Thalamic Volume Research Articles

Nevropsykologiske senskader hos boksere: en systematisk gjennomgang

Background: The aim of this systematic review was to investigate the risk of neuropsychological sequelae from boxing. Method: We conducted a systematic search in the databases Medline, Embase, PsychInfo and Web of Science. Studies with boxers, control groups, using neuropsychological assessment and brain-imaging/biomarkers were included. Nine articles met these criteria. Results: The results revealed that processing speed was reduced in six of the nine studies among both amateur and professional boxers. Processing speed correlated negatively with volume of thalamus and number of boxing fights (fight exposure). Three studies found reduced fine motoric skills among professional boxers, but not among amateur boxers. Boxers with more than 15 years of experience had significantly reduced verbal memory compared to controls. Eight of the nine studies found that both amateur and professional boxers had reduced cognitive capacity and/or positive findings on biomarkers. Conclusion: Based on the results, it is reasonable to assume that neuropsychological sequelae are related to career length and number of fights. There may be a dose–response relationship between the number of punches to the head and the risk of neuropsychological sequelae. Methodological limitations (such as low statistical power and short-term follow-up) should be taken into consideration. There is a need for more longitudinal studies to further investigate neuropsychological sequelae of boxing. Keywords: boxing, neuropsychological sequelae, head injury

Association of brain morphology and phenotypic profile in patients with unruptured intracranial aneurysm.

Studies have found a varying degree of cognitive, psychosocial, and functional impairments in patients with unruptured intracranial aneurysms (UIAs), whereas the neural correlates underlying these impairments remain unknown. To examine the brain morphological alterations and white matter lesions in patients with UIA, we performed a range of structural analyses to examine the brain morphological alterations in patients with UIA compared with healthy controls (HCs). Twenty-one patients with UIA and 23 HCs were prospectively enrolled into this study. Study assessment consisted of a brain magnetic resonance imaging (MRI) scan with high-resolution T1-weighted and T2-weighted imaging data, a Montreal Cognitive Assessment (MoCA), and laboratory tests including blood inflammatory markers and serum lipids. Brain MRI data were processed for cortical thickness, local gyrification index (LGI), volume and shape of subcortical nuclei, and white matter lesions. Compared to the HCs, patients with UIA showed no significant differences in cortical thickness but decreased LGI values in the right posterior cingulate cortex, retrosplenial cortex, cuneus, and lingual gyrus. In addition, decreased LGI values correlated with decreased MoCA score (r = 0.498, p = 0.021) and increased white matter lesion scores (r = -0.497, p = 0.022). The LGI values were correlated with laboratory values such as inflammatory markers and serum lipids. Patients with UIA also showed significant regional atrophy in bilateral thalami as compared to the HCs. Moreover, the LGI values were significantly correlated with thalamic volume in the HCs (r = 0.4728, p = 0.0227) but not in the patients with UIA (r = 0.11, p = 0.6350). The decreased cortical gyrification, increased white matter lesions, and regional thalamic atrophy in patients with UIA might be potential neural correlates of cognitive changes in UIA.

Metal deposits associated with brain atrophy in the deep gray matter nucleus in Wilson's disease.

Regional atrophy and metal deposition are typical manifestations in Wilson's disease, but their relationship has not been systematically investigated. We aim to investigate the association of regional brain atrophy and metal deposition in the deep gray matter nucleus at MRI in Wilson's disease. We acquired the structural and susceptibility mapping and performed a cross-sectional comparison of volume and susceptibility in deep gray matter nucleus. The most extensive and severe atrophy was detected in brain regions in neuro-Wilson's disease, as well as the most widespread and heaviest metal deposits. Metal deposits were significantly negatively correlated with volume in the bilateral thalamus, caudate, and putamen. None of correlation was found between the clinical score with volume or susceptibility in the focused regions. In the 1-year follow-up analysis, the volume of right thalamus, globus pallidus, and brainstem and the susceptibility of the left caudate have decreased significantly as the symptom improvement. In Wilson's disease, phenotypes have varied scope and extend of volumetric atrophy and metal deposits. This study is expected to take the lead in revealing that in neuro-Wilson's disease, greater regional atrophy associated with heavier metal deposits in Wilson's disease. Moreover, after 1-year treatment, the imaging data have changed as the patient's condition improvement.

