Double Trouble: Association of Malignant Melanoma with Sporadic and Genetic Forms of Parkinson's Disease and Asymptomatic Carriers of Related Genes: A Brief Report.

Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.

Cortical involvement and leptomeningeal inflammation in myelin oligodendrocyte glycoprotein antibody disease: A three-dimensional fluid-attenuated inversion recovery MRI study.

BACKGROUND: Cortical demyelination and meningeal inflammation have been detected neuropathologically in multiple sclerosis (MS) and recently in myelin oligodendrocyte glycoprotein antibody disease (MOGAD). OBJECTIVES: To assess in vivo cortical and leptomeningeal involvement in MOGAD. METHODS: We prospectively evaluated 11 MOGAD and 12 relapsing-remitting MS (RRMS) patients combining three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) and 3D-T1-weighted (3D-T1w) sequences at 3-Tesla magnetic resonance imaging (MRI). Leptomeningeal contrast enhancement (LMCE) was assessed on 3D-FLAIR post-gadolinium (3D-FLAIRGd). Cerebral cortical lesions (CCLs) were classified as either intracortical-subpial (IC-SP) or leukocortical (LC). RESULTS: CCLs were present in 8/11 MOGAD and 12/12 RRMS patients, with the number of CCLs being significantly lower in MOGAD (median (interquartile range (IQR)) 3 (0.5-4) vs 12 (4.75-19), p = 0.0032). In MOGAD, IC-SP lesions were slightly more prevalent than LC lesions (2 (0-2.5) vs 1 (0-2), p = 0.6579); whereas in RRMS, IC-SP lesions were less prevalent than LC lesions (3.5 (2.75-5.5) vs 9 (2-12.75), p = 0.27). LMCE was observed in 3/11 MOGAD and 1/12 RRMS patients; MOGAD with LMCE showed an increased median number of CCLs compared with MOGAD without LMCE (8 (4-9) vs 2.5 (0.75-3.25), p = 0.34). No correlation was observed between MOGAD MRI findings and (a) MOGAD duration, (b) serum MOG-immunoglobulin G1 titers, and (c) oligoclonal band presence. CONCLUSION: We described cortical lesion topography and detected for the first time LMCE using 3D-FLAIRGd sequences in MOGAD patients.

Structural and functional brain changes in X-linked Charcot-Marie-Tooth disease: insights from a multimodal neuroimaging study.

PURPOSE: Brain involvement in X-linked Charcot-Marie-Tooth disease (CMTX) has been previously reported. We studied the brain structural and functional integrity using a multimodal neuroimaging approach in patients with no current central nervous system (CNS) symptoms, in order to further delineate the disease's phenotype. METHODS: Seventeen CMTX patients with no current CNS symptoms and 24 matched healthy controls underwent brain magnetic resonance imaging (MRI). Structural integrity was evaluated performing Gray matter analysis with voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI). Functional integrity was evaluated with resting-state functional MRI (rs-fMRI). RESULTS: Decreased gray matter density was detected in CMTX patients compared to healthy controls in bilateral hippocampus, left thalamus, left postcentral gyrus, left superior parietal lobule, left cerebellum crus I and II, and vermis VI. DTI analysis showed increased fractional anisotropy and radial diffusivity in the right anterior insula and increased axial diffusivity in right cerebellum crus I in CMTX patients. rs-fMRI revealed decreased spontaneous neural activity on left precentral gyrus in patients compared to healthy controls. CONCLUSION: Advanced magnetic resonance (MR) neuroimaging techniques in CMTX patients revealed structural and functional involvement of multiple motor and extra-motor brain areas. MR neuroimaging techniques have the potential to delineate the CNS phenotype of a peripheral neuropathy like CMTX.

Executive Dysfunction, Social Cognition Impairment, and Gray Matter Pathology in Myotonic Dystrophy Type 2: A Pilot Study.

