Atrophy network mapping of clinical subtypes and main symptoms in frontotemporal dementia.

Frontotemporal dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different FTD clinical subtypes and determine the specific localization of the network for apathy and disinhibition. Eighty FTD patients [45 behavioural variant FTD (bvFTD) and 35 semantic variant progressive primary aphasia (svPPA)] and 58 healthy controls at Xuanwu Hospital were enrolled as Dataset 1; 112 FTD patients including 50 bvFTD, 32 svPPA and 30 non-fluent variant PPA (nfvPPA) cases, and 110 healthy controls from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) dataset were included as Dataset 2. Initially, single-subject atrophy maps were defined by comparing cortical thickness in each FTD patient versus healthy controls. Next, the network of brain regions functionally connected to each FTD patient's location of atrophy was determined using seed-based functional connectivity in a large (n = 1000) normative connectome. Finally, we used atrophy network mapping to define clinical subtype-specific network (45 bvFTD, 35 svPPA and 58 healthy controls in Dataset 1; 50 bvFTD, 32 svPPA, 30 nfvPPA and 110 healthy controls in Dataset 2) and symptom-specific networks [combined Datasets 1 and 2, apathy without depression versus non-apathy without depression (80:26), disinhibition versus non-disinhibition (88:68)]. We compare the result with matched symptom networks derived from patients with focal brain lesions or conjunction analysis. Through the analysis of two datasets, we identified heterogeneity in atrophy patterns among FTD patients. However, these atrophy patterns are connected to a common brain network. The primary regions affected by atrophy in FTD included the frontal and temporal lobes, particularly the anterior temporal lobe. bvFTD connects to frontal and temporal cortical areas, svPPA mainly impacts the anterior temporal region and nfvPPA targets the inferior frontal gyrus and precentral cortex regions. The apathy-specific network was localized in the orbital frontal cortex and ventral striatum, while the disinhibition-specific network was localized in the bilateral orbital frontal gyrus and right temporal lobe. Apathy and disinhibition atrophy networks resemble known motivational and criminal lesion networks, respectively. A significant correlation was found between the apathy/disinhibition scores and functional connectivity between atrophy maps and the peak of the networks. This study localizes the common network of clinical subtypes and main symptoms in FTD, guiding future FTD neuromodulation interventions.

Regional Glymphatic Abnormality in Behavioral Variant Frontotemporal Dementia.

OBJECTIVES: Glymphatic function has not yet been explored in behavioral variant frontotemporal dementia (bvFTD). The spatial correlation between regional glymphatic function and bvFTD remains unknown. METHOD: A total of 74 patients with bvFTD and 67 age- and sex-matched healthy controls (HCs) were selected from discovery dataset and replication dataset. All participants underwent neuropsychological assessment. Glymphatic measures including choroid plexus (CP) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling between blood-oxygen-level-dependent signals and cerebrospinal fluid signals (BOLD-CSF coupling), were compared between the two groups. Regional glymphatic function was evaluated by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, and posterior regions. The bvFTD-related metabolic pattern was identified using spatial covariance analysis based on l8 F-FDG-PET. RESULTS: Patients with bvFTD showed higher CP volume (p < 0.001); anterior and middle DTI-ALPS (p < 0.001); and weaker anterior BOLD-CSF coupling (p < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI-ALPS was negatively associated with the expression of the bvFTD-related metabolic pattern (r = -0.52, p = 0.034) and positively related with regional standardized uptake value ratios of l8 F-FDG-PET in bvFTD-related brain regions (r range: 0.49 to 0.62, p range: 0.017 to 0.047). Anterior and middle glymphatic functions were related to global cognition and disease severity. INTERPRETATION: Our findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD. ANN NEUROL 2023;94:442-456.

Human anterior thalamic stimulation evoked cortical potentials align with intrinsic functional connectivity.

Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.

Integrative roles of human amygdala subdivisions: Insight from direct intracerebral stimulations via stereotactic EEG.