Decreased thalamocortical connectivity in resolved Rolandic epilepsy

ObjectiveMedian nerve somatosensory evoked fields (SEFs) conduction times reflect the integrity of neural transmission across the thalamocortical circuit. We hypothesized median nerve SEF conduction time would be abnormal in children with Rolandic epilepsy (RE). Methods22 children with RE (10 active; 12 resolved) and 13 age-matched controls underwent structural and diffusion MRI and median nerve and visual stimulation during magnetoencephalography (MEG). N20 SEF responses were identified in contralateral somatosensory cortices. P100 were identified in contralateral occipital cortices as controls. Conduction times were compared between groups in linear models controlling for height. N20 conduction time was also compared to thalamic volume and Rolandic thalamocortical structural connectivity inferred using probabilistic tractography. ResultsThe RE group had slower N20 conduction compared to controls (p = 0.042, effect size 0.6 ms) and this difference was driven by the resolved RE group (p = 0.046). There was no difference in P100 conduction time between groups (p = 0.83). Ventral thalamic volume positively correlated with N20 conduction time (p = 0.014). ConclusionsChildren with resolved RE have focally decreased Rolandic thalamocortical connectivity. SignificanceThese results identify a persistent focal thalamocortical circuit abnormality in resolved RE and suggest that decreased Rolandic thalamocortical connectivity may support symptom resolution in this self-limited epilepsy.

477-P: Thalamic Mitochondrial and Neuronal Function Is Preserved in Painful Diabetic Peripheral Neuropathy—A Multimodal Magnetic Resonance Imaging Study

Aims: Previous neuroimaging studies have demonstrated cerebral structural, functional, and vascular alterations in Painful-Diabetic Peripheral Neuropathy (DPN). We present a multi-modal Magnetic Resonance Imaging (MRI) study to determine the structure, and neuronal and mitochondrial function of the thalamus in Painful-DPN. Methods: A total of 49 participants were enrolled, 38 with type 2 diabetes (9 without DPN [No-DPN]; 11 with Painless-DPN; and 18 with Painful-DPN) and 11 healthy volunteers (HV). Participants underwent detailed clinical and neurophysiological assessments, and multi-modal MR imaging of the thalami bilaterally including: Proton-Magnetic Spectroscopy (1H-MRS); 31-Phosphorus MRS (31P-MRS); and brain morphometric analysis. We calculated the N-acetyl aspartate to choline (NAA:Cho), a measure of neuronal function, and inorganic phosphate (Pi) to ATP (Pi:ATP), a measure of mitochondrial function. Results: There were no significant differences in thalamic volume between groups (ANOVA, p=0.927). There was a significant group effect in both metabolite ratios: NAA:Cho (ANOVA, p=0.013); Pi:ATP (p=0.021). The NAA:Cho was numerically the lowest in Painless-DPN, reaching significance compared with HV (p=0.001) and Painful-DPN (p=0.019). Additionally, the Pi:ATP was significantly higher in Painless-DPN compared with HV (p=0.013) and Painful-DPN (p=0.008). There was also a significant correlation between the NAA:Cho and Pi:PCr (Pearson’s r -0.336, p=0.034). Conclusion: This is the first study to determine perform cerebral 1H- and 31P-MRS in human DPN. We have demonstrated altered 1H- and 31P-MRS ratios in Painless- but not Painful-DPN, suggesting that mitochondrial dysfunction may underlie thalamic neuronal dysfunction in Painless-DPN. Conversely, in Painful-DPN, preservation of thalamic mitochondrial and neuronal function may be involved in the maintenance of neuropathic pain signaling. Disclosure G.P.Sloan: None. K.Teh: None. D.Selvarajah: None. S.Tesfaye: Advisory Panel; Bayer Inc., Wörwag Pharma GmbH & Co. KG, Angelini, Speaker's Bureau; Viatris Inc., Nevro Corp., Procter & Gamble, Novo Nordisk, Berlin-Chemie AG.

CSF Markers of Oxidative Stress Are Associated with Brain Atrophy and Iron Accumulation in a 2-Year Longitudinal Cohort of Early MS.

