Down-Regulation of Tinnitus Negative Valence via Concurrent HD-tDCS and PEI Technique: A Pilot Study.

Around 30% of the general population experience subjective tinnitus, characterized by conscious attended awareness perception of sound without an external source. Clinical distress tinnitus is more than just experiencing a phantom sound, as it can be highly disruptive and debilitating, leading those affected to seek clinical help. Effective tinnitus treatments are crucial for psychological well-being, but our limited understanding of the underlying neural mechanisms and a lack of a universal cure necessitate further treatment development. In light of the neurofunctional tinnitus model predictions and transcranial electrical stimulation, we conducted an open-label, single-arm, pilot study that utilized high-definition transcranial direct current stimulation (HD-tDCS) concurrent with positive emotion induction (PEI) techniques for ten consecutive sessions to down-regulate tinnitus negative valence in patients with clinical distress tinnitus. We acquired resting-state functional magnetic resonance imaging scans of 12 tinnitus patients (7 females, mean age = 51.25 ± 12.90 years) before and after the intervention to examine resting-state functional connectivity (rsFC) alterations in specific seed regions. The results showed reduced rsFC at post-intervention between the attention and emotion processing regions as follows: (1) bilateral amygdala and left superior parietal lobule (SPL), (2) left amygdala and right SPL, (3) bilateral dorsolateral prefrontal cortex (dlPFC) and bilateral pregenual anterior cingulate cortex (pgACC), and (4) left dlPFC and bilateral pgACC (FWE corrected p < 0.05). Furthermore, the post-intervention tinnitus handicap inventory scores were significantly lower than the pre-intervention scores (p < 0.05). We concluded that concurrent HD-tDCS and PEI might be effective in reducing tinnitus negative valence, thus alleviating tinnitus distress.

Dose-Response Transcranial Electrical Stimulation Study Design: A Well-Controlled Adaptive Seamless Bayesian Method to Illuminate Negative Valence Role in Tinnitus Perception.

The use of transcranial Electrical Stimulation (tES) in the modulation of cognitive brain functions to improve neuropsychiatric conditions has extensively increased over the decades. tES techniques have also raised new challenges associated with study design, stimulation protocol, functional specificity, and dose-response relationship. In this paper, we addressed challenges through the emerging methodology to investigate the dose-response relationship of High Definition-transcranial Direct Current Stimulation (HD tDCS), identifying the role of negative valence in tinnitus perception. In light of the neurofunctional testable framework and tES application, hypotheses were formulated to measure clinical and surrogate endpoints. We posited that conscious pairing adequately pleasant stimuli with tinnitus perception results in correction of the loudness misperception and would be reinforced by concurrent active HD-tDCS on the left Dorsolateral Prefrontal Cortex (dlPFC). The dose-response relationship between HD-tDCS specificity and the loudness perception is also modeled. We conducted a double-blind, randomized crossover pilot study with six recruited tinnitus patients. Accrued data was utilized to design a well-controlled adaptive seamless Bayesian dose-response study. The sample size (n = 47, for 90% power and 95% confidence) and optimum interims were anticipated for adaptive decision-making about efficacy, safety, and single session dose parameters. Furthermore, preliminary pilot study results were sufficient to show a significant difference (90% power, 99% confidence) within the longitudinally detected self-report tinnitus loudness between before and under positive emotion induction. This study demonstrated a research methodology used to improve emotion regulation in tinnitus patients. In the projected method, positive emotion induction is essential for promoting functional targeting under HD-tDCS anatomical specificity to indicate the efficacy and facilitate the dose-finding process. The continuous updating of prior knowledge about efficacy and dose during the exploratory stage adapts the anticipated dose-response model. Consequently, the effective dose range to make superiority neuromodulation in correcting loudness misperception of tinnitus will be redefined. Highly effective dose adapts the study to a standard randomized trial and transforms it into the confirmatory stage in which active HD-tDCS protocol is compared with a sham trial (placebo-like). Establishing the HD-tDCS intervention protocols relying on this novel method provides reliable evidence for regulatory agencies to approve or reject the efficacy and safety. Furthermore, this paper supports a technical report for designing multimodality data-driven complementary investigations in emotion regulation, including EEG-driven neuro markers, Stroop-driven attention biases, and neuroimaging-driven brain network dynamics.

Analysis of Spatially Distributed Data in Internet of Things in the Environmental Context.

The Internet of Things consists of "things" made up of small sensors and actuators capable of interacting with the environment. The combination of devices with sensor networks and Internet access enables the communication between the physical world and cyberspace, enabling the development of solutions to many real-world problems. However, most existing applications are dedicated to solving a specific problem using only private sensor networks, which limits the actual capacity of the Internet of Things. In addition, these applications are concerned with the quality of service offered by the sensor network or the correct analysis method that can lead to inaccurate or irrelevant conclusions, which can cause significant harm for decision makers. In this context, we propose two systematic methods to analyze spatially distributed data Internet of Things. We show with the results that geostatistics and spatial statistics are more appropriate than classical statistics to do this analysis.

