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Background: Ozone therapy has been utilized for over a hundred years for multiple indications, one of which is knee osteoarthritis. The current study compared the effect of ozone injections versus the current standard of care (corticosteroid injections) on knee pain. The study focuses on pain reduction, functionality, and quality of life. Methods: In this temporally stratified, single-blinded, controlled clinical trial, 40 patients with symptomatic knee osteoarthritis (OA) were stratified into two groups receiving intra-articular 30 μg/ml of ozone (OZ) or steroids (GS) for 3 weeks. The efficacy outcomes for knee OA were the Visual Analogue Scale (VAS), SF-12 KOOS. Patients were followed up for up to 6 months. Results: After 6 weeks from first injection, VAS score in the ozone group declined more than in the corticosteroid injection [mean inter group difference (MD) = 1.5±0.6, p < 0.05 (CI 95% 0.2–2.7)]. Maximal difference between the groups was observed at 12 weeks [mean difference (MD) = 3.9, p < 0.01 (CI 95% 2–5.2)]. The OZ group superiority was maintained at 24 weeks as well [mean difference (MD) = 2.8, p < 0.05 (CI 95% 2–4.8)]. KOOS pain subscale followed a similar trend with maximal difference between the groups at 12 weeks [mean difference (MD) = 18, p < 0.01 (CI 95% 8–32)]. SF-12 (PCS) in the OZ group was similar between groups at BL but was significantly higher at 6 to 24 weeks [(maximal mean difference at 12 weeks = 14, p < 0.01 (CI 95% 10-32)], SF-12 (MCS) was similar in both groups at all timepoints [no statistically significant difference]. At 6 months results were similar in both groups. Conclusions: In all criteria, including pain relief, functionality, and quality of life, the efficacy of ozone was confirmed.

Introduction: Hypertension affects nearly half of adults in the U.S. and is more prevalent in non-Hispanic black and Hispanic people than other groups. HEDIS now includes blood pressure readings from remote monitoring devices that are digitally stored and transmitted to the provider. Digital interventions used to support self-management of hypertension are effective in reducing blood pressure. Healthcare policies that support adoption of innovative digital interventions can positively impact groups with greater health disparities. Hypothesis: We tested the hypothesis that systolic blood pressure (SBP) change observed after 6 months in a smartphone-based hypertension self-management program would demonstrate similar outcomes across subgroups and not be impacted by known health inequities based on sex, language or race. Methods: A cohort study of individuals who enrolled in a digital-only hypertension self-management program without live coaching was used to evaluate SBP change at 6 months and its association with age, sex, language (English/Spanish), and race. Because race information was only available in a subset of the cohort who shared electronic medical records, the largest sub-groups (432 white and 127 non-Hispanic black adults) were compared. Results: 15,361 (age 57 ± .8y, 37% female) people uploaded SBP data at both time points. A reduction in SBP was observed (t = 15.1, p .05). Females had a greater reduction in SBP than males (1.5 ± 0.19 mm Hg, p Conclusions: This study supports the use of a smartphone-based hypertension program incorporating AI driven, digital-only self-management and lifestyle coaching to reduce SBP similarly across age, race, and preferred language groups. Results indicate that digital self-management tools have the potential to bridge health inequity gaps. Future studies could assess whether digital behavioral change coaching leads to reduced SBP across disadvantaged groups based on Area of Deprivation Index (ADI).

Resolving approach-avoidance conflicts relies on encoding motivation outcomes and learning from past experiences. Accumulating evidence points to the role of the Medial Temporal Lobe (MTL) and Medial Prefrontal Cortex (mPFC) in these processes, but their differential contributions have not been convincingly deciphered in humans. We detect 310 neurons from mPFC and MTL from patients with epilepsy undergoing intracranial recordings and participating in a goal-conflict task where rewards and punishments could be controlled or not. mPFC neurons are more selective to punishments than rewards when controlled. However, only MTL firing following punishment is linked to a lower probability for subsequent approach behavior. mPFC response to punishment precedes a similar MTL response and affects subsequent behavior via an interaction with MTL firing. We thus propose a model where approach-avoidance conflict resolution in humans depends on outcome value tagging in mPFC neurons influencing encoding of such value in MTL to affect subsequent choice., Optimizing approach-avoidance behavior calls for neural encoding of related motivation outcomes. Here, the authors show that behavioral choice under conflict relies on differential neuronal firing patterns after punishment, in which mPFC neurons decode the outcome’s value and MTL neurons follow by reducing subsequent approach.

