Thalamic Atrophy Research Articles

Complex Regional Pain Syndrome: Thalamic GMV Atrophy and Associations of Lower GMV With Clinical and Sensorimotor Performance Data.

Results on gray matter alterations in complex regional pain syndrome (CRPS) showed heterogeneous findings. Since CRPS is a rare disease, most studies included only small and heterogeneous samples resulting in a low reliability of findings between studies. We investigated 24 CRPS patients with right upper limb affection in the chronic stage of disease using structural MRI and clinical testing. We focused on gray matter volume (GMV) alterations of the brain in comparison to 33 age matched healthy controls, their association to clinical characteristics (duration of pain syndrome and pain intensity ratings) and sensorimotor performance (finger dexterity and spatiotactile resolution). When applying an explorative whole brain analysis CRPS patients showed lower GMV in the bilateral medial thalamus. No other areas showed a relevant GMV difference for the group comparisons. When applying a region of interest driven approach using anatomical masks of the thalamus, ACC/mPFC, putamen, and insula we found relevant associations of clinical and behavioral data in ACC and insula. Whereas, the GMV in ACC showed negative associations with pain intensity and CRPS duration, the GMV of the left posterior insula was negatively associated with sensorimotor performance of the affected hand side. Overall, our results are in accordance to results of others describing a thalamic reduction of GMV in patients with neuropathic pain and are also in accordance with associations of pain intensity and duration with reduced ACC in general in patients with chronic pain syndromes. Sensorimotor performance seems to be related to posterior insula GMV reduction, which has not been described yet for other patient groups.

Cortical Thickness and Serum NfL Explain Cognitive Dysfunction in Newly Diagnosed Patients With Multiple Sclerosis.

Background and ObjectivesTo determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS).MethodsThirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment.ResultsCompared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT.DiscussionThalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS.

Effect of 5 Years of Exercise Intervention at Different Intensities on Brain Structure in Older Adults from the General Population: A Generation 100 Substudy.

PurposeThe aim was to examine the effect of a 5-year exercise intervention at different intensities on brain structure in older adults from the general population partaking in the randomized controlled trial Generation 100 Study.Participants and MethodsGeneration 100 Study participants were invited to a longitudinal neuroimaging study before randomization. A total of 105 participants (52 women, 70–77 years) volunteered. Participants were randomized into supervised exercise twice a week performing high intensity interval training in 4×4 intervals at ~90% peak heart rate (HIIT, n = 33) or 50 minutes of moderate intensity continuous training at ~70% of peak heart rate (MICT, n = 24). The control group (n = 48) followed the national physical activity guidelines of ≥30 min physical activity daily. Brain MRI at 3T, clinical and cardiorespiratory fitness (CRF), measured as peak oxygen uptake, were collected at baseline, and after 1, 3, and 5 years of intervention. Brain volumes and cortical thickness were derived from T1 weighted 3D MRI data using FreeSurfer. The effect of HIIT or MICT on brain volumes over time was investigated with linear mixed models, while linear regressions examined the effect of baseline CRF on brain volumes at later time points.ResultsAdherence in each group was between 79 and 94% after 5 years. CRF increased significantly in all groups during the first year. Compared to controls, the HIIT group had significantly increased hippocampal atrophy located to CA1 and hippocampal body, though within normal range, and the MICT group greater thalamic atrophy. No other effects of intervention group were found. CRF across the intervention was not associated with brain structure, but CRF at baseline was positively associated with cortical volume at all later time points.ConclusionHigher baseline CRF reduced 5-year cortical atrophy rate in older adults, while following physical activity guidelines was associated with the lowest hippocampal and thalamic atrophy rates.