BACKGROUND: In contrast to myotonic dystrophy type 1, the cognitive and radiologic profile of myotonic dystrophy type 2 (DM2) is relatively poorly characterized. OBJECTIVE: To conduct a pilot study to systematically evaluate cognitive and radiologic features in a cohort of Greek individuals with DM2. METHOD: Eleven genetically confirmed individuals with DM2 and 26 age- and education-matched healthy controls were administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) to screen for impairment in multiple cognitive domains. MRI data were evaluated by morphometric analyses to identify disease-specific gray and white matter alterations. The following statistical thresholds were used for cognitive comparisons: PFDR < 0.05 and Bayes factor (BF 10 ) >10. RESULTS: The DM2 group exhibited cognitive impairment (ECAS Total score; PFDR = 0.001; BF 10 = 108.887), which was dominated by executive impairment ( PFDR = 0.003; BF 10 = 25.330). A trend toward verbal fluency impairment was also identified. No significant impairments in memory, language, or visuospatial function were captured. The analysis of subscores revealed severe impairments in social cognition and alternation. Voxel-based morphometry identified widespread frontal, occipital, and subcortical gray matter atrophy, including the left superior medial frontal gyrus, right medial orbitofrontal gyrus, right operculum, right precuneus, bilateral fusiform gyri, and bilateral thalami. CONCLUSION: DM2 may be associated with multifocal cortical and thalamic atrophy, which is likely to underpin the range of cognitive manifestations mostly characterized by executive impairment and specifically by impaired social cognition.

Neurometabolic Alterations in Motor Neuron Disease: Insights from Magnetic Resonance Spectroscopy.

Magnetic resonance spectroscopy (MRS) has contributed important academic insights in motor neuron diseases (MNDs), particularly in amyotrophic lateral sclerosis (ALS). Over the past three decades momentous methodological advances took place, including the emergence of high-field magnetic resonance imaging (MRI) platforms, multi-voxel techniques, whole-brain protocols, novel head-coil designs, and a multitude of open-source imaging suites. Technological advances in MRS are complemented by important conceptual developments in MND, such as the recognition of the importance of extra-motor brain regions, multi-timepoint longitudinal study designs, assessment of asymptomatic mutation carriers, description of genotype-associated signatures, and the gradual characterisation of non-ALS MND phenotypes. We have conducted a systematic review of published MRS studies in MND to identify important emerging research trends, key lessons from pioneering studies, and stereotyped shortcomings. We also sought to highlight notable gaps in the current literature so that research priorities for future studies can be outlined. While MRS remains relatively underutilised in MND compared to other structural, diffusivity and functional imaging modalities, our review suggests that MRS can not only advance our academic understanding of MND biology, but has a multitude of practical benefits for clinical and pharmaceutical trial applications.

Genotype-associated cerebellar profiles in ALS: focal cerebellar pathology and cerebro-cerebellar connectivity alterations.

OBJECTIVE: Cerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition. METHODS: A prospective imaging study has been undertaken with 271 participants to systematically evaluate cerebellar grey and white matter alterations, cerebellar peduncle integrity and cerebro-cerebellar connectivity in ALS. Participants were stratified into four groups: (1) patients testing positive for GGGGCC repeat expansions in C9orf72, (2) patients carrying an intermediate-length repeat expansion in ATXN2, (3) patients without established ALS-associated mutations and (4) healthy controls. Additionally, the cerebellar profile of a single patient with ALS who had an ATXN2 allele length of 62 was evaluated. Cortical thickness, grey matter and white matter volumes were calculated in each cerebellar lobule complemented by morphometric analyses to characterise genotype-associated atrophy patterns. A Bayesian segmentation algorithm was used for superior cerebellar peduncle volumetry. White matter diffusivity parameters were appraised both within the cerebellum and in the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed using deterministic tractography. RESULTS: Cerebellar pathology was confined to lobules I-V of the anterior lobe in patients with sporadic ALS in contrast to the considerable posterior lobe and vermis disease burden identified in C9orf72 mutation carriers. Patients with intermediate ATXN2 expansions did not exhibit significant cerebellar pathology. CONCLUSIONS: Focal rather than global cerebellar degeneration characterises ALS. Pathognomonic ALS symptoms which are typically attributed to other anatomical regions, such as dysarthria, dysphagia, pseudobulbar affect, eye movement abnormalities and cognitive deficits, may be modulated, exacerbated or partially driven by cerebellar changes in ALS.

Chemotherapy-Induced Brain Effects in Small-Cell Lung Cancer Patients: A Multimodal MRI Study.

