Neuroimaging Features Research Articles

Neurodegeneration with iron accumulation in the brain, peculiarities of course and approach to treatment

Neurodegenerations with brain iron accumulation (NBIA) constitute a group of genetically determined and clinically heterogeneous forms of progressive neurological pathology associated with the accumulation of iron in the basal ganglia and other structures of the brain, which, in turn, causes their dysfunction. Both childhood and adulthood onset of the disease is possible. Objective: to draw the attention of doctors to the importance of timely diagnosis of neurodegenerative diseases, which are manifested by movement disorders and abnormal accumulation of iron in various structures of the brain. Movement disorders, mostly a combination of parkinsonism, dystonia, pyramidal insufficiency and ataxia, are dominant in the clinical picture of NBIA. Areas of iron deposition are detected on magnetic resonance imaging as bilateral hypodense zones, in the center of which hyperdense foci are determined in many cases, probably due to the gliosis, mainly in the area of the globus pallidus (eye-of-the-tiger sign). Typical neuroimaging signs help make a preliminary diagnosis of NBIA with a high probability, in the presence and sometimes even before the appearance of clinical manifestations of the disease, reducing costs and time for additional research. The paper describes a clinical case of NBIA associated with the protein of the mitochondrial membrane, and also highlights the latest data on clinical manifestations, diagnosis and modern management of this pathology. The possibility and importance of modern diagnosis and therapy in childhood have been demonstrated. Genetic examination remains crucial for the verification of the hereditary degenerative disease and determination of its form. The analysis of literature data and the results of own observations confirm the importance of the given main directions of available symptomatic treatment, as well as approaches to pathogenetic therapy, which still require further clinical trials. The given clinical observation and the analysis of literature data on the problem of NBIA reflect the expediency of searching for characteristic neuroimaging patterns in patients with motor (extrapyramidal, pyramidal, coordination) disorders with further verification of the diagnosis by means of molecular genetic research.

Multitracer PET/CT Findings in a Case of Behavioral Variant Frontotemporal Dementia With Parkinsonism.

We report the clinical and multimodal PET/CT manifestations in a patient with behavioral variant frontotemporal dementia and parkinsonism. The 18F-FDG PET scan revealed hypometabolism in the left supratentorial cortex. The 18F-fluorodopa PET scan demonstrated decreased uptake in the bilateral striatum, most prominent in the head of caudate nucleus. The 18F-florbetapir PET scan indicated an absence of β-amyloid deposition, whereas the 18F-flortaucipir PET scan showed uptake in the left hemisphere neocortex. The clinical presentation and asymmetric neuroimaging features supported the underlying frontotemporal lobar degeneration-tau pathology.

Multiclass Classification of Alzheimer's Disease Prodromal Stages using Sequential Feature Embeddings and Regularized Multikernel Support Vector Machine

The detection of patients in the cognitive normal (CN), mild cognitive impairment (MCI), and Alzheimer's disease (AD) stages of neurodegeneration is crucial for early treatment interventions. However, the heterogeneity of MCI data samples poses a challenge for CN vs. MCI vs. AD multiclass classification, as some samples are closer to AD while others are closer to CN in the feature space. Previous attempts to address this challenge produced inaccurate results, leading most frameworks to break the assessment into binary classification tasks such as AD vs. CN, AD vs. MCI, and CN vs. MCI. Other methods proposed sequential binary classifications such as CN vs. others and dividing others into AD vs. MCI. While those approaches may have yielded encouraging results, the sequential binary classification method makes interpretation and comparison with other frameworks challenging and subjective. Those frameworks exhibited varying accuracy scores for different binary tasks, making it unclear how to compare the model performance with other direct multiclass methods. Therefore, we introduce a classification framework comprising unsupervised ensemble manifold regularized sparse low-rank approximation and regularized multikernel support vector machine (SVM). This framework first extracts a joint feature embedding from MRI and PET neuroimaging features, which were then combined with the Apoe4, Adas11, MPACC digits, and Intracranial volume features using a regularized multikernel SVM. Using that framework, we achieved a state-of-the-art (SOTA) result in a CN vs. MCI vs. AD multiclass classification (mean accuracy: 84.87±6.09, F1 score: 84.83±6.12 vs 67.69). The methods generalize well to binary classification tasks, achieving SOTA results in all but the CN vs. MCI category, which was slightly lower than the best score by just 0.2%.

Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q 10 Biosynthesis Disorders

Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q ₁₀ Biosynthesis Disorders

Short-Term Frequently Relapsing Ischemic Strokes Followed by Rapidly Progressive Dementia in CADASIL: A Case Report and Literature Review.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease with slow natural progression. Ischemic stroke and cognitive impairment are its most common clinical symptoms. Here, we report a rare 50-year-old woman who had rapid disease progression with c.457C>T, p.Argl53Cys heterozygous mutation in exon 4 of NOTCH3 and discuss the possible reasons. Furthermore, we summarized the clinical and neuroimaging characteristics of 14 CADASIL patients with Arg153Cys mutation in exon 4. The proband suffered acute ischemic stroke 5 times in 5 months, followed by rapidly progressive dementia (RPD) and inability to live independently, though she didn't have vascular risk factors and had been under standardized secondary prevention therapy since the first stroke. Magnetic resonance imaging showed extensive white matter hyperintensities, numerous ischemic infarcts and microbleeds, and severe brain atrophy. Her elder brother and other patients with Arg153Cys mutation in exon 4 all did not progress so quickly. Her multiple strokes may be associated with the poor self-regulation of vessels, which may promote the occurrence of RPD. Antiplatelet and anticoagulant drugs were difficult to prevent ischemic strokes. Severe imaging findings may indicate rapid progression of CADASIL. In addition, we found that headache was a very frequent symptom in CADASIL patients with Arg153Cys mutation in exon 4, accounting for 76.9%. CADASIL can also appear to have rapid progression, as illustrated by our proband, which is worthy of clinicians' attention and intervention timely. Headache may present in a relatively higher proportion of CADASIL patients with Arg153Cys mutation in exon 4.

Neurological and psychiatric phenotype of a multicenter cohort of patients with SETD5-related neurodevelopmental disorder

Pathogenic variants in the SETD5 gene cause a neurodevelopmental disorder characterized by intellectual disability, autism, and facial dysmorphisms, with incomplete penetrance. To date, no distinctive neurological, psychiatric, electroencephalographic, and neuroimaging features have been identified in this condition. We expand the clinical phenotype of SETD5-related disorder by describing 28 previously unreported patients, 26 carrying single nucleotide variants, and 2 with copy number variations involving SETD5 gene, focusing on neurological, psychiatric, EEG, and brain MRI data. In our cohort neurological symptoms include hypotonia (39.2 %), hyperkinetic movement disorders including stereotypies and chorea (21.4 %) and gait abnormalities ranging from tip-toe or unsteady walking and alterations of fine motor skills (35.7 %). Epilepsy was present in about 14 % of patients, including different types of seizures as epileptic spasms, focal motor, and non-motor seizures. Concerning the cognitive phenotype, intellectual disability or global developmental delay depending on age, ranging from mild to severe, was present in 75 % of cohort, 21.4 % exhibit borderline intellectual functioning while an individual has a normal intelligence quotient.Other psychiatric comorbidities include autism, ADHD, psychotic disorder and other internalizing and externalizing symptoms.Finally, we conduct a comprehensive review of the available literature, suggesting a possible genotype-phenotype correlation.

Crossed Brainstem Syndrome of the Tectal Plate's Inferior Colliculus Revealing Quadrigeminal Midbrain Cavernous Malformation

Cavernous malformations are low-flow fragile vascular lesion, prone to extralesional bleeding that can occur in the cerebral hemispheres, the brainstem, or the spinal cord. We report the case of a 32-years-old right-handed male patient with acute-onset headaches associated with right-sided tinnitus, right-sided hemianesthesia, and binocular diplopia related to cranial nerve IV palsy. Neuroimaging displayed left-sided isolated cavernous malformation of the inferior tectal plate, with evidence of extralesional bleeding. Clinical presentation and neuroimaging features were compatible with inferior colliculus crossed brainstem syndrome. Thanks to clinical improvement and the absence of mass effect on neuroimaging, surgical intervention was delayed. At the 3 months follow-up consultation, symptoms had improved aside from diplopia which required wearing prism eyeglasses. Tectal cavernous malformations account for 18% of midbrain cavernomas. It was explained that surgical excision using the supracerebellar infratentorial approach would be performed within 2 months following a second extralesional bleeding episode causing disabling symptoms.

