A regulatory pathway model of neuropsychological disruption in Havana syndrome

IntroductionIn 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both.MethodAutomated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects.ResultsPredicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be “locked in” persistent illness but rather appear to be engaged in a slow recovery trajectory.DiscussionThis computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI

Coherent Energy Transfer and the Potential Implications for Consciousness

The argument that biological systems are too “warm and wet” to support quantum effects is becoming increasingly antiquated as research in the field of quantum biology progresses. In fact, not only is it becoming apparent that quantum processes may regularly take place in biological systems, but these processes may underlie the mechanisms of consciousness and propel our models of conceptualizing the human brain into the next era of scientific understanding. The phenomena of consciousness have allured scientists and philosophers for thousands of years, while a precise technical understanding has remained elusive. If possible, developing this understanding will likely be one of humanity’s greatest achievements. Knowing the fundamental processes that create conscious experience has far-reaching implications, from the potential birth of true artificial intelligence to a better understanding of mental health disorder etiologies and treatments. One major challenge in the mental health professions, and, ultimately, in empathy of any kind, is being able to see from and appreciate another person’s unique, subjective experience. Discoveries in the field of consciousness could help bridge this gap

Mapping the network biology of metabolic response to stress in posttraumatic stress disorder and obesity

The co-occurrence of stress-induced posttraumatic stress disorder (PTSD) and obesity is common, particularly among military personnel but the link between these conditions is unclear. Individuals with comorbid PTSD and obesity manifest other physical and psychological problems, which significantly diminish their quality of life. Current understanding of the pathways connecting stress to PTSD and obesity is focused largely on behavioral mediators alone with little consideration of the biological regulatory mechanisms that underlie their co-occurrence. In this work, we leverage prior knowledge to systematically highlight such bio-behavioral mechanisms and inform on the design of confirmatory pilot studies. We use natural language processing (NLP) to extract documented regulatory interactions involved in the metabolic response to stress and its impact on obesity and PTSD from over 8 million peer-reviewed papers. The resulting network describes the propagation of stress to PTSD and obesity through 34 metabolic mediators using 302 documented regulatory interactions supported by over 10,000 citations. Stress jointly affected both conditions through 21 distinct pathways involving only two intermediate metabolic mediators out of a total of 76 available paths through this network. Moreover, oxytocin (OXT), Neuropeptide-Y (NPY), and cortisol supported an almost direct propagation of stress to PTSD and obesity with different net effects. Although stress upregulated both NPY and cortisol, the downstream effects of both markers are reported to relieve PTSD severity but exacerbate obesity. The stress-mediated release of oxytocin, however, was found to concurrently downregulate the severity of both conditions. These findings highlight how a network-informed approach that leverages prior knowledge might be used effectively in identifying key mediators like OXT though experimental verification of signal transmission dynamics through each path will be needed to determine the actual likelihood and extent of each marker\u27s participation

Exploring the Role of Homeostatic Drive in the Perpetuation of Depression and Anxiety Disorders

Background: Feedback mechanisms throughout the brain play a significant role in maintaining physiological homeostasis. Specifically, brain chemicals and neurotransmitters contribute important oversight of psychological activity and homeostatic regulation. We propose that these components form an overarching regulatory system capable of supporting multiple homeostatic regimes. These regimes give rise to psychological behaviors that emerge as a result of the extensive feedback mechanisms involved in neurotransmitter signaling. Methods: Here we explore the possible role of such alternate regulatory programs in perpetuating chronic psychological and mental dysfunction. To do this we represent documented interactions within and between components of the neurotransmitter network as a set of discrete logic circuits. Neuro-transmitter levels are linked to psychological constructs based on current literature. These networks were analyzed via discrete ternary logic and compared to gene expression profiles for subjects diagnosed with depression and post-traumatic stress disorder. Results: Analysis of these regulatory circuits indicated that even in the absence of external perturbations that this model neurotransmitter-psychological network supported two distinct and stable homeostatic regimes. The first corresponds to typical health and behavior, while the second displays depression and anxiety accompanied by decreased serotonin, physical fatigue, and attention, and elevated glutamate, GABA, cortisol, and epinephrine. Conclusion: From this analysis we conclude that the complexity of neurotransmitter- psychological network is capable of supporting alternate homeostatic regimes that are not characteristic of a typically healthy profile, but are nonetheless naturally supported by the circuitry. Furthermore, our analysis suggests that depression and anxiety may be perpetuated under certain conditions at least in part by the brain’s own homeostatic regulation

A regulatory pathway model of neuropsychological disruption in Havana syndrome

Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both. Method: Automated text-mining of \u3e 9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects. Results: Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR \u3c 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be locked in persistent illness but rather appear to be engaged in a slow recovery trajectory. Discussion: This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI

Network Modeling of Complex Time-Dependent Changes in Patient Adherence to Adjuvant Endocrine Treatment in ER+ Breast Cancer

Early patient discontinuation from adjuvant endocrine treatment (ET) is multifactorial and complex: Patients must adapt to various challenges and make the best decisions they can within changing contexts over time. Predictive models are needed that can account for the changing influence of multiple factors over time as well as decisional uncertainty due to incomplete data. AtlasTi8 analyses of longitudinal interview data from 82 estrogen receptor-positive (ER+) breast cancer patients generated a model conceptualizing patient-, patient-provider relationship, and treatment-related influences on early discontinuation. Prospective self-report data from validated psychometric measures were discretized and constrained into a decisional logic network to refine and validate the conceptual model. Minimal intervention set (MIS) optimization identified parsimonious intervention strategies that reversed discontinuation paths back to adherence. Logic network simulation produced 96 candidate decisional models which accounted for 75% of the coordinated changes in the 16 network nodes over time. Collectively the models supported 15 persistent end-states, all discontinued. The 15 end-states were characterized by median levels of general anxiety and low levels of perceived recurrence risk, quality of life (QoL) and ET side effects. MIS optimization identified 3 effective interventions: reducing general anxiety, reinforcing pill-taking routines, and increasing trust in healthcare providers. Increasing health literacy also improved adherence for patients without a college degree. Given complex regulatory networks\u27 intractability to end-state identification, the predictive models performed reasonably well in identifying specific discontinuation profiles and potentially effective interventions