Thalamic Resting-state Functional Connectivity Research Articles

The effect of erenumab on brain network function in episodic migraine patients: a randomized, placebo-controlled clinical trial (RESET BRAIN)

BackgroundWe aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation.MethodsThis was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in adult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12 weeks of erenumab 140 mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain networks involved in migraine were investigated using a seed-based correlation approach.ResultsSixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at week 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major protocol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was performed as a parallel comparison of erenumab vs placebo of the first 12 weeks of treatment. From baseline to week 12, compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal gray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a 50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed when erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab.ConclusionErenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, erenumab-induced brain RS FC changes tend to reverse when treatment is stopped.

Abnormal Thalamic Functional Connectivity Correlates With Cardiorespiratory Fitness and Physical Activity in Progressive Multiple Sclerosis (P12-8.011)

Abnormal Thalamic Functional Connectivity Correlates With Cardiorespiratory Fitness and Physical Activity in Progressive Multiple Sclerosis (P12-8.011)

Abnormal thalamic functional connectivity correlates with cardiorespiratory fitness and physical activity in progressive multiple sclerosis.

Altered thalamic volumes and resting state (RS) functional connectivity (FC) might be associated with physical activity (PA) and cardiorespiratory fitness (CRF) in people with progressive multiple sclerosis (PMS). To assess thalamic structural and functional alterations and investigate their correlations with PA/CRF levels in people with PMS. Seven-day accelerometry and cardiopulmonary exercise testing were used to assess PA/CRF levels in 91 persons with PMS. They underwent 3.0T structural and RS fMRI acquisition with 37 age/sex-matched healthy controls (HC). Between-group comparisons of MRI measures and their correlations with PA/CRF variables were assessed. PMS people had lower volumes compared to HC (all p < 0.001). At corrected threshold, PMS showed decreased intra- and inter-thalamic RS FC, and increased RS FC between the thalamus and the hippocampus, bilaterally. At uncorrected threshold, decreased thalamic RS FC with caudate nucleus, cerebellum and anterior cingulate cortex (ACC), as well as increased thalamic RS FC with occipital regions, were also detected. Lower CRF, measured as peak oxygen consumption (VO2peak), correlated with lower white matter volume (r = 0.31, p = 0.03). Moreover, lower levels of light PA correlated with increased thalamic RS FC with the right hippocampus (r = -0.3, p = 0.05). People with PMS showed widespread brain atrophy, as well as pronounced intra-thalamic and thalamo-hippocampal RS FC abnormalities. White matter atrophy correlated with CRF, while increased thalamo-hippocampal RS FC was associated to worse PA levels. Thalamic RS FC might be used to monitor physical impairment and efficacy of rehabilitative and disease-modifying treatments in future studies.

Altered sensorimotor integration in multiple sclerosis: A combined neurophysiological and functional MRI study

ObjectiveTo explore whether abnormal thalamic resting-state functional connectivity (rsFC) contributes to altered sensorimotor integration and hand dexterity impairment in multiple sclerosis (MS). MethodsTo evaluate sensorimotor integration, we recorded kinematic features of index finger abductions during somatosensory temporal discrimination threshold (STDT) testing in 36 patients with relapsing-remitting MS and 39 healthy controls (HC). Participants underwent a multimodal 3T structural and functional MRI protocol. ResultsPatients had lower index finger abduction velocity during STDT testing compared to HC. Thalamic rsFC with the precentral and postcentral gyri, supplementary motor area (SMA), insula, and basal ganglia was higher in patients than HC. Intrathalamic rsFC and thalamic rsFC with caudate and insula bilaterally was lower in patients than HC. Finger movement velocity positively correlated with intrathalamic rsFC and negatively correlated with thalamic rsFC with the precentral and postcentral gyri, SMA, and putamen. ConclusionsAbnormal thalamic rsFC is a possible substrate for altered sensorimotor integration in MS, with high intrathalamic rsFC facilitating finger movements and increased thalamic rsFC with the basal ganglia and sensorimotor cortex contributing to motor performance deterioration. SignificanceThe combined study of thalamic functional connectivity and upper limb sensorimotor integration may be useful in identifying patients who can benefit from early rehabilitation to prevent upper limb motor impairment.

Reduced thalamic resting-state functional connectivity and impaired cognition in acute abstinent heroin users.

As a critical component of cortico‐striato‐thalamo‐cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting‐state functional connectivity (RSFC) differences of the thalamus were investigated between age‐, gender‐, and alcohol‐matched 37 HU and 33 healthy controls (HCs). Trail making test‐A (TMT‐A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT‐A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU.