Polymorphic low-grade neuroepithelial tumors of the young: disease characteristics and treatment decisions from the epilepsy surgery perspective.

The Polymorphic Low-Grade Neuroepithelial Tumor of the Young (PLNTY) is a rare, epilepsy-associated brain tumor that has been increasingly recognized but is not well understood due to the scarcity of clinical reports. Our study reviews the clinical characteristics and treatment outcomes of 14 patients with PLNTY to enhance the understanding of this condition from an epilepsy surgery perspective. We performed a retrospective analysis of 14 PLNTY cases at our hospital. A literature review on prior studies was also conducted. Our study included 8 males and 6 females, all presenting with epilepsy. Despite anti-seizure medication, 92.3% of patients continued to have seizures, with 58.3% diagnosed as having drug-resistant epilepsy. Neuroimaging revealed that 64.3% of the lesions were in the temporal lobe, with 75.0% showing calcification on CT, 71.4% exhibiting mixed signals on T2-weighted images, and 92.7% showing tumor enhancement. The transmantle sign was noted in 57.1% of T2 FLAIR sequences. EEGs indicated abnormal activity in 69.2% of patients, with 30.7% showing bilateral discharges. SEEG in two patients confirmed the tumor's epileptogenicity. A 78.6% total resection rate was achieved, with a 90.0% postoperative seizure-free rate and an 85.7% excellent Engel grade 1 rate. No instances co-occurring with focal cortical dysplasia (FCD) were observed. PLNTY is characterized by unique neuroimaging features and a strong association with epilepsy. SEEG is pivotal for cases with unclear lateralization, aiding in identifying the link between the tumor and seizures. Following established epilepsy surgery protocols for brain tumor management, early intervention and extended resection can improve the rate of postoperative seizure freedom.

Abnormalities along the cortico-medullary junction on brain MRI caused by 1,2-dichloroethane-induced toxic encephalopathy

Background1,2-dichloroethane (DCE) induced toxic encephalopathy, a rare toxic disease of the central nervous system, is mainly reported in developing countries. Although clinicians have got some understanding about the clinical and neuroimaging features of 1,2-DCE-induced toxic encephalopathy, abnormality along the cortico-medullary junction on diffusion-weighted image (DWI) mimicking neuronal intranuclear inclusion disease (NIID) has not yet been described in this entity.Case presentationWe reported a patient with 1,2-DCE-induced toxic encephalopathy who was admitted to our department due to a 7-day history of nausea, vomiting, and cognitive decline. Brain magnetic resonance imaging (MRI) showed symmetrical hyperintensities in bilateral subcortical white matte on T2-weghted and Fluid-attenuated inversion recovery (FLAIR) images. In addition, abnormal signal intensity could also be found in the cortico-medullary junction on DWI, mimicking NIID. After treated with glucocorticoid, dehydrating agents, neuroprotective agents, and hyperbaric oxygen, our patient received a partial recovery.ConclusionOur case highlights a special MRI finding—abnormalities along the cortico-medullary junction—that can be seen in 1,2-DCE-induced toxic encephalopathy. When confronted with patients with lesion located in the cortico-medullary junction and neuropsychiatric symptoms, our clinicians should not neglect the detailed inquiry of history of toxic exposure.

Primary Progressive Aphasia Lacking Core Features of Nonfluent and Semantic Variants: Clinical, Neuroimaging, and Neuropathologic Features.