Robotic Kinematic measures of the arm in chronic Stroke: part 1 - Motor Recovery patterns from tDCS preceding intensive training.

BACKGROUND: Effectiveness of robotic therapy and transcranial direct current stimulation is conventionally assessed with clinical measures. Robotic metrics may be more objective and sensitive for measuring the efficacy of interventions on stroke survivor's motor recovery. This study investigated if robotic metrics detect a difference in outcomes, not seen in clinical measures, in a study of transcranial direct current stimulation (tDCS) preceding robotic therapy. Impact of impairment severity on intervention response was also analyzed to explore optimization of outcomes by targeting patient sub-groups. METHODS: This 2020 study analyzed data from a double-blind, sham-controlled, randomized multi-center trial conducted from 2012 to 2016, including a six-month follow-up. 82 volunteers with single chronic ischemic stroke and right hemiparesis received anodal tDCS or sham stimulation, prior to robotic therapy. Robotic therapy involved 1024 repetitions, alternating shoulder-elbow and wrist robots, for a total of 36 sessions. Shoulder-elbow and wrist kinematic and kinetic metrics were collected at admission, discharge, and follow-up. RESULTS: No difference was detected between the tDCS or sham stimulation groups in the analysis of robotic shoulder-elbow or wrist metrics. Significant improvements in all metrics were found for the combined group analysis. Novel wrist data showed smoothness significantly improved (P < ·001) while submovement number trended down, overlap increased, and interpeak interval decreased. Post-hoc analysis showed only patients with severe impairment demonstrated a significant difference in kinematics, greater for patients receiving sham stimulation. CONCLUSIONS: Robotic data confirmed results of clinical measures, showing intensive robotic therapy is beneficial, but no additional gain from tDCS. Patients with severe impairment did not benefit from the combined intervention. Wrist submovement characteristics showed a delayed pattern of motor recovery compared to the shoulder-elbow, relevant to intensive intervention-related recovery of upper extremity function in chronic stroke. TRIAL REGISTRATION: http://www.clinicaltrials.gov . Actual study start date September 2012. First registered on 15 November 2012. Retrospectively registered. Unique identifiers: NCT01726673 and NCT03562663 .

Influence of gender-related differences in transcranial direct current stimulation: A Computational Study.

Gender-related anatomical differences have been reported with respect to brain and cerebrospinal fluid. The cortical induced electric field (EF) in transcranial direct current stimulation (tDCS) depends both on the dose (electrode montage and applied current) and the individual anatomical details. Therefore in spite of fixed dose, one can expect gender-related differences to impact induced EF which in turn would influence tDCS outcome. The abundance of promise with tDCS in both research and clinical domains is also accompanied with variability in response. The in-constant induced cortical EF is one of the main contributors of this variability.The aim of this study is to quantify the effects of the gender-related morphological changes on tDCS induced cortical EF. MRI data were obtained for 10 healthy individuals (5 males: M1-M5 and 5 females: F1-F5) spanning ages 27-47 years. Finite element models derived from the individual MRI and simulating the classic left motor cortex-contralateral supraorbital (C3-SO) montage were used to predict the cortical EF. The percentage tissue volume were also determined to illustrate anatomical differences in the dataset considered.Findings indicate that induced EF is higher in female head models on an average than male head models across several metrics. While the average peak EF value in female head models was comparable to that of male head models, the mean and median values were 11.6% and 10% higher. On an individual basis, the highest peak value was observed in a female subject F3 (0.83 V/m) while the lowest peak value was observed in male subject M2 (0.34 V/m) -indicating a variation of ~2.4-fold across the dataset considered. The average gray matter percentage volume in females was 11.6% higher than in males. The average white matter percentage volume was 8.7% higher in females while negligible CSF percentage volume difference was noted across gender. The results of our study indicate gender-related differences in tDCS induced current flow and quantify the extent of this variation.

Manipulation of Human Verticality Using High-Definition Transcranial Direct Current Stimulation.

Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications. Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol. Methods: We designed three separate randomized, double-blind, crossover phase I clinical trials in different cohorts of healthy adults using the same stimulation protocol. The primary outcome measure for trial 1 was SVV; trial 2, weight-bearing asymmetry (WBA); and trial 3, electroencephalography power spectral density (EEG-PSD). The HD-tDCS montage comprised a single central, and 3 surround electrodes (HD-tDCS3x1) over the right TPJ. For each study, we tested 3x2 min HD-tDCS3x1 at 1, 2 and 3 mA; with anode center, cathode center, or sham stimulation, in random order across days. Results: We found significant SVV deviation relative to baseline, specific to the cathode center condition, with consistent direction and increasing with stimulation intensity. We further showed significant WBA with direction governed by stimulation polarity (cathode center, left asymmetry; anode center, right asymmetry). EEG-PSD in the gamma band was significantly increased at 3 mA under the cathode. Conclusions: The present series of studies provide converging evidence for focal neuromodulation that can modify physiology and have behavioral consequences with clinical potential.

