Thalamic Stroke Patients Research Articles

Exploring the impact of the interthalamic adhesion on human cognition: insights from healthy subjects and thalamic stroke patients

The interthalamic adhesion (IA) is a structure that connects the median borders of both thalami. Its anatomical variants and functions remain poorly studied. The main objective of this study was to explore the role of the IA on cognition. 42 healthy subjects and 40 patients with chronic isolated thalamic strokes underwent a neuroimaging and a neuropsychological assessment. The presence, absence, or lesion of the IA and its anatomical variants were evaluated. 76% of participants had an IA, with a higher prevalence among women (92%) than men (61%). The presence or absence of an IA did not affect the neuropsychological performance of healthy subjects nor did the type of IA variant. Across all the tests and when compared to healthy subjects using a Bayesian rmANOVA, patients exhibiting more cognitive impairments were those without an IA (n = 10, BF10 = 10,648), while those with an IA were more preserved (n = 18, BF10 = 157). More specifically, patients without an IA performed more poorly in verbal memory or the Stroop task versus healthy subjects. This was not explained by age, laterality of the infarct, volume or localization of the lesion. Patients with a lesioned IA (n = 12) presented a similar trend to patients without an IA, which could however be explained by a greater volume of lesions. The IA does not appear to play a major role in cognition in healthy subjects, but could play a compensatory role in patients with thalamic lesions.

Abstract TMP27: Structural Network Dysfunction and Aberrant Structural-Functional Connectivity Coupling Correlate With Central Post-Stroke Pain of Thalamic Origin

Introduction and Hypothesis: As the most frequent subtype of central post-stroke pain (CPSP), CPSP of thalamic origin can often be refractory to treatments and affect long-term prognosis of thalamic-stroke patients, while the mechanism remains unclear. We assumed that post-thalamic stroke CPSP might be a brain network disorder and aimed to investigate brain network alterations in post-thalamic stroke CPSP patients and explore whether these changes underlie clinical symptoms. Methods: A total of 92 participants were finally enrolled, of whom 62 were chronic thalamic stroke patients (26 had CPSP) and 30 were healthy controls. Using graph theory approaches, we compared the structural and functional brain network topological characteristics and structural-functional connectivity (SC-FC) couplings at multi-modular levels among the groups, and further explored their potential relationships with pain severity. Results: Distinct SC topological changes were found in CPSP patients, characterized as a higher clustering coefficient (Cp), global efficiency (Eg), local efficiency (Eloc), and lower characteristic path length (Lp) and normalized characteristic path length (Lambda) values than that in non-CPSP group. No significant differences were found in the FC network among the three groups. CPSP patients had significantly lower SC-FC couplings at the global and the structural Hub-modular levels. Further, we found significant and various correlations between pain severity and structural Lp, Eloc, global and Hub-modular SC-FC couplings. Results: These results indicated that thalamic stroke-induced distinct structural network dysfunction and SC-FC decoupling may be a novel neural mechanism for CPSP. It may provide new insights for future targeted neuromodulation therapies and individualized rehabilitative strategies in CPSP patients.

Thalamic Stroke: An Opportunity to Study the Brain Mechanisms of Sleep–Wake and Cognition

The thalamus, and its projections to the cerebral cortex, are crucial for regulating sleep rhythms, such as sleep spindles, and for maintaining arousal and sleep homeostasis. Moreover, they play a significant role in memory, executive functioning, and attention. Altered thalamocortical circuitry caused by vascular lesions affects sleep–wake architecture and may contribute to cognitive deficits observed in thalamic stroke patients. This review summarizes the biology of the thalamus and current knowledge regarding the impact of thalamic circuitry on sleep regulation and cognition, drawing from clinical and pre-clinical studies. Furthermore, deep brain stimulation and transcranial magnetic stimulation are discussed as possible therapeutic approaches targeting thalamic circuits. Understanding the role of the thalamus in sleep and cognition opens new avenues for developing novel therapeutic strategies to improve sleep and cognitive functions in affected individuals.