Evidence has accumulated that the 2011 consensus criteria for primary progressive aphasia (PPA) do not fully capture features of logopenic variant PPA (lvPPA/LPA). We aimed to examine clinical, neuroimaging, and neuropathologic features of PPA lacking features of nonfluent/semantic variants and to provide practical additions to the 2011 consensus criteria. This was a retrospective examination of data from 2 observational cohort studies where patients with PPA were prospectively recruited at Mayo Clinic. Based on performance on 2 cardinal features (repetition and comprehension), patients were classified as: pure-LPA (poor repetition, acceptable comprehension), Wernicke-like (poor in both), anomic-like (acceptable in both), and transcortical sensory aphasia-like (TCSA-like) (acceptable repetition, poor comprehension). The entire cohort consisted of 102 patients with PPA lacking features of nonfluent/semantic variants (median age at onset 63.5 years, 56% female). Thirty-one patients were followed up at 1 year. Twenty-three patients were included in a neuropathologic cohort. The proportion of repetition-preserved PPA (anomic-like and TCSA-like) was more than double that of repetition-impaired PPA (pure-LPA and Wernicke-like) (73% vs 27%). Regarding clinical course, the anomic-like subgroup was a prodromal state of the pure-LPA or TCSA-like subgroup, whereas the pure-LPA and TCSA-like subgroups were a prodromal state of the Wernicke-like subgroup. There was left temporoparietal atrophy on MRI and/or hypometabolism on 18F-fluorodeoxyglucose-PET in all groups. Furthermore, repetition-impaired PPA showed severe hypometabolism in the left superior temporal lobe associated with repetition ability. Regarding pathologic diagnoses, 70% had Alzheimer disease (AD). The pure-LPA, Wernicke-like, and TCSA-like subgroups all showed AD pathology. Only 53% of the anomic-like subgroup had AD. The remaining 47% showed Pick disease (7%), frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (20%), and Lewy body disease (20%). This observed clinical heterogeneity reflects different time points/severities of the same disease process and hence can be reconceptualized as an AD-related aphasia spectrum, incorporating lvPPA and the 4 subgroups (pure-LPA, Wernicke-like, anomic-like, and TCSA-like). Specifying moderate/severe repetition deficits as a core feature of lvPPA in the 2011 consensus criteria can enhance its pathologic correlations. Recognizing progressive anomic aphasia (anomic-like) as an additional PPA variant could lessen pathologic heterogeneity of lvPPA.

PATH-05. CLINICAL, PATHOLOGICAL AND MOLECULAR DISEASE CHARACTERISTICS OF DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT

Abstract BACKGROUND Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, is a pediatric-type diffuse high-grade glioma newly defined in the World Health Organization (WHO) classification of central nervous system tumors 2021. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors. METHODS We retrospectively assembled a cohort of 114 patients with diffuse hemispheric glioma, H3 G34-mutant and profiled the imaging presentation and the molecular landscape of their tumors. RESULTS Compared with glioblastoma, H3 G34-mutant tumors exhibited less avid contrast enhancement, less necrosis and less edema on MRI. Comprehensive analyses of mutational and DNA copy number profiles revealed recurrent mutations in TP53 and ATRX, homozygous deletions of CDKN2A/B, and amplifications of PDGFRA, EGFR, CCND2, and MYCN. MGMT promoter methylation was detected in 79 tumors (75%); 11 tumors (13%) showed DNA copy number profiles suggestive of circumscribed deletions on 10q26.3 involving the MGMT locus. Median survival was 21.5 months (95% CI 15.3-27.7) and eight patients (7.0%) survived for ≥ five years. Female sex, gross total resection, and MGMT promoter methylation were positive prognostic factors on univariate analysis. Among radiological, pathological and molecular features, absence of pial invasion, and presence of microvascular proliferation and CDK6 amplification were positive prognostic factors on univariate analyses. CONCLUSION This study refines the clinical and molecular landscape of H3 G34-mutant diffuse hemispheric gliomas. Dedicated trials for this novel tumor type are urgently needed.

Somatosensory integration in robot-assisted motor restoration post-stroke.

Disruption of somatosensorimotor integration (SMI) after stroke is a significant obstacle to achieving precise motor restoration. Integrating somatosensory input into motor relearning to reconstruct SMI is critical during stroke rehabilitation. However, current robotic approaches focus primarily on precise control of repetitive movements and rarely effectively engage and modulate somatosensory responses, which impedes motor rehabilitation that relies on SMI. This article discusses how to effectively regulate somatosensory feedback from target muscles through peripheral and central neuromodulatory stimulations based on quantitatively measured somatosensory responses in real time during robot-assisted rehabilitation after stroke. Further development of standardized recording protocols and diagnostic databases of quantitative neuroimaging features in response to post-stroke somatosensory stimulations for real-time precise detection, and optimized combinations of peripheral somatosensory stimulations with robot assistance and central nervous neuromodulation are needed to enhance the recruitment of targeted ascending neuromuscular pathways in robot-assisted training, aiming to achieve precise muscle control and integrated somatosensorimotor functions, thereby improving long-term neurorehabilitation after stroke.

