Thalamic Changes Research Articles

Trajectories of intrinsic connectivity one year post pediatric mild traumatic brain injury: Neural injury superimposed on neurodevelopment.

The developing brain undergoes rapid changes throughout middle childhood and adolescence. The disambiguation of long-term changes in intrinsic activity following pediatric mild traumatic brain injury (pmTBI) from typical development can therefore only be ascertained in longitudinal studies with large sample size and at least three serial assessments. A comprehensive clinical battery and resting-state fMRI data were collected approximately 1-week (N=263; 8-18 years old), 4-months (N=192) and 1-year (N=153) post-injury, with identical visits in a large cohort (N=228) of age- and sex-matched healthy controls (HC). Results indicated persistent frontocerebellar and thalamic connectivity changes up to 1-year post-injury in pmTBI relative to controls (P's<.001), with similar longitudinal connectivity trajectories (i.e., typical neurodevelopment). Alterations in precuneal midline connectivity (p's<.05) and occupancy of a default mode/limbic dynamic brain state were present only up to 4-months (p's<.001) rather than 1-year (p's>.44) post-injury. However, absent group differences at 1-year post-injury may be explained as pseudo-normalization due to altered longitudinal connectivity trajectories in pmTBI associated with neurodevelopment. Persistent alterations of precuneal connectivity were also associated with lower executive function and long-term memory scores. In conclusion, pmTBI may result in chronic changes to both static and dynamic intrinsic connectivity which further interact with typical neurodevelopment. Longer follow-up studies may be needed to unravel this interaction.

Thalamic changes in patients with chronic facial pain.

To investigate structural alterations in the thalamus in patients with primary trigeminal neuralgia and provide a detailed perspective on thalamic remodeling in response to chronic pain at the level of individual thalamic nuclei. METHODS: We analyzed a sample of 62 patients with primary trigeminal neuralgia who underwent surgical treatment, along with 28 healthy participants. Magnetic resonance imaging (MRI) data were acquired using a 3T system equipped with a 16-channel receiver head coil. Segmentation of the thalamic nuclei was performed using FreeSurfer 7.2.0. We divided the group of patients with trigeminal neuralgia into two subgroups: those with right-sided pain and those with left-sided pain. Each subgroup was compared to a control group by means of one-way ANOVA. Associations between morphometric and clinical variables were assessed with Spearman correlation coefficient. Our results revealed significant gray matter volume changes in thalamic nuclei among patients with trigeminal neuralgia. Notably, the intralaminar nuclei (centromedian/parafascicular) and nuclei associated with visual and auditory signal processing (lateral and medial geniculate bodies) exhibited significant alterations, contrasting with the ventral group nuclei involved in nociceptive processing. Additionally, we found no substantial volume increase in any of the studied nuclei following successful surgical intervention 6 months later. The volumes of thalamic nuclei were negatively correlated with pain intensity and disease duration. The results of this study, although preliminary, hold promise for clinical applications as they reveal previously unknown structural alterations in the thalamus that occur in patients with chronic trigeminal neuralgia.

Subcortical Alterations in Newly Diagnosed Epilepsy and Associated Changes in Brain Connectivity and Cognition.

Patients with chronic focal epilepsy commonly exhibit subcortical atrophy, particularly of the thalamus. The timing of these alterations remains uncertain, though preliminary evidence suggests that observable changes may already be present at diagnosis. It is also not yet known how these morphological changes are linked to the coherence of white matter pathways throughout the brain, or to neuropsychological function often compromised before antiseizure medication treatment. This study investigates localized atrophy in subcortical regions using surface shape analysis in individuals with newly diagnosed focal epilepsy (NDfE) and assesses their implications on brain connectivity and cognitive function. We collected structural (T1w) and diffusion-weighted MRI and neuropsychological data from 104 patients with NDfE and 45 healthy controls (HCs) matched for age, sex, and education. A vertex-based shape analysis was performed on subcortical structures to compare patients with NDfE and HC, adjusting for age, sex, and intracranial volume. The mean deformation of significance areas (pcor < 0.05) was used to identify white matter pathways associated with overall shape alterations in patients relative to controls using correlational tractography. Additionally, the relationship between significant subcortical shape values and neuropsychological outcomes was evaluated using a generalized canonical correlation approach. Shape analysis revealed bilateral focal inward deformation (a proxy for localized atrophy) in anterior areas of the right and left thalamus and right pallidum in patients with NDfE compared to HC (FWE corrected). No structures showed areas of outward deformation in patients. The connectometry analysis revealed that fractional anisotropy (FA) was positively correlated with thalamic and pallidal shape deformation, that is, reduced FA was associated with inward deformation in tracts proximal to and or connecting with the thalamus including the fornix, frontal, parahippocampal, and corticothalamic pathways. Thalamic and pallidal shape changes were also related to increased depression and anxiety and reduced memory and cognitive function. These findings suggest that atrophy of the thalamus, which has previously been associated with the generation and maintenance of focal seizures, may present at epilepsy diagnosis and relate to alterations in both white matter connectivity and cognitive performance. We suggest that at least some alterations in brain structure and consequent impact on cognitive and affective processes are the result of early epileptogenic processes rather than exclusively due to the chronicity of longstanding epilepsy, recurrent seizures, and treatment with antiseizure medication.