Differential association of cortical, subcortical and spinal cord damage with multiple sclerosis disability milestones: A multiparametric MRI study

Background: In multiple sclerosis (MS), cortical, subcortical and infratentorial structural damage may have a differential contribution to clinical disability according to disease phases. Purpose: To determine the relative contributions of cortical, deep (D) grey matter (GM), cerebellar and cervical cord damage to MS disability milestones. Methods: Multi-centre 3T brain and cervical cord T2- and three-dimensional (3D) T1-weighted images were acquired from 198 MS patients (139 relapsing-remitting (RR) MS, 59 progressive (P) MS) and 67 healthy controls. Brain/cord lesion burden, cortical thickness (CTh), DGM and cerebellar volumetry and cord cross-sectional area (CSA) were quantified. Random forest analyses identified predictors of expanded disability status scale (EDSS) disability milestones (EDSS = 3.0, 4.0 and 6.0). Results: MS patients had widespread atrophy in all investigated compartments versus controls (p-range: ⩽0.001–0.05). Informative determinants of EDSS = 3.0 were cord CSA, brain lesion volume, frontal CTh and thalamic and cerebellar atrophy (out-of-bag (OOB) accuracy = 0.84, p-range: ⩽0.001–0.05). EDSS = 4.0 was mainly predicted by cerebellar and cord atrophy, frontal and sensorimotor CTh and cord lesion number (OOB accuracy = 0.84, p-range: ⩽0.001–0.04). Cervical cord CSA (p = 0.001) and cord lesion number (p = 0.003) predicted EDSS = 6.0 (OOB accuracy = 0.77). Conclusion: Brain lesion burden, cortical and thalamic atrophy were the main determinants of EDSS = 3.0 and 4.0, while cord damage played a major contribution to EDSS = 6.0.

Thalamic nuclei degeneration in multiple sclerosis

ObjectivesTo define both the severity and extent of structural alteration in certain thalamic nuclei by means of MR morphometry and to compare these findings with clinical performance in different phenotypes of multiple sclerosis (MS). MethodsWe comparatively measured the thalamus nuclei volumes of patients with remitting-relapsing (RRMS) and secondary-progressive (SPMS) phenotypes of multiple sclerosis and healthy control subjects (HC). The evaluation of neurological performance was based on the results of Expanded Disability Status Scale and Multiple Sclerosis Severity Scale. Cognitive and mental state was rated according to the results of Mini-Mental State Examination, Frontal Assessment Battery, Montreal Cognitive Assessment and Symbol Digit Modalities Test. Freesurfer 6.0 was used for thalamic nuclei volumes calculation. ResultsThe median volume decline in thalamic pulvinar nuclei in RRMS group on the left side (anterior nucleus − 186,6 mm3, posterior nucleus – 149,4 mm3, medial nucleus 852,4 mm3) compared to HC (anterior nucleus – 229,2 mm3, posterior nucleus – 187,5 mm3, medical nucleus – 1081,3 mm3). Same group, right side – anterior nucleus – 219,5 mm3, posterior nucleus 187,1 mm3, medial nucleus – 989,6 mm3; HC group – anterior nucleus 261,1 mm3, posterior nucleus 240,5 mm3, medial nucleus – 1196,7 mm3 (p < 0,05). The highest correlation of the written section of SDMT was observed with the left ventral anterior nucleus (r = 0,71). ConclusionThese findings indicate the credible correlation between clinical progression of neurological and cognitive impairment in MS patients with asymmetry left-sided thalamic nuclei atrophy and may be considered a potential predicting tool of MS progression.

Unraveling Deep Gray Matter Atrophy and Iron and Myelin Changes in Multiple Sclerosis.