Unveiling connections between venous disruption and cerebral small vessel disease using diffusion tensor image analysis along perivascular space (DTI-ALPS): A 7-T MRI study.

Cerebral venous disruption is one of the characteristic findings in cerebral small vessel disease (CSVD), and its disruption may impede perivascular glymphatic drainage. And lower diffusivity along perivascular space (DTI-ALPS) index has been suggested to be with the presence and severity of CSVD. However, the relationships between venous disruption, DTI-ALPS index, and CSVD neuroimaging features remain unclear. To investigate the association between venous integrity and perivascular diffusion activity, and explore the mediating role of DTI-ALPS index between venous disruption and CSVD imaging features. In this cross-sectional study, 31 patients (mean age, 59.0 ± 9.9 years) were prospectively enrolled and underwent 7-T magnetic resonance (MR) imaging. DTI-ALPS index was measured to quantify the perivascular diffusivity. The visibility and continuity of deep medullary veins (DMVs) were evaluated based on a brain region-based visual score on high-resolution susceptibility-weighted imaging. White matter hyperintensity (WMH) and perivascular space (PVS) were assessed using qualitative and quantitative methods. Linear regression and mediation analysis were performed to analyze the relationships among DMV scores, DTI-ALPS index, and CSVD features. The DTI-ALPS index was significantly associated with the parietal DMV score (β = -0.573, p corrected = 0.004). Parietal DMV score was associated with WMH volume (β = 0.463, p corrected = 0.013) and PVS volume in basal ganglia (β = 0.415, p corrected = 0.028). Mediation analyses showed that DTI-ALPS index manifested a full mediating effect on the association between parietal DMV score and WMH (indirect effect = 0.115, Pm = 43.1%), as well as between parietal DMV score and PVS volume in basal ganglia (indirect effect = 0.161, Pm = 42.8%). Cerebral venous disruption is associated with glymphatic activity, and with WMH and PVS volumes. Our results suggest cerebral venous integrity may play a critical role in preserving perivascular glymphatic activity; while disruption of small veins may impair the perivascular diffusivity, thereby contributing to the development of WMH and PVS enlargement.

Post-procedural Brachial Neuritis: Clinical, Electrodiagnostic and Neuroimaging features.

Brachial neuritis is a monophasic condition affecting the brachial plexus and its branches, manifesting as acute shoulder and upper arm pain, followed by weakness and paresthesias. It can be triggered by antecedent events, including procedures such as surgery. Misdiagnosis and delay in diagnosis is common. Imaging is important to confirm the diagnosis of post-procedural brachial neuritis and exclude other etiologies. Clinical, electrodiagnostic, and neuroimaging features of patients with post-procedural brachial neuritis from a single quaternary care institution were identified and analyzed. Six (2 female) patients were identified with median age 62 (range 49-70) years. Antecedent procedures included 4 cervical spine surgeries, 1 rotator cuff repair, and 1 central venous catheter placement. Time to symptom onset ranged from 1-day to 2-weeks. The initial symptom for 5/6 patients was severe upper extremity pain followed by weakness. All patients had electrodiagnostic tests and MR neurography consistent with brachial neuritis. MR neurogram showed plexus and/or terminal branch abnormalities with associated muscular denervation edema. The C5 or C6 root, and/or upper trunk were always involved. The most common branches affected were the suprascapular, long thoracic, and axillary nerves. Hourglass constrictions of these nerves were seen in 3/6 patients. The average time to diagnosis was 3.4 (range 1.5-5) months. Post-procedural brachial neuritis is an underrecognized cause of acute upper extremity pain and weakness. MR neurography can exclude iatrogenic causes and document the presence of hourglass constrictions in affected nerves. Diagnostic neuroradiologists should be aware of this clinical entity and associated neuroimaging findings. HGC = hourglass constriction; EDX = electrodiagnostic; IRB = Institutional Review Board; ACDF = anterior cervical discectomy and fusion; NRS = Numerical Rating Scale; MUAP = motor unit action potential.

