Thalamic Volume Loss Research Articles

Structural and functional brain markers of cognitive impairment in healthcare workers following mild SARS-CoV-2 infection during the original stream.

Severe acute respiratory syndrome coronavirus 2 infection often involves the nervous system, leading to cognitive dysfunctions, fatigue and many other neurological signs that are becoming increasingly recognized. Despite mild forms of the disease accounting for most cases worldwide, research on the pathophysiology driving mild coronavirus disease 2019 (COVID-19) has received little attention. In this respect, recent evidence has pointed out that around 30-40% of non-critical, mild-to-moderate severity COVID-19 survivors may display cognitive disturbances several months post-illness. Hence, the impact of COVID-19 on the brain structure and function, through potential neuropathological mechanisms underpinning cognitive alterations in post-mild COVID-19 infections, remains largely unexplored. This retrospective multicentre observational cohort study, entirely based on a healthcare worker sample (n = 65; 55% females, aged 21-61), investigated the cognitive status and the structural and functional brain integrity among non-hospitalized individuals who developed mild COVID-19 symptoms during the occurrence of severe acute respiratory syndrome coronavirus 2 variants Alpha to Delta, compared with healthy controls tested before the pandemic onset. All evaluations were performed at an average of 9-month follow-up post-infection period. Participants completed a comprehensive neuropsychological assessment and structural and functional MRI exams. Radiological inspection sought to detect the presence of white matter hyperintensities on axial fluid-attenuated inversion recovery images. Global and regional grey matter integrity assessment, analysing changes in grey matter volumes and cortical thinning, and functional connectivity alterations of resting-state brain networks were also conducted. Regression analyses tested the relationships between the presence of specific cognitive impairments and potential structural and functional brain findings. Our results revealed that clinical, cognitive screening and neuropsychological examinations were average between both groups, except for specific impairments related to executive functions in the mild COVID-19. Compared to healthy controls, mild COVID-19 subjects exhibited increased juxtacortical white matter hyperintensities, thalamic and occipital volume loss and diminished resting-state functional connectivity involving the left precuneus and cuneus in default-mode network and affecting the right angular gyrus and left precuneus in the dorsal attentional network. Reduced thalamic volume was the only variable selected in the final model explaining the observed executive function impairment in mild COVID-19. The presence of cognitive, structural and functional brain abnormalities over time suggests that the action of widespread neurovascular and inflammatory phenomena on the nervous system might also occur in mild forms following COVID-19 infection rather than permanent brain damage linked to the direct or indirect action of the virus. Our findings emphasize the need to pay attention to the long-term brain-related consequences of mild COVID-19 infections during the original stream.

Intrinsic and extrinsic contributors to subregional thalamic volume loss in multiple sclerosis.

To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo high-gradient diffusion MRI. In this cross-sectional study, 41 people with multiple sclerosis and 34 age and sex-matched healthy controls underwent 3T MRI with up to 300 mT/m gradients using a multi-shell diffusion protocol consisting of eight b-values and diffusion time of 19 ms. Each thalamus was parcellated into 25 subregions for volume determination and diffusion metric estimation. The soma and neurite density imaging model was applied to obtain estimates of intra-neurite, intra-soma, and extra-cellular signal fractions for each subregion and within structurally connected white matter trajectories and cortex. Multiple sclerosis-related volume loss was more pronounced in posterior/medial subregions than anterior/ventral subregions. Intra-soma signal fraction was lower in multiple sclerosis, reflecting reduced cell body density, while the extra-cellular signal fraction was higher, reflecting greater extra-cellular space, both of which were observed more in posterior/medial subregions than anterior/ventral subregions. Lower intra-neurite signal fraction in connected normal-appearing white matter and lower intra-soma signal fraction of structurally connected cortex were associated with reduced subregional thalamic volumes. Intrinsic and extrinsic microstructural measures independently related to subregional volume with heterogeneity across atrophy-prone thalamic nuclei. Extrinsic microstructural alterations predicted left anteroventral, intrinsic microstructural alterations predicted bilateral medial pulvinar, and both intrinsic and extrinsic factors predicted lateral geniculate and medial mediodorsal volumes. Our results might be reflective of the involvement of anterograde and retrograde degeneration from white matter demyelination and cerebrospinal fluid-mediated damage in subregional thalamic volume loss.