Substantial studies of human amygdala function have revealed its importance in processing emotional experience, autonomic regulation, and sensory information; however, the neural substrates and circuitry subserving functions have not been directly mapped at the level of the subnuclei in humans. We provide a useful overview of amygdala functional characterization by using direct electrical stimulation to various amygdala regions in 48 patients with drug-resistant epilepsy undergoing stereoelectroencephalography recordings. This stimulation extends beyond the anticipated emotional, neurovegetative, olfactory, and somatosensory responses to include visual, auditory, and vestibular sensations, which may be explained by the functional connectivity with cortical and subcortical regions due to evoked amygdala-cortical potentials. Among the physiological symptom categories for each subnucleus, the most frequently evoked neurovegetative symptoms were distributed in almost every subnucleus. Laterobasal subnuclei are mainly associated with emotional responses, somatosensory responses, and vestibular sensations. Superficial subnuclei are mainly associated with emotional responses and olfactory and visual hallucinations. Our findings contribute to a better understanding of the functional architecture of the human amygdala at the subnuclei level and as a mechanistic basis for the clinical practice of amygdala stimulation in treating patients with neuropsychiatric disorders.

Causal associations between sleep traits and brain structure: a bidirectional Mendelian randomization study.

BACKGROUND: Emerging evidence suggests bidirectional causal relationships between sleep disturbance and psychiatric disorders, but the underlying mechanisms remain unclear. Understanding the bidirectional causality between sleep traits and brain imaging-derived phenotypes (IDPs) will help elucidate the mechanisms. Although previous studies have identified a range of structural differences in the brains of individuals with sleep disorders, it is still uncertain whether grey matter (GM) volume alterations precede or rather follow from the development of sleep disorders. RESULTS: After Bonferroni correction, the forward MR analysis showed that insomnia complaint remained positively associated with the surface area (SA) of medial orbitofrontal cortex (ß, 0.26; 95% CI, 0.15-0.37; P = 5.27 × 10-6). In the inverse MR analysis, higher global cortical SA predisposed individuals less prone to suffering insomnia complaint (OR, 0.89; 95%CI, 0.85-0.94; P = 1.51 × 10-5) and short sleep (≤ 6 h; OR, 0.98; 95%CI, 0.97-0.99; P = 1.51 × 10-5), while higher SA in posterior cingulate cortex resulted in a vulnerability to shorter sleep durations (ß, - 0.09; 95%CI, - 0.13 to - 0.05; P = 1.21 × 10-5). CONCLUSIONS: Sleep habits not only result from but also contribute to alterations in brain structure, which may shed light on the possible mechanisms linking sleep behaviours with neuropsychiatric disorders, and offer new strategies for prevention and intervention in psychiatric disorders and sleep disturbance.

COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.

Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.

Stable maintenance of multiple representational formats in human visual short-term memory.

Visual short-term memory (VSTM) enables humans to form a stable and coherent representation of the external world. However, the nature and temporal dynamics of the neural representations in VSTM that support this stability are barely understood. Here we combined human intracranial electroencephalography (iEEG) recordings with analyses using deep neural networks and semantic models to probe the representational format and temporal dynamics of information in VSTM. We found clear evidence that VSTM maintenance occurred in two distinct representational formats which originated from different encoding periods. The first format derived from an early encoding period (250 to 770 ms) corresponded to higher-order visual representations. The second format originated from a late encoding period (1,000 to 1,980 ms) and contained abstract semantic representations. These representational formats were overall stable during maintenance, with no consistent transformation across time. Nevertheless, maintenance of both representational formats showed substantial arrhythmic fluctuations, i.e., waxing and waning in irregular intervals. The increases of the maintained representational formats were specific to the phases of hippocampal low-frequency activity. Our results demonstrate that human VSTM simultaneously maintains representations at different levels of processing, from higher-order visual information to abstract semantic representations, which are stably maintained via coupling to hippocampal low-frequency activity.

Deep brain stimulation of the subthalamic nucleus for epilepsy.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a promising palliative option for patients with refractory epilepsy. However, crucial questions remain unanswered: Which patients are the optimal candidates? How, where, and when to stimulate the STN? And what is the mechanism of STN-DBS action on epilepsy? Thus, we reviewed the clinical evidence on the antiepileptic effects of STN-DBS and its possible mechanisms on drug-resistant epilepsy, its safety, and the factors influencing stimulation outcomes. This information may guide clinical decision-making. In addition, based on the current knowledge on the effect of STN-DBS on epilepsy, we suggest research that needs to be carried out in the future.