A family with neuronal intranuclear inclusion disease with focal segmental glomerulosclerosis.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease caused by the expansion of GGC repeats in the 5'-untranslated region (5'-UTR) of NOTCH2NLC. Although increasing evidence suggests that NIID affects various organs, its association with renal involvement remains unclear. We studied the genetic background of a family with NIID, in which four of five members presented with proteinuria as the initial manifestation. The renal pathology of three patients was diagnosed as focal segmental glomerulosclerosis (FSGS) at a previous hospital. These patients also presented with tremors, retinal degeneration, and episodic neurological events. Finally, one patient exhibited reversible bilateral thalamic high-intensity signal changes on diffusion-weighted imaging during episodic neurological events. Exome sequencing (ES) and nanopore long-read whole-genome sequencing (LR-WGS) were performed on the index case, followed by nanopore target sequencing using Cas9-mediated PCR-free enrichment and methylation analysis. ES revealed no candidate variants; however, nanopore LR-WGS in the index case revealed expansion of short tandem repeats (STR) in NOTCH2NLC. Subsequent nanopore target sequencing using Cas9-mediated PCR-free enrichment showed STR expansion of NOTCH2NLC in an affected sibling and asymptomatic father. Methylation analysis using nanopore data revealed hypermethylation of the expanded allele in the asymptomatic father and partial hypermethylation in a mildly symptomatic sibling, whereas the expanded allele was hypomethylated in the index case. This investigation expands the clinical spectrum of NIID, suggesting that STR expansion of NOTCH2NLC is a cause of renal diseases, including FSGS.

Tracking longitudinal thalamic volume changes during early stages of SCA1 and SCA2

PurposeSpinocerebellar ataxia SCA1 and SCA2 are adult-onset hereditary disorders, due to triplet CAG expansion in their respective causative genes. The pathophysiology of SCA1 and SCA2 suggests alterations of cerebello-thalamo-cortical pathway and its connections to the basal ganglia. In this framework, thalamic integrity is crucial for shaping efficient whole-brain dynamics and functions. The aims of the study are to identify structural changes in thalamic nuclei in presymptomatic and symptomatic SCA1 and SCA2 patients and to assess disease progression within a 1-year interval.Material and methodsA prospective 1-year clinical and MRI assessment was conducted in 27 presymptomatic and 23 clinically manifest mutation carriers for SCA1 and SCA2 expansions. Cross-sectional and longitudinal changes of thalamic nuclei volume were investigated in SCA1 and SCA2 individuals and in healthy participants (n = 20).ResultsBoth SCA1 and SCA2 patients had significant atrophy in the majority of thalamic nuclei, except for the posterior and partly medial nuclei. The 1-year longitudinal evaluation showed a specific pattern of atrophy in ventral and posterior thalamus, detectable even at the presymptomatic stage of the disease.ConclusionFor the first time in vivo, our exploratory study has shown that different thalamic nuclei are involved at different stages of the degenerative process in both SCA1 and SCA2. It is therefore possible that thalamic alterations might significantly contribute to the progression of the disease years before overt clinical manifestations occur.

Regional structural abnormalities in thalamus in idiopathic cervical dystonia

BackgroundThe thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD.MethodsStructural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD.ResultsCompared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group.ConclusionThis study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.