The golden standard of treating Small Cell Lung Cancer (SCLC) entails application of platinum-based chemotherapy, is often accompanied by Prophylactic Cranial Irradiation (PCI), which have been linked to neurotoxic side-effects in cognitive functions. The related existing neuroimaging research mainly focuses on the effect of PCI treatment in life quality and expectancy, while little is known regarding the distinct adverse effects of chemotherapy. In this context, a multimodal MRI analysis based on structural and functional brain data is proposed in order to evaluate chemotherapy-specific effects on SCLC patients. Data from 20 patients (after chemotherapy and before PCI) and 14 healthy controls who underwent structural MRI, DTI and resting state fMRI were selected in this study. From a structural aspect, the proposed analysis included volumetry and thickness measurements on structural MRI data for assessing gray matter dissimilarities, as well as deterministic tractography and Tract-Based Spatial Statistics (TBSS) on DTI data, aiming to investigate potential white matter abnormalities. Functional data were also processed on the basis of connectivity analysis, evaluating brain network parameters to identify potential manifestation of functional inconsistencies. By comparing patients to healthy controls, the obtained results revealed statistically significant differences, with the patients' brains presenting reduced volumetry/thickness and fractional anisotropy values, accompanied by prominent differences in functional connectivity measurements. All above mentioned findings were observed in patients that underwent chemotherapy.

MRI evidence of extraocular muscle atrophy and fatty replacement in myasthenia gravis.

PURPOSE: The aim of the study was to evaluate extraocular muscle (EOM) atrophy and fatty replacement in ocular myasthenia gravis (OMG) and generalized myasthenia gravis (GMG) patients with chronic and untreated ocular symptoms or with inadequate response to immunotherapy and unprovoked ocular exacerbations despite chronic immunotherapy. METHODS: Nineteen patients with either OMG or GMG and 19 healthy age-matched controls underwent an orbital MRI. Visually obvious muscle atrophy and muscle fatty replacement were evaluated by two raters independently. Maximum thickness of EOM was measured. Measurements of the muscles of each participant were added up, in order to calculate the total thickness. RESULTS: Eleven patients suffered from AChR-positive GMG, and 8 patients from OMG. All patients had chronic ocular symptoms or inadequate response to corticosteroids and unprovoked ocular exacerbations in spite of immunotherapy. Fatty replacement was reported in 6/19 (31.6%) patients and 0/19 (0%) controls (p = 0.02). Obvious atrophy in at least one muscle was reported in 8/19 (42.1%) patients and 1/19 (5.3%) controls (p = 0.019). Statistically significant differences between the two groups were also found in the mean total thickness, as well as in the thickness of superior recti, levator palpebrae, inferior recti, and superior oblique muscles. CONCLUSION: EOM atrophy and fatty replacement were seen frequently in our series of MG patients with treatment difficulties and frequent relapses of ocular involvement.

Neuropsychological Assessment Should Always be Considered in Myotonic Dystrophy Type 2.

Myotonic dystrophies (DMs) are hereditary, multisystem, slowly progressive myopathies. One of the systems they affect is the CNS. In contrast to the well-established cognitive profile of myotonic dystrophy type 1 (DM1), only a few studies have investigated cognitive dysfunction in individuals with myotonic dystrophy type 2 (DM2), and their findings have been inconsistent. To identify the most commonly affected cognitive domains in individuals with DM2, we performed a formal comprehensive review of published DM2 studies. Using the terms "myotonic dystrophy type 2" AND "cognitive deficits," "cognitive," "cognition," "neuropsychological," "neurocognitive," and "neurobehavioral" in all fields, we conducted an advanced search on PubMed. We read and evaluated all of the available original research articles (13) and one case study, 14 in total, and included them in our review. Most of the research studies of DM2 reported primary cognitive deficits in executive functions (dysexecutive syndrome), memory (short-term nonverbal, verbal episodic memory), visuospatial/constructive-motor functions, and attention and processing speed; language was rarely reported to be affected. Based on the few neuroimaging and/or multimodal DM2 studies we could find, the cognitive profile of DM2 is associated with brain abnormalities in several secondary and high-order cortical and subcortical regions and associative white matter tracts. The limited sample size of individuals with DM2 was the most prominent limitation of these studies. The multifaceted profile of cognitive deficits found in individuals with DM2 highlights the need for routine neuropsychological assessment at both baseline and follow-up, which could unveil these individuals' cognitive strengths and deficits.

Multimodal Neurophysiological and Neuroimaging Evidence of Genetic Influence on Motor Control: A Case Report of Monozygotic Twins.