Characterizing the hyper- and hypometabolism in temporal lobe epilepsy using multivariate machine learning.

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy, presenting both structural and metabolic abnormalities in the ipsilateral mesial temporal lobe. While it has been demonstrated that the metabolic abnormalities in MTLE actually extend beyond the epileptogenic zone, how such multidimensional information is associated with the diagnosis of MTLE remains to be tested. Here, we explore the whole-brain metabolic patterns in 23 patients with MTLE and 24 healthy controls using [18 F]fluorodeoxyglucose PET imaging. Based on a multivariate machine learning approach, we demonstrate that the brain metabolic patterns can discriminate patients with MTLE from controls with a superior accuracy (>95%). Importantly, voxels showing the most extreme contributing weights to the classification (i.e., the most important regional predictors) distribute across both hemispheres, involving both ipsilateral negative weights over the anterior part of lateral and medial temporal lobe, posterior insula, and lateral orbital frontal gyrus, and contralateral positive weights over the anterior frontal lobe, temporal lobe, and lingual gyrus. Through region-of-interest analyses, we verify that in patients with MTLE, the negatively weighted regions are hypometabolic, and the positively weighted regions are hypermetabolic, compared to controls. Interestingly, despite that both hypo- and hypermetabolism have mutually contributed to our model, they may reflect different pathological and/or compensative responses. For instance, patients with earlier age at epilepsy onset present greater hypometabolism in the ipsilateral inferior temporal gyrus, while we find no evidence of such association with hypermetabolism. In summary, quantitative models utilizing multidimensional brain metabolic information may provide additional assistance to presurgical workups in TLE.

Subthalamic Nucleus Stimulation Modulates Motor Epileptic Activity in Humans.

OBJECTIVE: Pharmaco-refractory focal motor epileptic seizures pose a significant challenge. Deep brain stimulation (DBS) is a recently recognized therapeutic option for the treatment of refractory epilepsy. To identify the specific target for focal motor seizures, we evaluate the modulatory effects of the subthalamic nucleus (STN) stimulation because of the critical role of STN in cortico-subcortical motor processing. METHODS: Seven patients with epilepsy with refractory seizures who underwent chronic stereoelectroencephalography (SEEG) monitoring were studied in presurgical evaluation. Seizure onset zone was hypothesized to be partially involved in the motor areas in 6 patients. For each patient, one electrode was temporally implanted into the STN that was ipsilateral to the seizure onset zone. The cortical-subcortical seizure propagation was systemically evaluated. The simultaneously electrophysiological responses over distributed cortical areas to STN stimulation at varied frequencies were quantitatively assessed. RESULTS: We observed the consistent downstream propagation of seizures from the motor cortex toward the ipsilateral STN and remarkable cortical responses on motor cortex to single-pulse STN stimulation. Furthermore, we showed frequency-dependent upstream modulatory effect of STN stimulation on motor cortex specifically. In contrast to the enhanced effects of low frequency stimulation, high-frequency stimulation of the STN can significantly reduce interictal spikes, high-frequency oscillations over motor cortex disclosing effective connections to the STN. INTERPRETATION: This result showed that the STN is not only engaged in as a propagation network of focal motor seizures but STN stimulation can profoundly modulate the epileptic activity of motor cortex in humans, suggesting a mechanism-based alternative for patients suffering from refractory focal motor seizures. ANN NEUROL 2020;88:283-296.

Clinical application of intraoperative trial-free online-based language mapping for patients with refractory epilepsy.

OBJECTIVE: The objective of the study was to develop and clinically test a trial-free online-based language mapping method for localizing the eloquent cortex easily in epilepsy operation. METHODS: Nine patients with refractory epilepsy were included in this study according to the results of preoperative evaluation for their epileptogenic zones (EZs) located adjacent to the eloquent cortex. When patients were awakened up from general anesthesia during operation, the trial-free online-based language-mapping paradigm was performed. All positive points marked on the cortex in each test were labeled and superimposed together as the result of functional mapping for each patient. The eloquent cortex was mapped according to the results obtained both from the intraoperative trial-free task localization method and the traditional electrical cortical stimulation (ECS). RESULTS: All patients completed this paradigms twice within 10 min. Based on the results of mapping, the EZs were tried to fully resected on the premise of preserving the mapped eloquent cortex as much as possible. The postoperative follow-up showed the outcome of Engel I in six patients and Engel II in three patients, whereas only two patients had aphemia after surgery and recovered within one week and three months, respectively. SIGNIFICANCE: The intraoperative trial-free online-based language mapping method was primarily identified to be safe and effective. This novel method seems to be promising and worthy of improvement.

