Hyperbaric oxygen therapy in children with post-concussion syndrome improves cognitive and behavioral function: a randomized controlled trial.

Persistent post-concussion syndrome (PPCS) is a common and significant morbidity among children following traumatic brain injury (TBI) and the evidence for effective PPCS treatments remains limited. Recent studies have shown the beneficial effects of hyperbaric oxygen therapy (HBOT) in PPCS adult patients. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT) on children (age 8-15) suffering from PPCS from mild-moderate TBI events six months to 10 years prior. Twenty-five children were randomized to receive 60 daily sessions of HBOT (n = 15) or sham (n = 10) treatments. Following HBOT, there was a significant increase in cognitive function including the general cognitive score (d = 0.598, p = 0.01), memory (d = 0.480, p = 0.02), executive function (d = 0.739, p = 0.003), PPCS symptoms including emotional score (p = 0.04, d = - 0.676), behavioral symptoms including hyperactivity (d = 0.244, p = 0.03), global executive composite score (d = 0.528, p = 0.001), planning/organizing score (d = 1.09, p = 0.007). Clinical outcomes correlated with significant improvements in brain MRI microstructural changes in the insula, supramarginal, lingual, inferior frontal and fusiform gyri. The study suggests that HBOT improves both cognitive and behavioral function, PPCS symptoms, and quality of life in pediatric PPCS patients at the chronic stage, even years after injury. Additional data is needed to optimize the protocol and to characterize the children who can benefit the most.

Brain Network Integrity Changes in Subjective Cognitive Decline: A Possible Physiological Biomarker of Dementia.

Objective: The current study seeks to illustrate potential early and objective neurophysiological biomarkers of neurodegenerative cognitive decline by evaluating features of brain network physiological performance and structure utilizing different modalities. Methods: This study included 17 clinically healthy individuals with self-reported cognitive decline (Subjective Cognitive Decline group, SCD, no objective finding of cognitive decline), 12 individuals diagnosed with amnestic Mild Cognitive Impairment (aMCI), 11 individuals diagnosed with Dementia, and 15 healthy subjects. All subjects underwent computerized cognitive performance testing, MRI scans including T1 for gray matter (GM) volume quantification, DTI for quantification of white matter (WM) microstructure fractional anisotropy (FA) and mean diffusivity (MD), and brain network function evaluation using DELPHI (TMS-EEG) measures of connectivity, excitability, and plasticity. Results: Both DELPHI analysis of network function and DTI analysis detected a significant decrease in connectivity, excitability, and WM integrity in the SCD group compared to healthy control (HC) subjects; a significant decrease was also noted for aMCI and Dementia groups compared to HC. In contrast, no significant decrease was observed in GM volume in the SCD group compared to healthy norms, a significant GM volume decrease was observed only in objectively cognitively impaired aMCI subjects and in dementia subjects. Conclusions: This study results suggest that objective direct measures of brain network physiology and WM integrity may provide early-stage biomarkers of neurodegenerative-related changes in subjects that have not yet displayed any other objective measurable cognitive or GM volume deficits which may facilitate early preventive care for neurodegenerative decline and dementia.

Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals.

Cognition is a crucial element of human functionality. Like any other physical capability, cognition is both enabled and limited by tissue biology. The aim of this study was to investigate whether oxygen is a rate-limiting factor for any of the main cognitive domains in healthy young individuals. Fifty-six subjects were randomly assigned to either increased oxygen supply using hyperbaric oxygen (two atmospheres of 100% oxygen) or to a "sham" treatment (a simulation of increased pressure in a chamber with normal air). While in the chamber, participants went through a battery of tests evaluating the major cognitive domains including information processing speed, episodic memory, working memory, cognitive flexibility, and attention. The results demonstrated that from all evaluated cognitive domains, a statistically significant improvement was found in the episodic memory of the hyper-oxygenized group. The hyper-oxygenized group demonstrated a better learning curve and a higher resilience to interference. To conclude, oxygen delivery is a rate-limiting factor for memory function even in healthy young individuals under normal conditions. Understanding the biological limitations of our cognitive functions is important for future development of interventional tools that can be used in daily clinical practice.

Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial.

More than half of community-dwelling individuals sixty years and older express concern about declining cognitive abilities. The current study's aim was to evaluate hyperbaric oxygen therapy (HBOT) effect on cognitive functions in healthy aging adults.A randomized controlled clinical trial randomized 63 healthy adults (>64) either to HBOT(n=33) or control arms(n=30) for three months. Primary endpoint included the general cognitive function measured post intervention/control. Cerebral blood flow (CBF) was evaluated by perfusion magnetic resonance imaging.There was a significant group-by-time interaction in global cognitive function post-HBOT compared to control (p=0.0017). The most striking improvements were in attention (net effect size=0.745) and information processing speed (net effect size=0.788).Voxel-based analysis showed significant cerebral blood flow increases in the HBOT group compared to the control group in the right superior medial frontal gyrus (BA10), right and left supplementary motor area (BA6), right middle frontal gyrus (BA6), left middle frontal gyrus (BA9), left superior frontal gyrus (BA8) and the right superior parietal gyrus (BA7).In this study, HBOT was shown to induce cognitive enhancements in healthy aging adults via mechanisms involving regional changes in CBF. The main improvements include attention, information processing speed and executive functions, which normally decline with aging.

Hyperbaric oxygen therapy improves neurocognitive functions of post-stroke patients - a retrospective analysis.

BACKGROUND: Previous studies have shown that hyperbaric oxygen therapy (HBOT) can improve the motor functions and memory of post-stroke patients in the chronic stage. OBJECTIVE: The aim of this study is to evaluate the effects of HBOT on overall cognitive functions of post-stroke patients in the chronic stage. The nature, type and location of the stroke were investigated as possible modifiers. METHODS: A retrospective analysis was conducted on patients who were treated with HBOT for chronic stroke (>3 months) between 2008-2018. Participants were treated in a multi-place hyperbaric chamber with the following protocols: 40 to 60 daily sessions, 5 days per week, each session included 90 min of 100% oxygen at 2 ATA with 5 min air brakes every 20 minutes. Clinically significant improvements (CSI) were defined as > 0.5 standard deviation (SD). RESULTS: The study included 162 patients (75.3% males) with a mean age of 60.75±12.91. Of them, 77(47.53%) had cortical strokes, 87(53.7%) strokes were located in the left hemisphere and 121 suffered ischemic strokes (74.6%).HBOT induced a significant increase in all the cognitive function domains (p < 0.05), with 86% of the stroke victims achieving CSI. There were no significant differences post-HBOT of cortical strokes compared to sub-cortical strokes (p > 0.05). Hemorrhagic strokes had a significantly higher improvement in information processing speed post-HBOT (p < 0.05). Left hemisphere strokes had a higher increase in the motor domain (p < 0.05). In all cognitive domains, the baseline cognitive function was a significant predictor of CSI (p < 0.05), while stroke type, location and side were not significant predictors. CONCLUSIONS: HBOT induces significant improvements in all cognitive domains even in the late chronic stage. The selection of post-stroke patients for HBOT should be based on functional analysis and baseline cognitive scores rather than the stroke type, location or side of lesion.

Differences in Semantic Memory Encoding Strategies in Young, Healthy Old and MCI Patients.

Associative processes, such as the encoding of associations between words in a list, can enhance episodic memory performance and are thought to deteriorate with age. Here, we examine the nature of age-related deficits in the encoding of associations, by using a free recall paradigm with visual arrays of objects. Fifty-five participants (26 young students; 20 cognitive healthy older adults; nine patients with Mild Cognitive Impairment, MCI) were shown multiple slides (experimental trials), each containing an array of nine common objects for recall. Most of the arrays contained three objects from three semantic categories, each. In the remaining arrays, the nine objects were unrelated. Eye fixations were also monitored during the viewing of the arrays, in a subset of the participants. While for young participants the immediate recall was higher for the semantically related arrays, this effect was diminished in healthy elderly and totally absent in MCI patients. Furthermore, only in the young group did the sequence of eye fixations show a semantic scanning pattern during encoding, even when the related objects were non- adjacent in the array. Healthy elderly and MCI patients were not influenced by the semantic relatedness of items during the array encoding, to the same extent as young subjects, as observed by a lack of (or reduced) semantic scanning. The results support a version of the encoding of the association aging-deficit hypothesis.