In this prospective longitudinal study, we quantified regional brain volume and susceptibility changes during the first two years after the diagnosis of multiple sclerosis (MS) and identified their association with cerebrospinal fluid (CSF) markers at baseline. Seventy patients underwent MRI (T1 and susceptibility weighted images processed to quantitative susceptibility maps, QSM) with neurological examination at the diagnosis and after two years. In CSF obtained at baseline, the levels of oxidative stress, products of lipid peroxidation, and neurofilaments light chain (NfL) were determined. Brain volumetry and QSM were compared with a group of 58 healthy controls. In MS patients, regional atrophy was identified in the striatum, thalamus, and substantia nigra. Magnetic susceptibility increased in the striatum, globus pallidus, and dentate and decreased in the thalamus. Compared to controls, MS patients developed greater atrophy of the thalamus, and a greater increase in susceptibility in the caudate, putamen, globus pallidus and a decrease in the thalamus. Of the multiple calculated correlations, only the decrease in brain parenchymal fraction, total white matter, and thalamic volume in MS patients negatively correlated with increased NfL in CSF. Additionally, negative correlation was found between QSM value in the substantia nigra and peroxiredoxin-2, and QSM value in the dentate and lipid peroxidation levels.

Therapy effect on AI-derived thalamic atrophy using clinical routine MRI protocol: A longitudinal, multi-center, propensity-matched multiple sclerosis study.

The effect of disease modifying therapies (DMTs) on brain atrophy in persons with multiple sclerosis (pwMS) is typically investigated in highly standardized clinical trial settings or single-center academic institutions. We aimed at utilizing artificial intelligence (AI)-based volumetric analysis on routine unstandardized T2-FLAIR scans in determining the effect of DMTs on lateral ventricular volume (LVV) and thalamic volume (TV) changes in pwMS. The DeepGRAI (Deep Gray Rating via Artificial Intelligence) registry is a multi-center, longitudinal, observational, real-word study with a convenience sample of 1002 relapsing-remitting (RR) pwMS from 30 United States sites. Brain MRI exams acquired as part of the routine clinical management were collected at baseline and on average at 2.6-years follow-up. The MRI scans were acquired either on 1.5T or 3T scanners with no prior harmonization. TV was determined using the DeepGRAI tool and lateral ventricular volume LVV was measured using NeuroSTREAM software. After propensity matching based on baseline age, disability and time of follow-up, untreated pwRRMS had significantly greater TV change when compared to treated pwRRMS (-1.2% vs. -0.3%, p=0.044). PwRRMS treated with high-efficacy DMTs had significant and two-fold lower% LVV change when compared to pwRRMS treated on moderate-efficacy DMTs (3.5% vs. 7.0%, p=0.001). PwRRMS who stopped DMT during the follow-up had significantly greater annualized% TV change compared to pwRRMS who remained on their DMT (-0.73% vs. -0.14%, p=0.012) and significantly greater annualized% LVV change (3.4% vs. 1.7%, p=0.047). These findings were also observed in a propensity analysis that additionally incorporated matching for scanner model at both baseline and follow-up visits. LVV and TV measured on T2-FLAIR scans can detect treatment-induced short-term neurodegenerative changes measured in a real-word unstandardized, multicenter, clinical routine setting.

Thalamic nuclei volumes in schizophrenia and bipolar spectrum disorders - Associations with diagnosis and clinical characteristics.

The thalamus is central to brain functions ranging from primary sensory processing to higher-order cognition. Structural deficits in thalamic association nuclei such as the pulvinar and mediodorsal nuclei have previously been reported in schizophrenia. However, the specificity with regards to clinical presentation, and whether or not bipolar disorder (BD) is associated with similar alterations is unclear. We investigated thalamic nuclei volumes in 334 patients with schizophrenia spectrum disorders (SSD) (median age 29years, 59% male), 322 patients with BD (30years, 40% male), and 826 healthy controls (HC) (34years, 54% male). Volumes of 25 thalamic nuclei were extracted from T1-weighted magnetic resonance imaging using an automated Bayesian segmentation method and compared between groups. Furthermore, we explored associations with clinical characteristics across diagnostic groups, including psychotic and mood symptoms and medication use, as well as diagnostic subtype in BD. Significantly smaller volumes were found in the mediodorsal, pulvinar, and lateral and medial geniculate thalamic nuclei in SSD. Similarly, smaller volumes were found in BD in the same four regions, but mediodorsal nucleus volume alterations were limited to its lateral part and pulvinar alterations to its anterior region. Smaller volumes in BD compared to HC were seen only in BD type I, not BD type II. Across diagnoses, having more negative symptoms was associated with smaller pulvinar volumes. Structural alterations were found in both SSD and BD, mainly in the thalamic association nuclei. Structural deficits in the pulvinar may be of relevance for negative symptoms.

Default mode network functional connectivity strength in utero and the association with fetal subcortical development.