Radiological and clinical biomarkers in patients with central post stroke pain

Background. Central post-stroke pain (CPSP) occurs following cerebrovascular accidents and is a neuropathic pain syndrome that is characterized by stimulation-independent pain; shooting, burning, or electric shock-like sensation and paresthesia. Multiple pathogenetic theories have been proposed for the CPSP including disinhibition, central sensitization, thalamic changes, and altered function of spinothalamic tract (STT). Investigations such as MRI DTI can help to understand the pathogenesis of CPSP. Objective. To determine the radiological and clinical biomarkers in cases with CPSP. Methods. This case-control study was retrospectively conducted upon 60 persons divided into 20 CPSP cases (group 1), 20 cases with no CPSP (group 2) and 20 healthy controls (group 3). All subjects had Routine MRI and complete neurological examination including “Sensory testing but stroke patients were evaluated by quantitative assessment of neuropathic pain, the National Institutes of Health Stroke Scale (NIHSS), Ashworth scale, Modified Rankin Scale (MRS) and Hamilton depression rating scale (HAM-D scale). Results. Significant differences existed among studied groups as regard motor examination, sensory examination, NIHSS score and Hamilton depression score. A non-significant difference was detected among the groups regarding MRS findings. A significant difference existed between groups 1 and 2, between groups 1 and 3 while no significant difference was detected between groups 2 and 3 for all FA readings and all ADC readings in ipsilateral affected side assessed at internal capsule, midbrain, and pons. No significant difference existed between groups 1 and 2, between groups 1 and 3 and between groups 2 and 3 as regard FA readings and ADC readings in contralateral side assessed at internal capsule, midbrain, and pons. Conclusion. Our study highlighted the significance of white matter tracts (WMT) other than the conventional pain pathways in CPSP and can thus serve as a predictive marker for CPSP onset or a prognostic marker after any drug therapy or neuromodulatory treatment.

Atypical co-development of the thalamus and cortex in autism: Evidence from age-related white-gray contrast change.

Recent studies have shown that white-gray contrast (WGC) of either cortical or subcortical gray matter provides for accurate predictions of age in typically developing (TD) children, and that, at least for the cortex, it changes differently with age in subjects with autism spectrum disorder (ASD) compared to their TDpeers. Our previous study showed different patterns of contrast change between ASD and TD in sensorimotor and association cortices. While that study was confined to the cortex, we hypothesized that subcortical structures, particularly the thalamus, were involved in the observed cortical dichotomy between lower and higher processing. The current paper investigates that hypothesis using the WGC measures from the thalamus in addition to those from the cortex. We compared age-related WGC changes in the thalamus to those in the cortex. To capture the simultaneity of this change across the two structures, we devised a metric capturing the co-development of the thalamus and cortex (CoDevTC), proportional to the magnitude of cortical and thalamic age-related WGC change. We calculated this metric for each of the subjects in a large homogeneous sample taken from the Autism Brain Imaging Data Exchange (ABIDE) (N = 434). We used structural MRI data from the largest high-quality cross-sectional sample (NYU) as well as two other large high-quality sites, GU and OHSU, all three using Siemens 3T scanners. We observed that the co-development features in ASD and TD exhibit contrasting patterns; specifically, some higher-order thalamic nuclei, such as the lateral dorsal nucleus, exhibited reduction in codevelopment with most of the cortex in ASD compared to TD. Moreover, this difference in the CoDevTC pattern correlates with a number of behavioral measures across multiple cognitive and physiological domains. The results support previous notions of altered connectivity in autism, but add more specific evidence about the heterogeneity in thalamocortical development that elucidates the mechanisms underlying the clinical features of ASD.

Increased Thalamic Connectivity in Juvenile Myoclonic Epilepsy Based on Electroencephalography Source-Level Analysis.

Background: This study investigated alterations in the intrinsic thalamic network of patients with juvenile myoclonic epilepsy (JME) based on an electroencephalography (EEG) source-level analysis. Materials and Methods: We enrolled patients newly diagnosed with JME as well as healthy controls. The assessments were conducted in the resting state. We computed sources based on the scalp electrical potentials using a minimum-norm imaging method and a standardized, low-resolution, brain electromagnetic tomography approach. To create a functional connectivity matrix, we used the Talairach atlas to define thalamic nodes and applied the coherence method to measure brain synchronization as edges. We then calculated the intrinsic thalamic network using graph theory. We compared the intrinsic thalamic network of patients with JME with those of healthy controls. Results: This study included 67 patients with JME and 66 healthy controls. EEG source-level analysis revealed significant differences in the intrinsic thalamic networks between patients with JME and healthy controls. The measures of functional connectivity (radius, diameter, and characteristic path length) were significantly lower in patients with JME than in healthy controls (radius: 2.769 vs. 3.544, p = 0.015; diameter: 4.464 vs. 5.443, p = 0.024; and characteristic path length: 2.248 vs. 2.616, p = 0.046). Conclusions: We demonstrated alterations in the intrinsic thalamic network in patients with JME compared with those in healthy controls based on the EEG source-level analysis. These findings indicated increased thalamic connectivity in the JME group. These intrinsic thalamic network changes may be related to the pathophysiology of JME.