Depression and anxiety in acute ischemic stroke involving the anterior but not paramedian or inferolateral thalamus.

Emotional and cognitive deficits are prevalent in strokes involving the thalamus. In contrast to cognitive deficits, emotional deficits have not been studied prospectively in isolated thalamic stroke. In 37 ischemic thalamic stroke patients (57.0 [50.0; 69.5] years [median (Q1; Q3)], 21 males, 5 anterior, 12 paramedian, 20 inferolateral vascular territory), and 37 non-stroke control patients matched for age and sex, we prospectively examined depression, anxiety, activities of daily living, and quality of life at 1, 6, 12, and 24 months post-stroke using the Hospital-Anxiety-and-Depression Scale (HADS), Nürnberger-Alters-Alltagsaktivitäten scale (NAA), and Short Form-36 (SF36) questionnaire. Voxel-based lesion-symptom mapping (VLSM) and lesion-subtraction analyzes were performed to determine associations between questionnaire scores and thalamic stroke topography. At 1 month post-stroke, anterior thalamic stroke patients had higher depression scores [8.0 (7.5; 10.5)] than paramedian [4.5 (1.0; 5.8)] and inferolateral [4.0 (1.0; 7.0)] thalamic stroke patients. Furthermore, anterior thalamic stroke patients had higher anxiety scores [11.0 (8.0; 14.5)] than their matched controls [2.5 (2.0; 2.5)], paramedian [4.5 (1.0; 5.8)] and inferior [4.0 (1.0; 7.0)] thalamic stroke patients. Depression and anxiety scores in anterior thalamic stroke patients remained high across the follow-up [depression: 9.0 (3.5; 13,8); anxiety:10.05 (2.8, 14.5)].Physical health assessed by SF36 was intact in anterior [1 month post-stroke: T-score = 55.9 (37.0; 57.6)] but reduced in inferolateral [44.5(32.4; 53.1)] thalamic stroke, whereas mental health was reduced in anterior thalamic stroke [32.0 (29.8; 47.3)].VLSM confirmed that voxels in the anterior thalamus around Montreal Neurological Institute (MNI) coordinates X = -8, Y = -12, Z = 2 were more often affected by the stroke in depressed (HADS-score ≥ 8) than non-depressed (HADS-score < 8) patients and voxels around coordinates X = -10, Y = -12, Z = 2 were more often affected in anxious (HADS-score ≥ 8) than non-anxious (HADS-score < 8) patients. Anterior, but not paramedian or inferolateral thalamic stroke was associated with depression and anxiety. Even though our results are mostly significant in the left thalamus, this observation on stroke laterality might be confounded by the fact that the right hemisphere was underrepresented in our study.

Evolution of Neuropsychological Deficits in First-Ever Isolated Ischemic Thalamic Stroke and Their Association With Stroke Topography: A Case-Control Study.