Natalizumab reduces loss of gray matter and thalamic volume in patients with relapsing-remitting multiple sclerosis: A post hoc analysis from the randomized, placebo-controlled AFFIRM trial

Background: Loss of brain gray matter fractional volume predicts multiple sclerosis (MS) progression and is associated with worsening physical and cognitive symptoms. Within deep gray matter, thalamic damage is evident in early stages of MS and correlates with physical and cognitive impairment. Natalizumab is a highly effective treatment that reduces disease progression and the number of inflammatory lesions in patients with relapsing-remitting MS (RRMS). Objective: To evaluate the effect of natalizumab on gray matter and thalamic atrophy. Methods: A combination of deep learning–based image segmentation and data augmentation was applied to MRI data from the AFFIRM trial. Results: This post hoc analysis identified a reduction of 64.3% (p = 0.0044) and 64.3% (p = 0.0030) in mean percentage gray matter volume loss from baseline at treatment years 1 and 2, respectively, in patients treated with natalizumab versus placebo. The reduction in thalamic fraction volume loss from baseline with natalizumab versus placebo was 57.0% at year 2 (p < 0.0001) and 41.2% at year 1 (p = 0.0147). Similar findings resulted from analyses of absolute gray matter and thalamic fraction volume loss. Conclusion: These analyses represent the first placebo-controlled evidence supporting a role for natalizumab treatment in mitigating gray matter and thalamic fraction atrophy among patients with RRMS. ClinicalTrials.gov identifier: NCT00027300 URL: https://clinicaltrials.gov/ct2/show/NCT00027300

A second dimension of somatosensory system injury? Thalamic volume loss and neuropathic pain in adults with cerebral palsy and periventricular white matter injury.

Lemniscal (motor-related) and spinothalamic (neuropathic pain-related) somatosensory abnormalities affect different subsets of adults with cerebral palsy (CP). Lemniscal/motor abnormalities are associated with posterior thalamic radiation white matter disruption in individuals with CP and white matter injury. We tested the hypothesis that neuropathic pain symptoms in this population are rather associated with injury of the somatosensory (posterior group nuclei) thalamus. In this cross-sectional study, communicative adults with CP and bilateral white matter injury and neurotypical control participants volunteered to self-report pain symptoms and undergo research MRI. Posterior group thalamic nuclei volume was computed and correlated against neuropathic pain scores. Participants with CP (n=6) had, on average, 24% smaller posterior group thalamic volumes (95% CI [10-39%]; corrected p=0.01) than control participants. More severe volume loss was correlated with more severe neuropathic pain scores (ρ=-0.87 [-0.99,-0.20]; p=0.02). Association with thalamic volume loss suggests that neuropathic pain in adults with CP may frequently be central neuropathic pain. Complementing assessments of white matter microstructure, regional brain volumes hold promise as diagnostic biomarkers for central neuropathic pain in individuals with structural brain disorders.

The effect of ibudilast on thalamic volume in progressive multiple sclerosis

Background: Thalamic volume loss is known to be associated with clinical and cognitive disability in progressive multiple sclerosis (PMS). Objective: To investigate the treatment effect of ibudilast on thalamic atrophy more than 96 weeks in the phase 2 trial in progressive(MS Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis [SPRINT-MS]). Methods: A total of 231 participants were randomized to either ibudilast (n = 114) or placebo (n = 117). Thalamic volume change was computed using Bayesian Sequence Adaptive Multimodal Segmentation tool (SAMseg) incorporating T1, fluid-attenuated inversion recovery (FLAIR), and fractional anisotropy maps and analyzed with a mixed-effects repeated-measures model. Results: There was no significant difference in thalamic volumes between treatment groups. On exploratory analysis, participants with primary progressive multiple sclerosis (PPMS) on placebo had a 0.004% greater rate of thalamic atrophy than PPMS participants on ibudilast (p = 0.058, 95% confidence interval (CI) = −0.008 to <0.001). Greater reductions in thalamic volumes at more than 96 weeks were associated with worsening multiple sclerosis functional composite (MSFC-4) scores (p = 0.002) and worsening performance on the symbol digit modality test (SDMT) (p < 0.001). Conclusion: In a phase 2 trial evaluating ibudilast in PMS, no treatment effect was demonstrated in preventing thalamic atrophy. Participants with PPMS exhibited a treatment effect that trended toward significance. Longitudinal changes in thalamic volume were related to worsening of physical and cognitive disability, highlighting this outcome’s clinical importance.

