Connectome-based predictive modeling for functional recovery of acute ischemic stroke.

Patients of acute ischemic stroke possess considerable chance of recovery of various levels in the first several weeks after stroke onset. Prognosis of functional recovery is important for decision-making in poststroke patient care and placement. Poststroke functional recovery has conventionally been based on demographic and clinical variables such as age, gender, and severity of stroke impairment. On the other hand, the concept of connectome has become a basis of interpreting the functional impairment and recovery of stroke patients. In this research, the connectome-based predictive modeling was used to provide predictive models for prognosing poststroke functional recovery. Predictive models were developed to use the brain connectivity at stroke onset to predict functional assessment scores at one or three months later, or to use the brain connectivity one-month poststroke to predict functional assessment scores at three months after stroke onset. The brain connectivity was computed from the resting-state fMRI signals. The functional assessment scores used in this research included modified Rankin Scale (mRS) and Barthel Index (BI). This research found significant models that used the brain connectivity at onset to predict the mRS one-month poststroke and to predict the BI three-month poststroke for patients with supratentorial infarction, as well as predictive models that used the brain connectivity one-month poststroke to predict the mRS three-month poststroke for patients with supratentorial infarction in the right hemisphere. The connectome-based predictive modeling could provide clinical value in prognosis of acute ischemic stroke.

Gamma Knife Radiosurgery as a Salvage Treatment for Nasopharyngeal Carcinoma with Skull Base and Intracranial Invasion (T4b).

It is usually difficult to achieve good outcomes with salvage treatment for recurrent nasopharyngeal carcinoma (NPC) because of its deep-seated location, surrounding critical structures, and patient history of high-dose irradiation. Gamma Knife radiosurgery (GKS) is a treatment option for malignancies with skull base and intracranial invasion. We conducted a retrospective, observational, single-center study including 15 patients with recurrent NPC (stage T4b) involving the skull base and intracranial invasion, who underwent GKS as a salvage treatment. Patients were enrolled over 12 years. Per a previous study, the TNM classification T4b was subclassified into T4b1 and T4b2, defined as the involvement of the skull base or cavernous sinus with an intracranial extension of <5 mm and >5 mm, respectively. The effect of prognostic factors, including age, sex, survival period, magnetic resonance imaging (MRI) presentation, presence of other distant metastases, tumor volume, marginal dose, maximal dose, and Karnofsky Performance Status (KPS), on outcomes was analyzed. The patients with T4b1 NPC (p = 0.041), small tumor volume (p = 0.012), higher KPS (p < 0.001), and no other metastasis (p = 0.007) had better outcomes after GKS treatment, suggesting that it is a viable treatment modality for NPC. We also suggest that detailed brain imaging studies may enable the early detection of intracranial invasion.

Automated Cerebral Infarct Detection on Computed Tomography Images Based on Deep Learning.

The limited accuracy of cerebral infarct detection on CT images caused by the low contrast of CT hinders the desirable application of CT as a first-line diagnostic modality for screening of cerebral infarct. This research was aimed at utilizing convolutional neural network to enhance the accuracy of automated cerebral infarct detection on CT images. The CT images underwent a series of preprocessing steps mainly to enhance the contrast inside the parenchyma, adjust the orientation, spatially normalize the images to the CT template, and create a t-score map for each patient. The input format of the convolutional neural network was the t-score matrix of a 16 × 16-pixel patch. Non-infarcted and infarcted patches were selected from the t-score maps, on which data augmentation was conducted to generate more patches for training and testing the proposed convolutional neural network. The convolutional neural network attained a 93.9% patch-wise detection accuracy in the test set. The proposed method offers prompt and accurate cerebral infarct detection on CT images. It renders a frontline detection modality of ischemic stroke on an emergent or regular basis.

Optimal Cut-Off Points of Sagittal Spinopelvic Parameters as a Morphological Parameter to Predict Efficiency in Nerve Block and Pulsed Radiofrequency for Lumbar Facet Joint Pain: A Retrospective Study.

