19 Channel Z-Score and LORETA Neurofeedback: Does the Evidence Support the Hype?

Neurofeedback is a well-investigated treatment for ADHD and epilepsy, especially when restricted to standard protocols such as theta/beta, slow cortical potentials and sensori-motor rhythm neurofeedback. Advances in any field are welcome and other techniques are being pursued. Manufacturers and clinicians are marketing 'superior' neurofeedback approaches including 19 channel Z-score neurofeedback (ZNFB) and 3-D LORETA neurofeedback (with or without Z-scores; LNFB). We conducted a review of the empirical literature to determine if such claims were warranted. This review included the above search terms in Pubmed, Google scholar and any references that met our criteria from the ZNFB publication list and was restricted to group based studies examining improvement in a clinical population that underwent peer review (book chapters, magazine articles or conference presentations are not included since these are not peer reviewed). Fifteen relevant studies emerged with only six meeting our criterion. Based on review of these studies it was concluded that empirical validation of these approaches is sorely lacking. There is no empirical data that supports the notion that 19-channel z-score neurofeedback is effective or superior. The quality of studies for LNFB was better compared to ZNFB and some suggestion for efficacy was demonstrated for ADHD and Tinnitus distress. However, these findings need to be replicated, extended to other populations and have yet to show any "superiority." Our conclusions continue to emphasize the pervasive lack of evidence supporting these approaches to neurofeedback and the implications of this are discussed.

EEG biofeedback for autism spectrum disorder: a commentary on Kouijzer et al. (2013).

Research conducted by Kouijzer et al. (Appl Psychophysiol Biofeedback 38(1):17-28, 2013) compared the effects of skin conductance biofeedback and EEG-biofeedback on patients with autistic spectrum disorders to determine their relative efficacy. While they found a difference between treatment and control groups, there was no significant difference on many variables between the two treatment groups. From this, the increase in symptom alleviation from autistic spectrum disorder was attributed to non-specific factors surrounding the study. We now offer alternative explanations for their findings and propose different options for future studies. We hypothesize that the location and type of neurofeedback used adversely impacted the findings. We speculate that had they used a form of EEG-biofeedback that can combat deficiencies in connectivity and also trained the areas of the brain most affected by autism, there may have then been a significant difference between the effectiveness of EEG-biofeedback versus skin conductance biofeedback.

Treatment of Gastrointestinal Bleeding in the Biliopancreatic Limb with Embolization in a Patient with Duodenal Switch Anatomy.

Introduction: Biliopancreatic diversion with duodenal switch (BPD/DS) is an uncommon type of bariatric surgery that can rarely lead to bleeding in the biliopancreatic limb. The altered anatomy poses significant diagnostic and therapeutic challenges. Case Presentation: We present an unusual case of a woman status post-BPD/DS nearly a decade ago who presented with gastrointestinal bleeding in the duodenum of the biliopancreatic limb, a rare phenomenon given the unique surgery. Conclusion: We illustrate a promising minimally invasive option of successfully treating the bleeding by interventional radiology (IR) embolization as an alternative to more invasive and challenging options of balloon-assisted enteroscopy, lumen-apposing metal stent placement and surgical intraoperative enteroscopy.

Recurrent bleeding duodenal and colonic ulcers due to post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation as the result of immunosuppressant medications. Epstein-Barr virus (EBV) has been implicated in most of these cases, specifically with B-cell predominant lymphoma. This case report describes a 24-year-old female who presented with recurrent GI bleed within 6 months post-orthostatic heart transplant. Endoscopic evaluations including video capsule study, push enteroscopy, and colonoscopy revealed multiple ulcerated lesions in duodenum, jejunum, and colon secondary to Epstein-Barr Virus-associated monomorphic PTLD. Despite continuation of rituximab after discharge, she returned to the hospital for recurrent GI bleed requiring additional endoscopic intervention. PTLD is a devastating disease of the post-transplant population. Due to a high risk of recurrent GI bleeding, patients with PTLD may benefit from careful monitoring by gastroenterology as an outpatient with a low threshold for repeat endoscopic evaluation despite being on immunotherapy or chemotherapy.

Identification of sentinel lymph nodes in esophageal cancer patients using contrast-enhanced EUS with peritumoral injections.