Introducing a Novel Approach for Evaluation and Monitoring of Brain Health Across Life Span Using Direct Non-invasive Brain Network Electrophysiology.

OBJECTIVE: Evaluation and monitoring of brain health throughout aging by direct electrophysiological imaging (DELPHI) which analyzes TMS (transcranial magnetic stimulation) evoked potentials. METHODS: Transcranial magnetic stimulation evoked potentials formation, coherence and history dependency, measured using electroencephalogram (EEG), was extracted from 80 healthy subjects in different age groups, 25-85 years old, and 20 subjects diagnosed with mild dementia (MD), over 70 years old. Subjects brain health was evaluated using MRI scans, neurocognitive evaluation, and computerized testing and compared to DELPHI analysis of brain network functionality. RESULTS: A significant decrease in signal coherence is observed with age in connectivity maps, mostly in inter-hemispheric temporal, and parietal areas. MD patients display a pronounced decrease in global and inter-hemispheric frontal connectivity compared to healthy controls. Early and late signal slope ratio also display a significant, age dependent, change with pronounced early slope, phase shift, between normal healthy aging, and MD. History dependent analysis demonstrates a binary step function classification of healthy brain vs. abnormal aging subjects mostly for late slope. DELPHI measures demonstrate high reproducibility with reliability coefficients of around 0.9. CONCLUSION: These results indicate that features of evoked response, as charge transfer, slopes of response, and plasticity are altered during abnormal aging and that these fundamental properties of network functionality can be directly evaluated and monitored using DELPHI.

Effects of Hyperbaric Oxygen Therapy on Brain Perfusion, Cognition and Behavior in Fetal Alcohol Spectrum Disorder-A Case Study.

A 15-year-old girl diagnosed with FASD underwent 100 courses of hyperbasic oxygen therapy (HBOT). Prior to HBOT, single motion emission compute tomographic begin imaging (SPECT) revealed areas of hypo-perfusion bilaterally in the orbitofrontal region, temporal lobes and right dorsolateral-frontal, as well the medial aspect of the left cerebellum. Following two sets of HBOT treatments (60 plus 40), over 6 months, there was improvement in perfusion to the left cerebellum as well as the right frontal lobe. This was paralleled by improvement in immediate cognitive tests and an increase in functional brain volume. A follow-up 18 months after HBOT showed sustained improvement in attention with no need for methylphenidate, as well as in math skills and writing.

Effect of hyperbaric oxygen therapy on chronic neurocognitive deficits of post-traumatic brain injury patients: retrospective analysis.

OBJECTIVES: The aim of the study is to evaluate the effect of hyperbaric oxygen therapy (HBOT) in participants suffering from chronic neurological deficits due to traumatic brain injury (TBI) of all severities in the largest cohort evaluated so far with objective cognitive function tests and metabolic brain imaging. METHODS: A retrospective analysis was conducted of 154 patients suffering from chronic neurocognitive damage due to TBI, who had undergone computerised cognitive evaluations pre-HBOT and post-HBOT treatment. RESULTS: The average age was 42.7±14.6 years, and 58.4% were men. All patients had documented TBI 0.3-33 years (mean 4.6±5.8, median 2.75 years) prior to HBOT. HBOT was associated with significant improvement in all of the cognitive domains, with a mean change in global cognitive scores of 4.6±8.5 (p<0.00001). The most prominent improvements were in memory index and attention, with mean changes of 8.1±16.9 (p<0.00001) and 6.8±16.5 (p<0.0001), respectively. The most striking changes observed in brain single photon emission computed tomography images were in the anterior cingulate and the postcentral cortex, in the prefrontal areas and in the temporal areas. CONCLUSIONS: In the largest published cohort of patients suffering from chronic deficits post-TBI of all severities, HBOT was associated with significant cognitive improvements. The clinical improvements were well correlated with increased activity in the relevant brain areas.