Characterizing the role of the microbiota-gut-brain axis in cerebral small vessel disease: An integrative multi‑omics study

BackgroundPrior efforts have revealed changes in gut microbiome, circulating metabolome, and multimodal neuroimaging features in cerebral small vessel disease (CSVD). However, there is a paucity of research integrating the multi-omic information to characterize the role of the microbiota-gut-brain axis in CSVD. MethodsWe collected gut microbiome, fecal and blood metabolome, multimodal magnetic resonance imaging data from 37 CSVD patients with white matter hyperintensities and 46 healthy controls. Between-group comparison was performed to identify the differential gut microbial taxa, followed by performance of multi-stage microbiome-metabolome-neuroimaging-neuropsychology correlation analyses in CSVD patients. ResultsOur data showed both depleted and enriched gut microbes in CSVD patients. Among the differential microbes, Haemophilus and Akkermansia were associated with a range of metabolites enriched for Aminoacyl-tRNA biosynthesis pathway. Furthermore, the affected metabolites were associated with neuroimaging measures involving gray matter morphology, spontaneous intrinsic brain activity, white matter integrity, and global structural network topology, which were in turn related to cognition and emotion in CSVD patients. ConclusionOur findings provide an integrative framework to understand the pathophysiological mechanisms underlying the interplay between gut microbiota dysbiosis and CSVD, highlighting the potential of targeting the microbiota-gut-brain axis as a therapeutic strategy in CSVD patients.

Morphological similarity and white matter structural mapping of new daily persistent headache: a structural connectivity and tract-specific study

BackgroundNew daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH.MethodsThe regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features.ResultsT1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression.ConclusionsOur research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores.

Volumetric Integrated Classification Index: An Integrated Voxel-Based Morphometry and Machine Learning Interpretable Biomarker for Post-Traumatic Stress Disorder.

PTSD is a complex mental health condition triggered by individuals' traumatic experiences, with long-term and broad impacts on sufferers' psychological health and quality of life. Despite decades of research providing partial understanding of the pathobiological aspects of PTSD, precise neurobiological markers and imaging indicators remain challenging to pinpoint. This study employed VBM analysis and machine learning algorithms to investigate structural brain changes in PTSD patients. Data were sourced ADNI-DoD database for PTSD cases and from the ADNI database for healthy controls. Various machine learning models, including SVM, RF, and LR, were utilized for classification. Additionally, the VICI was proposed to enhance model interpretability, incorporating SHAP analysis. The association between PTSD risk genes and VICI values was also explored through gene expression data analysis. Among the tested machine learning algorithms, RF emerged as the top performer, achieving high accuracy in classifying PTSD patients. Structural brain abnormalities in PTSD patients were predominantly observed in prefrontal areas compared to healthy controls. The proposed VICI demonstrated classification efficacy comparable to the optimized RF model, indicating its potential as a simplified diagnostic tool. Analysis of gene expression data revealed significant associations between PTSD risk genes and VICI values, implicating synaptic integrity and neural development regulation. This study reveals neuroimaging and genetic characteristics of PTSD, highlighting the potential of VBM analysis and machine learning models in diagnosis and prognosis. The VICI offers a promising approach to enhance model interpretability and guide clinical decision-making. These findings contribute to a better understanding of the pathophysiological mechanisms of PTSD and provide new avenues for future diagnosis and treatment.

Common and divergent neuroimaging features in major depression, posttraumatic stress disorder, and their comorbidity.