The default mode network is essential for higher-order cognitive processes and is composed of an extensive network of functional and structural connections. Early in fetal life, the default mode network shows strong connectivity with other functional networks; however, the association with structural development is not well understood. In this study, resting-state functional magnetic resonance imaging and anatomical images were acquired in 30 pregnant women with singleton pregnancies. Participants completed 1 or 2 MR imaging sessions, on average 3weeks apart (43 data sets), between 28- and 39-weeks postconceptional ages. Subcortical volumes were automatically segmented. Activation time courses from resting-state functional magnetic resonance imaging were extracted from the default mode network, medial temporal lobe network, and thalamocortical network. Generalized estimating equations were used to examine the association between functional connectivity strength between default mode network-medial temporal lobe, default mode network-thalamocortical network, and subcortical volumes, respectively. Increased functional connectivity strength in the default mode network-medial temporal lobe network was associated with smaller right hippocampal, left thalamic, and right caudate nucleus volumes, but larger volumes of the left caudate. Increased functional connectivity strength in the default mode network-thalamocortical network was associated with smaller left thalamic volumes. The strong associations seen among the default mode network functional connectivity networks and regionally specific subcortical volume development indicate the emergence of short-range connectivity in the third trimester.

Deviation From Normative Whole Brain and Deep Gray Matter Growth in Children With MOGAD, MS, and Monophasic Seronegative Demyelination.

Pediatric-acquired demyelination of the CNS associated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG; MOG antibody-associated disease [MOGAD]) occurs as a monophasic or relapsing disease and with variable but often extensive T2 lesions in the brain. The impact of MOGAD on brain growth during maturation is unknown. We quantified the effect of pediatric MOGAD on brain growth trajectories and compared this with the growth trajectories of age-matched and sex-matched healthy children and children with multiple sclerosis (MS, a chronic relapsing disease known to lead to failure of normal brain growth and to loss of brain volume) and monophasic seronegative demyelination. We included children enrolled at incident attack in the prospective longitudinal Canadian Pediatric Demyelinating Disease Study who were recruited at the 3 largest enrollment sites, underwent research brain MRI scans, and were tested for serum MOG-IgG. Children seropositive for MOG-IgG were diagnosed with MOGAD. MS was diagnosed per the 2017 McDonald criteria. Monophasic seronegative demyelination was confirmed in children with no clinical or MRI evidence of recurrent demyelination and negative results for MOG-IgG and aquaporin-4-IgG. Whole and regional brain volumes were computed through symmetric nonlinear registration to templates. We computed age-normalized and sex-normalized z scores for brain volume using a normative dataset of 813 brain MRI scans obtained from typically developing children and used mixed-effect models to assess potential deviation from brain growth trajectories. We assessed brain volumes of 46 children with MOGAD, 26 with MS, and 51 with monophasic seronegative demyelinating syndrome. Children with MOGAD exhibited delayed (p < 0.001) age-expected and sex-expected growth of thalamus, caudate, and globus pallidus, normalized for the whole brain volume. Divergence from expected growth was particularly pronounced in the first year postonset and was detected even in children with monophasic MOGAD. Thalamic volume abnormalities were less pronounced in children with MOGAD compared with those in children with MS. The onset of MOGAD during childhood adversely affects the expected trajectory of growth of deep gray matter structures, with accelerated changes in the months after an acute attack. Further studies are required to better determine the relative impact of monophasic vs relapsing MOGAD and whether relapsing MOGAD with attacks isolated to the optic nerves or spinal cord affects brain volume over time.

Association of age of adverse childhood experiences with thalamic volumes and post-traumatic stress disorder in adulthood.

Adverse childhood experiences (ACEs) have been linked to brain development and mental disorders, however, the impact of the age of occurrence of ACEs on thalamic volume and post-traumatic stress disorder (PTSD) after adult trauma remains unclear. This study assessed associations between ACEs at different ages to thalamic volumes and PTSD development following acute adult trauma. Seventy-nine adult trauma survivors were recruited immediately after trauma. Within 2 weeks of the traumatic event, participants completed the PTSD Checklist (PCL) to assess PTSD symptoms, the Childhood Trauma Questionnaire (CTQ) and Childhood Age Range Stress Scale (CARSS) to evaluate ACEs and perceived stress level at preschool (<6 years old) and school (6-13 years old) ages, and structural magnetic resonance imaging (sMRI) to measure thalamic volumes. Participants were divided into three groups: those who experienced no childhood trauma or stress (non-ACEs), those who experienced childhood trauma and stress onset at preschool ages (Presch-ACEs), and those who experienced childhood trauma and stress onset at school ages (Sch-ACEs). At 3 months, participants underwent PTSD symptom evaluation using the Clinician Administered PTSD Scale (CAPS). Adult trauma survivors in the Presch-ACEs group had higher CTQ and CAPS scores. In addition, survivors in the Presch-ACEs group had smaller thalamic volume compared to survivors in the non-ACEs and Sch-ACEs groups. Furthermore, smaller thalamic volume moderated a positive association between post-trauma 2-week PCL and subsequent 3-month CAPS scores. Earlier occurrence of ACEs was associated with smaller thalamic volume, which appears to moderate a positive association between early posttraumatic stress symptom severity and PTSD development after adult trauma. This raises the possibility that early occurrence of ACEs may impact thalamic structure, specifically a reduction in thalamic volume, and that smaller thalamic volume may contribute to susceptibility to PTSD development after adult trauma.