BACKGROUND: After proper patient selection, anatomically correct pulsed radiofrequency of the lumbar facet joints provide long-term pain relief in a routine clinical setting. In the study, we performed an analysis of clinical and radiological predictive factors and provide the scientific basis for this promising modality. METHODS: The study included 198 patients with lower back pain due to lumbar facet joint disease who underwent medial branch block and pulsed radiofrequency during the period 2015-2019. According to the improvement in pain score, the patients were divided into good and poor outcome groups. Clinical and radiological data were collected and analyzed. RESULTS: The multivariable analysis revealed the predictive factors, including lumbar lordosis, lower lumbar lordosis, pelvic tilt, the number of facet joints, old compression fracture with/without vertebroplasty, and post lumbar fusion procedures. CONCLUSION: With the results of this study, we demonstrated that the improved outcome after the surgery was related to lumbar lordosis, lower lumbar lordosis, pelvic tilt, the number of facet joints, old compression fracture with/without vertebroplasty, and the lumbar fusion procedures. Old compression fractures and lumbar fusion would change the radiological factors and cause refractory lumbar facet joint pain.

Simvastatin-Ezetimibe enhances growth factor expression and attenuates neuron loss in the hippocampus in a model of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a common and severe neurological disorder associated with high morbidity and mortality rates. Despite extensive research into its pathology, there are no clinically approved neuroprotective treatments for ICH. Increasing evidence has revealed that inflammatory responses mediate the pathophysiological processes of brain injury following ICH. Experimental ICH was induced by direct infusion of 100 µL fresh (non-heparinized) autologous whole blood into the right basal ganglia of Sprague-Dawley rats at a constant rate (10 µL/min). The simvastatin group was administered simvastatin (15 mg/kg) and the combination therapy group was administered simvastatin (10 mg/kg) and ezetimibe (10 mg/kg). Magnetic resonance imaging (MRI), the forelimb use asymmetry test, the Morris water maze test, and two biomarkers were used to evaluate the effect of simvastatin and combination therapy. MRI imaging revealed that combination therapy resulted in significantly reduced perihematomal edema. Biomarker analyses revealed that both treatments led to significantly reduced endothelial inflammatory responses. The forelimb use asymmetry test revealed that both treatment groups had significantly improved neurological outcomes. The Morris water maze test revealed improved neurological function after combined therapy, which also led to less neuronal loss in the hippocampal CA1 region. In conclusion, simvastatin-ezetimibe combination therapy can improve neurological function, attenuate the endothelial inflammatory response and lead to less neuronal loss in the hippocampal CA1 region in a rat model of ICH.

Haemorrhage rates of ruptured and unruptured brain arteriovenous malformation after radiosurgery: a nationwide population-based cohort study.

OBJECTIVES: The present nationwide population-based cohort study aims to assess the effectiveness of gamma knife radiosurgery (GKS) on ruptured and unruptured brain arteriovenous malformations (AVMs) by evaluating the haemorrhage rates. DESIGN: A nationwide, retrospective cohort study. SETTING: Taiwan National Health Insurance Research Database (NHIRD). PARTICIPANTS: An observational study of 1515 patients who were diagnosed with brain AVMs between 1997 and 2013 from the Taiwan NHIRD. PRIMARY OUTCOME AND SECONDARY OUTCOME MEASURES: We performed a survival analysis using the Kaplan-Meier method. Multivariate Cox proportional hazards regression models were used to explore the relationship between treatment modalities (GKS vs non-GKS) and haemorrhage, adjusted for age and sex. RESULTS: The GKS and non-GKS groups included 317 and 1198 patients, respectively. Patients in the GKS group (mean±SD, 33.08±15.48 years of age) tended to be younger than those in the non-GKS group (37.40±17.62) (p<0.001). The 15-year follow-up revealed that the rate of bleeding risk was lower in the GKS group than in the non-GKRS group (adjusted HR (aHR) 0.61; 95% CI 0.40 to 0.92). The bleeding risk of ruptured AVMs was significantly lower in GKS group than in the non-GKS group (aHR 0.34; 95% CI 0.19 to 0.62). On the other hand, the bleeding risk of unruptured AVMs was higher in the GKS group than in the non-GKS group (aHR 1.95; 95% CI 1.04 to 3.65). In the unruptured AVM group, the incidence of bleeding was significantly higher among patients in the GKS group that were of >40 years of age (aHR 3.21; 95% CI 1.12 to 9.14). CONCLUSIONS: GKS is safe and it reduces the risk of haemorrhage in patients with ruptured AVMs. The administration of GKS to patients with unruptured AVMs who are above the age of 40 years old male might increase the risk of haemorrhage.

Simvastatin and Simvastatin-Ezetimibe Improve the Neurological Function and Attenuate the Endothelial Inflammatory Response after Spinal Cord Injury in Rat.