Detection of grey matter microstructural substrates of neurodegeneration in multiple sclerosis.

Multiple sclerosis features complex pathological changes in grey matter that begin early and eventually lead to diffuse atrophy. Novel approaches to image grey-matter microstructural alterations in vivo are highly sought after and would enable more sensitive monitoring of disease activity and progression. This cross-sectional study aimed to assess the sensitivity of high-gradient diffusion MRI for microstructural tissue damage in cortical and deep grey matter in people with multiple sclerosis and test the hypothesis that reduced cortical cell body density is associated with cortical and deep grey-matter volume loss. Forty-one people with multiple sclerosis (age 24-72, 14 females) and 37 age- and sex-matched healthy controls were scanned on a 3 T Connectom MRI scanner equipped with 300 mT/m gradients using a multi-shell diffusion MRI protocol. The soma and neurite density imaging model was fitted to high-gradient diffusion MRI data to obtain estimates of intra-neurite, intra-cellular and extra-cellular signal fractions and apparent soma radius. Cortical and deep grey-matter microstructural imaging metrics were compared between multiple sclerosis and healthy controls and correlated with grey-matter volume, clinical disability and cognitive outcomes. People with multiple sclerosis showed significant cortical and deep grey-matter volume loss compared with healthy controls. People with multiple sclerosis showed trends towards lower cortical intra-cellular signal fraction and significantly lower intra-cellular and higher extra-cellular signal fractions in deep grey matter, especially the thalamus and caudate, compared with healthy controls. Changes were most pronounced in progressive disease and correlated with the Expanded Disability Status Scale, but not the Symbol Digit Modalities Test. In multiple sclerosis, normalized thalamic volume was associated with thalamic microstructural imaging metrics. Whereas thalamic volume loss did not correlate with cortical volume loss, cortical microstructural imaging metrics were significantly associated with thalamic volume, and not with cortical volume. Compared with the short diffusion time (Δ = 19 ms) achievable on the Connectom scanner, at the longer diffusion time of Δ = 49 ms attainable on clinical scanners, multiple sclerosis-related changes in imaging metrics were generally less apparent with lower effect sizes in cortical and deep grey matter. Soma and neurite density imaging metrics obtained from high-gradient diffusion MRI data provide detailed grey-matter characterization beyond cortical and thalamic volumes and distinguish multiple sclerosis-related microstructural pathology from healthy controls. Cortical cell body density correlates with thalamic volume, appears sensitive to the microstructural substrate of neurodegeneration and reflects disability status in people with multiple sclerosis, becoming more pronounced as disability worsens.

Ocrelizumab-treated patients with relapsing multiple sclerosis show volume loss rates similar to healthy aging

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by two major and interconnected hallmarks: inflammation and progressive neurodegeneration. Objective: The aim of this work was to compare neurodegenerative processes, in the form of global and regional brain volume loss rates, in healthy controls (HCs) and in patients with relapsing MS (RMS) treated with ocrelizumab, which suppresses acute inflammation. Methods: Whole brain, white matter, cortical gray matter, thalamic, and cerebellar volume loss rates were assessed in 44 HCs that were part of a substudy in the OPERA II randomized controlled trial (NCT01412333) and 59 patients with RMS enrolled in the same substudy as well as age- and sex-matched patients in OPERA I (NCT01247324) and II. Volume loss rates were computed using random coefficients models over a period of 2 years. Results: Ocrelizumab-treated patients showed global and regional brain volume loss rates that were approaching that of HCs. Conclusion: These findings are consistent with an important role of inflammation on overall tissue loss and the role of ocrelizumab in reducing this phenomenon.

The contribution of thalamic pathology to the clinical manifestations of frontotemporal dementia phenotypes (P5-12.004)