Structural and functional differences of the thalamus between drug-naïve Parkinson's disease motor subtypes.

The thalamus is an integrative hub of motor circuits in Parkinson's disease (PD). This study aimed to investigate the alterations of structure and functional connectivity (FC) of the thalamic subregions in the tremor-dominant (TD) subtype and the postural instability and gait difficulty (PIGD) subtype in PD. A total of 59 drug-naïve patients (24 TD and 35 PIGD) and 37 healthy controls were recruited. The volumes of the thalamus and the thalamic subregions were calculated using FreeSurfer. Functional connectivity (FC) analysis of the resting-state functional MRI (rsfMRI) was conducted on the thalamic subregions. Finally, the altered structure and FC were used for correlation analysis with clinical motor scores and for further motor subtypes differentiation. The volumes of the left posterior parietal thalamus (PPtha) in TD patients were significantly lower than those of PIGD patients. Compared with PIGD patients, TD patients exhibited higher FC between the thalamic subregions, the left middle temporal gyrus (MTG), the right dorsolateral superior frontal gyrus (SFGdl), the left middle occipital gyrus (MOG), and the right superior temporal gyrus (STG). Compared with HCs, TD patients showed higher FC between the thalamic subregions and the right SFGdl, as well as the left MOG. Compared with HCs, PIGD patients showed lower FC between the thalamic subregions and the left MTG. In addition, the altered FC was closely related to clinical symptoms and performed high-discriminative power in differentiating the motor subtypes. Increased FC between the thalamic subregions and the sensory cortices in TD patients may indicate a better compensatory capacity for impairment of sensory information integration than that in PIGD patients. The altered FC between the thalamus and the MTG was a potential biomarker for the distinction of the PD motor subtypes.

Intrauterine exposure to chorioamnionitis and neuroanatomical alterations at term-equivalent age in preterm infants.

Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age. A total of 58 preterm infants born before 34weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer). The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates. Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age.

Increased thalamic gray matter volume induced by repetitive transcranial magnetic stimulation treatment in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy in improving depressive symptoms in MDD patients, but the intrinsic mechanism is still unclear. In this study, we investigated the influence of rTMS on brain gray matter volume for alleviating depressive symptoms in MDD patients using structural magnetic resonance imaging (sMRI) data. Patients with first episode, unmedicated patients with MDD (n = 26), and healthy controls (n = 31) were selected for this study. Depressive symptoms were assessed before and after treatment by using the HAMD-17 score. High-frequency rTMS treatment was conducted in patients with MDD over 15 days. The rTMS treatment target is located at the F3 point of the left dorsolateral prefrontal cortex. Structural magnetic resonance imaging (sMRI) data were collected before and after treatment to compare the changes in brain gray matter volume. Before treatment, patients with MDD had significantly reduced gray matter volumes in the right fusiform gyrus, left and right inferior frontal gyrus (triangular part), left inferior frontal gyrus (orbital part), left parahippocampal gyrus, left thalamus, right precuneus, right calcarine fissure, and right median cingulate gyrus compared with healthy controls (P < 0.05). After rTMS treatment, significant growth in gray matter volume of the bilateral thalamus was observed in depressed patients (P < 0.05). Bilateral thalamic gray matter volumes were enlarged in the thalamus of MDD patients after rTMS treatment and may be the underlying neural mechanism for the treatment of rTMS on depression.

Evaluation of the cognitive outcome after out-of-hospital cardiac arrest: The role of thalamus.