Considering genetic influence on brain structure and function, including motor control, we report a case of right-handed monozygotic twins with atypical organization of fine motor movement control that might imply genetic influence. Structural and functional organization of the twins' motor function was assessed using transcranial magnetic stimulation (TMS), fMRI with a motor-task paradigm, and diffusion tensor imaging (DTI) tractography. TMS revealed that both twins presented the same unexpected activation and inhibition of both motor cortices during volitional unilateral fine hand movement. The right ipsilateral corticospinal tract was weaker than the left contralateral one. The motor-task fMRI identified activation in the left primary motor cortex and bilateral secondary motor areas during right-hand (dominant) movement and activation in the bilateral primary motor cortex and secondary motor areas during left-hand movement. Based on DTI tractography, both twins showed a significantly lower streamline count (number of fibers) in the right corticospinal tract compared with a control group, which was not the case for the left corticospinal tract. Neither twin reported any difficulty in conducting fine motor movements during their activities of daily living. The combination of TMS and advanced neuroimaging techniques identified an atypical motor control organization that might be influenced by genetic factors. This combination emphasizes that activation of the unilateral uncrossed pyramidal tract represents an alternative scheme to a "failure" of building a standard pattern but may not necessarily lead to disability.

X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association.

OBJECTIVE: X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, a gap junction protein expressed in Schwann cells, but also found in oligodendrocytes. Four patients with CMTX developing central nervous system (CNS) demyelination compatible with multiple sclerosis (MS) have been individually published. We presently sought to systematically investigate the relationship between CMTX and MS. METHODS: Over 20 years, 70 consecutive patients (36 men) with GJB1 mutations were identified at our Neurogenetics Unit, Athens, Greece, and assessed for clinical features suggestive of MS. Additionally, 18 patients with CMTX without CNS symptoms and 18 matched controls underwent brain MRI to investigate incidental findings. Serum from patients with CMTX and MS was tested for CNS immunoreactivity. RESULTS: We identified three patients with CMTX who developed clinical features suggestive of inflammatory CNS demyelination fulfilling MS diagnostic criteria. The resulting 20-year MS incidence (4.3%) differed significantly from the highest background 20-year MS incidence ever reported from Greece (p=0.00039). The search for incidental brain MRI findings identified two CMTX cases (11%) with lesions suggestive of focal demyelination compared with 0 control. Moreover, 10 cases in the CMTX cohort had hyperintensity in the splenium of the corpus callosum compared with 0 control (p=0.0002). No specific CNS-reactive humoral factors were identified in patients with CMTX and MS. CONCLUSIONS: We have demonstrated a higher than expected frequency of MS in patients with CMTX and identified incidental focal demyelinating lesions on brain MRI in patients with CMTX without CNS symptoms. This provides circumstantial evidence for GJB1 mutations acting as a possible MS risk factor.

The Neural Correlates of Impaired Self-Monitoring Among Individuals With Neurodegenerative Dementias.

OBJECTIVE: Self-monitoring is a crucial component of human empathy and necessary for the formation and repair of social relations. Several studies have brought to light possible neuronal substrates associated with self-monitoring, but the information that they have provided is inconclusive. The authors, therefore, studied a large group of patients with dementia to assess what brain structures are necessary for the self-monitoring function.Methods: Seventy-seven patients with dementia of various types were screened using voxel-based morphometry to assess possible volume reduction in the brain structures of patients with self-monitoring problems, and the decrease of socioemotional expressiveness and modification of self-presentation was estimated using the Revised Self-Monitoring Scale. Regression analysis was employed to investigate the correlation between gray matter loss and deficient self-monitoring.Results: The socioemotional expressiveness scores were associated with decreased gray matter volume in the right olfactory cortex, inferior frontal gyrus, superior temporal pole, parahippocampal gyrus, insula, and medial temporal gyrus bilaterally. Self-presentation scores were associated with bilateral gray matter volume reduction in the olfactory cortex, insula, rectus gyrus and inferior frontal gyrus, right superior temporal pole, and parahippocampal gyrus, as well as the left medial temporal gyrus and anterior superior frontal gyrus.Conclusions: These results suggest that patients with dementia present decreased ability of self-monitoring, probably due to impaired insula and orbitofrontal cortex and their disconnection from structures of the salience network.

Ipsilateral and contralateral cerebro-cerebellar white matter connections: A diffusion tensor imaging study in healthy adults.