Clinical predictivity of thalamic sub-regional connectivity in clinically isolated syndrome: a 7-year study.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability.

Nuclei-specific thalamic connectivity predicts seizure frequency in drug-resistant medial temporal lobe epilepsy.

Background and objectivesWe assessed correlations between the resting state functional connectivity (RSFC) of different thalamic nuclei and seizure frequency in patients with drug-resistant medial temporal lobe epilepsy (mTLE).MethodsSeventeen patients with mTLE and 17 sex-/age-/handedness-matched controls participated. A seed-based correlation method for the resting-state FMRI data was implemented to get RSFC maps of 70 thalamic nuclei seed masks. Group statistics for individual RSFC for subjects and seed masks were performed to obtain within-group characteristics and between-group differences with age covariates. A linear regression was applied to test whether seizure frequency correlated with thalamic nuclear RSFC with the whole brain in mTLE patients.ResultsRSFC of thalamic nuclei showed spatially distinguishable connectivity patterns that reflected principal inputs and outputs that were derived from priori anatomical knowledge. We found group differences between normal control and mTLE groups in RSFC for nuclei seeds located in various subdivisions of thalamus. The RSFCs in some of those nuclei were strongly correlated with seizure frequency.ConclusionsMediodorsal thalamic nuclei may play important roles in seizure activity or in the regulation of neuronal activity in the limbic system. The RSFC of motor- and sensory-relay nuclei may help elucidate sensory-motor deficits associated with chronic seizure activity. RSFC of the pulvinar nuclei of the thalamus could also be a key reflection of symptom-related functional deficits in mTLE.

Problem Drinking, Alcohol Expectancy, and Thalamic Resting-State Functional Connectivity in Nondependent Adult Drinkers.

Alcohol misuse is associated with thalamic dysfunction. The thalamus comprises subnuclei that relay and integrate information between cortical and subcortical structures. However, it is unclear how the subnuclei contribute to thalamic dysfunctions in problem drinking. We investigated resting-state functional connectivity (rsFC) of thalamic subregions in 107 nondependent drinkers (57 women), using masks delineated by white matter tractography. Thalamus was parceled into motor, somatosensory, visual, premotor, frontal association, parietal association, and temporal association subregions. Whole-brain linear regression, each against Alcohol Use Disorders Identification Test (AUDIT) and positive alcohol expectancy (AE) score with age as a covariate, was performed for each seed, for men and women combined, and separately. Overall, problem drinking was associated with increased thalamic connectivities, whereas AE was associated with a mixed pattern of increased and decreased connectivities. Motor, premotor, somatosensory, and frontal association thalamic connectivity with bilateral caudate head was positively correlated with AUDIT score in men and women combined. Connectivity of the right caudate head with frontal association and premotor thalamus was also positively correlated with AE score in men and women combined. In contrast, motor and premotor thalamic connectivity with a number of cortical and subcortical structures showed sex differences in the correlation each with AUDIT and AE score. In mediation analyses, AE score completely mediated the correlation between thalamic caudate connectivity and AUDIT score, whereas the model where AE contributed to problem drinking and, in turn, altered thalamic caudate connectivity was not supported. To conclude, thalamic subregional rsFCs showed both shared and distinct changes and sex differences in association with problem drinking and AE. Increased thalamic caudate connectivity may contribute to problem drinking via enhanced AE. The findings suggest the importance of examining thalamic subdivisions and sex in investigating the functional roles of thalamus in problem drinking.

Structural connectivity-defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations.

In spite of the well-known importance of thalami in multiple sclerosis (MS), only limited data on whole and subregional thalamic functional connectivity (FC) changes are available. Using diffusion tensor imaging, we performed a structural connectivity based thalamic parcellation and investigated subregional thalamic resting-state (RS) FC alterations and their relationship with clinical/cognitive measures in MS. MRI data from a reference set of healthy controls (HC) were used to parcellate the thalami into five subregions, according to their structural connectivity. For each thalamic subregion, a seed-based RS FC analysis was performed in 187 MS patients and 94 HC. Correlations between thalamic RS FC and clinical/cognitive variables were assessed. Compared to HC, MS patients showed increased intra- and inter-thalamic RS FC for almost all thalamic subregions, and increased RS FC between all thalamic subregions and the left insula. Frontal and motor thalamic subregions also showed reduced RS FC with the caudate nucleus. For the temporal thalamic subregion, we observed reduced RS FC with the ipsilateral thalamus, anterior and middle cingulate cortex, and cerebellum. Compared to cognitively preserved, cognitively impaired MS patients had higher thalamic RS FC with several temporal areas. In MS patients, lower RS FC between thalamic subregions and the caudate and cingulate cortex correlated with worse motor performance, whereas higher RS FC with the insula correlated with better motor performance. The main thalamic subregions have different RS-FC abnormalities in MS patients. Increased thalamic RS FC with the insula may have a compensatory role, whereas increased RS FC with temporal areas, observed in patients with cognitive impairment may reflect maladaptive mechanisms. Hum Brain Mapp 38:6005-6018, 2017. © 2017 Wiley Periodicals, Inc.