Theoretical Tinnitus Framework: A Neurofunctional Model.

Subjective tinnitus is the conscious (attended) awareness perception of sound in the absence of an external source and can be classified as an auditory phantom perception. Earlier literature establishes three distinct states of conscious perception as unattended, attended, and attended awareness conscious perception. The current tinnitus development models depend on the role of external events congruently paired with the causal physical events that precipitate the phantom perception. We propose a novel Neurofunctional Tinnitus Model to indicate that the conscious (attended) awareness perception of phantom sound is essential in activating the cognitive-emotional value. The cognitive-emotional value plays a crucial role in governing attention allocation as well as developing annoyance within tinnitus clinical distress. Structurally, the Neurofunctional Tinnitus Model includes the peripheral auditory system, the thalamus, the limbic system, brainstem, basal ganglia, striatum, and the auditory along with prefrontal cortices. Functionally, we assume the model includes presence of continuous or intermittent abnormal signals at the peripheral auditory system or midbrain auditory paths. Depending on the availability of attentional resources, the signals may or may not be perceived. The cognitive valuation process strengthens the lateral-inhibition and noise canceling mechanisms in the mid-brain, which leads to the cessation of sound perception and renders the signal evaluation irrelevant. However, the "sourceless" sound is eventually perceived and can be cognitively interpreted as suspicious or an indication of a disease in which the cortical top-down processes weaken the noise canceling effects. This results in an increase in cognitive and emotional negative reactions such as depression and anxiety. The negative or positive cognitive-emotional feedbacks within the top-down approach may have no relation to the previous experience of the patients. They can also be associated with aversive stimuli similar to abnormal neural activity in generating the phantom sound. Cognitive and emotional reactions depend on general personality biases toward evaluative conditioning combined with a cognitive-emotional negative appraisal of stimuli such as the case of people with present hypochondria. We acknowledge that the projected Neurofunctional Tinnitus Model does not cover all tinnitus variations and patients. To support our model, we present evidence from several studies using neuroimaging, electrophysiology, brain lesion, and behavioral techniques.

A GPU-Based Implementation of the Firefly Algorithm for Variable Selection in Multivariate Calibration Problems.

Several variable selection algorithms in multivariate calibration can be accelerated using Graphics Processing Units (GPU). Among these algorithms, the Firefly Algorithm (FA) is a recent proposed metaheuristic that may be used for variable selection. This paper presents a GPU-based FA (FA-MLR) with multiobjective formulation for variable selection in multivariate calibration problems and compares it with some traditional sequential algorithms in the literature. The advantage of the proposed implementation is demonstrated in an example involving a relatively large number of variables. The results showed that the FA-MLR, in comparison with the traditional algorithms is a more suitable choice and a relevant contribution for the variable selection problem. Additionally, the results also demonstrated that the FA-MLR performed in a GPU can be five times faster than its sequential implementation.

WeFold: a coopetition for protein structure prediction.

The protein structure prediction problem continues to elude scientists. Despite the introduction of many methods, only modest gains were made over the last decade for certain classes of prediction targets. To address this challenge, a social-media based worldwide collaborative effort, named WeFold, was undertaken by 13 labs. During the collaboration, the laboratories were simultaneously competing with each other. Here, we present the first attempt at "coopetition" in scientific research applied to the protein structure prediction and refinement problems. The coopetition was possible by allowing the participating labs to contribute different components of their protein structure prediction pipelines and create new hybrid pipelines that they tested during CASP10. This manuscript describes both successes and areas needing improvement as identified throughout the first WeFold experiment and discusses the efforts that are underway to advance this initiative. A footprint of all contributions and structures are publicly accessible at http://www.wefold.org.

Ant-Based Phylogenetic Reconstruction (ABPR): A new distance algorithm for phylogenetic estimation based on ant colony optimization

We propose a new distance algorithm for phylogenetic estimation based on Ant Colony Optimization (ACO), named Ant-Based Phylogenetic Reconstruction (ABPR). ABPR joins two taxa iteratively based on evolutionary distance among sequences, while also accounting for the quality of the phylogenetic tree built according to the total length of the tree. Similar to optimization algorithms for phylogenetic estimation, the algorithm allows exploration of a larger set of nearly optimal solutions. We applied the algorithm to four empirical data sets of mitochondrial DNA ranging from 12 to 186 sequences, and from 898 to 16,608 base pairs, and covering taxonomic levels from populations to orders. We show that ABPR performs better than the commonly used Neighbor-Joining algorithm, except when sequences are too closely related (e.g., population-level sequences). The phylogenetic relationships recovered at and above species level by ABPR agree with conventional views. However, like other algorithms of phylogenetic estimation, the proposed algorithm failed to recover expected relationships when distances are too similar or when rates of evolution are very variable, leading to the problem of long-branch attraction. ABPR, as well as other ACO-based algorithms, is emerging as a fast and accurate alternative method of phylogenetic estimation for large data sets.