Modifications of magnetic susceptibility have been consistently demonstrated in the subcortical gray matter of MS patients, but some uncertainties remain concerning the underlying neurobiological processes and their clinical relevance. We applied quantitative susceptibility mapping and longitudinal relaxation rate relaxometry to clarify the relative contribution of atrophy and iron and myelin changes to deep gray matter damage and disability in MS. Quantitative susceptibility mapping and longitudinal relaxation rate maps were computed for 91 patients and 55 healthy controls from MR images acquired at 3T. Applying an external model, we estimated iron and myelin concentration maps for all subjects. Subsequently, changes of deep gray matter iron and myelin concentration (atrophy-dependent) and content (atrophy-independent) were investigated globally (bulk analysis) and regionally (voxel-based and atlas-based thalamic subnuclei analyses). The clinical impact of the observed MRI modifications was evaluated via regression models. We identified reduced thalamic (P < .001) and increased pallidal (P < .001) mean iron concentrations in patients with MS versus controls. Global myelin and iron content in the basal ganglia did not differ between the two groups, while actual iron depletion was present in the thalamus (P < .001). Regionally, patients showed increased iron concentration in the basal ganglia (P ≤ .001) and reduced iron and myelin content in thalamic posterior-medial regions (P ≤ .004), particularly in the pulvinar (P ≤ .001). Disability was predicted by thalamic volume (B = -0.341, P = .02), iron concentration (B = -0.379, P = .005) and content (B = -0.406, P = .009), as well as pulvinar iron (B = -0.415, P = .003) and myelin (B = -0.415, P = .02) content, independent of atrophy. Quantitative MRI suggests an atrophy-related iron increase within the basal ganglia of patients with MS, along with an atrophy-independent reduction of thalamic iron and myelin correlating with disability. Absolute depletions of thalamic iron and myelin may represent sensitive markers of subcortical GM damage, which add to the clinical impact of thalamic atrophy in MS.

Disability in multiple sclerosis is related to thalamic connectivity and cortical network atrophy

Background: Thalamic atrophy is proposed to be a major predictor of disability progression in multiple sclerosis (MS), while thalamic function remains understudied. Objectives: To study how thalamic functional connectivity (FC) is related to disability and thalamic or cortical network atrophy in two large MS cohorts. Methods: Structural and resting-state functional magnetic resonance imaging (fMRI) was obtained in 673 subjects from Amsterdam (MS: N = 332, healthy controls (HC): N = 96) and Graz (MS: N = 180, HC: N = 65) with comparable protocols, including disability measurements in MS (Expanded Disability Status Scale, EDSS). Atrophy was measured for the thalamus and seven well-recognized resting-state networks. Static and dynamic thalamic FC with these networks was correlated with disability. Significant correlates were included in a backward multivariate regression model. Results: Disability was most strongly related (adjusted R2 = 0.57, p < 0.001) to higher age, a progressive phenotype, thalamic atrophy and increased static thalamic FC with the sensorimotor network (SMN). Static thalamus–SMN FC was significantly higher in patients with high disability (EDSS ⩾ 4) and related to network atrophy but not thalamic atrophy or lesion volumes. Conclusion: The severity of disability in MS was related to increased static thalamic FC with the SMN. Thalamic FC changes were only related to cortical network atrophy, but not to thalamic atrophy.

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

Grey matter (GM) alterations may contribute to cognitive decline in individuals with white matter hyperintensities (WMH) but no consensus has yet emerged. Here, we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment (WMH-MCI), 43 WMH patients without cognitive impairment, and 55 healthy controls. Both WMH groups showed GM atrophy in the bilateral thalamus, fronto-insular cortices, and several parietal-temporal regions, and the WMH-MCI group showed more extensive and severe GM atrophy. The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients. Furthermore, the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses. These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

Contribution of Gray Matter Atrophy and White Matter Damage to Cognitive Impairment in Mildly Disabled Relapsing-Remitting Multiple Sclerosis Patients.

Cognitive impairment (CI) is frequently present in multiple sclerosis patients. Despite ongoing research, the neurological substrates have not been fully elucidated. In this study we investigated the contribution of gray and white matter in the CI observed in mildly disabled relapsing-remitting multiple sclerosis (RRMS) patients. For that purpose, 30 patients with RRMS (median EDSS = 2), and 30 age- and sex-matched healthy controls were studied. CI was assessed using the symbol digit modalities test (SDMT) and the memory alteration test. Brain magnetic resonance imaging, diffusion tensor imaging (DTI), voxel-based morphometry (VBM), brain segmentation, thalamic vertex analysis, and connectivity-based thalamic parcellation analyses were performed. RRMS patients scored significantly lower in both cognitive tests. In the patient group, significant atrophy in the thalami was observed. Multiple regression analyses revealed associations between SDMT scores and GM volume in both hemispheres in the temporal, parietal, frontal, and occipital lobes. The DTI results pointed to white matter damage in all thalamocortical connections, the corpus callosum, and several fasciculi. Multiple regression and correlation analyses suggested that in RRMS patients with mild disease, thalamic atrophy and thalamocortical connection damage may lead to slower cognitive processing. Furthermore, white matter damage at specific fasciculi may be related to episodic memory impairment.