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are common stress-related psychiatric disorders. Genetic and neurobiology research has supported the viewpoint that PTSD and MDD may possess common and disorder-specific underlying mechanisms. In this systematic review, we summarize evidence for the similarities and differences in brain functional and structural features of MDD, PTSD, and their comorbidity, as well as the effects of extensively used therapies in patients with comorbid PTSD and MDD (PTSD+MDD). These functional magnetic resonance imaging (MRI) studies highlight the (i) shared hypoactivation in the prefrontal cortex during cognitive and emotional processing in MDD and PTSD; (ii) higher activation in fear processing regions including amygdala, hippocampus, and insula in PTSD compared to MDD; and (iii) distinct functional deficits in brain regions involved in fear and reward processing in patients with PTSD+MDD relative to those with PTSD alone. These structural MRI studies suggested that PTSD and MDD share features of reduced volume in focal frontal areas. The treatment effects in patients with PTSD+MDD may correlate with the normalization trend of structural alterations. Neuroimaging predictors of repetitive transcranial magnetic stimulation response in patients with PTSD+MDD may differ from the mono-diagnostic groups. In summary, neuroimaging studies to date have provided limited information about the shared and disorder-specific features in MDD and PTSD. Further research is essential to pave the way for developing improved diagnostic markers and eventually targeted treatment approaches for the shared and distinct brain alterations presented in patients with MDD and PTSD.

Latent cognitive phenotypes in juvenile myoclonic epilepsy: Clinical, sociodemographic, and neuroimaging associations.

Application of cluster analytic procedures has advanced understanding of the cognitive heterogeneity inherent in diverse epilepsy syndromes and the associated clinical and neuroimaging features. Application of this unsupervised machine learning approach to the neuropsychological performance of persons with juvenile myoclonic epilepsy (JME) has yet to be attempted, which is the intent of this investigation. A total of 77 JME participants, 19 unaffected siblings, and 44 unrelated controls, 12 to 25 years of age, were administered a comprehensive neuropsychological battery (intelligence, language, memory, executive function, and processing speed), which was subjected to factor analysis followed by K-means clustering of the resultant factor scores. Identified cognitive phenotypes were characterized and related to clinical, family, sociodemographic, and cortical and subcortical imaging features. Factor analysis revealed three underlying cognitive dimensions (general ability, speed/response inhibition, and learning/memory), with JME participants performing worse than unrelated controls across all factor scores, and unaffected siblings performing worse than unrelated controls on the general mental ability and learning/memory factors, with no JME vs sibling differences. K-means clustering of the factor scores revealed three latent groups including above average (31.4% of participants), average (52.1%), and abnormal performance (16.4%). Participant groups differed in their distributions across the latent groups (p < 0.001), with 23% JME, 22% siblings, and 2% unrelated controls in the abnormal performance group; and 18% JME, 21% siblings, and 59% unrelated controls in the above average group. Clinical epilepsy variables were unassociated with cluster membership, whereas family factors (lower parental education) and abnormally increased thickness and/or volume in the frontal, parietal, and temporal-occipital regions were associated with the abnormal cognition group. Distinct cognitive phenotypes characterize the spectrum of neuropsychological performance of patients with JME for which there is familial (sibling) aggregation. Phenotypic membership was associated with parental (education) and imaging characteristics (increased cortical thickness and volume) but not basic clinical seizure features.

Relationship between MRI brain-age heterogeneity, cognition, genetics and Alzheimer’s disease neuropathology

Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD). Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age range spanning 42-85 years. Participants were categorised into four groups based on the difference between their chronological and predicted age in each modality: advanced age in both (n=291), resilient in both (n=260) or advanced in one/resilient in the other (n=163/153). With the resilient group as the reference, brain-age groups were compared across neuroimaging features of neuropathology (white matter hyperintensity volume, neuronal loss measured with Neurite Orientation Dispersion and Density Imaging, AD-specific atrophy patterns measured with the Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease index, amyloid burden using amyloid positron emission tomography (PET), progression to mild cognitive impairment and baseline and longitudinal cognitive measures (trail making task, mini mental state examination, digit symbol substitution task). Individuals with advanced structural and functional brain-ages had more features indicative of neurodegeneration and they had poor cognition. Individuals with a resilient brain-age in both modalities had a genetic variant that has been shown to be associated with age of onset of AD. Mixed brain-age was associated with selective cognitive deficits. The advanced group displayed evidence of increased atrophy across all neuroimaging features that was not found in either of the mixed groups. This is in line with biomarkers of preclinical AD and cerebrovascular disease. These findings suggest that the variation in structural and functional brain ageing across individuals reflects the degree of underlying neuropathological processes and may indicate the propensity to develop dementia in later life. The National Institute on Aging, the National Institutes of Health, the Swiss National Science Foundation, the Kaiser Foundation Research Institute and the National Heart, Lung, and Blood Institute.