Understanding the Scientific Basis of Post-traumatic Stress Disorder (PTSD): Precision Behavioral Management Overrides Stigmatization.

Post-traumatic stress disorder (PTSD) is a severe polygenic disorder triggered by environmental factors. Many polymorphic genes, particularly the genetic determinants of hypodopaminergia (low dopamine function), associate with a predisposition to PTSD as well as substance use disorder. Support from the National Institutes of Health for neuroimaging research and molecular, genetic applied technologies has improved understanding of brain reward circuitry functions that have inspired the development of new innovative approaches to their early diagnosis and treatment of some PTSD symptomatology and addiction. This review presents psychosocial and genetic evidence that vulnerability or resilience to PTSD can theoretically be impacted by dopamine regulation. From a neuroscience perspective, dopamine is widely accepted as a major neurotransmitter. Questions about how to modulate dopamine clinically in order to treat and prevent PTSD and other types of reward deficiency disorders remain. Identification of genetic variations associated with the relevant genotype-phenotype relationships can be characterized using the Genetic Addiction Risk Score (GARS®) and psychosocial tools. Development of an advanced genetic panel is under study and will be based on a new array of genes linked to PTSD. However, for now, the recommendation is that enlistees for military duty be given the opportunity to voluntarily pre-test for risk of PTSD with GARS, before exposure to environmental triggers or upon return from deployment as part of PTSD management. Dopamine homeostasis may be achieved via customization of neuronutrient supplementation "Precision Behavioral Management" (PBM™) based on GARS test values and other pro-dopamine regulation interventions like exercise, mindfulness, biosensor tracking, and meditation.

Insurance Companies Fighting the Peer Review Empire without any Validity: the Case for Addiction and Pain Modalities in the face of an American Drug Epidemic.

The United States are amid an opioid overdose epidemic; we are challenged to provide non-addicting/non-pharmacological alternatives to assist in pain attenuation. There are proven strategies available to manage chronic pain effectively without opioids. Utilization review providers for insurance companies often ignore medicine based scientific peer-reviewed studies that warn against the chronic use of opioid medications, as well as the lack of evidence to support long-term use of opioids for pain. This paradigm must change if we are to indeed change the drug-embracing culture in American chronic pain management. A barrier to treatment is pushback on the part of insurance companies especially as it relates to fighting against pain relief alternatives compared to classical analgesic agents. Pain specialists in the U.S., are compelled to find alternative solutions to help pain victims without promoting unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain." It is noteworthy that reward center of the brain plays a crucial role in the modulation of nociception, and that adaptations in dopaminergic circuitry may affect several sensory and affective components of chronic pain syndromes. Possibly knowing a patient's genetic addiction risk score (GARS™) could eliminate guessing as it relates to becoming addicted.

Would induction of dopamine homeostasis via coupling genetic addiction risk score (GARS®) and pro-dopamine regulation benefit benzodiazepine use disorder (BUD)?

Prescriptions for Benzodiazepines (BZDs) have risen continually. According to national statistics, the combination of BZDs with opioids has increased since 1999. BZDs (sometimes called "benzos") work to calm or sedate a person by raising the level of the inhibitory neurotransmitter GABA in the brain. In terms of neurochemistry, BZDs act at the GABAA receptors to inhibit excitatory neurons, reducing VTA glutaminergic drive to reduce dopamine release at the Nucleus accumbens. Benzodiazepine Use Disorder (BUD) is very difficult to treat, partly because BZDs are used to reduce anxiety which paradoxically induces hypodopaminergia. Considering this, we are proposing a paradigm shift. Instead of simply targeting chloride channel direct GABAA receptors for replacement or substitution therapy, we propose the induction of dopamine homeostasis. Our rationale is supported by the well-established notion that the root cause of drug and non-drug addictions (i.e. Reward Deficiency Syndrome [RDS]), at least in adults, involve dopaminergic dysfunction and heightened stress. This proposition involves coupling the Genetic Addiction Risk Score (GARS) with a subsequent polymorphic matched genetic customized Pro-Dopamine Regulator known as KB220ZPBM (Precision Behavioral Management). Induction of dopamine homeostasis will be clinically beneficial in attempts to combat BUD for at least three reasons: 1) During detoxification of alcoholism, the potential induction of dopamine regulation reduces the need for BZDs; 2) A major reason for BZD abuse is because people want to achieve stress reduction and subsequently, the potential induction of dopamine regulation acts as an anti-stress factor; and 3) BUD and OUD are known to reduce resting state functional connectivity, and as such, potential induction of dopamine regulation enhances resting state functional connectivity. Future randomized placebo-controlled studies will investigate this forward thinking proposed novel modality.

Reproducibility of visual activation during checkerboard stimulation in functional magnetic resonance imaging at 4 Tesla.

PURPOSE: To investigate the reproducibility of visual activation by checkerboard stimulation, we used functional magnetic resonance imaging (fMRI) at 4 Tesla (T). METHODS: Four subjects were studied with fMRI at 4 T during checkerboard visual stimulation. The functional images were realigned and spatially normalized to the standard brain. For each subject, statistical parametric maps were made for each study, and the reproducibility was determined based on the number of supra-threshold voxels (Z > 3.5, 4.5, and 5.5). RESULTS: The mean ratio for the number of supra-threshold (Z > 4.5) voxels was 0.75, and the mean ratio for the overlapping voxels was 0.61. Restricting the region of interest within the posterior half of the brain improved reproducibility values at the low threshold (Z > 3.5), but did not improve the values at the higher thresholds. CONCLUSIONS: Despite the fact that more than half of the supra-threshold voxels were found to be active for the repeated scans, visual activation with checkerboard stimulation seems to be less reproducible than that by flash stimulation.

Functional magnetic resonance imaging of the visual system.

Functional magnetic resonance imaging (fMRI), which is a technique useful for non-invasive mapping of brain function, is well suited for studying the visual system. This review highlights current clinical applications and research studies involving patients with visual deficits. Relevant reports regarding the investigation of the brain's role in visual processing and some newer fMRI techniques are also reviewed. Functional magnetic resonance imaging has been used for presurgical mapping of visual cortex in patients with brain lesions and for studying patients with amblyopia, optic neuritis, and residual vision in homonymous hemianopia. Retinotopic borders, motion processing, and visual attention have been the topics of several fMRI studies. These reports suggest that fMRI can be useful in clinical and research studies in patients with visual deficits.

Visual activation in functional magnetic resonance imaging at very high field (4 Tesla).

OBJECTIVES: Functional magnetic resonance imaging (fMRI) at very high field strengths provides functional brain mapping with the enhanced signal to noise ratio and the larger blood oxygenation level-dependent (BOLD) effect. We report activated areas in the standard space detected by fMRI at 4 Tesla (T) during simple visual stimulation. MATERIALS AND METHODS: Twelve healthy young subjects were scanned using a 4 T scanner during binocular flashing visual stimulation. Functional images were realigned to the first scan and then spatially normalized. Individual and group data analyses were performed to identify areas of visual activation. RESULTS: Activation of the bilateral primary visual cortex (V1/V2) was observed along the entire calcarine fissure in all subjects. The activated area extended to the extrastriate cortex in all subjects. Activation of the bilateral lateral geniculate nucleus (LGN) was detected in all subjects. The group data showed activation of the bilateral primary visual cortex and the bilateral lateral geniculate nucleus. CONCLUSIONS: Robust activation of the vision-related areas was successfully obtained in all subjects using a 4 T magnetic resonance scanner. These results suggest that fMRI at very high field strengths may be effective in showing visual system physiology, and that it can be a promising method to assess visual function of human subjects.