BACKGROUND AND PURPOSE: The cerebellum has a pivotal role in regulating human behavior; yet whether this function is mediated only through contralateral cerebro-cerebellar pathways is under-investigated. Thus, we examined feed-backward and feed-forward ipsilateral and contralateral cerebro-cerebellar connections using a detereministic diffusion tensor imaging (DTI) algorithm, the robustness of which was also estimated using phantom DTI data. MATERIALS AND METHODS: Fifty-one healthy controls (22-60 years old; 15 males/36 females) were scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of-interest (ROI) method was applied for the reconstruction of the ipsilateral and contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto-cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally using the Brainance DTI Suite. A realistic diffusion MR phantom was used to evaluate the fiber tracking methodology for 16 fibers containing crossing, kissing, splitting and bending configurations. RESULTS: Both contralateral and ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully reconstructed; the contralateral DRTC tract was not reconstructed in all subjects. Also, the TPC tract was not reproduced in several subjects mostly regarding the contralateral connection. Descriptive DTI measures (number of fibers, fractional anisotropy, radial and axial diffusivity) are presented for each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16 fibers that almost perfectly matched the 16 ground truth fibers. CONCLUSIONS: We identified ipsilateral and contralateral connections using a clinically applicable DTI sequence, a robust deterministic algorithm and an unbiased methodology, which can be applied in daily practice in different brain pathologies.

Verbal and Figural Fluency in Temporal Lobe Epilepsy: Does Hippocampal Sclerosis Affect Performance?

BACKGROUND AND OBJECTIVES: Clinicians commonly use verbal and nonverbal measures to test fluency in patients with epilepsy, either during routine cognitive assessment or as part of pre- and postsurgical evaluation. We hypothesized that patients with mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis would perform worse than patients with lateral TLE in both verbal and design fluency. METHODS: We assessed semantic, phonemic, and nonverbal fluency in 49 patients with TLE: 31 with lateral TLE and 18 with mesial TLE plus hippocampal sclerosis. We also gave non-fluency cognitive measures: psychomotor speed, attentional set shifting, selective attention, abstract reasoning, verbal and visual episodic memory, and incidental memory. RESULTS: Patients with mesial TLE performed significantly worse on figural fluency than patients with lateral TLE. Even though group differences on verbal fluency measures were not significant, the patients with mesial TLE had a pattern of poorer performance. The patients with mesial TLE scored significantly worse on measures of selective attention, verbal episodic memory, and incidental memory. CONCLUSIONS: Our study underlines differences in cognitive function between patients with mesial and lateral TLE, particularly in figural fluency. Although we cannot directly assess the role of the hippocampus in cognitive aspects of creative and divergent thinking related to figural fluency, the cognitive discrepancies between these two TLE groups could be ascribed to the mesial TLE hippocampal pathology shown in our study and addressed in the literature on hippocampal involvement in divergent thinking. Our findings could benefit cognitive rehabilitation programs tailored to the needs of patients with TLE.

Evaluating cognitive models of visual word recognition using fMRI: Effects of lexical and sublexical variables.

In this study predictions of the dual-route cascaded (DRC) model of word reading were tested using fMRI. Specifically, patterns of co-localization were investigated: (a) between pseudoword length effects and a pseudowords vs. fixation contrast, to reveal the sublexical grapho-phonemic conversion (GPC) system; and (b) between word frequency effects and a words vs. pseudowords contrast, to reveal the orthographic and phonological lexicon. Forty four native speakers of Greek were scanned at 3T in an event-related lexical decision task with three event types: (a) 150 words in which frequency, length, bigram and syllable frequency, neighborhood, and orthographic consistency were decorrelated; (b) 150 matched pseudowords; and (c) fixation. Whole-brain analysis failed to reveal the predicted co-localizations. Further analysis with participant-specific regions of interest defined within masks from the group contrasts revealed length effects in left inferior parietal cortex and frequency effects in the left middle temporal gyrus. These findings could be interpreted as partially consistent with the existence of the GPC system and phonological lexicon of the model, respectively. However, there was no evidence in support of an orthographic lexicon, weakening overall support for the model. The results are discussed with respect to the prospect of using neuroimaging in cognitive model evaluation.

A Magnetic Resonance Spectroscopy Study on Polarity Subphenotypes in Bipolar Disorder.