Background:The thalamus plays an essential role in cognition. Cognitive deficits have to date mostly been studied retrospectively in chronic thalamic stroke in small cohorts. Studies prospectively evaluating the evolution of cognitive deficits and their association with thalamic stroke topography are lacking. This knowledge is relevant for targeted patient diagnostics and rehabilitation.Methods:Thirty-seven patients (57.5±17.5 [mean±SD] years, 57% men) with first-ever acute isolated ischemic stroke covering the anterior (n=5), paramedian (n=12), or inferolateral (n=20) thalamus and 37 in-patient controls without stroke with similar vascular risk factors matched for age and sex were prospectively studied. Cognition was evaluated using predefined tests at 1, 6, 12, and 24 months. Voxel-based lesion-symptom mapping was used to determine associations between neuropsychological deficits and stroke topography.Results:Patients with anterior thalamic stroke revealed severe deficits in verbal memory (median T score [Q1–Q3]: 39.1 [36.1–44.1]), language (31.8 [31.0–43.8]), and executive functions (43.8 [35.5–48.1]) at 1 month compared with controls (verbal memory: 48.5 [43.6–61.0], language: 55.7 [42.3–61.1], executive functions: 51.3 [50.1–56.8]). Patients with paramedian thalamic stroke showed moderate language (44.7 [42.8–55.9]) and executive (49.5 [44.3–55.1]) deficits and no verbal memory deficits (48.1 [42.5–54.7]) at 1 month compared with controls (59.0 [47.0–64.5]; 59.6 [51.1–61.3]; 52.5 [44.2–55.3]). The language and executive deficits in paramedian thalamic stroke patients almost completely recovered during follow-up. Intriguingly, significant deficits in verbal memory (44.7 [41.5–51.9]), language (47.5 [41.8–54.1]), and executive functions (48.2 [46.2–59.7]) were found in inferolateral thalamic stroke patients at 1 month compared with controls (50.5 [46.7–59.9]; 57.0 [51.2–62.9]; 57.4 [51.2–60.7]). Language, but not executive deficits persisted during follow-up. Voxel-based lesion-symptom mapping revealed an association of verbal memory deficits with anterior thalamus lesions and an association of non-verbal memory, language, and executive deficits with lesions at the anterior/paramedian/inferolateral border.Conclusions:All 3 stroke topographies exhibited significant deficits in diverse cognitive domains, which recovered to a different degree depending on the stroke localization. Our study emphasizes the need for comprehensive neuropsychological diagnostics to secure adequate patient rehabilitation.

Individual spindle detection and analysis in high-density recordings across the night and in thalamic stroke

Sleep spindles are thalamocortical oscillations associated with several behavioural and clinical phenomena. In clinical populations, spindle activity has been shown to be reduced in schizophrenia, as well as after thalamic stroke. Automatic spindle detection algorithms present the only feasible way to systematically examine individual spindle characteristics. We took an established algorithm for spindle detection, and adapted it to high-density EEG sleep recordings. To illustrate the detection and analysis procedure, we examined how spindle characteristics changed across the night and introduced a linear mixed model approach applied to individual spindles in adults (n = 9). Next we examined spindle characteristics between a group of paramedian thalamic stroke patients (n = 9) and matched controls. We found a high spindle incidence rate and that, from early to late in the night, individual spindle power increased with the duration and globality of spindles; despite decreases in spindle incidence and peak-to-peak amplitude. In stroke patients, we found that only left-sided damage reduced individual spindle power. Furthermore, reduction was specific to posterior/fast spindles. Altogether, we demonstrate how state-of-the-art spindle detection techniques, applied to high-density recordings, and analysed using advanced statistical approaches can yield novel insights into how both normal and pathological circumstances affect sleep.

P.060 Altered oculomotor learning in thalamic stroke patients

Background: Visuomotor learning can be elicited experimentally by displacing the target of a saccade during the ongoing eye movement. In healthy subjects, the resulting mismatch between expected and experienced visual error after saccade completion elicits a gradual adaptation of saccade amplitude. The goal of this project was to explore the role of cerebro-thalamo-cerebellar circuits in the dynamics of visuomotor learning. Methods: Patient RK is a 38-year-old right hand dominant male who suffered a focal thalamic stroke of the right thalamus, confined to ventral lateral posterior and ventral medial nuclei. We employed a standard saccadic adaptation paradigm and assessed dynamics of visuomotor learning by fitting a simple state-equation to saccade amplitudes towards the ipsi- and contralesional hemifield. Results: While RK was able to adapt saccade amplitudes in both directions, adaptation dynamics were different for leftward versus rightward saccades. Rightward, ipsilesional saccades exhibited a lower learning rate but similar retention of altered saccade metrics, compared to leftward, contralesional saccades. Conclusions: The present study assessed a patient with a focal lesion to the right cerebellar thalamus on a saccade adaptation paradigm. Results demonstrated slower visuomotor learning for saccades into the ipsilesional hemifield, suggesting an important contribution of cerebello-cortical projections mediated by thalamic relays for visuomotor learning.