OBJECTIVEPreoperative localization of seizure onset zones (SOZs) is an evolving field in the treatment of refractory epilepsy. Both magnetic source imaging (MSI), and the more recent EEG-correlated functional MRI (EEG-fMRI), have shown applicability in assisting surgical planning. The purpose of this study was to evaluate the capability of each method and their combination in localizing the seizure onset lobe (SL).METHODSThe study included 14 patients who underwent both MSI and EEG-fMRI before undergoing implantation of intracranial EEG (icEEG) as part of the presurgical planning of the resection of an epileptogenic zone (EZ) during the years 2012–2018. The estimated location of the SL by each method was compared with the location determined by icEEG. Identification rates of the SL were compared between the different methods.RESULTSMSI and EEG-fMRI showed similar identification rates of SL locations in relation to icEEG results (88% ± 31% and 73% ± 42%, respectively; p = 0.281). The additive use of the coverage lobes of both methods correctly identified 100% of the SL, significantly higher than EEG-fMRI alone (p = 0.039) and nonsignificantly higher than MSI (p = 0.180). False-identification rates of the additive coverage lobes were significantly higher than MSI (p = 0.026) and EEG-fMRI (p = 0.027). The intersecting lobes of both methods showed the lowest false identification rate (13% ± 6%, p = 0.01).CONCLUSIONSBoth MSI and EEG-fMRI can assist in the presurgical evaluation of patients with refractory epilepsy. The additive use of both tests confers a high identification rate in finding the SL. This combination can help in focusing implantation of icEEG electrodes targeting the SOZ.

Objective: Although simultaneous recording of EEG and MRI has gained increasing popularity in recent years, the extent of its clinical use remains limited by various technical challenges. Motion interference is one of the major challenges in EEG-fMRI. Here we present an approach which reduces its impact with the aid of an MR compatible dual-array EEG (daEEG) in which the EEG itself is used both as a brain signal recorder and a motion sensor. Methods: We implemented two arrays of EEG electrodes organized into two sets of nearly orthogonally intersecting wire bundles. The EEG was recorded using referential amplifiers inside a 3 T MR-scanner. Virtual bipolar measurements were taken both along bundles (creating a small wire loop and therefore minimizing artifact) and across bundles (creating a large wire loop and therefore maximizing artifact). Independent component analysis (ICA) was applied. The resulting ICA components were classified into brain signal and noise using three criteria: 1) degree of two-dimensional spatial correlation between ICA coefficients along bundles and across bundles; 2) amplitude along bundles vs. across bundles; 3) correlation with ECG. The components which passed the criteria set were transformed back to the channel space. Motion artifact suppression and the ability to detect interictal epileptic spikes following daEEG and Optimal Basis Set (OBS) procedures were compared in 10 patients with epilepsy. Results: The SNR achieved by daEEG was 11.05 +/- 3.10 and by OBS was 8.25 +/- 1.01 (p

OBJECTIVE Providing a reliable assessment of language lateralization is an important task to be performed prior to neurosurgery in patients with epilepsy. Over the last decade, functional MRI (fMRI) has emerged as a useful noninvasive tool for language lateralization, supplementing or replacing traditional invasive methods. In standard practice, fMRI-based language lateralization is assessed qualitatively by visual inspection of fMRI maps at a specific chosen activation threshold. The purpose of this study was to develop and evaluate a new computational technique for providing the probability of each patient to be left, right, or bilateral dominant in language processing. METHODS In 76 patients with epilepsy, a language lateralization index was calculated using the verb-generation fMRI task over a wide range of activation thresholds (from a permissive threshold, analyzing all brain regions, to a harsh threshold, analyzing only the strongest activations). The data were classified using a probabilistic logistic regression method. RESULTS Concordant results between fMRI and Wada lateralization were observed in 89% of patients. Bilateral and right-dominant groups showed similar fMRI lateralization patterns differentiating them from the left-dominant group but still allowing classification in 82% of patients. CONCLUSIONS These findings present the utility of a semi-supervised probabilistic learning approach for presurgical language-dominance mapping, which may be extended to other cognitive domains such as memory and attention.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task. Behaviorally, both conflict detection and adaptation to conflict were evident. The firing rate of neurons in the vACC represented current conflict, i.e., current-congruency. The late onset of the effect is compatible with a role in monitoring. Additionally, early responses of some neurons represented the immediate history of conflicts, i.e., previous-trial-congruency. Finally, in some neurons the response to the current-trial was modulated by previous-trial-congruency, laying the ground for adjusting-to-conflicts. Our results uncover a single neuron level mechanism in the vACC that encodes and integrates past and present emotional conflicts, allowing humans to accommodate their responses accordingly.