Cardiac arrest survivors develop a variety of neuropsychological impairments and neuroanatomical lesions. The goal of this study is to evaluate if brain voxel-based morphometry and lesional Magnetic Resonance Imaging (MRI) analyses performed in the acute phase of an Out-of-Hospital Cardiac Arrest (OHCA) can be sensitive enough to predict the persistence of neuropsychological disorders beyond 3 months. Survivors underwent a prospective brain MRI during the first month after an OHCA and performed neuropsychological assessments at 1 and 3 months. According to the second neuropsychological assessment, survivors were separated into two subgroups, a deficit subgroup with persistent memory, executive functions, attention and/or praxis disorders (n = 11) and a preserved subgroup, disorders free (n = 14). Brain vascular lesion images were investigated, and volumetric changes were compared with healthy controls. Correlations were discussed between brain MRI results, OHCA data and the second neuropsychological assessment. Analyses of acute ischemic lesions did not reveal significant differences between the two subgroups (p= .35), and correlations with cognitive impairments could not be assessed. voxel-based morphometry analyses revealed a global cerebral volume reduction for the two subgroups and a clear decrease of the right thalamic volume for the deficit subgroup. It was associated with a cognitive dysexecutive syndrome represented by four executive indexes according to the 'Groupe de Réflexion pour l'Evaluation des Fonctions EXécutives' criteria. The right thalamus atrophy seems to be more predictive than the vascular lesions and more specific than a global cerebral volume reduction of post-OHCA neuropsychological executive disorders.

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.

Mild Autonomous Cortisol Secretion May Be Related To Decreased Thalamic Volume

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Altered thalamic volume in patients with mild autonomous cortisol secretion: a structural brain MRI study.

To compare thalamic volume and cognitive functions of patients with mild autonomous cortisol secretion (MACS) with control subjects and patients with overt Cushing's syndrome (CS). In this cross-sectional study, volumes of regions of interest were assessed using 3T magnetic resonance imaging and a voxel-based morphometry approach in 23 patients with MACS, 21 patients with active CS, 27 patients with CS in remission, and 21 control subjects. Cognitive functions were assessed using validated questionnaires. Patients with MACS had smaller left thalamic (F = 3.8, p = 0.023), left posterior thalamic (F = 4.9, p = 0.01), left medial thalamic (F = 4.7, p = 0.028), and right lateral thalamic (F = 4.1, p = 0.025) volumes than control subjects. Patients with active CS also had smaller left thalamic (F = 3.8, p = 0.044), left posterior thalamic (F = 4.9, p = 0.007), left medial thalamic (F = 4.7, p = 0.006), and right lateral thalamic (F = 4.1, p = 0.042) volumes compared to controls. Patients with CS in remission had smaller left medial (F = 4.7, p = 0.030) and right lateral thalamic (F = 4.1, p = 0.028) volumes than controls. Neuropsychological tests showed no difference between the groups. MACS may decrease thalamic volume.

Dissociable Contributions of Thalamic-Subregions to Cognitive Impairment in Small Vessel Disease.

Structural network damage is a potentially important mechanism by which cerebral small vessel disease (SVD) can cause cognitive impairment. As a central hub of the structural network, the role of thalamus in SVD-related cognitive impairments remains unclear. We aimed to determine the associations between the structural alterations of thalamic subregions and cognitive impairments in SVD. In this cross-sectional study, 205 SVD participants without thalamic lacunes from the third follow-up (2020) of the prospective RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort), which was initiated in 2006, Nijmegen, were included. Cognitive functions included processing speed, executive function, and memory. Probabilistic tractography was performed from thalamus to 6 cortical regions, followed by connectivity-based thalamic segmentation to assess each thalamic subregion volume and connectivity (measured by mean diffusivity [MD] of the connecting white matter tracts) with the cortex. Least absolute shrinkage and selection operator regression analysis was conducted to identify the volumes or connectivity of the total thalamus and 6 thalamic subregions that have the strongest association with cognitive performance. Linear regression and mediation analyses were performed to test the association of least absolute shrinkage and selection operator-selected thalamic subregion volume or MD with cognitive performance, while adjusting for age and education. We found that higher MD of the thalamic-motor tract was associated with worse processing speed (β=-0.27; P<0.001), higher MD of the thalamic-frontal tract was associated with worse executive function (β=-0.24; P=0.001), and memory (β=-0.28; P<0.001), respectively. The mediation analysis showed that MD of thalamocortical tracts mediated the association between corresponding thalamic subregion volumes and the cognitive performances in 3 domains. Our results suggest that the structural alterations of thalamus are linked to cognitive impairment in SVD, largely depending on the damage pattern of the white matter tracts connecting specific thalamic subregions and cortical regions.

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.