Abnormal functional connectivity of thalamic sub-regions contributes to fatigue in multiple sclerosis

Objective: To investigate sub-regional thalamic resting-state (RS) functional connectivity (FC) abnormalities in multiple sclerosis (MS) and their correlation with fatigue and its subcomponents (physical, cognitive, and psychosocial). Methods: From 122 MS patients and 94 healthy controls, 5 thalamic sub-regions (frontal, motor, postcentral, occipital, temporal) were parcellated based on their cortico-thalamic structural connectivity and used for a seed-based RS FC analysis. Abnormalities of thalamic RS FC in MS patients and their correlation with Modified Fatigue Impact Scale (MFIS) were assessed. Results: Compared to controls and non-fatigued MS (n = 86), fatigued MS patients (n = 36) showed thalamic RS FC abnormalities with middle frontal gyrus, sensorimotor network, precuneus, insula, and cerebellum, which correlated with global MFIS. Higher thalamic RS FC with precuneus and lower RS FC with posterior cerebellum correlated with cognitive MFIS. Higher thalamic RS FC with sensorimotor network in frontal-, motor-, and temporal thalamic sub-regions correlated with physical and psychosocial MFIS. Reduced thalamic RS FC with right insula in motor-, postcentral-, and occipital thalamic sub-regions correlated with psychosocial fatigue. Conclusion: Regional thalamic RS FC abnormalities with different cortical regions, including the frontal lobe, sensorimotor network, precuneus, insular cortices, and cerebellum contribute to fatigue in MS. Abnormal RS FC of selected thalamo-cortical connections explains different components of fatigue.

Altered thalamo-cortical resting state functional connectivity in smokers

The thalamus has widespread connections with the prefrontal cortex (PFC) and modulates communication between the striatum and PFC, which is crucial to the neural mechanisms of smoking. However, relatively few studies focused on the thalamic resting state functional connectivity (RSFC) patterns and their association with smoking behaviors in smokers. 24 young male smokers and 24 non-smokers were enrolled in our study. Fagerström Test for Nicotine Dependence (FTND) was used to assess the nicotine dependence level. The bilateral thalamic RSFC patterns were compared between smokers and non-smokers. The relationship between neuroimaging findings and smoking behaviors (FTND and pack-years) were also investigated in smokers. Relative to nonsmokers, smokers showed reduced RSFC strength between the left thalamus and several brain regions, i.e. the right dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC) and the bilateral caudate. In addition, the right thalamus showed reduced RSFC with the right dlPFC as well as the bilateral insula in smokers. Therefore, the findings in the current study revealed the reduced RSFC of the thalamus with the dlPFC, the ACC, the insula and the caudate in smokers, which provided new insights into the roles of the thalamus in nicotine addiction from a function integration perspective.

Functional network connectivity abnormalities in multiple sclerosis: Correlations with disability and cognitive impairment

Objective: To investigate resting state (RS) functional connectivity (FC) abnormalities within the principal brain networks in a large cohort of multiple sclerosis (MS) patients, to define the trajectory of FC changes over disease stages and their relation with clinical and structural magnetic resonance imaging (MRI) measures. Methods: RS functional magnetic resonance imaging (fMRI), clinical, and neuropsychological evaluation were obtained from 215 MS patients and 98 healthy controls. Connectivity abnormalities and correlations with clinical/neuropsychological/imaging measures were evaluated. We analyzed seed-voxel FC with seven major hubs, producing one visual/sensory, one motor, two cognitive, one cerebellar, and two subcortical networks. Results: MS patients showed reduced network average RS FC versus controls in the default-mode network. At regional level, a complex pattern of decreased and increased RS FC was found. Reduced RS FC mainly involved sensorimotor, cognitive, thalamic, and cerebellar networks, whereas increased RS FC involved visual/sensory and subcortical networks. Reduced RS FC correlated with T2 lesions. Reduced thalamic RS FC correlated with better neuropsychological performance, whereas for all remaining networks reduced FC correlated with more severe clinical/cognitive impairment. Conclusion: Increased and decreased RS FC occurs in MS and contributes to a wide spectrum of clinical manifestations. RS FC reduction is related to T2 lesions. Such a paradigm is inverted for the thalamic network.

