CVR impairments in cortical regions, the thalamus and globus pallidus were observed in zQ175DN HET mice at 9 months, with whole brain reactivity diminished at 15 months of age. Interestingly, blood vessel density was increased in the motor cortex at 3 months, while average vessel length was reduced in the lateral portion of the caudate putamen at 6 months of age.
CONCLUSION
Our findings reveal early cortical resting-state hyperperfusion and impaired CVR at ages that present motor anomalies in this HD model, suggesting that further characterization of brain perfusion alterations in animal models is warranted as a potential therapeutic target in HD.
Topics: Humans; Mice; Animals; Infant; Huntington Disease; Cross-Sectional Studies; Hypercapnia; Brain; Disease Models, Animal; Perfusion
PubMed: 38627751
DOI: 10.1186/s12929-024-01028-3 -
Frontiers in Neuroanatomy 2024The presence of a widespread cortical synucleinopathy is the main neuropathological hallmark underlying clinical entities such as Parkinson's disease with dementia (PDD)...
INTRODUCTION
The presence of a widespread cortical synucleinopathy is the main neuropathological hallmark underlying clinical entities such as Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). There currently is a pressing need for the development of non-human primate (NHPs) models of PDD and DLB to further overcome existing limitations in drug discovery.
METHODS
Here we took advantage of a retrogradely-spreading adeno-associated viral vector serotype 9 coding for the alpha-synuclein A53T mutated gene (AAV9-SynA53T) to induce a widespread synucleinopathy of cortical and subcortical territories innervating the putamen. Four weeks post-AAV deliveries animals were sacrificed and a comprehensive biodistribution study was conducted, comprising the quantification of neurons expressing alpha-synuclein, rostrocaudal distribution and their specific location.
RESULTS
Intraputaminal deliveries of AAV9-SynA53T lead to a disseminated synucleinopathy throughout ipsi- and contralateral cerebral cortices, together with transduced neurons located in the ipsilateral caudal intralaminar nuclei and in the substantia nigra pars compacta (leading to thalamostriatal and nigrostriatal projections, respectively). Cortical afferent systems were found to be the main contributors to putaminal afferents (superior frontal and precentral gyri in particular).
DISCUSSION
Obtained data extends current models of synucleinopathies in NHPs, providing a reproducible platform enabling the adequate implementation of end-stage preclinical screening of new drugs targeting alpha-synuclein.
PubMed: 38601798
DOI: 10.3389/fnana.2024.1355940