During a spinal cord injury (SCI), mechanical trauma rapidly leads to a blood-spinal cord barrier (BSB) disruption, neural cell damage, axonal damage, and demyelination, followed by a cascade of secondary inflammatory reactions. These inflammatory responses spread the damage to the neural cells and impair the recovery of neurological functions. In the present study, we evaluated the efficacy of simvastatin and a simvastatin-ezetimibe combination therapy in managing the endothelial inflammatory response in an SCI rat model. Adult male Sprague-Dawley rats were group-housed and SCI was induced by using the modified weight-drop method. The animals were divided into 4 groups: (1) sham group, laminectomy only (n=6); (2) no-treatment group, SCI without therapy (n=8); (3) simvastatin group (n=8), and (4) ezetimibe and simvastatin combination therapy group (n=8). A high dose (15 mg/kg) of simvastatin was given to the simvastatin group, and 10 mg/kg simvastatin and 10 mg/kg ezetimibe were given to the combination group. Neurological function was assessed using the Basso, Beattie, and Bresnahan locomotor scale score. Intercellular adhesion molecule-1 (ICAM-1) level was used as an SCI biomarker. ICAM-1 level was the highest at 72 hours after SCI in the no-treament group. The treatment groups showed significant reduction in ICAM-1 levels at 72 hours. The treatment groups, especially the combination treatment group, showed better neurological function scores. Simvastatin and simvastatin- ezetimibe all could improve the neurological function and attenuate the endothelial inflammatory response after spinal cord injury in rat.

Is traumatic brain injury a risk factor for neurodegeneration? A meta-analysis of population-based studies.

BACKGROUND: To determine the association of prior traumatic brain injury (TBI) with subsequent diagnosis of neurodegeneration disease. METHODS: All studies from 1980 to 2016 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, Embase, study references, and review articles. The data and study design were assessed by 2 investigators independently. A meta-analysis was performed by RevMan 5.3. RESULTS: There were 18 studies comprising 3,263,207 patients. Meta-analysis revealed a significant association of prior TBI with subsequent dementia. The pooled odds ratio (OR) for TBI on development of dementia, FTD and TDP-43 associated disease were 1.93 (95% CI 1.47-2.55, p < 0.001), 4.44 (95% CI 3.86-5.10, p < 0.001), and 2.97 (95% CI 1.35-6.53, p < 0.001). However, analyses of individual diagnoses found no evidence that the risk of Alzheimer's disease, and Parkinson's disease in individuals with previous TBI compared to those without TBI. CONCLUSIONS: History of TBI is not associated with the development of subsequent neurodegeneration disease. Care must be taken in extrapolating from these results because no suitable criteria define post TBI neurodegenerative processes. Therefore, further research in this area is needed to confirm these questions and uncover the link between TBI and neurodegeneration disease.

Comparative Cost Analysis for the Surgical and Endovascular Treatment of Ruptured Intracranial Aneurysms in Taiwan: A Nationwide Population-Based Cohort Study.

OBJECTIVE: Using a database that enabled longitudinal follow-up, we assessed the cost, outcome, complications, and readmission rate of ruptured cerebral aneurysms repaired by surgical clipping and endovascular coiling. METHODS: This study was a retrospective review of data from a series of patients who underwent surgical clipping or endovascular coiling of ruptured cerebral aneurysms between 1996 and 2013. The medical records and hospital cost data were all examined. RESULTS: A total of 7690 and 1380 cases were treated with clipping and coiling, respectively. Patients treated with clipping had more comorbidities and were older. The average total cost for endovascular coiling was $13,974.3, whereas the average total cost for surgical clipping was $16,581.7. Perioperative (30-day) mortality was 10.7% in patients with coiled aneurysms, compared with 12.6% in those with clipped aneurysms (P = 0.045). After 1 year of follow-up, clipping was associated with a significantly longer length of hospital stay (P < 0.001) and significantly higher total hospital costs (P < 0.001). CONCLUSIONS: In Taiwan, the total hospital costs for the surgical clipping of cerebral aneurysms were higher than for endovascular coiling, and the surgical results were associated with significant complications. We suggest that the indications for coiling might need to be expanded from the current standards dictated by the guidelines in Taiwan.

Risk of dementia in patients with primary insomnia: a nationwide population-based case-control study.