Abstract P359: Secondary Thalamic Atrophy Related to Brain Infarction is Associated With Post-Stroke Cognitive Impairment

Background: The thalamus is globally connected to many brain regions. Previous work highlights thalamic contributions to multiple cognitive functions, but few studies have measured thalamic volume changes or explored correlates of such changes with post-stroke cognition. Hence this study investigates possible associations of thalamic volumes with post-stroke cognitive functions. Methods: Participants with brain infarcts (6-42 months) underwent volumetric brain MRI and cognitive testing, including the Montreal Cognitive Assessment (MoCA). Focal Brain infarcts and thalami were traced manually. If the patient had bilateral infarcts, the side of the primary infarct volume defined the hemisphere involved. Brain parcellation and volumetrics used our comprehensive semi-automatic brain region and vascular lesion extraction pipeline (Ramirez, Neuroimage, 2011). MRI in 24 age and gender-matched healthy people provided normal comparative thalamic volumes. Thalamic atrophy was defined by percent thalamic volume loss in the stroke hemisphere compared to the other side. Spearman correlation assessed relationships between thalamic and infarct volumes and MoCA scores. Logistic regression analysis assessed whether thalamic atrophy correlated with MoCA score. Results: Thalami volumes ipsilateral to the infarct in stroke patients (n=55) were smaller than left (4.4 ± 1.4 vs. 5.4 ± 0.8 cc, p = 0.012) and right (4.4 ± 1.4 vs. 5.3 ± 0.7 cc, p = 0.024) thalamic volumes in the controls. Thalamic volumes were inversely correlated with ipsilateral infarct volumes (r = -0.384, p = 0.004). After controlling for head-size and brain atrophy, infarct volume independently correlated with ipsilateral thalamic volume s (β= -0.068, P=0.026), and only frontal infarcts (β = 2.300, p = 0.021) independently contributed to &gt; 15% ipsilateral thalamic atrophy. Left thalamic atrophy of &gt; 10% correlated significantly with poorer MoCA performance (β = 3.139, p = 0.023), after controlling for demographics and infarct volumes. Conclusions: Our results suggest that remote effects of infarction on ipsilateral thalamic volume, presumably related to disrupted thalamic-cortical interconnectivity, is associated with a commonly used metric of post-stroke cognitive impairment.

Thalamic Injury and Cognition in Multiple Sclerosis.

Multiple sclerosis (MS) produces demyelination and degeneration in both gray and white matter. Both cortical and deep gray matter injury is observed during the course of MS. Among deep gray matter structures, the thalamus has received special attention, as it undergoes volume loss in different MS subtypes and is involved in the earliest form of the disease, radiologically isolated syndrome. The thalamus plays an important role as an information relay center, and involvement of the thalamus in MS has been associated with a variety of clinical manifestations in MS, including fatigue, movement disorders, pain, and cognitive impairment (CI). Similar to thalamic volume loss, CI is seen from the earliest stages of MS and is potentially one of the most debilitating manifestations of the disease. The thalamus, particularly the dorsomedial nucleus as part of the basolateral limbic circuit and anterior thalamic nuclei through connections with the prefrontal cortex, has been shown to be involved in CI. Specifically, several cognitive performance measures such as processing speed and memory correlate with thalamic volume. Thalamic atrophy is one of the most important predictors of CI in MS, and both thalamic volume, diffusion tensor imaging measures, and functional activation correlate with the degree of CI in MS. Although the exact mechanism of thalamic atrophy is not well-understood, it is hypothesized to be secondary to degeneration following white matter injury resulting in secondary neurodegeneration and neuronal loss. The thalamus may represent an ideal biomarker for studies aiming to test neuroprotective or restorative therapies aimed at cognition.