The role of sleep on cognition and functional connectivity in patients with multiple sclerosis

Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC.

Structural and functional connectivity of the precuneus and thalamus to the default mode network.

Neuroimaging studies have identified functional interactions between the thalamus, precuneus, and default mode network (DMN) in studies of consciousness. However, less is known about the structural connectivity of the precuneus and thalamus to regions within the DMN. We used diffusion tensor imaging (DTI) to parcellate the precuneus and thalamus based on their probabilistic white matter connectivity to each other and DMN regions of interest (ROIs) in 37 healthy subjects from the Human Connectome Database. We further assessed resting-state functional connectivity (RSFC) among the precuneus, thalamus, and DMN ROIs. The precuneus was found to have the greatest structural connectivity with the thalamus, where connection fractional anisotropy (FA) increased with age. The precuneus also showed significant structural connectivity to the hippocampus and middle pre-frontal cortex, but minimal connectivity to the angular gyrus and midcingulate cortex. In contrast, the precuneus exhibited significant RSFC with the thalamus and the strongest RSFC with the AG. Significant symmetrical structural connectivity was found between the thalamus and hippocampus, mPFC, sFG, and precuneus that followed known thalamocortical pathways, while thalamic RSFC was strongest with the precuneus and hippocampus. Overall, these findings reveal high levels of structural and functional connectivity linking the thalamus, precuneus, and DMN. Differences between structural and functional connectivity (such as between the precuneus and AG) may be interpreted to reflect dynamic shifts in RSFC for cortical hub-regions involved with consciousness, but could also reflect the limitations of DTI to detect superficial white matter tracts that connect cortico-cortical regions. Hum Brain Mapp 38:938-956, 2017. © 2016 Wiley Periodicals, Inc.

Multiple Sclerosis: Changes in Thalamic Resting-State Functional Connectivity Induced by a Home-based Cognitive Rehabilitation Program.

Purpose To investigate thalamic connectivity changes after use of a video game-based cognitive rehabilitation program, as thalamic damage and alterations in thalamocortical functional connectivity (FC) are important factors in cognitive dysfunction in patients with multiple sclerosis (MS). Materials and Methods This prospective study was approved by the local ethical committee. Twenty-four patients with MS and cognitive impairment were randomly assigned to either an intervention or a wait-list group. Patients were evaluated with cognitive tests and 3-T resting-state functional magnetic resonance (MR) imaging at baseline and after an 8-week period. In addition, 11 healthy subjects underwent baseline resting-state functional MR imaging. Patients in the intervention group performed the video game-based cognitive rehabilitation program, while those in the wait-list group served as control subjects. Repeated measures analysis of variance was used to test efficacy of the intervention. The thalamic resting-state network was identified with a seed-based method; both first-level and high-level analyses were performed by using software tools. Results Patients showed lower baseline FC compared with healthy subjects. A significant improvement was seen in results of the Paced Auditory Serial Addition Test and the Stroop Test after 8 weeks of cognitive rehabilitation (F = 6.616, [P = .018] and F = 5.325 [P = .030], respectively). At follow-up, the intervention group had an increased FC in the cingulum, precuneus, and bilateral parietal cortex and a lower FC in the cerebellum and in left prefrontal cortex compared with the wait-list group (P < .05, family-wise error corrected); correlations were found between FC changes in these regions and cognitive improvement (P < .05, family-wise error corrected). Conclusion The results of this study show the relevance of thalamic regulation of the brain networks involved in cognition and suggest that changes in thalamic resting-state network connectivity may represent a functional substrate for cognitive improvement associated with a video game-based cognitive rehabilitation program. (©) RSNA, 2016.

Thalamic Functional Connectivity in Mild Traumatic Brain Injury

The purpose of this study was to examine the cross-sectional and longitudinal association between thalamic resting-state functional connectivity (FC) and psychological distress, clinical symptoms, and neuropsychological tests in patients with mild traumatic brain injury (mTBI).

Thalamic resting-state functional connectivity: disruption in patients with type 2 diabetes.