Thalamic pain: anatomical and physiological indices of prediction.

Thalamic pain is a severe and treatment-resistant type of central pain that may develop after thalamic stroke. Lesions within the ventrocaudal regions of the thalamus carry the highest risk to develop pain, but its emergence in individual patients remains impossible to predict. Because damage to the spino-thalamo-cortical system is a crucial factor in the development of central pain, in this study we combined detailed anatomical atlas-based mapping of thalamic lesions and assessment of spinothalamic integrity using quantitative sensory analysis and laser-evoked potentials in 42 thalamic stroke patients, of whom 31 had developed thalamic pain. More than 97% of lesions involved an area between 2 and 7 mm above the anterior-posterior commissural plane. Although most thalamic lesions affected several nuclei, patients with central pain showed maximal lesion convergence on the anterior pulvinar nucleus (a major spinothalamic target) while the convergence area lay within the ventral posterior lateral nucleus in pain-free patients. Both involvement of the anterior pulvinar nucleus and spinothalamic dysfunction (nociceptive thresholds, laser-evoked potentials) were significantly associated with the development of thalamic pain, whereas involvement of ventral posterior lateral nucleus and lemniscal dysfunction (position sense, graphaesthesia, pallaesthesia, stereognosis, standard somatosensory potentials) were similarly distributed in patients with or without pain. A logistic regression model combining spinothalamic dysfunction and anterior pulvinar nucleus involvement as regressors had 93% sensitivity and 87% positive predictive value for thalamic pain. Lesion of spinothalamic afferents to the posterior thalamus appears therefore determinant to the development of central pain after thalamic stroke. Sorting out of patients at different risks of developing thalamic pain may be achievable at the individual level by combining lesion localization and functional investigation of the spinothalamic system. As the methods proposed here do not need complex manipulations, they can be added to routine patients' work up, and the results replicated by other investigators in the field.

Analysis of correlation between white matter changes and functional responses in thalamic stroke: a DTI & EEG study.

Diffusion tensor imaging (DTI) allows in vivo structural brain mapping and detection of microstructural disruption of white matter (WM). One of the commonly used parameters for grading the anisotropic diffusivity in WM is fractional anisotropy (FA). FA value helps to quantify the directionality of the local tract bundle. Therefore, FA images are being used in voxelwise statistical analyses (VSA). The present study used Tract-Based Spatial Statistics (TBSS) of FA images across subjects, and computes the mean skeleton map to detect voxelwise knowledge of the tracts yielding to groupwise comparison. The skeleton image illustrates WM structure and shows any changes caused by brain damage. The microstructure of WM in thalamic stroke is investigated, and the VSA results of healthy control and thalamic stroke patients are reported. It has been shown that several skeleton regions were affected subject to the presence of thalamic stroke (FWE, p < 0.05). Furthermore the correlation of quantitative EEG (qEEG) scores and neurophysiological tests with the FA skeleton for the entire test group is also investigated. We compared measurements that are related to the same fibers across subjects, and discussed implications for VSA of WM in thalamic stroke cases, for the relationship between behavioral tests and FA skeletons, and for the correlation between the FA maps and qEEG scores.Results obtained through the regression analyses did not exceed the corrected statistical threshold values for multiple comparisons (uncorrected, p < 0.05). However, in the regression analysis of FA values and the theta band activity of EEG, cingulum bundle and corpus callosum were found to be related. These areas are parts of the Default Mode Network (DMN) where DMN is known to be involved in resting state EEG theta activity. The relation between the EEG alpha band power values and FA values of the skeleton was found to support the cortico-thalamocortical cycles for both subject groups. Further, the neurophysiological tests including Benton Face Recognition (BFR), Digit Span test (DST), Warrington Topographic Memory test (WTMT), California Verbal Learning test (CVLT) has been regressed with the FA skeleton maps for both subject groups. Our results corresponding to DST task were found to be similar with previously reported findings for working memory and episodic memory tasks. For the WTMT, FA values of the cingulum (right) that plays a role in memory process was found to be related with the behavioral responses. Splenium of corpus callosum was found to be correlated for both subject groups for the BFR.