Reduced Thalamic Volume and Metabolites in Type 1 Diabetes with Polyneuropathy.

Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy. 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored. In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume. In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4.

SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive spasticity and weakness of the lower limbs caused by degeneration of the corticospinal tract. In other neurodegenerative motor disorders, the thalamus and basal ganglia are affected, with a considerable impact on disease progression. However, only a few works have studied these brain structures in HSP, mainly in complex forms of this disease. Our research aims to detect potential alterations in the volume and shape of the thalamus and various basal ganglia structures by comparing 12 patients with pure HSP and 18 healthy controls. We used two neuroimaging procedures: automated segmentation of the subcortical structures (thalamus, hippocampus, caudate nucleus, globus pallidus, and putamen) in native space and shape analysis of the structures. We found a significant reduction in thalamic volume bilaterally, as well as an inward deformation, mainly in the sensory-motor thalamic regions in patients with pure HSP and a mutation in SPG4. We also observed a significant negative correlation between the shape of the thalamus and clinical scores (the Spastic Paraplegia Rating Scale score and disease duration). Moreover, we found a 'Group × Age' interaction that was closely related to the severity of the disease. No differences in volume or in shape were found in the remaining subcortical structures studied. Our results suggest that changes in structure of the thalamus could be an imaging biomarker of disease progression in pHSP.

DeepGRAI (Deep Gray Rating via Artificial Intelligence): Fast, feasible, and clinically relevant thalamic atrophy measurement on clinical quality T2-FLAIR MRI in multiple sclerosis

BackgroundThalamic volume loss is a key marker of neurodegeneration in multiple sclerosis (MS). T2-FLAIR MRI is a common denominator in clinical routine MS imaging, but current methods for thalamic volumetry are not applicable to it. ObjectiveTo develop and validate a robust algorithm to measure thalamic volume using clinical routine T2-FLAIR MRI. MethodsA dual-stage deep learning approach based on 3D U-net (DeepGRAI – Deep Gray Rating via Artificial Intelligence) was created and trained/validated/tested on 4,590 MRI exams (4288 2D-FLAIR, 302 3D-FLAIR) from 59 centers (80/10/10 train/validation/test split). As training/test targets, FIRST was used to generate thalamic masks from 3D T1 images. Masks were reviewed, corrected, and aligned into T2-FLAIR space. Additional validation was performed to assess inter-scanner reliability (177 subjects at 1.5 T and 3 T within one week) and scan-rescan-reliability (5 subjects scanned, repositioned, and then re-scanned). A longitudinal dataset including assessment of disability and cognition was used to evaluate the predictive value of the approach. ResultsDeepGRAI automatically quantified thalamic volume in approximately 7 s per case, and has been made publicly available. Accuracy on T2-FLAIR relative to 3D T1 FIRST was 99.4% (r = 0.94, p < 0.001,TPR = 93.0%, FPR = 0.3%). Inter-scanner error was 3.21%. Scan-rescan error with repositioning was 0.43%. DeepGRAI-derived thalamic volume was associated with disability (r = -0.427,p < 0.001) and cognition (r = -0.537,p < 0.001), and was a significant predictor of longitudinal cognitive decline (R2 = 0.081, p = 0.024; comparatively, FIRST-derived volume was R2 = 0.080, p = 0.025). ConclusionsDeepGRAI provides fast, reliable, and clinically relevant thalamic volume measurement on multicenter clinical-quality T2-FLAIR images. This indicates potential for real-world thalamic volumetry, as well as quantification on legacy datasets without 3D T1 imaging.