BACKGROUND: To investigate the association between primary insomnia and dementia using a Taiwanese population-based database. METHODS: This case-control study involved a subset of Taiwan's National Health Insurance Research Database of reimbursement claims. We included 51,734 patients who were diagnosed with primary insomnia from 2002 to 2004 as the test group and 258,715 nonprimary insomnia participants aged 20 years or older as the reference group. We excluded patients under 20 and those with depression, post-traumatic stress disorder, and/or sleep disorders caused by organic lesion(s), drugs, or alcohol. We used a Cox proportional hazards model to assess the primary insomnia on the risk of developing dementia after adjusting for sociodemographic characteristics and comorbidities. RESULTS: The primary insomnia cohort had a higher prevalence of diabetes, dyslipidemia, hypertension, coronary heart disease, chronic liver disease, and chronic kidney disease at baseline. After adjusting for select comorbidities, primary insomnia remained a significant predisposing factor for developing dementia, and was associated with a 2.14-fold (95% confidence interval, 2.01-2.29) increase in dementia risk. We also found a higher risk of dementia in younger patients. CONCLUSIONS: Taiwanese patients with primary insomnia, especially those under 40, had a higher risk of developing dementia than those without primary insomnia.

Population-based study suggests an increased risk of Alzheimer'sdisease in Sjögren's syndrome.

This population-based study was designed to estimate and compare the risk of Alzheimer's disease (AD) between patients with primary Sjögren's syndrome (SS) and non-SS patients during a 10-year follow-up period. This is a retrospective cohort study. Data were obtained from the Taiwan's National Health Insurance Research Database. We identified 4463 primary SS patients and 22,315 non-SS patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied to identify the subsequent manifestation of AD. Cox proportional hazard regression was used to study the subsequent manifestation of AD, and Kaplan-Meier survival curves were used to compare survival probability. During the 10-year follow-up period, 7 primary SS and 13 non-SS patients developed AD. During the 10-year follow-up period, the risk of AD was 2.68-fold higher in the primary SS cohort with an overall adjusted hazard ratio (HR) of 2.69 (95% CI 1.07-6.76), after adjusting for demographics and comorbidities. Within the 10-year period, patients with primary SS showed a 2.69-fold increased risk of developing AD. This risk increases with time, and the relative risk of AD is higher in older patients with primary SS.

Hexane fraction of Pluchea indica root extract inhibits proliferation and induces autophagy in human glioblastoma cells.

Pluchea indica (L.) Less. is a perennial plant known for its versatile uses in traditional medicine. Previous findings have shown that the extracts of Pluchea indica possess significant anti-inflammatory, anti-ulcer and anti-tuberculosis activity. The aim of this study was to demonstrate the anticancer activity of the hexane fraction of P. indica root extract (H-PIRE) in human glioblastoma cells using flow cytometric and western blot analysis. The results shoewd that, H-PIRE suppressed the growth of glioblastoma cells in a dose-dependent manner. H-PIRE treatment markedly decreased the population of cells in S and G2/M phases. The significant upregulation of acidic vesicular organelle (AVO) was detected during H-PIRE treatment. The expression levels of microtubule-associated light chain 3-II (LC3-II) protein, phosphorylated JNK and phosphorylated p38 were significantly increased, confirming the occurrence of autophagy during the process. Finally, the combination treatment of H-PIRE and LY294002, a pan PI3K inhibitor, further decreased cell viability, suggesting an additive anticancer effect. Taken together, our results suggest that H-PIRE suppresses the proliferation of glioblastoma cells by inducing cell cycle arrest and autophagy.

TDP-43 proteolysis is associated with astrocyte reactivity after traumatic brain injury in rodents.

The aggregation and deposition of transactivation response DNA-binding protein 43 (TDP-43) in neurons and astrocytes is characteristic in a number of neurodegenerative diseases including Alzheimer's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Nevertheless, the exact role of TDP-43 in astrocytes is unknown. Recently, TDP-43 was identified in neurons but not astrocytes after traumatic brain injury (TBI) in humans. In the present study, we evaluated TDP-43 expression and proteolysis in astrocytes in a rat model of TBI. We assessed TDP-43 fragment expression, astrocyte morphology, neuronal population numbers, and motor function after TBI with or without intracerebroventricular administration of a caspase-3 inhibitor. Motor dysfunction was observed after TBI in potential association astrocytic TDP-43 short fragment mislocalization and accumulation, astrogliosis, and neuronal loss. Notably, caspase-3 inhibition prevented these changes after TBI. Our findings suggest that TDP-43 proteolysis in astrocytes is related to astrogliosis and subsequent neuronal loss in TBI, and that TDP-43 may be an important therapeutic target for preventing motor dysfunction after TBI.

