Transcranial Photobiomodulation Treatment: Significant Improvements in Four Ex-Football Players with Possible Chronic Traumatic Encephalopathy.

Background: Chronic traumatic encephalopathy, diagnosed postmortem (hyperphosphorylated tau), is preceded by traumatic encephalopathy syndrome with worsening cognition and behavior/mood disturbances, over years. Transcranial photobiomodulation (tPBM) may promote improvements by increasing ATP in compromised/stressed cells and increasing local blood, lymphatic vessel vasodilation. Objective: Aim 1: Examine cognition, behavior/mood changes Post-tPBM. Aim 2: MRI changes - resting-state functional-connectivity MRI: salience, central executive, default mode networks (SN, CEN, DMN); magnetic resonance spectroscopy, cingulate cortex. Methods: Four ex-players with traumatic encephalopathy syndrome/possible chronic traumatic encephalopathy, playing 11- 16 years, received In-office, red/near-infrared tPBM to scalp, 3x/week for 6 weeks. Two had cavum septum pellucidum. Results: The three younger cases (ages 55, 57, 65) improved 2 SD (p < 0.05) on three to six neuropsychological tests/subtests at 1 week or 1 month Post-tPBM, compared to Pre-Treatment, while the older case (age 74) improved by 1.5 SD on three tests. There was significant improvement at 1 month on post-traumatic stress disorder (PTSD), depression, pain, and sleep. One case discontinued narcotic pain medications and had reduced tinnitus. The possible placebo effect is unknown. At 2 months Post-tPBM, two cases regressed. Then, home tPBM was applied to only cortical nodes, DMN (12 weeks); again, significant improvements were seen. Significant correlations for increased SN functional connectivity (FC) over time, with executive function, attention, PTSD, pain, and sleep; and CEN FC, with verbal learning/memory, depression. Increased n-acetyl-aspartate (NAA) (oxygen consumption, mitochondria) was present in anterior cingulate cortex (ACC), parallel to less pain and PTSD. Conclusion: After tPBM, these ex-football players improved. Significant correlations of increased SN FC and CEN FC with specific cognitive tests and behavior/mood ratings, plus increased NAA in ACC support beneficial effects from tPBM.

Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury.

OBJECTIVE: We review the general topic of traumatic brain injury (TBI) and our research utilizing transcranial photobiomodulation (tPBM) to improve cognition in chronic TBI using red/near-infrared (NIR) light-emitting diodes (LEDs) to deliver light to the head. tPBM improves mitochondrial function increasing oxygen consumption, production of adenosine triphosphate (ATP), and improving cellular energy stores. Nitric oxide is released from the cells increasing regional blood flow in the brain. Review of published studies: In our previously published study, 11 chronic TBI patients with closed-head TBI caused by different accidents (motor vehicle accident, sports-related, improvised explosive device blast injury) and exhibiting long-lasting cognitive dysfunction received 18 outpatient treatments (Monday, Wednesday, Friday for 6 weeks) starting at 10 months to 8 years post-TBI. LED therapy is nonthermal, painless, and noninvasive. An LED-based device classified as nonsignificant risk (FDA cleared) was used. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm2) was applied for 9 min 45 sec (13 J/cm2) using 11 locations on the scalp: midline from front-to-back hairline and bilaterally on frontal, parietal, and temporal areas. Testing was performed before and after transcranial LED (tLED; at 1 week, 1 month, and at 2 months after the 18th treatment) and showed significant improvements in executive function and verbal memory. There were also fewer post-traumatic stress disorder (PTSD) symptoms reported. Ongoing studies: Ongoing, current studies involve TBI patients who have been treated with tLED using either 26 J/cm2 per LED location on the head or treated with intranasal only (iLED) using red (633 nm) and NIR (810 nm) diodes placed into the nostrils. The NIR iLED is hypothesized to deliver photons to the hippocampus, and the red 633 nm iLED is believed to increase melatonin. Results have been similar to the previously published tLED study. Actigraphy sleep data showed increased time asleep (on average one additional hour per night) after the 18th tLED or iLED treatment. LED treatments may be performed in the home. Sham-controlled studies with veterans who have cognitive dysfunction from Gulf War Illness, blast TBI, and TBI/PTSD are currently ongoing.

Hypervigilance in college students: Associations with betrayal and dissociation and psychometric properties in a Brief Hypervigilance Scale.

Betrayal trauma theory (Freyd, 1994, 1996) proposes that traumas high in social betrayal are expected to lead to psychological outcomes of dissociation, amnesia, and/or shame because these responses are adaptive to a survivor trying to preserve a necessary relationship in the face of mistreatment. Within the field of trauma studies more generally, there is substantial support for the proposition that traumas that cause intense fear should lead to posttraumatic anxiety and hypervigilance. Despite ample evidence for both theorized causal pathways, very few studies have tested associations between betrayal exposure, hypervigilance, and dissociation. The current study had 2 aims: first, as no self-report measure of hypervigilance had been developed for nonveteran populations, we sought to identify a subset of Hypervigilance Questionnaire (Knight, 1993) items that validly and reliably measure hypervigilance within college undergraduates (n = 489; 62.6% female, 69.9% Caucasian) with and without elevated levels of posttraumatic stress. Second, we tested the associations among trauma history, hypervigilance, and dissociation. Psychometric analyses revealed 5 hypervigilance items we introduce as the Brief Hypervigilance Scale. Partial correlations revealed that each posttraumatic response was not related to a history of low betrayal trauma (i.e. non-interpersonal trauma) controlling for betrayal trauma (i.e. interpersonal trauma), but was related to betrayal trauma controlling for low betrayal trauma. These associations remained significant after controlling for the other posttraumatic response (i.e. hypervigilance or dissociation). Follow-up analyses revealed that hypervigilance was independently associated with adult, but not child high betrayal trauma, and the opposite was true for dissociation. Implications for theory, research, and clinical practice are discussed.

Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study.

This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13 J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo-controlled studies are warranted.

Examining impelling and disinhibiting factors for intimate partner violence in veterans.

We examined correlates of intimate partner violence (IPV) in a military Veteran sample (N = 129) using Finkel's (2007) framework for understanding the interactions between impelling and disinhibiting risk factors. Correlates investigated included head contact events (HCEs), posttraumatic stress disorder (PTSD) symptoms, and antisocial features. Results indicated that antisocial features were significantly associated with IPV at the bivariate level. PTSD symptoms also were associated with IPV, but this association was marginally significant. Tests of moderation provided support for the expectation that HCEs would potentiate associations between antisocial features and IPV. HCEs also moderated the association between PTSD symptoms and IPV. However, contrary to expectations, the opposite pattern emerged such that PTSD symptoms were associated with a higher rate of IPV for those without a history of HCEs. Study findings have potentially important implications for furthering our understanding of the complex etiology of IPV in this population.

Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports.

OBJECTIVE: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. BACKGROUND: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. METHODS: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1″ diameter, 61 diodes (9 × 633 nm, 52 × 870 nm); 12-15 mW per diode; total power: 500 mW; 22.2 mW/cm(2); 13.3 J/cm(2) at scalp (estimated 0.4 J/cm(2) to cortex)]. RESULTS: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment. CONCLUSIONS: Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted.

Genome-wide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility.

Therapy-related acute myeloid leukemia (t-AML) is a rare but fatal complication of cytotoxic therapy. Whereas sporadic cancer results from interactions between complex exposures and low-penetrance alleles, t-AML results from an acute exposure to a limited number of potent genotoxins. Consequently, we hypothesized that the effect sizes of variants associated with t-AML would be greater than in sporadic cancer, and, therefore, that these variants could be detected even in a modest-sized cohort. To test this, we undertook an association study in 80 cases and 150 controls using Affymetrix Mapping 10K arrays. Even at nominal significance thresholds, we found a significant excess of associations over chance; for example, although 6 associations were expected at P less than .001, we found 15 (P(enrich) = .002). To replicate our findings, we genotyped the 10 most significantly associated single nucleotide polymorphisms (SNPs) in an independent t-AML cohort (n = 70) and obtained evidence of association with t-AML for 3 SNPs in the subset of patients with loss of chromosomes 5 or 7 or both, acquired abnormalities associated with prior exposure to alkylator chemotherapy. Thus, we conclude that the effect of genetic factors contributing to cancer risk is potentiated and more readily discernable in t-AML compared with sporadic cancer.

Risk factors for mental, physical, and functional health in Gulf War veterans.

Risk factors associated with war-zone events and circumstances are implicated in the health and adjustment of military veterans. We assessed a national stratified sample of community-residing veterans of the Gulf War (N = 357) using scales from the Deployment Risk and Resilience Inventory, along with an array of mental (posttraumatic stress disorder, depression, and anxiety), physical (symptom and condition indicators especially pertinent to Gulf War illnesses), and functional (both mental and physical dimensions) health outcomes. We found that perceived threat or fear of bodily harm in the war zone and self-reported or perceived exposures to environmental hazards may play a critical role in all measured aspects of health. Moreover, a synergistic effect of these two risk factors was observed in the prediction of mental health and mental health functional status.

Ectoadenylate kinase and plasma membrane ATP synthase activities of human vascular endothelial cells.

Formation of ATP from ADP on the external surface of vascular endothelial cells has been attributed to plasma membrane ATP synthase, ectoadenylate kinase (ecto-AK), and/or ectonucleoside diphosphokinase. These enzymes or their catalytic products have been causatively linked to the elaboration of vascular networks and the regulation of capillary function. The amount of ATP generated extracellularly is small, requiring sensitive analytical methods for quantification. Human umbilical vein endothelial cells were used to revisit extracellular ATP synthesis using a reliable tetrazolium reduction assay and multiwell plate cultures. Test conditions compatible with AK stability were established. Extracellular AK activity was found to be <1% of the total (intracellular and extracellular), raising the possibility that the external enzyme could have leaked from living cells and/or a few dying cells. To determine whether AK inadvertently leaked from the cells, the activity of another cytoplasmic enzyme, glucose-6-phosphate dehydrogenase (G6PD), was also measured. G6PD is present in the cytoplasm in similar abundance to AK. The activity ratio of G6PD (extracellular/total) was found to be similar to that of AK. Because G6PD in the medium was probably due to leakage, other cytoplasmic macromolecules, including AK, should be released proportionately from the cells. The role of plasma membrane ATP synthase in extracellular ATP formation was examined using Hanks' balanced salt solution with and without selective inhibitors of AK and ATP synthase activities. With P(1),P(5)-di(adenosine 5')-pentaphosphate (inhibitor of AK activity), no extracellular ATP synthesis was detected, whereas with oligomycin, piceatannol, and aurovertin (inhibitors of F(1)F(0)-ATP synthase and F(1)-ATPase activities), no inhibition of extracellular ATP synthesis was observed. AK activity alone could account for the observed extracellular ATP synthesis. The possible impact of ADP impurity in the assays is discussed.