OBJECTIVEResection of intraaxial tumors adjacent to the optic radiation (OR) may be associated with postoperative visual field (VF) deficits. Intraoperative navigation using MRI-based tractography and electrophysiological monitoring of the visual pathways may allow maximal resection while preserving visual function. In this study, the authors evaluated the value of visual pathway mapping in a series of patients undergoing awake craniotomy for tumor resection.METHODSA retrospective analysis of prospectively collected data was conducted in 18 patients who underwent an awake craniotomy for resection of intraaxial tumors involving or adjacent to the OR. Preoperative MRI-based tractography was used for intraoperative navigation, and intraoperative acquisition of 3D ultrasonography images was performed for real-time imaging and correction of brain shift. Goggles with light-emitting diodes were used as a standard visual stimulus. Direct cortical visual evoked potential (VEP) recording, subcortical recordings from the OR, and subcortical stimulation of the OR were used intraoperatively to assess visual function and proximity of the lesion to the OR. VFs were assessed pre- and postoperatively.RESULTSBaseline cortical VEP recordings were available for 14 patients (77.7%). No association was found between preoperative VF status and baseline presence of cortical VEPs (p = 0.27). Five of the 14 patients (35.7%) who underwent subcortical stimulation of the OR reported seeing phosphenes in the corresponding contralateral VF. There was a positive correlation (r = 0.899, p = 0.04) between the subcortical threshold stimulation intensity (3–11.5 mA) and the distance from the OR. Subcortical recordings from the OR demonstrated a typical VEP waveform in 10 of the 13 evaluated patients (76.9%). These waveforms were present only when recordings were obtained within 10 mm of the OR (p = 0.04). Seven patients (38.9%) had postoperative VF deterioration, and it was associated with a length of < 8 mm between the tumor and the OR (p = 0.05).CONCLUSIONSIntraoperative electrophysiological monitoring of the visual pathways is feasible but may be of limited value in preserving the functional integrity of the posterior visual pathways. Subcortical stimulation of the OR may identify the location of the OR when done in proximity to the pathways, but such proximity may be associated with increased risk of postoperative worsening of the VF deficit.

Invasive brain–computer interfaces (BCI) provide better signal quality in terms of spatial localization, frequencies and signal/noise ratio, in addition to giving access to deep brain regions that play important roles in cognitive or affective processes. Despite some anecdotal attempts, little work has explored the possibility of integrating such BCI input into more sophisticated interactive systems like those which can be developed with game engines. In this article, we integrated an amygdala depth electrode recorder with a virtual environment controlling a virtual crowd. Subjects were asked to down regulate their amygdala using the level of unrest in the virtual room as feedback on how successful they were. We report early results which suggest that users adapt very easily to this paradigm and that the timing and fluctuations of amygdala activity during self-regulation can be matched by crowd animation in the virtual room. This suggests that depth electrodes could also serve as high-performance affective interfaces, notwithstanding their strictly limited availability, justified on medical grounds only.

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

Head movements during an MEG recording are commonly considered an obstacle. In this computer simulation study, we introduce an approach, the virtual MEG helmet (VMH), which employs the head movements for data quality improvement. With a VMH, a denser MEG helmet is constructed by adding new sensors corresponding to different head positions. Based on the Shannon's theory of communication, we calculated the total information as a figure of merit for comparing the actual 306-sensor Elekta Neuromag helmet to several types of the VMH. As source models, we used simulated randomly distributed source current (RDSC), simulated auditory and somatosensory evoked fields. Using the RDSC model with the simulation of 360 recorded events, the total information (bits/sample) was 989 for the most informative single head position and up to 1272 for the VMH (addition of 28.6%). Using simulated AEFs, the additional contribution of a VMH was 12.6% and using simulated SEF only 1.1%. For the distributed and bilateral sources, a VMH can provide a more informative sampling of the neuromagnetic field during the same recording time than measuring the MEG from one head position. VMH can, in some situations, improve source localization of the neuromagnetic fields related to the normal and pathological brain activity. This should be investigated further employing real MEG recordings.