Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.

Probabilistic stimulation mapping from intra-operative thalamic deep brain stimulation data in essential tremor.

Deep brain stimulation (DBS) is a therapy for Parkinson's disease (PD) and essential tremor (ET). The mechanism of action of DBS is still incompletely understood. Retrospective group analysis of intra-operative data recorded from ET patients implanted in the ventral intermediate nucleus of the thalamus (Vim) is rare. Intra-operative stimulation tests generate rich data and their use in group analysis has not yet been explored.Objective.To implement, evaluate, and apply a group analysis workflow to generate probabilistic stimulation maps (PSMs) using intra-operative stimulation data from ET patients implanted in Vim.Approach.A group-specific anatomical template was constructed based on the magnetic resonance imaging scans of 6 ET patients and 13 PD patients. Intra-operative test data (total:n= 1821) from the 6 ET patients was analyzed: patient-specific electric field simulations together with tremor assessments obtained by a wrist-based acceleration sensor were transferred to this template. Occurrence and weighted mean maps were generated. Voxels associated with symptomatic response were identified through a linear mixed model approach to form a PSM. Improvements predicted by the PSM were compared to those clinically assessed. Finally, the PSM clusters were compared to those obtained in a multicenter study using data from chronic stimulation effects in ET.Main results.Regions responsible for improvement identified on the PSM were in the posterior sub-thalamic area (PSA) and at the border between the Vim and ventro-oral nucleus of the thalamus (VO). The comparison with literature revealed a center-to-center distance of less than 5 mm and an overlap score (Dice) of 0.4 between the significant clusters. Our workflow and intra-operative test data from 6 ET-Vim patients identified effective stimulation areas in PSA and around Vim and VO, affirming existing medical literature.Significance.This study supports the potential of probabilistic analysis of intra-operative stimulation test data to reveal DBS's action mechanisms and to assist surgical planning.

Intraoperative changes in large-scale thalamic circuitry following laser ablation of hypothalamic hamartomas.

BACKGROUND AND OBJECTIVES: Gelastic seizures due to hypothalamic hamartomas (HH) are challenging to treat, in part due to an incomplete understanding of seizure propagation pathways. Although magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) is a promising intervention to disconnect HH from ictal propagation networks, the optimal site of ablation to achieve seizure freedom is not known. In this study, we investigated intraoperative post-ablation changes in resting-state functional connectivity to identify large-scale networks associated with successful disconnection of HH. METHODS: Children who underwent MRgLITT for HH at two institutions were consecutively recruited and followed for a minimum of one year. Seizure freedom was defined as Engel score of 1A at the last available follow-up. Immediate pre- and post- ablation resting-state functional MRI scans were acquired while maintaining a constant depth of general anesthetic. Multivariable generalized linear models were used to identify intraoperative changes in large-scale connectivity associated with seizure outcomes. RESULTS: Twelve patients underwent MRgLITT for HH, five of whom were seizure-free at their last follow-up. Intraprocedural changes in thalamocortical circuitry involving the anterior cingulate cortex were associated with seizure-freedom. Children who were seizure-free demonstrated an increase and decrease in connectivity to the pregenual and dorsal anterior cingulate cortices, respectively. In addition, children who became seizure-free demonstrated increased thalamic connectivity to the periaqueductal gray immediately following MRgLITT. DISCUSSION: Successful disconnection of HH is associated with intraoperative, large-scale changes in thalamocortical connectivity. These changes provide novel insights into the large-scale basis of gelastic seizures and may represent intraoperative biomarkers of treatment success.

Sex differences in neuronal oscillatory activity and memory in the methylazoxymethanol acetate model of schizophrenia.