Quantitative evaluation of movement disorder of wrist joint in patients with cerebral, thalamic and cerebellar stroke

Background: It is necessary to make objective and quantitative evaluation ofmotor disorders caused by brain damage such as stroke. Purpose: In this study, using quantitative analysis system of wrist joint movement which we devised, we aimed to compare the characteristics of disorder of wrist joint movement in the patients with cerebral, thalamic and cerebellar stroke. Methods: Five healthy subjects, four patients with cerebral stroke, two with thalamic and two with cerebellar stroke participated in this study. Concerning the upper limb motor function, motion Brunnstrom-Recovery Stage of afflicted side of all the patients was at the stage of V or more. The subjects were asked to sit in front of personal computer screen and to perform two movement tasks; (1) a step-tracking movement inwhich the subjectsmovedwrist joint of afflicted side to follow cursor according to the movement of the small circle to left and right and up and down from the center of the screen and (2) a smooth pursuit movement to follow a target drawing the shape “2”. In these movement tasks, we measured the motion time, average and maximum motion velocities, pursuit ratio, error distance, and smoothness of the trajectory. Results: In the step tracking task, the most characteristic feature was the slowest maximum velocity (47.9± 13.5deg/sec) in cerebral stroke patients. The maximum velocity in healthy subjects, in patients with thalamic and cerebellar stroke was 96.7± 19.9deg/sec, 74.1± 34.7deg/sec, and 90.1± 25.8deg/sec, respectively. In the smooth pursuit movement task, the smoothness of the trajectory was most remarkably disturbed in cerebellar and thalamic group, namely 2.5× 1010± 5 × 109deg in healthy subjects, 3.4 × 1010 ± 8.6× 109deg in cerebral group, 1.1× 1011 ± 4× 1010deg, 1.1× 1011± 4.6× 1010deg in thalamic and cerebellar group, respectively. Conclusion(s): In the cerebral stroke patients, the weakness of muscle caused the elongation of movement time and lowered the maximum velocity. In the cerebellar thalamic stroke patients, smoothness of the movement was mainly disturbed rather than muscle weakness. Implications: This analysis system should be useful tool to evaluate quantitatively the disorder and the training effect in wrist movement during the course of rehabilitation. The analysis system enabled us to display objectively the state of motor control of wrist movement and evaluate the disorder during the course of rehabilitation.

Accelerated forgetting of contextual details due to focal medio-dorsal thalamic lesion.

Effects of thalamic nuclei damage and related white matter tracts on memory performance are still debated. This is particularly evident for the medio-dorsal thalamus which has been less clear in predicting amnesia than anterior thalamus changes. The current study addresses this issue by assessing 7 thalamic stroke patients with consistent unilateral lesions focal to the left medio-dorsal nuclei for immediate and delayed memory performance on standard visual and verbal tests of anterograde memory, and over the long-term (>24 h) on an object-location associative memory task. Thalamic patients showed selective impairment to delayed recall, but intact recognition memory. Patients also showed accelerated forgetting of contextual details after a 24 h delay, compared to controls. Importantly, the mammillothalamic tract was intact in all patients, which suggests a role for the medio-dorsal nuclei in recall and early consolidation memory processes.

Thalamic sensory strokes with and without pain: differences in lesion patterns in the ventral posterior thalamus

ObjectiveVascular lesions of the posterolateral thalamus typically result in a somatosensory syndrome in which some patients develop central neuropathic post-stroke pain (CPSP). Damage to the spinothalamic tract terminus is assumed...