Although magnetic resonance spectroscopy (MRS) has provided in vivo measurements of brain chemical profiles in bipolar disorder (BD), there are no data on clinically and therapeutically important onset polarity (OP) and predominant polarity (PP). We conducted a proton MRS study in BD polarity subphenotypes, focusing on emotion regulation brain regions. Forty-one euthymic BD patients stratified according to OP and PP and sixteen healthy controls (HC) were compared. 1H-MRS spectra of the anterior and posterior cingulate cortex (ACC, PCC), left and right hippocampus (LHIPPO, RHIPPO) were acquired at 3.0T to determine metabolite concentrations. We found significant main effects of OP in ACC mI, mI/tNAA, mI/tCr, mI/tCho, PCC tCho, and RHIPPO tNAA/tCho and tCho/tCr. Although PP had no significant main effects, several medium and large effect sizes emerged. Compared to HC, manic subphenotypes (i.e., manic-OP, manic-PP) showed greater differences in RHIPPO and PCC, whereas depressive suphenotypes (i.e., depressive-OP, depressive-PP) in ACC. Effect sizes were consistent between OP and PP as high intraclass correlation coefficients (ICC) were confirmed. Our findings support the utility of MRS in the study of the neurobiological underpinnings of OP and PP, highlighting that the regional specificity of metabolite changes within the emotion regulation network consistently marks both polarity subphenotypes.

A Comprehensive Review on the Role of Resting-State Functional Magnetic Resonance Imaging in Predicting Post-Stroke Motor and Sensory Outcomes.

Stroke is a major leading cause of chronic disability, often affecting patients' motor and sensory functions. Functional magnetic resonance imaging (fMRI) is the most commonly used method of functional neuroimaging, and it allows for the non-invasive study of brain activity. The time-dependent coactivation of different brain regions at rest is described as resting-state activation. As a non-invasive task-independent functional neuroimaging approach, resting-state fMRI (rs-fMRI) may provide therapeutically useful information on both the focal vascular lesion and the connectivity-based reorganization and subsequent functional recovery in stroke patients. Considering the role of a prompt and accurate prognosis in stroke survivors along with the potential of rs-fMRI in identifying patterns of neuroplasticity in different post-stroke phases, this review provides a comprehensive overview of the latest literature regarding the role of rs-fMRI in stroke prognosis in terms of motor and sensory outcomes. Our comprehensive review suggests that with the advancement of MRI acquisition and data analysis methods, rs-fMRI emerges as a promising tool to study the motor and sensory outcomes in stroke patients and evaluate the effects of different interventions.

Brain multi-contrast, multi-atlas segmentation of diffusion tensor imaging and ensemble learning automatically diagnose late-life depression.

We investigated the potential of machine learning for diagnostic classification in late-life major depression based on an advanced whole brain white matter segmentation framework. Twenty-six late-life depression and 12 never depressed individuals aged > 55 years, matched for age, MMSE, and education underwent brain diffusion tensor imaging and a multi-contrast, multi-atlas segmentation in MRIcloud. Fractional anisotropy volume, mean fractional anisotropy, trace, axial and radial diffusivity (RD) extracted from 146 white matter parcels for each subject were used to train and test the AdaBoost classifier using stratified 12-fold cross validation. Performance was evaluated using various measures. The statistical power of the classifier was assessed using label permutation test. Statistical analysis did not yield significant differences in DTI measures between the groups. The classifier achieved a balanced accuracy of 71% and an Area Under the Receiver Operator Characteristic Curve (ROC-AUC) of 0.81 by trace, and a balanced accuracy of 70% and a ROC-AUC of 0.80 by RD, in limbic, cortico-basal ganglia-thalamo-cortical loop, brainstem, external and internal capsules, callosal and cerebellar structures. Both indices shared important structures for classification, while fornix was the most important structure for classification by both indices. The classifier proved statistically significant, as trace and RD ROC-AUC scores after permutation were lower than those obtained with the actual data (P = 0.022 and P = 0.024, respectively). Similar results were obtained with the Gradient Boosting classifier, whereas the RBF-kernel Support Vector Machine with k-best feature selection did not exceed the chance level. Finally, AdaBoost significantly predicted the class using all features together. Limitations are discussed. The results encourage further investigation of the implemented methods for computer aided diagnostics and anatomically informed therapeutics.