Objectives: The objective of this pilot study was to compare the performance of contrast-enhanced EUS (CE-EUS)-guided fine-needle aspiration (FNA) with EUS-FNA for lymph node (LN) staging in esophageal cancer. Methods: Thirty-seven subjects with esophageal cancer undergoing EUS staging were enrolled, and 30 completed this institutional review board-approved study. A Prosound F75 US system (Hitachi Medical Systems, Tokyo, Japan) with harmonic contrast imaging software and GF-UCT180 curvilinear endoscope (Olympus, Tokyo, Japan) was utilized. All LNs identified by standard EUS were first noted. Sonazoid (dose: 1 mL; GE Healthcare, Oslo, Norway) was administered peritumorally, and all enhanced LNs were recorded. Fine-needle aspiration was performed on LNs considered suspicious by EUS alone, as well as LNs enhanced on CE-EUS. Performance of each modality was compared using FNA cytology as reference standard. Results: A total of 132 LNs were detected with EUS, of which 59 showed enhancement on CE-EUS. Fifty-three LNs underwent FNA, and 22 LNs were determined to be malignant. Among the latter, 10 were considered suspicious by EUS, whereas the other 12 LNs underwent FNA only because of CE-EUS enhancement. Contrast-enhanced EUS showed enhancement in 19 of the 22 malignant LNs. The rate of metastatic node identification from EUS was 45% (10/22), and it was 86% (19/22; P = 0.008) for CE-EUS. Eight subjects (8/30 [27% of study total]) had nodal status upgraded by the addition of CE-EUS, which influenced LN staging and clinical management. Conclusions: Fine-needle aspiration of LNs identified by CE-EUS may increase metastasis positive rate by ruling out LNs not associated with the tumor drainage pattern. In addition, CE-EUS seems to identify more metastatic LNs that would not be biopsied under the standard EUS criteria.

Targeted cyst wall puncture and aspiration during EUS-FNA increases the diagnostic yield of premalignant and malignant pancreatic cysts.

BACKGROUND: Characterization of pancreatic cysts by using EUS-FNA includes chemical and cytologic analysis. OBJECTIVE: To evaluate whether material obtained from FNA of the cyst wall increases diagnostic yield. DESIGN: Prospective series. SETTING: Tertiary referral center. PATIENTS: Consecutive patients with pancreatic cysts referred for EUS-FNA between March 2010 and March 2011. INTERVENTION: FNA was performed with aspiration of cyst fluid for carcinoembryonic antigen (CEA) and cytology, followed by cyst wall puncture (CWP). CWP is defined as puncturing the far wall of the cyst and moving the needle back and forth through the wall to sample the wall epithelium. MAIN OUTCOME MEASUREMENTS: The diagnostic yield for mucinous cystic pancreatic neoplasms by CEA and cytology obtained from cyst fluid compared with cytology obtained from CWP. CEA ≥192 ng/mL was considered mucinous. RESULTS: A total of 69 pancreatic cysts from 66 patients were included. Adequate amounts of fluid were aspirated for CEA, amylase, and cytology in 60 cysts (81%). Cellular material adequate for cytologic assessment from CWP was obtained in 56 cysts (81%). Ten (30%) of 33 cysts with CEA <192 ng/mL and negative results of cyst fluid cytology had a mucinous diagnosis from CWP; 6 of 9 (67%) cysts with an insufficient amount of fluid for CEA analysis and cyst fluid cytology had a mucinous diagnosis from CWP. Furthermore, 4 malignant cysts were independently diagnosed by CWP cytology. The incremental diagnostic yield of CWP for mucinous or malignant cysts was therefore 29% (20 of 69 cysts, P = .0001). An episode of pancreatitis (1.45%) occurred. LIMITATION: Lack of surgical criterion standard. CONCLUSIONS: CWP during EUS-FNA is a safe and effective technique for improving the diagnostic yield for premalignant and malignant pancreatic cysts.

Estimating brain effective connectivity from EEG signals of patients with autism disorder and healthy individuals by reducing volume conduction effect.