Clinical Aspects of Screening Test Tools for Central Neuropathic Pain in Patients with Thalamic Stroke

[Purpose] The purpose of this study was to investigate clinical aspects of screen test tools for central neuropathic pain in thalamic stroke patients. [Subjects and Methods] Seven thalamic stroke patients were recruited as subjects. To classify the subjects into central neuropathic pain and non-neuropathic pain groups, the Leeds assessment of neuropathic symptoms and signs (LANSS) was used. Four patients were classified as having central neuropathic pain. To evaluate the central neuropathic pain, the quantitative somatosensory test, the median nerve somatosensory evoked potentials (SEPs), magnetic resonance imaging (MRI), and functional MRI (fMRI) were performed on average 31.5 months after stroke. [Results] The quantitative somatosensory test did not show a correlation between the central neuropathic pain group and the non-neuropathic pain group. The SEPs on the affected side showed a response in one of the patients without central neuropathic pain, and responses on the unaffected side were normal for all of the patients. MRI-based thalamic localization data indicate that this method is limited in its ability to distinguish the central neuropathic pain in thalamic stroke patients. Results of fMRI show that the secondary somatosensory areas of the central neuropathic pain group were more activated than those of non-neuropathic pain group. [Conclusion] Based on the results, we verified that functional MRI is useful for evaluating the central neuropathic pain in thalamic stroke patients.

Time-based prospective memory impairment in patients with thalamic stroke.

The role of the thalamus in memory is potentially very complex. However, most studies on the memory impairments of thalamic lesions have focused on retrospective memory, rarely on prospective memory. To explore the effect of thalamic lesions on event-based prospective memory (EBPM) and time-based prospective memory (TBPM), respectively, and to verify the hypothesis that the thalamus is involved in the prospective memory, EBPM and TBPM tasks were administered to 18 thalamic stroke patients and 18 age- and education-matched healthy controls. In the EBPM task, subjects were asked to perform an action whenever particular words were presented. In the TBPM task, subjects were asked to perform an action at certain times. Compared with the performance of healthy controls on EBPM and TBPM tasks (EBPM, 4.3 +/- 1.5; TBPM, 5.4 +/- 1.0), there was a significant difference in the performance of thalamic stroke patients in the TBPM tasks (2.4 +/- 1.6), but no difference was found in EBPM tasks (3.7 +/- 1.1). These results may indicate that the thalamus is involved in PM and particularly in TBPM.

Anteromedian, Central, and Posterolateral Infarcts of the Thalamus

Thalamic infarcts have traditionally been classified into 4 territories: anterior, paramedian, inferolateral, and posterior. The purpose of this study was to review this classical versus variant distribution in patients with thalamic stroke. We reviewed all patients with a first clinical stroke included in the Lausanne Stroke Registry between 1990 and 2002. Among 71 patients with an acute stroke isolated to the thalamus confirmed by MRI, we selected all patients with lesions outside the classical territories and studied their clinical, etiological, and radiological features. A total of 21 patients (30% of all thalamic stroke patients) showed infarction outside the classical territories, allowing us to delineate 3 variant distributions: (1) Anteromedian territory (9 patients [13%]) involving anterior and paramedian territories, with predominantly cognitive impairment, including executive dysfunction, anterograde amnesia, and aphasia in left-sided or bilateral lesions. The most frequent stroke mechanism was cardiac embolism. (2) Central territory (4 patients [6%]), with lesions on the central part of the thalamus, resulting in a variety of neurological and neuropsychological signs, reflecting the involvement of several adjacent structures. Microangiopathy was the most frequent etiology. (3) Posterolateral territory (8 patients [11%]), involving inferolateral and posterior territories, with hemihypesthesia as the most frequent manifestation, followed by hemiataxia, executive dysfunction, and aphasia in left-sided lesions. Artery-to-artery embolism and microangiopathy were the main stroke mechanisms. We describe 3 variant topographic patterns of thalamic infarction with distinct manifestations and etiologies. We postulate that these infarcts are the result of a variation in thalamic arterial supply or reflect borderzone ischemia.