The methylazoxymethanol acetate (MAM) rodent model is used to study aspects of schizophrenia. However, numerous studies that have employed this model have used only males, resulting in a dearth of knowledge on sex differences in brain function and behaviour. The purpose of this study was to determine whether differences exist between male and female MAM rats in neuronal oscillatory function within and between the prefrontal cortex (PFC), ventral hippocampus (vHIP) and thalamus, behaviour, and in proteins linked to schizophrenia neuropathology. We showed that female MAM animals exhibited region-specific alterations in theta power, elevated low and high gamma power in all regions, and elevated PFC-thalamus high gamma coherence. Male MAM rats had elevated beta and low gamma power in PFC, and elevated vHIP-thalamus coherence. MAM females displayed impaired reversal learning whereas MAM males showed impairments in spatial memory. Glycogen synthase kinase-3 (GSK-3) was altered in the thalamus, with female MAM rats displaying elevated GSK-3α phosphorylation. Male MAM rats showed higher expression and phosphorylation GSK-3α, and higher expression of GSK-ß. Sex-specific changes in phosphorylated Tau levels were observed in a region-specific manner. These findings demonstrate there are notable sex differences in behaviour, oscillatory network function, and GSK-3 signaling in MAM rats, thus highlighting the importance of inclusion of both sexes when using this model to study schizophrenia.

A modified neural circuit framework for semantic memory retrieval with implications for circuit modulation to treat verbal retrieval deficits.

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre-supplementary motor area (pre-SMA), striatum (particularly caudate nucleus), and thalamus. We aim to offer a modified neural circuit framework expanded upon a memory retrieval model proposed in 2013 by Hart et al., as evidence from electrophysiological, functional brain imaging, and noninvasive electrical brain stimulation studies have provided additional pieces of information that converge on a shared neural circuit for retrieval of memory and words. We propose that both the left inferior frontal gyrus and fronto-polar regions should be included in the expanded circuit. All these regions have their respective functional roles during verbal retrieval, such as selection and inhibition during search, initiation and termination of search, maintenance of co-activation across cortical regions, as well as final activation of the retrieved information. We will also highlight the structural connectivity from and to the pre-SMA (e.g., frontal aslant tract and fronto-striatal tract) that facilitates communication between the regions within this circuit. Finally, we will discuss how this circuit and its correlated activity may be affected by disease states and how this circuit may serve as a novel target engagement for neuromodulatory treatment of verbal retrieval deficits.

Exosomal miR-1202 mediates Brodmann Area 44 functional connectivity changes in medication-free patients with major depressive disorder: An fMRI study.

Previous large-sample postmortem study revealed that the expression of miR-1202 in brain tissues from Brodmann area 44 (BA44) was dysregulated in patients with major depressive disorder (MDDs). However, the specific in vivo neuropathological mechanism of miR-1202 as well as its interplay with BA44 circuits in the depressed brain are still unclear. Here, we performed a case-control study with imaging-genetic approach based on resting-state functional magnetic resonance imaging (MRI) data and miR-1202 quantification from 110 medication-free MDDs and 102 healthy controls. Serum-derived circulating exosomes that readily cross the blood-brain barrier were isolated to quantify miR-1202. For validation, repeated MR scans were performed after a six-week follow-up of antidepressant treatment on a cohort of MDDs. Voxelwise factorial analysis revealed two brain areas (including the striatal-thalamic region) in which the effect of depression on the functional connectivity with BA44 was significantly dependent on the expression level of exosomal miR-1202. Moreover, longitudinal change of the BA44 connectivity with the striatal-thalamic region in MDDs after antidepressant treatment was found to be significantly related to the level of miR-1202 expression. These findings revealed that the in vivo neuropathological effect of miR-1202 dysregulation in depression is possibly exerted by mediating neural functional abnormalities in BA44-striatal-thalamic circuits.

Subregional thalamic functional connectivity abnormalities and cognitive impairments in first-episode schizophrenia.