Studying brain connectivity has shed light on understanding brain functions. Electroencephalogram signals recorded from the scalp surface comprise inter-dependent multi-channel signals each of which is a linear combination of simultaneously active brain sources as well as adjacent non-brain sources whose activity is widely volume conducted to the scalp through overlapping patterns. Evaluation of brain connectivity based on multivariate autoregressive (MVAR) model identification from neurological time series can be a proper tool for brain signal analysis. However, the MVAR model only considers the lagged influences between time series while ignoring the instantaneous effects (zero-lagged interactions) among simultaneously recorded neurological signals. Hence predicting instant interactions may result in fake connectivity, which may lead to misinterpreting in results. In this study, we aim to find instantaneous effects from coefficients of the MVAR model acquired using an ADALINE neural network and investigate the efficiency of the proposed algorithm by applying it to a simulated signal. We show that our coefficients are estimated accurately from channels of the simulated signal. Moreover, we apply the proposed method on a dataset of a group of 18 healthy children and 10 children with autism by comparing their effective connectivity estimated by direct directed transfer function method using new and old coefficients. Finally, to show the efficiency of the algorithm we exploit the support vector machine method for classifying the dataset. We show that there is a significant improvement in the results obtained from the proposed method.

Cholestatic Liver Injury in a Patient with Tertiary Syphilis.

Syphilis is a common infection that has variable presentations. We report a rare case of a 64-year-old male with 3 weeks of abdominal pain, back pain, and neurologic deficits including memory impairment who was found to have neurosyphilis causing a cholestatic liver injury. Workup included a positive rapid plasma reagin (RPR) and enzyme immunoassay (EIA), a positive cerebrospinal fluid (CSF) venereal disease research laboratory (VDRL), and a liver biopsy, which was compatible with a diagnosis of syphilitic hepatitis. Completion of a 14-day course of penicillin and 1 month of physical therapy resulted in near full-functional and biochemical recovery.

The relative efficacy of connectivity guided and symptom based EEG biofeedback for autistic disorders.

Autism is a neurodevelopmental disorder characterized by deficits in communication, social interaction, and a limited range of interests with repetitive stereotypical behavior. Various abnormalities have been documented in the brains of individuals with autism, both anatomically and functionally. The connectivity theory of autism is a recently developed theory of the neurobiological cause of autisic symptoms. Different patterns of hyper- and hypo-connectivity have been identified with the use of quantitative electroencephalogray (QEEG), which may be amenable to neurofeedback. In this study, we compared the results of two published controlled studies examining the efficacy of neurofeedback in the treatment of autism. Specifically, we examined whether a symptom based approach or an assessment/connectivity guided based approach was more effective. Although both methods demonstrated significant improvement in symptoms of autism, connectivity guided neurofeedback demonstrated greater reduction on various subscales of the Autism Treatment Evaluation Checklist (ATEC). Furthermore, when individuals were matched for severity of symptoms, the amount of change per session was significantly higher in the Coben and Padolsky (J Neurother 11:5-23, 2007) study for all five measures of the ATEC. Our findings suggest that an approach guided by QEEG based connectivity assessment may be more efficacious in the treatment of autism. This permits the targeting and amelioration of abnormal connectivity patterns in the brains of people who are autistic.

Neurofeedback for autistic spectrum disorder: a review of the literature.

There is a need for effective interventions to address the core symptoms and problems associated with autistic spectrum disorder (ASD). Behavior therapy improves communication and behavioral functioning. Additional treatment options include psychopharmacological and biomedical interventions. Although these approaches help children with autistic problems, they may be associated with side effects, risks or require ongoing or long-term treatment. Neurofeedback is a noninvasive approach shown to enhance neuroregulation and metabolic function in ASD. We present a review of the literature on the application of Neurofeedback to the multiple problems associated with ASD. Directions for future research are discussed.

Effective brain connectivity estimation between active brain regions in autism using the dual Kalman-based method.

Brain connectivity estimation is a useful method to study brain functions and diagnose neuroscience disorders. Effective connectivity is a subdivision of brain connectivity which discusses the causal relationship between different parts of the brain. In this study, a dual Kalman-based method is used for effective connectivity estimation. Because of connectivity changes in autism, the method is applied to autistic signals for effective connectivity estimation. For method validation, the dual Kalman based method is compared with other connectivity estimation methods by estimation error and the dual Kalman-based method gives acceptable results with less estimation errors. Then, connectivities between active brain regions of autistic and normal children in the resting state are estimated and compared. In this simulation, the brain is divided into eight regions and the connectivity between regions and within them is calculated. It can be concluded from the results that in the resting state condition the effective connectivity of active regions is decreased between regions and is increased within each region in autistic children. In another result, by averaging the connectivity between the extracted active sources of each region, the connectivity between the left and right of the central part is more than that in other regions and the connectivity in the occipital part is less than that in others.