Amygdalar and hippocampal beta rhythm synchrony during human fear memory retrieval.

BACKGROUND: Fear, as one of the basic emotions, is crucial in helping humans to perceive hazards and adapt to social activities. Clinically, fear memory is also involved in a wide spectrum of psychiatric disorders. A better understanding of the neural mechanisms of fear thereby has both neuroscientific and clinical significance. In recent years, data from animal models have demonstrated the key role of the amygdala-hippocampal circuit in the development of fear. However, the neural processing of fear memory remains unclear in humans, which is mainly due to the limitation of indirect measure of neural activity. METHODS: Herein, we investigated fear memory by direct intracranial recordings from 8 intractable epilepsy patients with depth electrodes in both the hippocampus and ipsilateral amygdala. All the patients were subjected to a well-established Pavlovian fear memory paradigm consisted of the familiarization task, conditioning task, and retrieval task, respectively. Simultaneous local field potentials from the hippocampus and amygdala were recorded during different stages. The oscillatory activities from the amygdala and hippocampus were analyzed during fear memory retrieval compared with neutral stages. RESULTS: Consistent with previous rodent studies, our results showed that the amygdala was involved in fear memory retrieval rather than neutral memory retrieval, while the hippocampus was involved both in fear memory retrieval and neutral memory retrieval. In particular, we found that there was an enhanced synchronized activity between the amygdala and hippocampus at beta frequencies (14-30 Hz), which suggested that enhanced synchronized activity at beta frequencies between the amygdala and hippocampus play a pivotal role during retrieval of fear memory in human. CONCLUSIONS: Thus, our observation that the amygdala-hippocampal system contributing to fear memory retrieval in human with frequency-depended specificity has provided new insights into the mechanism of fear and have potential clinical relevance.

Automatic labeling of the fanning and curving shape of Meyer's loop for epilepsy surgery: an atlas extracted from high-definition fiber tractography.

BACKGROUND: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time. METHODS: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients). RESULTS: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively. CONCLUSION: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.

High-frequency stimulation of anterior nucleus of thalamus desynchronizes epileptic network in humans.

Epilepsy has been classically seen as a brain disorder resulting from abnormally enhanced neuronal excitability and synchronization. Although it has been described since antiquity, there are still significant challenges achieving the therapeutic goal of seizure freedom. Deep brain stimulation of the anterior nucleus of the thalamus has emerged as a promising therapy for focal drug-resistant epilepsy; the basic mechanism of action, however, remains unclear. Here, we show that desynchronization is a potential mechanism of deep brain stimulation of the anterior nucleus of the thalamus by studying local field potentials recordings from the cortex during high-frequency stimulation (130 Hz) of the anterior nucleus of the thalamus in nine patients with drug-resistant focal epilepsy. We demonstrate that high-frequency stimulation applied to the anterior nucleus of the thalamus desynchronizes ipsilateral hippocampal background electrical activity over a broad frequency range, and reduces pathological epileptic discharges including interictal spikes and high-frequency oscillations. Furthermore, high-frequency stimulation of the anterior nucleus of the thalamus is capable of decoupling large-scale neural activity involving the hippocampus and distributed cortical areas. We found that stimulation frequencies ranging from 15 to 45 Hz were associated with synchronization of hippocampal local field potentials, whereas higher frequencies (>45 Hz) promoted desynchronization of ipsilateral hippocampal activity. Moreover, reciprocal effective connectivity between the anterior nucleus of the thalamus and the hippocampus was demonstrated by hippocampal-thalamic evoked potentials and thalamic-hippocampal evoked potentials. In summary, high-frequency stimulation of the anterior nucleus of the thalamus is shown to desynchronize focal and large-scale epileptic networks, and here is proposed as the mechanism for reducing seizure generation and propagation. Our data also demonstrate position-specific correlation between deep brain stimulation applied to the anterior nucleus of the thalamus and patients with temporal lobe epilepsy and seizure onset zone within the Papaz circuit or limbic system. Our observation may prove useful for guiding electrode implantation to increase clinical efficacy.