BACKGROUND: Previous studies have documented thalamic functional connectivity (FC) abnormalities in schizophrenia, typically examining the thalamus as a whole. The specific link between subregional thalamic FC and cognitive deficits in first-episode schizophrenia (FES) remains unexplored. METHODS: Using data from resting-state functional magnetic resonance imaging, we compared whole-brain FC with thalamic subregions between patients and HCs, and analyzed FC changes in drug-naïve patients separately. We then examined correlations between FC abnormalities with both cognitive impairment and clinical symptoms. RESULTS: A total of 33 FES patients (20 drug-naïve) and 32 age- and sex-matched healthy controls (HCs) were included. Compared to HCs, FES patients exhibited increased FC between specific thalamic subregions and cortical regions, particularly bilateral middle temporal lobe and cuneus gyrus, left medial superior frontal gyrus, and right inferior/superior occipital gyrus. Decreased FC was observed between certain thalamic subregions and the left inferior frontal triangle. These findings were largely consistent in drug-naïve patients. Notably, deficits in social cognition and visual learning in FES patients correlated with increased FC between certain thalamic subregions and cortical regions involving the right superior occipital gyrus and cuneus gyrus. The severity of negative symptoms was associated with increased FC between a thalamic subregion and the left middle temporal gyrus. CONCLUSION: Our findings suggest FC abnormalities between thalamic subregions and cortical areas in FES patients. Increased FC correlated with cognitive deficits and negative symptoms, highlighting the importance of thalamo-cortical connectivity in the pathophysiology of schizophrenia.

Thalamic Alterations in Motor Neuron Diseases: A Systematic Review of MRI Findings.

BACKGROUND: Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes. METHODS: Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale. RESULTS: A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (C9orf72). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs. CONCLUSIONS: Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.

Simultaneous EEG-fMRI Investigation of Rhythm-Dependent Thalamo-Cortical Circuits Alteration in Schizophrenia.

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls ([Formula: see text]). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater ([Formula: see text]), and the degree of coupling was negatively correlated with the duration of disease ([Formula: see text], [Formula: see text]). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia.

Multi-timescale neuromodulation strategy for closed-loop deep brain stimulation in Parkinson's disease.

Objective.Beta triggered closed-loop deep brain stimulation (DBS) shows great potential for improving the efficacy while reducing side effect for Parkinson's disease. However, there remain great challenges due to the dynamics and stochasticity of neural activities. In this study, we aimed to tune the amplitude of beta oscillations with different time scales taking into account influence of inherent variations in the basal ganglia-thalamus-cortical circuit.Approach. A dynamic basal ganglia-thalamus-cortical mean-field model was established to emulate the medication rhythm. Then, a dynamic target model was designed to embody the multi-timescale dynamic of beta power with milliseconds, seconds and minutes. Moreover, we proposed a closed-loop DBS strategy based on a proportional-integral-differential (PID) controller with the dynamic control target. In addition, the bounds of stimulation amplitude increments and different parameters of the dynamic target were considered to meet the clinical constraints. The performance of the proposed closed-loop strategy, including beta power modulation accuracy, mean stimulation amplitude, and stimulation variation were calculated to determine the PID parameters and evaluate neuromodulation performance in the computational dynamic mean-field model.Main results. The Results show that the dynamic basal ganglia-thalamus-cortical mean-field model simulated the medication rhythm with the fasted and the slowest rate. The dynamic control target reflected the temporal variation in beta power from milliseconds to minutes. With the proposed closed-loop strategy, the beta power tracked the dynamic target with a smoother stimulation sequence compared with closed-loop DBS with the constant target. Furthermore, the beta power could be modulated to track the control target under different long-term targets, modulation strengths, and bounds of the stimulation increment.Significance. This work provides a new method of closed-loop DBS for multi-timescale beta power modulation with clinical constraints.

Modulation index predicts the effect of ethosuximide on developmental and epileptic encephalopathy with spike-and-wave activation in sleep.