<h3>Objective:</h3> To systematically characterise thalamus pathology in frontotemporal dementia (FTD) phenotypes <h3>Background:</h3> FTD is classically associated with distinctive cortical atrophy patterns. However, the spectrum of cognitive and behavioural manifestations in FTD arise from multi-synaptic network dysfunction. The thalamus is a key hub of several corticobasal and corticocortical circuits. The main circuits relayed via the thalamic nuclei include the dorsolateral prefrontal circuit; the anterior cingulate circuit; and the orbitofrontal circuit. <h3>Design/Methods:</h3> Thalamus pathology was quantitatively evaluated at a nuclear, vertex and morphometric level in a prospective, multimodal imaging study using a standardised neuroimaging protocol. 10 patients with behavioural FTD (bvFTD), 15 patients with non-fluent variant primary progressive aphasia (nfvPPA) and 5 patients with semantic variant PPA (svPPA) were evaluated with reference to 100 healthy controls. All patients underwent detailed clinical and neuropsychological profiling and whole-genome sequencing. <h3>Results:</h3> Volumetric analyses revealed widespread bilateral thalamic nuclear volume loss in bvFTD; selective bilateral with left-sided predominant thalamic degeneration was captured in nfvPPA; and more focal, left-lateralised thalamic volume loss identified in svPPA. Vertex analyses showed diffuse thalamic surface changes in bvFTD and nfvPPA, but not svPPA. Morphometric analyses demonstrated extensive symmetric intra-thalamic changes in nfvPPA, and mostly right-sided changes in both bvFTD and svPPA. <h3>Conclusions:</h3> FTD is associated with considerable focal thalamic degeneration. Phenotype-specific thalamic traits mirror established cortical vulnerability patterns. Thalamic nuclei associated with behaviour and language functions are preferentially involved. FTD is not solely associated with cortical atrophy. The manifestations of FTD are likely to stem from cortico-subcortical circuitry dysfunction and not exclusively driven by focal cortical changes. <b>Disclosure:</b> Dr. McKenna has nothing to disclose. Dr. Hutchinson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hutchinson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Hutchinson has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Teva. Dr. Bede has nothing to disclose.

A novel, likely pathogenic variant in UBTF-related neurodegeneration with brain atrophy is associated with a severe divergent neurodevelopmental phenotype.

A de novo, pathogenic, missense variant in UBTF, c.628G>A p.Glu210Lys, has been described as the cause of an emerging neurodegenerative disorder, Childhood-Onset Neurodegeneration with Brain Atrophy (CONDBA). The p.Glu210Lys alteration yields a positively charged stretch of three lysine residues. Functional studies confirmed this change results in a stronger interaction with negatively charged DNA and gain-of-function activity when compared to the wild-type sequence. The CONDBA phenotype reported in association with p.Glu210Lys consists of normal early-neurodevelopment followed by progressive motor, cognitive, and behavioral regression in early-to-middle childhood. The current proband presented at 9 months of age with baseline developmental delay and more extensive neuroradiological findings, including pontine hypoplasia, thalamic volume loss and signal abnormality, and hypomyelination. Like the recurrent CONDBA p.Glu210Lys variant, this novel variant, c.608A>G p.(Gln203Arg) lies within the highly conserved second HMG-box homology domain and involves the replacement of the wild-type residue with a positively charged residue, arginine. Computational structural modeling demonstrates that this amino acid substitution potentiates the interaction between UBTF and DNA, likely resulting in a gain-of-function effect for the UBTF protein, UBF. Here we present a new divergent phenotype associated with a novel, likely pathogenic, missense variant at a different position in the UBTF gene, c.608A>G p.(Gln203Arg).

Thalamic Volume Loss Is Greater in Children Than in Adults Following Middle Cerebral Artery Territory Arterial Ischemic Stroke.

Background: Younger stroke patients may suffer worse outcomes than older patients; however, the extent to which age at stroke impacts remote areas of the brain remains unclear. The objective of this study was to determine thalamic volume changes ipsilateral to middle cerebral artery territory strokes based on age at acute ischemic stroke onset. Methods: Acute ischemic stroke patients <9 years, 9-18 years, and >18 years old were retrospectively recruited from a large quaternary care system. Each subject underwent an acute (<72 hours from AIS) and chronic (>90 days) magnetic resonance imaging (MRI) scan. Manual thalamic segmentation was performed. Results: Younger and older children had significantly greater stroke-side thalamic volume loss compared to adults (48.2%, P = .022; 40.7%, P = .044, respectively). Conclusions: Stroke-side thalamic volumes decreased across the age spectrum but to a greater degree in pediatric patients. This observation can affect functional and cognitive outcomes post stroke and warrants further research.

Thalamic atrophy measured by artificial intelligence in a multicentre clinical routine real-word study is associated with disability progression

BackgroundThe thalamus is a key grey matter structure, and sensitive marker of neurodegeneration in multiple sclerosis (MS). Previous reports indicated that thalamic volumetry using artificial intelligence (AI) on clinical-quality T2-fluid-attenuated...

Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS

Background: In multiple sclerosis (MS), thalamic integrity is affected directly by demyelination and neuronal loss, and indirectly by gray/white matter lesions outside the thalamus, altering thalamic neuronal projections. Objective: To assess the efficacy of ocrelizumab compared with interferon beta-1a (IFNβ1a)/placebo on thalamic volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II; NCT01247324/NCT01412333) and in primary progressive MS (PPMS, ORATORIO; NCT01194570). Methods: Thalamic volume change was computed using paired Jacobian integration and analyzed using an adjusted mixed-effects repeated measurement model. Results: Over the double-blind period, ocrelizumab treatment significantly reduced thalamic volume loss with the largest effect size (Cohen’s d: RMS: 0.561 at week 96; PPMS: 0.427 at week 120) compared with whole brain, cortical gray matter, and white matter volume loss. At the end of up to 7 years of follow-up, patients initially randomized to ocrelizumab still showed less thalamic volume loss than those switching from IFNβ1a (p < 0.001) or placebo (p < 0.001). Conclusion: Ocrelizumab effectively reduced thalamic volume loss compared with IFNβ1a/placebo. Early treatment effects on thalamic tissue preservation persisted over time. Thalamic volume loss could be a potential sensitive marker of persisting tissue damage.

045 Effect of siponimod on cortical grey matter and thalamic volume in secondary progressive multiple sclerosis

BackgroundGrey matter (GM) loss is associated with cognitive decline and physical disability in multiple sclerosis (MS). In Phase 3 EXPAND study, siponimod significantly reduced disability progression, cognitive decline and whole brain volume loss in patients with secondary progressive MS (SPMS).MethodsMagnetic resonance imaging (MRI) from EXPAND were pooled and analysed using high reso- lution T1 and conventional MRI. Analysis included intent-to-treat population (full analysis set, FAS) and per protocol set (PPS). Change from baseline in cortical grey matter (cGM) and thalamic volumes were assessed.ResultsIn the FAS, adjusted mean percent change in volume from baseline at M12 and M24, respectively, was −0.07 versus −0.59 (88% reduction vs placebo, p&lt;0.0001) and −0.51 versus −0.90 (43% reduction; p&lt;0.0001) for cGM; −0.54 versus −1.01 (47% reduction; p&lt; 0.0001) and −1.20 versus −1.74 (31% reduction; p=0.0001) for the thalamus. PPS values were 0.01 versus −0.60 (100% reduction; p&lt; 0.0001) and −0.39 versus−1.04 (63% reduction; p&lt; 0.0001) for cGM; −0.47 vs −0.94 (50% reduction; p&lt; 0.0001) and −1.02 versus −1.77 (42% reduction; p&lt; 0.0001) for the thalamus.ConclusionsSiponimod significantly reduced cGM and thalamic volume loss compared with placebo in patients with SPMS.g.giovannoni@qmul.ac.uk

Grey Matter Loss at Different Stages of Cognitive Decline: A Role for the Thalamus in Developing Alzheimer's Disease.

Background:Alzheimer’s disease (AD) is characterized by cognitive impairment and large loss of grey matter volume and is the most prevalent form of dementia worldwide. Mild cognitive impairment (MCI) is the stage that precedes the AD dementia stage, but individuals with MCI do not always convert to the AD dementia stage, and it remains unclear why.Objective:We aimed to assess grey matter loss across the brain at different stages of the clinical continuum of AD to gain a better understanding of disease progression.Methods:In this large-cohort study (N = 1,386) using neuroimaging data from the Alzheimer’s Disease Neuroimaging Initiative, voxel-based morphometry analyses were performed between healthy controls, individuals with early and late and AD dementia stage.Results:Clear patterns of grey matter loss in mostly hippocampal and temporal regions were found across clinical stages, though not yet in early MCI. In contrast, thalamic volume loss seems one of the first signs of cognitive decline already during early MCI, whereas this volume loss does not further progress from late MCI to AD dementia stage. AD dementia stage converters already show grey matter loss in hippocampal and mid-temporal areas as well as the posterior thalamus (pulvinar) and angular gyrus at baseline.Conclusion:This study confirms the role of temporal brain regions in AD development and suggests additional involvement of the thalamus/pulvinar and angular gyrus that may be linked to visuospatial, attentional, and memory related problems in both early MCI and AD dementia stage conversion.