Hippocampal subfield and anterior-posterior segment volumes in patients with sporadic amyotrophic lateral sclerosis

Neuroimaging studies of hippocampal volumes in patients with amyotrophic lateral sclerosis (ALS) have reported inconsistent results. Our aims were to demonstrate that such discrepancies are largely due to atrophy of different regions of the hippocampus that emerge in different disease stages of ALS and to explore the existence of co-pathology in ALS patients. We used the well-validated King’s clinical staging system for ALS to classify patients into different disease stages. We investigated in vivo hippocampal atrophy patterns across subfields and anterior-posterior segments in different King’s stages using structural MRI in 76 ALS patients and 94 health controls (HCs). The thalamus, corticostriatal tract and perforant path were used as structural controls to compare the sequence of alterations between these structures and the hippocampal subfields. Compared with HCs, ALS patients at King’s stage 1 had lower volumes in the bilateral posterior subiculum and presubiculum; ALS patients at King’s stage 2 exhibited lower volumes in the bilateral posterior subiculum, left anterior presubiculum and left global hippocampus; ALS patients at King’s stage 3 showed significantly lower volumes in the bilateral posterior subiculum, dentate gyrus and global hippocampus. Thalamic atrophy emerged at King’s stage 3. White matter tracts remained normal in a subset of ALS patients. Our study demonstrated that the pattern of hippocampal atrophy in ALS patients varies greatly across King’s stages. Future studies in ALS patients that focus on the hippocampus may help to further clarify possible co-pathologies in ALS.

Manual and automated tissue segmentation confirm the impact of thalamus atrophy on cognition in multiple sclerosis: A multicenter study

Background and rationaleThalamus atrophy has been linked to cognitive decline in multiple sclerosis (MS) using various segmentation methods. We investigated the consistency of the association between thalamus volume and cognition in MS for two common automated segmentation approaches, as well as fully manual outlining. MethodsStandardized neuropsychological assessment and 3-Tesla 3D-T1-weighted brain MRI were collected (multi-center) from 57 MS patients and 17 healthy controls. Thalamus segmentations were generated manually and using five automated methods. Agreement between the algorithms and manual outlines was assessed with Bland-Altman plots; linear regression assessed the presence of proportional bias. The effect of segmentation method on the separation of cognitively impaired (CI) and preserved (CP) patients was investigated through Generalized Estimating Equations; associations with cognitive measures were investigated using linear mixed models, for each method and vendor. ResultsIn smaller thalami, automated methods systematically overestimated volumes compared to manual segmentations [ρ=(-0.42)-(-0.76); p-values < 0.001). All methods significantly distinguished CI from CP MS patients, except manual outlines of the left thalamus (p = 0.23). Poorer global neuropsychological test performance was significantly associated with smaller thalamus volumes bilaterally using all methods. Vendor significantly affected the findings. ConclusionAutomated and manual thalamus segmentation consistently demonstrated an association between thalamus atrophy and cognitive impairment in MS. However, a proportional bias in smaller thalami and choice of MRI acquisition system might impact the effect size of these findings.

Cognitive and Neuroimaging Profiles of Individuals With Dual Decline in Memory and Gait

Across 6 aging cohorts we showed that dual decline in memory and gait speed was associated with increased risk of dementia compared to memory or gait decline only. We now characterize dual decliners. Using longitudinal BLSA data, we examined associations of phenotypic groups with changes in cognition, depressive symptoms, and brain volumes in areas important for cognitive (dorsolateral prefrontal, medial temporal) and motor functions (precentral gyrus,striatum,thalamus,anterior cingulate cortex) using linear mixed effects models (usual agers=reference), adjusting for covariates. Compared to usual agers, dual decliners had faster decline in card rotation score, greater increase in CES-D, and greater atrophy in thalamus and anterior cingulate cortex. Rates of change in these parameters did not differ among the other three groups. Dual decliners experience faster decline in visuospatial ability, greater atrophy in selected motor areas, and greater increase in depressive symptoms, suggesting potential mechanisms underlying increased dementia risk in dual decliners.

Analysis of Interictal Epileptiform Discharges in Mesial Temporal Lobe Epilepsy Using Quantitative EEG and Neuroimaging.