Risk factors for myocardial dysfunction after traumatic brain injury: A one-year follow-up study.

INTRODUCTION: Traumatic brain injury has been associated with an increased risk of myocardial dysfunction. Common abnormalities accompanying this pathology include electrocardiographic abnormalities, elevated creatine kinase levels, arrhythmias, and pathologic changes of the myocardium. The aim of this study was to determine if TBI patients have a higher risk of myocardial dysfunction than the general population and to identify the risk factors of myocardial dysfunction in TBI patients. PATIENTS AND METHODS: The study sample was drawn from Taiwan's National Health Insurance Research Database of reimbursement claims, and comprised 26,860 patients who visited ambulatory care centers or were hospitalized with a diagnosis of TBI. The comparison group consisted of 134,300 randomly selected individuals. The stratified Fine and Gray regression was performed to evaluate independent risk factors for myocardial dysfunction in all patients and to identify risk factors in TBI patients. RESULTS: During a 1-year follow-up period, 664 patients with TBI and 1494 controls developed myocardial dysfunction. TBI was independently associated with increased risk of myocardial dysfunction. Diabetes, hypertension, peptic ulcer disease, chronic liver disease and chronic renal disease were risk factors of myocardial dysfunction in TBI patients. CONCLUSIONS: Individuals with TBI are at greater risk of developing myocardial dysfunction after adjustments for possible confounding factors. Early monitor should be initiated to decrease disability and dependence in patients with TBI.

Analysis of Patients with Myelopathy due to Benign Intradural Spinal Tumors with Concomitant Lumbar Degenerative Diseases Misdiagnosed and Erroneously Treated with Lumbar Surgery.

OBJECTIVE: When a cervical or thoracic benign intradural spinal tumor (BIST) coexists with lumbar degenerative diseases (LDD), diagnosis can be difficult. Symptoms of BIST-myelopathy can be mistaken as being related to LDD. Worse, an unnecessary lumbar surgery could be performed. This study was conducted to analyze cases in which an erroneous lumbar surgery was undertaken in the wake of failure to identify BIST-associated myelopathy. METHODS: Cases were found in a hospital database. Patients who underwent surgery for LDD first and then another surgery for BIST removal within a short interval were studied. Issues investigated included why the BISTs were missed, how they were found later, and how the patients reacted to the unnecessary lumbar procedures. RESULTS: Over 10 years, 167 patients received both surgeries for LDD and a cervical or thoracic BIST. In 7 patients, lumbar surgery preceded tumor removal by a short interval. Mistakes shared by the physicians included failure to detect myelopathy and a BIST, and a hasty decision for lumbar surgery, which soon turned out to be futile. Although the BISTs were subsequently found and removed, 5 patients believed that the lumbar surgery was unnecessary, with 4 patients expressing regrets and 1 patient threatening to take legal action against the initial surgeon. CONCLUSIONS: Concomitant symptomatic LDD and BIST-associated myelopathy pose a diagnostic challenge. Spine specialists should refrain from reflexively linking leg symptoms and impaired ability to walk to LDD. Comprehensive patient evaluation is fundamental to avoid misdiagnosis and wrong lumbar surgery.

The risk of cataractogenesis after gamma knife radiosurgery: a nationwide population based case-control study.

BACKGROUND: Medical radiation is considered a factor responsible for cataractogenesis. However, the incidence of this ophthalmologic complication resulting from gamma knife radiosurgery (GKRS) has not yet been reported. The present study aimed to determine the risk of cataractogenesis associated with radiation exposure from GKRS. METHODS: This study used information from a random sample of one million persons enrolled in the nationally representative Taiwan National Health Insurance Research Database. The GK group consisted of patients who underwent GKRS between 2000 and 2009. The non-GK group was composed of subjects who had never undergone GKRS, but who were matched with the case group for time of enrollment, age, sex, history of coronary artery disease, hypertension, and diabetes. RESULTS: There were 277 patients in the GK group and 2770 matched subjects in the non-GK group. The GK group had a higher overall incidence of cataracts (10.11% vs. 7.26%; crude hazard ratio [cHR], 1.59; 95% CI, 1.07-2.36; adjusted hazard ratio [aHR], 1.25; 95% CI, 0.82-1.90) than the non-GK group. Patients who had undergone computed tomography and/or cerebral angiography (CT/angio) studies had a higher risk of developing cataracts than those who did not (10.82% vs. 6.64%; cHR, 1.74; 95% CI, 1.31-2.30; aHR, 1.65; 95% CI, 1.22-2.23). The age group between 30 and 50 years had the highest risk of cataractogenesis in both the GK and CT/angio groups (cHR, 3.50; 95% CI, 1.58-7.72; aHR, 2.43; 95% CI, 1.02-5.81; cHR, 2.96; 95% CI, 1.47-5.99; aHR, 2.27; 95% CI, 1.05-4.93, respectively). CONCLUSIONS: Radiation exposure due to GKRS and CT/angio study may be independently associated with increased risk of cataractogenesis. We suggest routine dosimetry measurement of eye lens and proper protection for patients with benign lesions during GKRS. Regular follow-up imaging studies should avoid the use of CT/angio, and particular care should be taken in the 30-50-year-old age group, due to their significantly increased risk of cataract formation.