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.

Impact of Hippocampal Subfields and Amygdala and Thalamic Nuclei Volume Loss With Respect to Post-surgical Seizure Outcome

Impact of Hippocampal Subfields and Amygdala and Thalamic Nuclei Volume Loss With Respect to Post-surgical Seizure Outcome

Tracking Cortical Changes Throughout Cognitive Decline in Parkinson's Disease.

The objectives of this study were to investigate progressive cortical thinning and volume loss in Parkinson's disease (PD) patients with different longitudinal patterns of cognitive decline: with stable normal cognition, with stable mild cognitive impairment, with conversion to mild cognitive impairment, and with conversion to dementia. We recruited 112 patients (37 Parkinson's disease with stable normal cognition, 20 Parkinson's disease with stable mild cognitive impairment, 36 Parkinson's disease with conversion to mild cognitive impairment, 19 Parkinson's disease with conversion to dementia) and 38 healthy controls. All patients underwent at least 2 visits within 4 years including clinical/cognitive assessments and structural MRI (total visits, 393). Baseline cortical thickness and gray matter volumetry were compared between groups. In PD, gray matter changes over time were investigated and compared between groups. At baseline, compared with Parkinson's disease with stable normal cognition cases, Parkinson's disease with conversion to mild cognitive impairment patients showed cortical atrophy of the parietal and occipital lobes, similar to Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia patients. The latter groups (ie, patients with cognitive impairment from the study entry) showed additional involvement of the frontotemporal cortices. No baseline volumetric differences among groups were detected. The longitudinal analysis (group-by-time interaction) showed that, versus the other patient groups, Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia cases accumulated the least cortical damage, with Parkinson's disease with conversion to dementia showing unique progression of right thalamic and hippocampal volume loss; Parkinson's disease with conversion to mild cognitive impairment patients showing specific cortical thinning accumulation in the medial and superior frontal gyri, inferior temporal, precuneus, posterior cingulum, and supramarginal gyri bilaterally; and Parkinson's disease with stable normal cognition patients showing cortical thinning progression, mainly in the occipital and parietal regions bilaterally. Cortical thinning progression is more prominent in the initial stages of PD cognitive decline. The involvement of frontotemporoparietal regions, the hippocampus, and the thalamus is associated with conversion to a more severe stage of cognitive impairment. In PD, gray matter alterations of critical brain regions may be an MRI signature for the identification of patients at risk of developing dementia. © 2020 International Parkinson and Movement Disorder Society.

Change in cognitive processing speed is associated with cortical grey matter and thalamic volume loss in patients with relapsing-remitting multiple sclerosis (1905)

Change in cognitive processing speed is associated with cortical grey matter and thalamic volume loss in patients with relapsing-remitting multiple sclerosis (1905)

Variability Between Direct and Indirect Targeting of the Anterior Nucleus of the Thalamus

Preoperative thalamic targeting methods have historically relied on indirect targeting techniques that do not fully account for variances in anatomy or for thalamic atrophy in epilepsy. We aimed to address variability noted between traditional indirect targeting and direct targeting methods for the anterior nucleus of the thalamus (ANT). Fifteen consecutive patients undergoing ANT deep brain stimulator placement were evaluated (30 thalamic nuclei). Direct ANT targeting was performed using a fast gray matter acquisition T1 inversion recovery sequence and compared with standard stereotactic coordinates. Thalamic volumes were calculated for each patient, and degree of thalamic volume loss was assessed compared with matched control subjects. Vertex analysis was performed to assess shape changes in the thalamus compared with age- and sex-matched subjects. There was significant variation between direct and indirect targets in the y-axis and z-axis on both sides. On the left, the direct target was located at y= 2 ±1.3 mm and z= 9.3 ± 1.8 mm (both P= 0.02). On the right, the direct target was located at y= 2.9 ± 1.8 mm and z= 9.2 ± 2 mm (both P ≤ 0.0003). There was no significant difference in the x-coordinate on either side (P > 0.5). Additionally, there was a correlation between thalamic volume and difference between direct and indirect targets in the y-axis and the z-axis. We showed a significant difference in direct and indirect targeting in the y-axis and z-axis when targeting the ANT for deep brain stimulation for epilepsy. This difference is correlated to thalamic volume, with a larger difference noted in patients with thalamic atrophy.