Sensitivity and specificity of long wave infrared imaging for attention-deficit/hyperactivity disorder.

OBJECTIVE: This study was the first to investigate the efficacy of long wave infrared (LWIR) imaging as a diagnostic tool for ADHD. METHOD: This study was conducted to assess the sensitivity and specificity of LWIR imaging as a method of diagnosis among 190 patients (ages 4.4-57 years) with various diagnoses, including ADHD, who came into our office for neuropsychological evaluation. RESULTS: LWIR imaging demonstrated a moderate level of sensitivity (65.71%) in identifying patients with ADHD and a high level of specificity (94%) in discriminating those with ADHD from those with other diagnoses. The overall classification rate was 73.16%. This was indicative of a high level of discriminant validity in distinguishing between patients with and without ADHD. There was a moderate level of agreement between LWIR imaging and multiple other diagnostic tests for ADHD. CONCLUSIONS: LWIR imaging demonstrated high sensitivity and specificity as a diagnostic tool for ADHD. These results provide evidence for the efficacy of a novel, quick, and effective way to investigate the physiological basis of one of the most prevalent childhood psychiatric disorders.

nCREANN: Nonlinear Causal Relationship Estimation by Artificial Neural Network; Applied for Autism Connectivity Study.

Quantifying causal (effective) interactions between different brain regions are very important in neuroscience research. Many conventional methods estimate effective connectivity based on linear models. However, using linear connectivity models may oversimplify the functions and dynamics of the brain. In this paper, we propose a causal relationship estimator called nonlinear Causal Relationship Estimation by Artificial Neural Network (nCREANN) that identifies both linear and nonlinear components of effective connectivity in the brain. Furthermore, it can distinguish between these two types of connectivity components by calculating the linear and nonlinear parts of the network input-output mapping. The nCREANN performance has been verified using synthesized data and then it has been applied on EEG data collected during rest in children with autism spectrum disorder (ASD) and typically developing (TD) children. The results show that overall linear connectivity in TD subjects is higher, while the nonlinear connectivity component is more dominant in ASDs. We suggest that our findings may represent different underlying neural activation dynamics in ASD and TD subjects. The results of nCREANN may provide new insight into the connectivity between the interactive brain regions.

Acute Gastrointestinal Hemorrhage due to Epstein-Barr Virus Colitis.

Epstein-Barr virus (EBV) is a member of the herpesvirus family that is associated with various disease manifestations, including EBV-associated colitis. There are few case reports describing hemorrhage associated with EBV colitis. We report a 61-year-old woman with acute gastrointestinal bleeding due to EBV colitis after initiation of methylprednisolone and enoxaparin for spinal cord infarction. To our knowledge, there are only a few case reports of hemorrhagic EBV colitis. Perhaps we need to have a higher suspicion for EBV in cases of colitis associated with hemorrhage even in relatively immunocompetent patients.

Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure.

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

Esophageal adenocarcinoma in a first-degree relative increases risk for esophageal adenocarcinoma in patients with Barrett's esophagus.

Background: The significance of a family history of esophageal adenocarcinoma in the progression to esophageal adenocarcinoma in patients with Barrett's esophagus has not been thoroughly evaluated. The purpose of this study is to evaluate the presence of esophageal adenocarcinoma in a first-degree relative in patients with Barrett's esophagus. Methods: A retrospective cohort study was conducted of patients with Barrett's esophagus at a tertiary care center undergoing radiofrequency ablation. Family history, demographics, and pathology and endoscopy reports were assessed in all patients. Findings: Three hundred and one patients with Barrett's esophagus were assessed. Nineteen patients who had a diagnosis of esophageal adenocarcinoma on index endoscopy were excluded. Nineteen (6.7%) patients had a first-degree relative with esophageal adenocarcinoma. Four (21.1%) of these patients progressed to esophageal adenocarcinoma. Of patients without first-degree relative with esophageal adenocarcinoma 22/263 (8.7%) progressed to esophageal adenocarcinoma. In a logistic regression model adjusted for sex and the number of radiofrequency ablation treatments, we found that family history of esophageal adenocarcinoma was a significant independent predictor of progression to esophageal adenocarcinoma (odds ratio = 5.55, 95% confidence interval: 1.47-20.0). Conclusion: Our study indicates that Barrett's esophagus patients with a first-degree family member with esophageal adenocarcinoma are at 5.5-fold higher risk for disease progression to esophageal adenocarcinoma. Family history of esophageal adenocarcinoma in Barrett's esophagus patients should be considered in patient surveillance and radiofrequency ablation treatment, beyond recommended guidelines.