To explore the disrupted thalamic functional connectivity and its relationships with cognitive dysfunction in type 2 diabetes mellitus (T2DM) by using resting-state functional magnetic resonance imaging (fMRI). A total of 38 T2DM patients and 39 well-matched healthy controls participated in the resting-state fMRI and T1-weighted imaging scans. The thalamic functional connectivity was characterized by using a seed-based whole-brain correlation method and compared T2DM patients with healthy controls. Pearson correlation analysis was performed between thalamic functional connectivity and clinical data. When compared with healthy controls, T2DM showed significantly decreased functional connectivity of the thalamus mainly in the right middle temporal gyrus (MTG), right precentral gyrus and bilateral occipital cortex; Increased functional connectivity of the thalamus was detected in the left cerebellum, bilateral middle frontal gyrus and middle cingulate gyrus (p<0.05, corrected for AlphaSim). In T2DM patients, the decreased thalamic functional connectivity of the right MTG was positively associated with the Verbal Fluency Test score (r=0.438, p=0.006). Meanwhile, the decreased thalamic functional connectivity of the right cuneus was positively correlated with the Complex Figure Test-delayed score and negatively correlated with the Trail Making Test-B score, respectively (r=0.492, p=0.002; r=-0.504, p=0.001). Moreover, there was no structural damage in the thalamus of T2DM patients. T2DM patients develop disrupted thalamocortical functional connectivity, which is associated with cognitive impairment in selected brain regions. Resting-state thalamocortical connectivity disturbance may play a central role in the underlying neuropathological process of T2DM-related cognitive dysfunction.

Impairments of thalamic resting-state functional connectivity in patients with chronic tinnitus

PurposeThe phantom sound of tinnitus is believed to arise from abnormal functional coupling between the thalamus and cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to compare the degree of thalamocortical functional connectivity in chronic tinnitus patients and controls. Materials and methodsResting-state fMRI scans were obtained from 31 chronic tinnitus patients and 33 well-matched healthy controls. Thalamocortical functional connectivity was characterized using a seed-based whole-brain correlation method. The resulting thalamic functional connectivity measures were correlated with other clinical data. ResultsWe found decreased functional connectivity between the seed region in left thalamus and right middle temporal gyrus (MTG), right middle orbitofrontal cortex, left middle frontal gyrus, right precentral gyrus, and bilateral calcarine cortex. Decreased functional connectivity was detected between the seed in the right thalamus and the left superior temporal gyrus (STG), left amygdala, right superior frontal gyrus, left precentral gyrus, and left middle occipital gyrus. Tinnitus distress correlated negatively with thalamic functional connectivity in right MTG; tinnitus duration correlated negatively with thalamic functional connectivity in left STG. Increased functional connectivity between the bilateral thalamus and a set of regions were also observed. ConclusionsChronic tinnitus patients have disrupted thalamocortical functional connectivity to selected brain regions which is associated with specific tinnitus characteristics. Resting-state thalamic functional connectivity disturbances may play an important role in neuropathological features of tinnitus.

Fampridine Modulates Thalamic Resting State Functional Connectivity and Ameliorates Fatigue in Multiple Sclerosis Patients (P4.005)

Fampridine Modulates Thalamic Resting State Functional Connectivity and Ameliorates Fatigue in Multiple Sclerosis Patients (P4.005)

Thalamus structure and function determine severity of cognitive impairment in multiple sclerosis.

This study investigates whether changes in functional connectivity, diffusivity, and volume of the thalamus can explain different severities of cognitive impairment in multiple sclerosis (MS). An inception cohort of 157 patients with MS (104 women, mean age 41 years), 6 years postdiagnosis, was divided into 3 groups: cognitively preserved (CP, n = 108), mildly cognitively impaired (MCI, n = 22), and more severely cognitively impaired (SCI, n = 27). These groups were matched to 47 healthy controls (HC, 28 women, mean age 41 years). Thalamic volume, thalamic skeleton diffusivity (fractional anisotropy [FA] and mean diffusivity [MD]), and thalamic resting-state functional connectivity (FC) were compared between groups. Thalamic volume was significantly lower in all patient groups compared to controls, with lowest volumes in patients with SCI, and no difference between CP and MCI. Thalamic skeleton FA was decreased in SCI compared to HC only; MD was increased in SCI compared to all other groups. Thalamic FC was increased in SCI with a total of 15 regions, mainly sensorimotor, frontal, and occipital parts of the brain. Thalamic volume, FC, and MD remained independent predictors in a linear regression model (R(2) = 0.46), together with male sex and a lower level of education. Lesion and whole-brain volumes were not significant predictors. These findings indicate that thalamic changes in structure and function are highly informative regarding overall cognitive performance in MS. Increased thalamic FC only became apparent in SCI, possibly as a sign of maladaption.