Fluoroscopically Guided C2 Percutaneous Vertebroplasty: A Surgical Technique Note on an Anterior Ascending Approach.

BACKGROUND: C2 vertebroplasty is more challenging than transpedicular percutaneous vertebroplasty in the thoracic and lumbar spine. OBJECTIVE: We report an anterior ascending approach for C2 percutaneous vertebroplasty to avoid potential injury to vital structures surrounding the C2 vertebra. STUDY DESIGN: A technique note with 5 consecutive cases. SETTING: Neurosurgery department of a university hospital. METHODS: Fluoroscopically guided manual compression was applied using 3 fingers at the C5 level between the muscle and trachea. The larynx and trachea were displaced medially and the carotid artery laterally. The anterior cervical spine was palpated, and a 15-gauge 4-inch bone marrow biopsy needle was introduced through an anterior ascending approach. When the tip touched the intervertebral disc between C2 and C3, the needle was pushed through the disc until it penetrated into the C2 vertebral body. After confirming adequate needle insertion, vertebroplasty was performed. RESULTS: Pain relief was achieved in 4/5 (80%) patients. One patient possibly did not benefit from percutaneous vertebroplasty, and asymptomatic cement extravasation was detected in 2 patients. LIMITATIONS: Sample size; impossibility of placebo control. CONCLUSION: An anterior ascending approach for C2 percutaneous vertebroplasty is a valuable alternative for relieving pain caused by metastatic spinal tumors. This approach is familiar to surgeons performing anterior cervical discectomies, percutaneous nucleoplasty, or odontoid screw placement surgeries. KEY WORDS: Vertebroplasty, pain, axis, cement leak, metastases, palliative medicine, spine, fracture.

Extractions of steady-state auditory evoked fields in normal subjects and tinnitus patients using complementary ensemble empirical mode decomposition.

BACKGROUND: Auditory steady-state response (ASSR) induced by repetitive auditory stimulus is commonly used for audiometric testing. ASSR can be measured using electro-encephalography (EEG) and magnetoencephalography (MEG), referred to as steady-state auditory evoked potential (SSAEP) and steady-state auditory evoked field (SSAEF), respectively. However, the signal level of SSAEP and SSAEF are weak so that signal processing technique is required to increase its signal-to-noise ratio. In this study, a complementary ensemble empirical mode decomposition (CEEMD)-based approach is proposed in MEG study and the extraction of SSAEF has been demonstrated in normal subjects and tinnitus patients. METHODS: The CEEMD utilizes noise assisted data analysis (NADA) approach by adding positive and negative noise to decompose MEG signals into complementary intrinsic mode functions (IMF). Ten subjects (five normal and five tinnitus patients) were studied. The auditory stimulus was designed as 1 kHz carrier frequency with 37 Hz modulation frequency. Two channels in the vicinities of right and left temporal areas were chosen as channel-of-interests (COI) and decomposed into IMFs. The spatial distribution of each IMF was correlated with a pair of left- and right-hemisphere spatial templates, designed from each subject's N100m responses in pure-tone auditory stimulation. IMFs with spatial distributions highly correlated with spatial templates were identified using K-means and those SSAEF-related IMFs were used to reconstruct noise-suppressed SSAEFs. RESULTS: The current strengths estimated from CEEMD processed SSAEF showed neural activities greater or comparable to those processed by conventional filtering method. Both the normal and tinnitus groups showed the phenomenon of right-hemisphere dominance. The mean current strengths of auditory-induced neural activities in tinnitus group were larger than the normal group. CONCLUSIONS: The present study proposes an effective method for SSAEF extraction. The enhanced SSAEF in tinnitus group echoes the decreased inhibition in tinnitus's central auditory structures as reported in previous studies.