Ictal swearing network confirmed by stereoencephalography: a case report.

Ictal swearing, characterized by episodic utterance of deistic, visceral and other taboo words and phrases, is a rare manifestation of epilepsy. Limited manifestation of that elucidate neural network about manifestation of. Here we report a 43-year-old right-handed man who has suffered from refractory epilepsy manifestation of ictal swearing. The stereoencephalography(SEEG) investigation located the seizure onset zone in left orbito-frontal cortex and the involvement of left orbito-frontal and right hippocampus in the propagation of epileptic activities. Surgical resection has made the patient seizure-free. The present case gives us better understanding of these ictal phenomena and helps to optimize the placement of SEEG electrodes in refractory epilepsy patient with ictal swearing.

[An analysis of clinical and imaging characteristics of atopic myelitis].

OBJECTIVE: To study the clinical and imaging characteristics of Chinese atopic myelitis (AM) patients. METHODS: Three diagnosed AM patients were retrospectively analyzed for the clinical data, serum IgE level, antigen specific IgE, cerebrospinal fluid, spinal MRI and therapeutic efficacy profiles. RESULTS: All the three patients were male and presented as subacute AM with the onset at 25, 47 and 49 years old respectively. Two patients were allergic to pollen and other drugs, while another patient suffered from allergic rhinitis. Elevated serum total IgE and mite antigen specific IgE were found in all cases. Paraesthesia in limb extremities and positive Lhermitte sign were the main clinical features, while no optic, motor, urinary and defecation disturbance were found. Oligoclonal banding of cerebrospinal fluid and serum aquaporin 4 (AQP4) antibody were both negative in all cases. Spinal MRI showed lesions were hypointense on T1 and hyperintense on T2 at the posterior column of T2-3 segment with abnormal enhancement in case 1, hypointense on T1 and hyperintense on T2 at C2/3 segment with mild swelling in case 2 and hypointense on T1 and hyperintense on T2 at C3-5 segments with swelling and abnormal enhancement in case 3. Vitamin B were used in one patient, while the other two patients improved after the treatment with high-dose corticosteroids. CONCLUSIONS: Subacute myelitis predominantly presents as paraesthesia in limb extremities with elevated serum total IgE and mite antigen specific IgE, while severe motor disorders are rare. Swelling and abnormal enhancement lesions at the posterior column of cervical cord are the common imaging features. Treatment with corticosteroids is recommended to be sustained for 3-6 months.

Differential cortical layer engagement during seizure initiation and spread in humans.

Despite decades of research, we still do not understand how spontaneous human seizures start and spread - especially at the level of neuronal microcircuits. In this study, we used laminar arrays of micro-electrodes to simultaneously record the local field potentials and multi-unit neural activities across the six layers of the neocortex during focal seizures in humans. We found that, within the ictal onset zone, the discharges generated during a seizure consisted of current sinks and sources only within the infra-granular and granular layers. Outside of the seizure onset zone, ictal discharges reflected current flow in the supra-granular layers. Interestingly, these patterns of current flow evolved during the course of the seizure - especially outside the seizure onset zone where superficial sinks and sources extended into the deeper layers. Based on these observations, a framework describing cortical-cortical dynamics of seizures is proposed with implications for seizure localization, surgical targeting, and neuromodulation techniques to block the generation and propagation of seizures.

Association of sleep complaints with all-cause and heart disease mortality among US adults.