Objective: Investigate areas of correlation between gray matter volumes by MRI and interictal EEG source maps in subtypes of mesial temporal lobe epilepsy (MTLE).Method: 71 patients and 36 controls underwent 3T MRI and and routine EEG was performed. Voxel-based morphometry (VBM) was used for gray matter analysis and analysis of interictal discharge sources for quantitative EEG. Voxel-wise correlation analysis was conducted between the gray matter and EEG source maps in MTLE subtypes.Results: The claustrum was the main structure involved in the individual source analysis. Twelve patients had bilateral HA, VBM showed bilateral hippocampal. Twenty-one patients had right HA, VBM showed right hippocampal and thalamic atrophy and negatively correlated involving the right inferior frontal gyrus and insula. Twenty-two patients had left HA, VBM showed left hippocampal atrophy and negatively correlated involving the left temporal lobe and insula. Sixteen patients had MTLE without HA, VBM showed middle cingulate gyrus atrophy and were negatively correlated involving extra-temporal regions, the main one located in postcentral gyrus.Conclusions: Negative correlations between gray matter volumes and EEG source imaging. Neuroanatomical generators of interictal discharges are heterogeneous and vary according to MTLE subtype.Significance: These findings suggest different pathophysiological mechanisms among patients with different subtypes of MTLE.

Structural and functional brain changes in hepatic and neurological Wilson disease.

Wilson disease (WD) can manifest with hepatic or neuropsychiatric symptoms. Our understanding of the in vivo brain changes in WD, particularly in the hepatic phenotype, is limited. Thirty subjects with WD and 30 age- and gender-matched controls participated. WD group underwent neuropsychiatric assessment. Unified WD Rating Scale neurological exam scores were used to determine neurological (WDN, score > 0) and hepatic-only (WDH, score 0) subgroups. All subjects underwent 3 Tesla anatomical and resting-state functional MRI. Diffusion tensor imaging (DTI) and susceptibility-weighted imaging (SWI) were performed only in the WD group. Volumetric, DTI, and functional connectivity analyses were performed to determine between-group differences. WDN and WDH groups were matched in demographic and psychiatric profiles. The entire WD group compared to controls showed significant thinning in the bilateral superior frontal cortex. The WDN group compared to control and WDH groups showed prominent structural brain changes including significant striatal and thalamic atrophy, more subcortical hypointense lesions on SWI, and diminished white matter integrity in the bilateral anterior corona radiata and corpus callosum. However, the WDH group also showed significant white matter volume loss compared to controls. The functional connectivity between the frontostriatal nodes was significantly reduced in the WDN group, whereas that of the hippocampus was significantly increased in the WDH group compared to controls. In summary, structural and functional brain changes were present even in neurologically non-manifesting WD patients in this cross-sectional study. Longitudinal brain MRI scans may be useful as biomarkers for prognostication and optimization of treatment strategies in WD.

Damage in the Thalamocortical Tracts is Associated With Subsequent Thalamus Atrophy in Early Multiple Sclerosis.

Background: In early multiple sclerosis (MS), thalamus atrophy and decreased integrity of the thalamocortical white matter (WM) tracts have been observed.Objective: To investigate the temporal association between thalamus volume and WM damage in the thalamocortical tract in subjects with early MS.Methods: At two time points, 72 subjects with early MS underwent T1, FLAIR and diffusion tensor imaging. Thalamocortical tracts were identified with probabilistic tractography using left and right thalamus as seed regions. Regression analysis was performed to identify predictors of annual percentage change in both thalamus volumes and integrity of the connected tracts.Results: Significant atrophy was seen in left and right thalamus (p < 0.001) over the follow-up period (13.7 ± 4.8 months), whereas fractional anisotropy (FA) and mean diffusivity (MD) changes of the left and right thalamus tracts were not significant, although large inter-subject variability was seen. Annual percentage change in left thalamus volume was significantly predicted by baseline FA of the left thalamus tracts F(1.71) = 4.284, p = 0.042; while no such relation was found for the right thalamus. Annual percentage change in FA or MD of the thalamus tracts was not predicted by thalamus volume or any of the demographic parameters.Conclusion: Over a short follow-up time, thalamus atrophy could be predicted by decreased integrity of the thalamic tracts, but changes in the integrity of the thalamic tracts could not be predicted by thalamus volume. This is the first study showing directionality in the association between thalamus atrophy and connected WM tract damage. These results need to be verified over longer follow-up periods.