PURPOSE: In developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS), the thalamocortical network is suggested to play an important role in the pathophysiology of the progression from focal epilepsy to DEE-SWAS. Ethosuximide (ESM) exerts effects by blocking T-type calcium channels in thalamic neurons. With the thalamocortical network in mind, we studied the prediction of ESM effectiveness in DEE-SWAS treatment using phase-amplitude coupling (PAC) analysis. METHODS: We retrospectively enrolled children with DEE-SWAS who had an electroencephalogram (EEG) recorded between January 2009 and September 2022 and were prescribed ESM at Okayama University Hospital. Only patients whose EEG showed continuous spike-and-wave during sleep were included. We extracted 5-min non-rapid eye movement sleep stage N2 segments from EEG recorded before starting ESM. We calculated the modulation index (MI) as the measure of PAC in pair combination comprising one of two fast oscillation types (gamma, 40-80 Hz; ripples, 80-150 Hz) and one of five slow-wave bands (delta, 0.5-1, 1-2, 2-3, and 3-4 Hz; theta, 4-8 Hz), and compared it between ESM responders and non-responders. RESULTS: We identified 20 children with a diagnosis of DEE-SWAS who took ESM. Fifteen were ESM responders. Regarding gamma oscillations, significant differences were seen only in MI with 0.5-1 Hz slow waves in the frontal pole and occipital regions. Regarding ripples, ESM responders had significantly higher MI in coupling with all slow waves in the frontal pole region, 0.5-1, 3-4, and 4-8 Hz slow waves in the frontal region, 3-4 Hz slow waves in the parietal region, 0.5-1, 2-3, 3-4, and 4-8 Hz slow waves in the occipital region, and 3-4 Hz slow waves in the anterior-temporal region. SIGNIFICANCE: High MI in a wider area of the brain may represent the epileptic network mediated by the thalamus in DEE-SWAS and may be a predictor of ESM effectiveness.

Profiling functional networks identify activation of corticostriatal connectivity in ET patients after MRgFUS thalamotomy.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) thalamotomy is a novel and effective treatment for medication-refractory tremor in essential tremor (ET), but how the brain responds to this deliberate lesion is not clear. OBJECTIVE: The current study aimed to evaluate the immediate and longitudinal alterations of functional networks after MRgFUS thalamotomy. METHODS: We retrospectively obtained preoperative and postoperative 30-day, 90-day, and 180-day data of 31 ET patients subjected with MRgFUS thalamotomy from 2018 to 2020. Their archived resting-state functional MRI data were used for functional network comparison as well as graph-theory metrics analysis. Both partial least squares (PLS) regression and linear regression were conducted to associate functional features to tremor symptoms. RESULTS: MRgFUS thalamotomy dramatically abolished tremors, while global functional network only sustained immediate fluctuation within one week after the surgery. Network-based statistics have identified a long-term enhanced corticostriatal subnetwork by comparison between 180-day and preoperative data (P = 0.019). Within this subnetwork, network degree, global efficiency and transitivity were significantly recovered in ET patients right after MRgFUS thalamotomy compared to the pre-operative timepoint (P < 0.05), as well as hemisphere lateralization (P < 0.001). The PLS main component significantly accounted for 33.68 % and 34.16 % of the total variances of hand tremor score and clinical rating scale for tremor (CRST)-total score (P = 0.037 and 0.027). Network transitivity of this subnetwork could serve as a reliable biomarker for hand tremor score control prediction at 180-day after the surgery (ß = 2.94, P = 0.03). CONCLUSION: MRgFUS thalamotomy promoted corticostriatal connectivity activation correlated with tremor improvement in ET patient after MRgFUS thalamotomy.

Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

BACKGROUND: Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor. METHODS: All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters. RESULTS: Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups. CONCLUSIONS: GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET.

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.

Mapping Subcortico-Cortical Coupling-A Comparison of Thalamic and Subthalamic Oscillations.

BACKGROUND: The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation in tremor patients. Despite its therapeutic importance, its oscillatory coupling to cortical areas has rarely been investigated in humans. OBJECTIVES: The objective of this study was to identify the cortical areas coupled to the VIM in patients with essential tremor. METHODS: We combined resting-state magnetoencephalography with local field potential recordings from the VIM of 19 essential tremor patients. Whole-brain maps of VIM-cortex coherence in several frequency bands were constructed using beamforming and compared with corresponding maps of subthalamic nucleus (STN) coherence based on data from 19 patients with Parkinson's disease. In addition, we computed spectral Granger causality. RESULTS: The topographies of VIM-cortex and STN-cortex coherence were very similar overall but differed quantitatively. Both nuclei were coupled to the ipsilateral sensorimotor cortex in the high-beta band; to the sensorimotor cortex, brainstem, and cerebellum in the low-beta band; and to the temporal cortex, brainstem, and cerebellum in the alpha band. High-beta coherence to sensorimotor cortex was stronger for the STN (P = 0.014), whereas low-beta coherence to the brainstem was stronger for the VIM (P = 0.017). Although the STN was driven by cortical activity in the high-beta band, the VIM led the sensorimotor cortex in the alpha band. CONCLUSIONS: Thalamo-cortical coupling is spatially and spectrally organized. The overall similar topographies of VIM-cortex and STN-cortex coherence suggest that functional connections are not necessarily unique to one subcortical structure but might reflect larger frequency-specific networks involving VIM and STN to a different degree. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Thalamic deep brain stimulation for tourette syndrome increases cortical beta activity.