Introduction: Compared with sleep disorders, no consensus has been reached on whether a subjective complaint of having trouble sleeping is associated with increased all-cause and heart disease mortality risk. Previous studies displayed considerable heterogeneity in population disease characteristics and duration of follow-up. Therefore, the aims of this study were to examine the relationship between sleep complaints and all-cause and heart disease mortality and whether the associations were influenced by follow-up time and population disease characteristics. In addition, we aimed to figure out the influence of the joint effects of sleep duration and sleep complaints on mortality risk. Methods: The present study utilized data from five cycles of the National Health and Nutrition Examination Survey (NHANES) (2005~2014) linked with the most updated 2019 National Death Index (NDI). Sleep complaints were determined by answers to "Have you ever told a doctor or other health professional that you have trouble sleeping?" and "Have you ever been told by a doctor or other health professional that you have a sleep disorder?". Those who answered 'Yes' to either of the aforementioned two questions were considered as having sleep complaints. Results: A total of 27,952 adult participants were included. During a median follow-up of 9.25 years (interquartile range, 6.75-11.75 years), 3,948 deaths occurred and 984 were attributable to heart disease. A multivariable-adjusted Cox model revealed that sleep complaints were significantly associated with all-cause mortality risk (HR, 1.17; 95% CI, 1.07-1.28). Subgroup analysis revealed that sleep complaints were associated with all-cause (HR, 1.17; 95% CI, 1.05-1.32) and heart disease (HR, 1.24; 95% CI, 1.01-1.53) mortality among the subgroup with cardiovascular disease (CVD) or cancer. In addition, sleep complaints were more strongly associated with short-term mortality than long-term mortality. The joint analysis of sleep duration and sleep complaints showed that sleep complaints mainly increased the mortality risk in those with short (< 6 h/day, sleep complaints HR, 1.40; 95% CI, 1.15-1.69) or recommended (6-8 h/day, sleep complaints HR, 1.15; 95% CI, 1.01-1.31) sleep duration group. Discussion: In conclusion, sleep complaints were associated with increased mortality risk, indicating a potential public benefit of monitoring and managing sleep complaints in addition to sleep disorders. Of note, persons with a history of CVD or cancer may represent a potentially high-risk group that should be targeted with a more aggressive intervention of sleep problems to prevent premature all-cause and heart disease death.

Deep brain stimulation for patients with refractory epilepsy: nuclei selection and surgical outcome.

Objective: By studying the surgical outcome of deep brain stimulation (DBS) of different target nuclei for patients with refractory epilepsy, we aimed to explore a clinically feasible target nucleus selection strategy. Methods: We selected patients with refractory epilepsy who were not eligible for resective surgery. For each patient, we performed DBS on a thalamic nucleus [anterior nucleus of the thalamus (ANT), subthalamic nucleus (STN), centromedian nucleus (CMN), or pulvinar nucleus (PN)] selected based on the location of the patient's epileptogenic zone (EZ) and the possible epileptic network involved. We monitored the clinical outcomes for at least 12 months and analyzed the clinical characteristics and seizure frequency changes to assess the postoperative efficacy of DBS on the different target nuclei. Results: Out of the 65 included patients, 46 (70.8%) responded to DBS. Among the 65 patients, 45 underwent ANT-DBS, 29 (64.4%) responded to the treatment, and four (8.9%) of them reported being seizure-free for at least 1 year. Among the patients with temporal lobe epilepsy (TLE, n = 36) and extratemporal lobe epilepsy (ETLE, n = 9), 22 (61.1%) and 7 (77.8%) responded to the treatment, respectively. Among the 45 patients who underwent ANT-DBS, 28 (62%) had focal to bilateral tonic-clonic seizures (FBTCS). Of these 28 patients, 18 (64%) responded to the treatment. Out of the 65 included patients, 16 had EZ related to the sensorimotor cortex and underwent STN-DBS. Among them, 13 (81.3%) responded to the treatment, and two (12.5%) were seizure-free for at least 6 months. Three patients had Lennox-Gastaut syndrome (LGS)-like epilepsy and underwent CMN-DBS; all of them responded to the treatment (seizure frequency reductions: 51.6%, 79.6%, and 79.5%). Finally, one patient with bilateral occipital lobe epilepsy underwent PN-DBS, reducing the seizure frequency by 69.7%. Significance: ANT-DBS is effective for patients with TLE or ETLE. In addition, ANT-DBS is effective for patients with FBTCS. STN-DBS might be an optimal treatment for patients with motor seizures, especially when the EZ overlaps the sensorimotor cortex. CMN and PN may be considered modulating targets for patients with LGS-like epilepsy or occipital lobe epilepsy, respectively.