Region-specific MRI predictors of surgical outcome in temporal lobe epilepsy

ObjectiveIn drug-resistant temporal lobe epilepsy (TLE), it is not well-established in how far surgery should target morphological anomalies to achieve seizure freedom. Here, we assessed interactions between structural brain compromise and surgery to identify region-specific predictors of seizure outcome. MethodsWe obtained pre- and post-operative 3D T1-weighted MRI in 55 TLE patients who underwent selective amygdalo-hippocampectomy (SAH) or anterior temporal lobectomy (ATL) and 40 age and sex-matched healthy subjects. We measured surface-based morphological alterations of the mesiotemporal lobe structures (hippocampus, amygdala, entorhinal and piriform cortices), the neocortex and the thalamus on both pre- and post-operative MRI. Using precise co-registration, in each patient we mapped the surgical cavity onto the MRI acquired before surgery, thereby quantifying the amount of pathological tissue resected; these features, together with the preoperative morphometric data, served as input to a supervised classification algorithm for postsurgical outcome prediction. ResultsOn pre-operative MRI, patients who became seizure-free (TLE-SF) presented with severe ipsilateral amygdalar and hippocampal atrophy, while not seizure-free patients (TLE-NSF) displayed amygdalar hypertrophy. Stratifying patients based on the surgical approach, post-operative MRI showed similar patterns of mesiotemporal and thalamic changes, but divergent neocortical thinning affecting the parieto-temporo-occipital regions following ATL and the frontal lobes after SAH. Irrespective of the surgical approach, hippocampal atrophy on pre-operative MRI and its extent of resection were the most predictive features of seizure-freedom in 89% of patients (selected 100% across validations). SignificanceOur study indicates a critical role of the extent of resection of MRI-derived hippocampal morphological anomalies on seizure outcome. Precise pre-operative quantification of the mesiotemporal lobe provides non-invasive prognostics for individualized surgery.

Segmentation and quantification of venous structures and perivascular spaces in the thalamus in epilepsy using 7 Tesla MRI

Background and purposeEpilepsy is a complex neurological disorder affecting 50 million people worldwide. Persistent seizures may correlate with neural network, microstructural, and vascular changes within the thalamus. These thalamic changes may result from seizure activity or broader alterations involving neuronal vasculature and neuroinflammatory processes linked to glymphatic drainage. Improved resolution with Ultra-high field (UHF) magnetic resonance imaging (MRI) may be useful in identifying possible thalamic vascular abnormalities not otherwise detectable at lower field strengths. Materials and methodsWe outline a novel method which leverages UHF neuroimaging for detection and quantification of vessels and perivascular spaces (PVS) within the thalamus in 25 epilepsy patients and 16 controls, to uncover possible underlying imaging biomarkers of epilepsy. In our analysis, we optimize a MATLAB-based Frangi-based detection tool called Perivascular Space Semi-Automated Segmentation (PVSSAS) to detect thalamic PVSs, and additionally use a second Frangi-based segmentation tool method to automate detection of vascular structures in the thalamus. The resulting PVS and vessel masks were used to quantify differences in the number of vessels, PVS, overlaps, and number of PVS overlaps per vessel detected between groups, using a Hessian detection filter linked on an 18-connected network. ResultsWe found significantly more thalamic PVS (p = 0.0307) and a significant increase in the number of thalamic vessels (p = 0.038) in patients compared to controls. ConclusionHere we have developed a novel process which leverages UHF MRI to quantify and detect thalamic vessels and PVS that may provide a potential neuroimaging biomarker of epilepsy. Statement of SignificanceWe use 7T, ultra-high field MRI and employed an innovative combination of semi-automated perivascular space segmentation and automated vessel segmentation to visualize and quantify vessels and perivascular spaces (PVS) within the thalamus, a highly cited region of interest in epilepsy. To our knowledge, this is the first study to semi-automatically visualize and segment PVS in the thalamus and automatically detect thalamic vessels. We uncovered detectable differences in thalamic vasculature and PVS. These findings suggests that increases in the number of thalamic PVS and vessels may be a potential neuroimaging biomarker in epilepsy. This tool may be useful in the detection of subtle vascular changes in other regions of the brain related to epilepsy or can be employed in other neurological conditions.