BACKGROUND: Deep brain stimulation (DBS) of the thalamus can effectively reduce tics in severely affected patients with Tourette syndrome (TS). Its effect on cortical oscillatory activity is currently unknown. OBJECTIVE: We assessed whether DBS modulates beta activity at fronto-central electrodes. We explored concurrent EEG sources and probabilistic stimulation maps. METHODS: Resting state EEG of TS patients treated with thalamic DBS was recorded in repeated DBS-on and DBS-off states. A mixed linear model was employed for statistical evaluation. EEG sources were estimated with eLORETA. Thalamic probabilistic stimulation maps were obtained by assigning beta power difference scores (DBS-on minus DBS-off) to stimulation sites. RESULTS: We observed increased beta power in DBS-on compared to DBS-off states. Modulation of cortical beta activity was localized to the midcingulate cortex. Beta modulation was more pronounced when stimulating the thalamus posteriorly, peaking in the ventral posterior nucleus. CONCLUSION: Thalamic DBS in TS patients modulates beta frequency oscillations presumably important for sensorimotor function and relevant to TS pathophysiology.

Cerebello-thalamofrontal dysconnectivity in paroxysmal kinesigenic dyskinesia: A resting-state fMRI study.

INTRODUCTION: The pathophysiology of paroxysmal kinesigenic dyskinesia (PKD) remains elusive to date; however, several lines of evidence from neuroimaging studies suggest involvement of the basal ganglia-thalamocortical network in PKD. We combined fractional amplitude of low-frequency fluctuation (fALFF) and seed-based functional connectivity (FC) analyses in order to comprehensively investigate intrinsic brain activity alterations and their relationships with disease severity in patients with idiopathic PKD. METHODS: Resting-state functional MRI data were obtained and processed in 34 PKD patients and 34 matched controls. fALFF and seed-based FC maps were computed and compared between patients and controls. Linear regression analysis was further performed between regional fALFF values or FC strengths and clinical parameters in patients. RESULTS: PKD patients had a significant increase in fALFF in bilateral thalamus and cerebellum compared with controls. FC analysis seeding at the thalamic clusters revealed significant FC increases in motor cortex and supplementary motor area in PKD patients relative to controls. Longer disease duration was associated with increasing FC strength between the thalamus and motor cortex. CONCLUSION: We have provided evidence for abnormal intrinsic activity in the cerebello-thalamic circuit and increased thalamofrontal FC in PKD patients, implicating interictal cerebello-thalamofrontal dysconnectivity in the pathophysiology of PKD. Given the increasing FC strength in proportion to disease duration, the thalamofrontal hyperconnectivity might reflect either a consequence of recurrent dyskinesias on the brain or an innate pathology causing dyskinesias in PKD.

Factors affecting postural instability after more than one-year bilateral subthalamic stimulation in Parkinson's disease: A cross-sectional study.