Recovery of Repressed Memories in Fibromyalgia Patients Treated With Hyperbaric Oxygen - Case Series Presentation and Suggested Bio-Psycho-Social Mechanism.

Fibromyalgia Syndrome (FMS) is a condition considered to represent a prototype of central sensitization syndrome, characterized by chronic widespread pain and along with symptoms of fatigue, non-restorative sleep and cognitive difficulties. FMS can be induced by trauma, infection or emotional stress with cumulative evidence that dissociation is relatively frequent in FMS patients. Two randomized controlled trials have shown that hyperbaric oxygen therapy (HBOT) can induce neuroplasticity and be effective in patients suffering from FMS. In this paper we present, for the first time, case series of female fibromyalgia patients who, in the course of HBOT, suddenly recalled repressed traumatic memories of childhood sexual abuse (CSA). The surfacing of the repressed (dissociative) memories decades after the sexual abuse events was sudden and utterly surprising. No psychological intervention was involved. As the memories surfaced, the physical pain related to FMS subsided. In one patient who had brain single photon emission CT (SPECT) before and after HBOT, the prefrontal cortex appeared suppressed before and reactivated after. The 3 cases reported in this article are representative of a total of nine fibromyalgia patients who experienced a retrieval of repressed memory during HBOT. These cases provide insights on dissociative amnesia and suggested mechanism hypothesis that is further discussed in the article. Obviously, prospective studies cannot be planned since patients are not aware of their repressed memories. However, it is very important to keep in mind the possibility of surfacing memories when treating fibromyalgia patients with HBOT or other interventions capable of awakening dormant brain regions.

[HYPERBARIC OXYGEN THERAPY- BASICS AND NEW APPLICATIONS].

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) serves as primary or adjunctive therapy for a diverse range of medical conditions. The indication for HBOT can be related to either pressure (decompression sickness or air emboli) or tissue hypoxia. It is now realized, that the combined action of hyperoxia and hyperbaric pressure, leads to significant improvement in tissue oxygenation while targeting both oxygen and pressure sensitive genes, resulting in improved mitochondrial metabolism with anti-apoptotic and anti-inflammatory effects. Clinical studies published in recent year's present convincing evidence that HBOT can be the coveted neurotherapeutic method for brain repair. Here we discuss the multi-faceted role of HBOT in wound care in general and in neurotherapeutics in detail. The recent evidence for HBOT efficacy in brain repair and the new understanding of brain energy management and response to damage opens new therapeutically fields that will be further investigated in the upcoming years.

Hyperbaric Oxygen Therapy Can Induce Angiogenesis and Regeneration of Nerve Fibers in Traumatic Brain Injury Patients.

Background: Recent clinical studies in stroke and traumatic brain injury (TBI) victims suffering chronic neurological injury present evidence that hyperbaric oxygen therapy (HBOT) can induce neuroplasticity. Objective: To assess the neurotherapeutic effect of HBOT on prolonged post-concussion syndrome (PPCS) due to TBI, using brain microstructure imaging. Methods: Fifteen patients afflicted with PPCS were treated with 60 daily HBOT sessions. Imaging evaluation was performed using Dynamic Susceptibility Contrast-Enhanced (DSC) and Diffusion Tensor Imaging (DTI) MR sequences. Cognitive evaluation was performed by an objective computerized battery (NeuroTrax). Results: HBOT was initiated 6 months to 27 years (10.3 ± 3.2 years) from injury. After HBOT, DTI analysis showed significantly increased fractional anisotropy values and decreased mean diffusivity in both white and gray matter structures. In addition, the cerebral blood flow and volume were increased significantly. Clinically, HBOT induced significant improvement in the memory, executive functions, information processing speed and global cognitive scores. Conclusions: The mechanisms by which HBOT induces brain neuroplasticity can be demonstrated by highly sensitive MRI techniques of DSC and DTI. HBOT can induce cerebral angiogenesis and improve both white and gray microstructures indicating regeneration of nerve fibers. The micro structural changes correlate with the neurocognitive improvements.