Maturation-dependent changes in cortical and thalamic activity during sleep slow waves: Insights from a combined EEG-fMRI study

IntroductionStudies using scalp EEG have shown that slow waves (0.5–4 Hz), the most prominent hallmark of NREM sleep, undergo relevant changes from childhood to adulthood, mirroring brain structural modifications and the acquisition of cognitive skills. Here we used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes. MethodsWe analyzed data from 14 school-age children with self-limited focal epilepsy of childhood who fell asleep during EEG-fMRI recordings. Brain regions associated with slow-wave occurrence were identified using a voxel-wise regression that also modelled interictal epileptic discharges and sleep spindles. At the group level, a mixed-effects linear model was used. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults. ResultsSlow waves were associated with hemodynamic-signal decreases in bilateral somatomotor areas. Such changes extended more posteriorly relative to those in adults. Moreover, the involvement of areas belonging to the default mode network changes as a function of age. No significant hemodynamic responses were observed in subcortical structures. However, we identified a significant correlation between age and thalamic hemodynamic changes. ConclusionsPresent findings indicate that the somatomotor cortex may have a key role in slow-wave expression throughout the lifespan. At the same time, they are consistent with a posterior-to-anterior shift in slow-wave distribution mirroring brain maturational changes. Finally, our results suggest that slow-wave changes may not reflect only neocortical modifications but also the maturation of subcortical structures, including the thalamus.

The effects of P2 segment of posterior cerebral artery to thalamus blood supply pattern on gait in cerebral small vessel disease: A 7 T MRI based study

Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.

Quantification of Thalamic Atrophy in MS: From the Multicenter Italian Neuroimaging Network Initiative Data Set to Clinical Application.

Thalamic atrophy occurs from the earliest phases of MS; however, this measure is not included in clinical practice. Our purpose was to obtain a reliable segmentation of the thalamus in MS by comparing existing automatic methods cross-sectionally and longitudinally. MR images of 141 patients with relapsing-remitting MS (mean age, 38 years; range, 19-58 years; 95 women) and 69 healthy controls (mean age, 36 years; range, 22-69 years; 47 women) were retrieved from the Italian Neuroimaging Network Initiative repository: T1WI, T2WI, and DWI at baseline and after 1 year (136 patients, 31 healthy controls). Three segmentation software programs (FSL-FIRST, FSL-MIST, FreeSurfer) were compared. At baseline, agreement among pipelines, correlations with age, disease duration, clinical score, and T2-hyperintense lesion volume were evaluated. Effect sizes in differentiating patients and controls were assessed cross-sectionally and longitudinally. Variability of longitudinal changes in controls and sample sizes were assessed. False discovery rate-adjusted P < .05 was considered significant. At baseline, FSL-FIRST and FSL-MIST showed the highest agreement in the results of thalamic volume (R = 0.87, P < .001), with the highest effect size for FSL-MIST (Cohen d = 1.11); correlations with demographic and clinical variables were comparable for all software. Longitudinally, FSL-MIST showed the lowest variability in estimating thalamic volume changes for healthy controls (SD = 1.07%), the highest effect size (Cohen d = 0.44), and the smallest sample size at 80% power level (15 subjects per group). Multimodal segmentation by FSL-MIST increased the robustness of the results with better capability to detect small variations in thalamic volumes.

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.

Cortical thickness and cognition in older people with multiple sclerosis.

The structural changes associated with cognitive performance in older people with multiple sclerosis (PwMS; age ≥ 50years old) remain unknown. To determine the relationship between whole-brain (WBV), thalamus as the largest deep gray matter nuclei, and cortex-specific volume measurements with both cognitive impairment and numerical performance in older PwMS. The main hypothesis is that cognitive impairment (CI) in older PwMS is explained by cortical thinning in addition to global and thalamic neurodegenerative changes. A total of 101 older PwMS underwent cognitive and neuroimaging assessment. Cognitive assessment included tests established as sensitive in MS samples (Minimal Assessment of Cognitive Function in MS; MACFIMS), as well as those tests often utilized in Alzheimer's dementia studies (Wechsler's Memory Scale, Boston Naming Test, Visual Motor Integration and language). Cognitive impairment (CI) was based on -1.5 standard deviations in at least 2 cognitive domains (executive function, learning and memory, spatial processing, processing speed and working memory and language) when compared to healthy controls. WBV and thalamic volume were calculated using SIENAX/FIRST and cortical thickness using FreeSurfer. Differences in cortical thickness between CI and cognitively preserved (CP) were determined using age, sex, education, depression and WBV-adjusted analysis of covariance (ANCOVA). The relationship between domain-specific cognitive performance and cortical thickness was analyzed by linear regression models adjusted for age, sex, education, depression, WBV and thalamic volume. Benjamini-Hochberg-adjusted p-values lower than 0.05 were considered significant. The average age of the study population was 62.6 (5.9) years old. After adjustment, CI PwMS had significantly thinner left fusiform (p = 0.0003), left inferior (p = 0.0032), left transverse (p = 0.0013), and bilateral superior temporal gyri (p = 0.002 and p = 0.0011) when compared to CP PwMS. After adjusting for age, sex, education, depression WBV, and thalamic volume, CI status was additionally predicted by the thickness of the left fusiform (p = 0.001) and left cuneus gyri (p = 0.004). After the adjustment, SDMT scores were additionally associated with left fusiform gyrus (p < 0.001) whereas letter-based verbal fluency performance with left pars opercularis gyrus (p < 0.001). In addition to global and thalamic neurodegenerative changes, the presence of CI in older PwMS is additionally explained by the thickness of multiple cortical regions.