BACKGROUND: Balance impairment in Parkinson's disease is multifactorial and its changes due to subthalamic stimulation vary in different studies. OBJECTIVE: We aimed to analyze the combination of predictive clinical factors of balance impairment in patients with Parkinson's disease treated with bilateral subthalamic stimulation for at least one year. METHODS: We recruited 24 patients with Parkinson's disease treated with bilateral subthalamic stimulation and 24 healthy controls. They wore an Opal monitor (APDM Inc.) consisting of three-dimensional gyroscopes and accelerometers in the lumbar region. We investigated four stimulation conditions (bilateral stimulation OFF, bilateral stimulation ON, and unilateral right- and left-sided stimulation ON) with four tests: stance on a plain ground with eyes open and closed, stance on a foam platform with eyes open and closed. Age, disease duration, the time elapsed after implantation, levodopa, and stimulation responsiveness were analyzed. The distance of stimulation location from the subthalamic motor center was calculated individually in each plane of the three dimensions. We analyzed the sway values in the four stimulation conditions in the patient group and compared them with the control values. We explored factor combinations (with age as confounder) in the patient group predictive for imbalance with cluster analysis and a machine-learning-based multiple regression method. RESULTS: Sway combined from the four tasks did not differ in the patients and controls on a group level. The combination of the disease duration, the preoperative levodopa responsiveness, and the stimulation responsiveness predicted individual stimulation-induced static imbalance. The more affected patients had more severe motor symptoms; primarily, the proprioceptive followed by visual sensory feedback loss provoked imbalance in them when switching on the stimulation. CONCLUSIONS: The duration of the disease, the severity of motor symptoms, the levodopa responsiveness, and additional sensory deficits should be carefully considered during preoperative evaluation to predict subthalamic stimulation-induced imbalance in Parkinson's disease.

Cerebello-Thalamo-Cortical Hyperconnectivity Classifies Patients and Predicts Long-Term Treatment Outcome in First-Episode Schizophrenia.

It has previously been shown that cerebello-thalamo-cortical (CTC) hyperconnectivity is likely a state-independent neural signature for psychosis. However, the potential clinical utility of this change has not yet been evaluated. Here, using fMRI and clinical data acquired from 214 untreated first-episode patients with schizophrenia (62 of whom were clinically followed-up at least once at the 12th and 24th months after treatment initiation) and 179 healthy controls, we investigated whether CTC hyperconnectivity would serve as an individualized biomarker for diagnostic classification and prediction of long-term treatment outcome. Cross-validated LASSO regression was conducted to estimate the accuracy of baseline CTC connectivity for patient-control classification, with the generalizability of classification performance tested in an independent sample including 42 untreated first-episode patients and 65 controls. Associations between baseline CTC connectivity and clinical outcomes were evaluated using linear mixed model and leave-one-out cross validation. We found significantly increased baseline CTC connectivity in patients (P = .01), which remained stable after treatment. Measures of CTC connectivity discriminated patients from controls with moderate classification accuracy (AUC = 0.68, P < .001), and the classification model had good generalizability in the independent sample (AUC = 0.70, P < .001). Higher CTC connectivity at baseline significantly predicted poorer long-term symptom reduction in negative symptoms (R = 0.31, P = .01) but not positive or general symptoms. These findings provide initial evidence for the putative "CTC hyperconnectivity" anomaly as an individualized diagnostic and prognostic biomarker for schizophrenia, and highlight the potential of this measure in precision psychiatry.

Thalamocortical Dysconnectivity In Lifelong Premature Ejaculation: A Functional MRI Study.

OBJECTIVES: To detect seed-based functional connectivity (FC) between various cortical sub-regions and the thalamus in lifelong premature ejaculation (LPE) patients and explore whether specific thalamocortical networks are significantly altered in PE patients compared to healthy controls (HCs) METHODS: Fifty non-medicated LPE patients and 40 age-matched HCs underwent a resting-state functional MRI. FC was adopted to identify specific thalamocortical connectivity between the thalamus and 6 cortical regions of interest (i.e., the motor cortex/supplementary motor, the prefrontal cortex, the temporal lobe, the posterior parietal cortex, the somatosensory cortex and the occipital lobe). In LPE patients, regression analysis was subsequently conducted to assess relationships of thalamocortical connectivity with the Premature Ejaculation Diagnostic Tool (PEDT) score and the Intravaginal Ejaculatory Latency Time (IELT). RESULTS: LPE patients had significantly decreased FC between the motor cortex and bilateral ventral thalamus, between the prefrontal cortex and left dorsomedial thalamus, as well as between the temporal cortex and bilateral ventromedial thalamus. In LPE patients, PEDT score was significantly positively associated with the thalamus-posterior parietal cortex FC, and negatively associated with the thalamus-temporal cortex FC, while IELT was positively associated with the thalamus-temporal cortex and thalamus-motor cortex FC. CONCLUSION: These results enrich the imaging evidence for the understanding of the neurobiological mechanisms and/or consequences of LPE.