EEG power and coherence in autistic spectrum disorder.

OBJECTIVE: Autistic spectrum disorder (ASD) has been defined as a neurodevelopmental disorder with associated deficits in executive function, language, emotional, and social function. ASD has been associated with pathophysiology in cerebral organization. The current study investigated quantitative EEG findings in twenty children diagnosed with autistic disorders as compared to 20 controls matched for gender, age and IQ. METHODS: The EEG was recorded during an eyes-closed resting condition and topographical differences in cerebral functioning were examined using estimates of absolute, relative, and total power, as well as intrahemispheric and interhemispheric coherences. RESULTS: There were group differences in power, intrahemispheric and interhemispheric coherences. Findings included excessive theta, primarily in right posterior regions, in autistics. There was also a pattern of deficient delta over the frontal cortex and excessive midline beta. More significantly, there was a pattern of underconnectivity in autistics compared to controls. This included decreased intrahemispheric delta and theta coherences across short to medium and long inter-electrode distances. Interhemispherically, delta and theta coherences were low across the frontal region. Delta, theta and alpha hypocoherence was also evident over the temporal regions. Lastly, there were low delta, theta and beta coherence measurements across posterior regions. CONCLUSIONS: These results suggest dysfunctional integration of frontal and posterior brain regions in autistics along with a pattern of neural underconnectivity. This is consistent with other EEG, MRI and fMRI research suggesting that neural connectivity anomalies are a major deficit leading to autistic symptomatology. SIGNIFICANCE: This paper reports the largest integrated study of EEG power and coherence during a resting state in children suffering autism spectrum disorder.

Four Channel Multivariate Coherence Training: Development and Evidence in Support of a New Form of Neurofeedback.

As the field of neurofeedback and neuromodulation grows, trends toward using neurofeedback to treat problems of brain dysfunction have emerged. While the use of connectivity based fMRI guided neurofeedback has shown itself to be efficacious, the expense related to the treatment calls for a more practical solution. The use of QEEG guided neurofeedback in the treatment has shown promise as an emerging treatment. To date, EEG based neurofeedback approaches have used technology with limited sophistication. We designed a new form of neurofeedback that uses four channels of EEG with a multivariate calculation of coherence metrics. Following a mathematical presentation of this model, we present findings of a multi-site study with clinical subjects with various diagnoses. We compared this form of multivariate coherence neurofeedback to the more standard two channel coherence training. Findings showed that there was a significant difference between the groups with four channel multivariate coherence neurofeedback leading to greater changes in EEG metrics. Compared to two channel coherence training, four channel multivariate coherence neurofeedback led to a greater than 50% change in power and 400% in coherence values per session. The significance of these findings is discussed in relation to complex calculations of effective connectivity and how this might lead to even greater enhancements in neurofeedback efficacy.

Update Treatment for HBV Infection and Persistent Risk for Hepatocellular Carcinoma: Prospect for an HBV Cure.

Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, its genome, sequence, epidemiology, and hepatocarcinogenesis have been elucidated. Globally, hepatitis B virus (HBV) is still responsible for the majority of hepatocellular carcinoma (HCC). HCC is the sixth-most common cancer in the world and the second-most common cancer death. The ultimate goal of treating HBV infection is the prevention of HCC. Fortunately, anti-HBV treatment with nucleos(t)ide analogues (NAs), which began with lamivudine in 1998, has resulted in remarkable improvements in the survival of patients with chronic hepatitis B and a reduced incidence of HCC. These results were documented with lamivudine, entecavir, and tenofovir. Nonetheless, as the duration of antiviral treatment increases, the risk for HCC still remains despite undetectable HBV DNA in serum, as reported by different investigators with observation up to 4⁻5 years. In our own experience, we are witnessing the development of HCC in patients who have received antiviral treatment. Some have enjoyed negative serum HBV DNA for over 12 years before developing HCC. Current treatment with NAs can effectively suppress the replication of the virus but cannot eradicate the covalently closed circular DNA (cccDNA) that is within the nucleus of hepatocytes. There still remains a great need for a cure for HBV. Fortunately, several compounds have been identified that have the potential to eradicate HBV, and there are ongoing clinical trials in progress in their early stages.