Structural changes in the thalamus and its subregions in regulating different symptoms of posttraumatic stress disorder

As a key center for sensory information processing and transmission, the thalamus plays a crucial role in the development of posttraumatic stress disorder (PTSD). However, the changes in the thalamus and its role in regulating different PTSD symptoms remain unclear. In this study, fourteen PTSD patients and eighteen healthy controls (HCs) were recruited. All subjects underwent whole-brain T1-weighted three-dimensional Magnetization Prepared Rapid Gradient Echo Imaging scans. Gray matter volume (GMV) in the thalamus and its subregions were estimated using voxel-based morphometry (VBM). Compared to HCs, PTSD patients exhibited significant GMV reduction in the left thalamus and its subregions, including anterior, mediodorsal, ventral-lateral-dorsal (VLD), ventral-anterior, and ventral-lateral-ventral (VLV). Among the significantly reduced thalamic subregions, we found positive correlations between the GMV values of the left VLD and VLV and the re-experiencing symptoms score, arousal symptoms score, and total CAPS score. When using the symptom-related GMV values of left VLV and VLD in combination as a predictor, receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for binary classification reached 0.813. This study highlights the neurobiological mechanisms of PTSD related to thalamic changes and may provide potential imaging markers for diagnosis and therapy targets.

Thalamic neurometabolite alterations in chronic low back pain: a common phenomenon across musculoskeletal pain conditions?

Recently, we showed that patients with knee osteoarthritis (KOA) demonstrate alterations in the thalamic concentrations of several metabolites compared with healthy controls: higher myo-inositol (mIns), lower N-acetylaspartate (NAA), and lower choline (Cho). Here, we evaluated whether these metabolite alterations are specific to KOA or could also be observed in patients with a different musculoskeletal condition, such as chronic low back pain (cLBP). Thirty-six patients with cLBP and 20 healthy controls were scanned using 1 H-magnetic resonance spectroscopy (MRS) and a PRESS (Point RESolved Spectroscopy) sequence with voxel placement in the left thalamus. Compared with healthy controls, patients with cLBP demonstrated lower absolute concentrations of NAA ( P = 0.0005) and Cho ( P < 0.05) and higher absolute concentrations of mIns ( P = 0.01) when controlling for age, as predicted by our previous work in KOA. In contrast to our KOA study, mIns levels in this population did not significantly correlate with pain measures (eg, pain severity or duration). However, exploratory analyses revealed that NAA levels in patients were negatively correlated with the severity of sleep disturbance ( P < 0.01), which was higher in patients compared with healthy controls ( P < 0.001). Additionally, also in patients, both Cho and mIns levels were positively correlated with age ( P < 0.01 and P < 0.05, respectively). Altogether, these results suggest that thalamic metabolite changes may be common across etiologically different musculoskeletal chronic pain conditions, including cLBP and KOA, and may relate to symptoms often comorbid with chronic pain, such as sleep disturbance. The functional and clinical significance of these brain changes remains to be fully understood.

Characteristics of ictal thalamic EEG in pediatric-onset neocortical focal epilepsy

ObjectiveTo characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings. MethodsForty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2–25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured. ResultsVisual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400 ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from −18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings. ConclusionsIctal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures. SignificanceIt may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.

Serial deep gray nuclear DTI changes in Parkinson's disease over twelve years.

Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson's disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years. Participating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time. MD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores. Pallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.