Command in air war : centralized vs. decentralized control of combat airpower

Thesis (Ph. D.)--Massachusetts Institute of Technology, Engineering Systems Division, Technology, Management, and Policy Program, 2005.Includes bibliographical references.This study answers the question, "What has been the impact of the Information Age on the Air Force's doctrinal tenet of "centralized control and decentralized execution?" It traces the evolution of command and control of airpower through operations Desert Storm, Allied Force, Enduring Freedom, and Iraqi Freedom and compares its practice with classic theories established by Huntington, Cohen, Van Creveld, and Air Force doctrine. In the absence of a peer superpower in the 1990s, U.S. decision-makers often resorted to the use of detailed constraints to gain direct influence on military operations. The more detailed the constraints from the strategic level, the closer the theater military commander held authority for planning air strikes, and the less proactive the air component was in coordinating with other components. The Air Force developed the Air Operations Center (AOC) to put together battlespace information; it is not yet possible to do this at lower levels, so the AOC has become dominant in controlling air operations. Initially resistant to get involved in ongoing missions, commanders found the AOC was needed to accomplish some "time-sensitive targeting" missions; however, they have also learn to delegate to speed up the processes.(cont.) But the insertion of the AOC into ongoing operations also led to distribution of tasks-where before the aircrew had performed the whole "kill chain" sequence, now the aircrew often performed only the end game tasks. This distribution could increase the potential for system accidents because people tend to drift from procedures during slack times and thus to be disintegrated when the system becomes tightly coupled. Technology has not changed the fundamental principles of command and control. The information, telecommunications, sensor and weapons technology have altered the way these humans perform their jobs, and even the jobs they perform. But commanders still need to cultivate a learning organization. Uncertainty and the coupling of diverse organizations still require that they balance empowerment with accountability by developing depth in the command relationships among their subordinates. Commanders can best gain this depth through deliberate delegation, a bruising debate, and assessment of results rather than management of specific details.by Michael W. Kometer.Ph.D

The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions

Rationale: Both glutamate and serotonin (5-HT) play a key role in the pathophysiology of emotional biases. Recent studies indicate that the glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine and the 5-HT receptor agonist psilocybin are implicated in emotion processing. However, as yet, no study has systematically compared their contribution to emotional biases. Objectives: This study used event-related potentials (ERPs) and signal detection theory to compare the effects of the NMDA (via S-ketamine) and 5-HT (via psilocybin) receptor system on non-conscious or conscious emotional face processing biases. Methods: S-ketamine or psilocybin was administrated to two groups of healthy subjects in a double-blind within-subject placebo-controlled design. We behaviorally assessed objective thresholds for non-conscious discrimination in all drug conditions. Electrophysiological responses to fearful, happy, and neutral faces were subsequently recorded with the face-specific P100 and N170 ERP. Results: Both S-ketamine and psilocybin impaired the encoding of fearful faces as expressed by a reduced N170 over parieto-occipital brain regions. In contrast, while S-ketamine also impaired the encoding of happy facial expressions, psilocybin had no effect on the N170 in response to happy faces. Conclusion: This study demonstrates that the NMDA and 5-HT receptor systems differentially contribute to the structural encoding of emotional face expressions as expressed by the N170. These findings suggest that the assessment of early visual evoked responses might allow detecting pharmacologically induced changes in emotional processing biases and thus provides a framework to study the pathophysiology of dysfunctional emotional biase

Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat

Meditation and psychedelics have played key roles in humankind’s search for self-transcendence and personal change. However, neither their possible synergistic effects, nor related state and trait predictors have been experimentally studied. To elucidate these issues, we administered double-blind the model psychedelic drug psilocybin (315 μg/kg PO) or placebo to meditators (n = 39) during a 5-day mindfulness group retreat. Psilocybin increased meditation depth and incidence of positively experienced self-dissolution along the perception-hallucination continuum, without concomitant anxiety. Openness, optimism, and emotional reappraisal were predictors of the acute response. Compared with placebo, psilocybin enhanced post-intervention mindfulness and produced larger positive changes in psychosocial functioning at a 4-month follow-up, which were corroborated by external ratings, and associated with magnitude of acute self-dissolution experience. Meditation seems to enhance psilocybin’s positive effects while counteracting possible dysphoric responses. These findings highlight the interactions between non-pharmacological and pharmacological factors, and the role of emotion/attention regulation in shaping the experiential quality of psychedelic states, as well as the experience of selflessness as a modulator of behavior and attitudes. A better comprehension of mechanisms underlying most beneficial psychedelic experiences may guide therapeutic interventions across numerous mental conditions in the form of psychedelic-assisted applications

Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin

Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down contro

Modeling Ketamine Effects on Synaptic Plasticity During the Mismatch Negativity

This paper presents a model-based investigation of mechanisms underlying the reduction of mismatch negativity (MMN) amplitudes under the NMDA-receptor antagonist ketamine. We applied dynamic causal modeling and Bayesian model selection to data from a recent ketamine study of the roving MMN paradigm, using a cross-over, double-blind, placebo-controlled design. Our modeling was guided by a predictive coding framework that unifies contemporary "adaptation” and "model adjustment” MMN theories. Comparing a series of dynamic causal models that allowed for different expressions of neuronal adaptation and synaptic plasticity, we obtained 3 major results: 1) We replicated previous results that both adaptation and short-term plasticity are necessary to explain MMN generation per se; 2) we found significant ketamine effects on synaptic plasticity, but not adaptation, and a selective ketamine effect on the forward connection from left primary auditory cortex to superior temporal gyrus; 3) this model-based estimate of ketamine effects on synaptic plasticity correlated significantly with ratings of ketamine-induced impairments in cognition and control. Our modeling approach thus suggests a concrete mechanism for ketamine effects on MMN that correlates with drug-induced psychopathology. More generally, this demonstrates the potential of modeling for inferring on synaptic physiology, and its pharmacological modulation, from electroencephalography dat

Aberrant Current Source-Density and Lagged Phase Synchronization of Neural Oscillations as Markers for Emerging Psychosis

Background: Converging evidence indicates that neural oscillations coordinate activity across brain areas, a process which is seemingly perturbed in schizophrenia. In particular, beta (13-30 Hz) and gamma (30-50 Hz) oscillations were repeatedly found to be disturbed in schizophrenia and linked to clinical symptoms. However, it remains unknown whether abnormalities in current source density (CSD) and lagged phase synchronization of oscillations across distributed regions of the brain already occur in patients with an at-risk mental state (ARMS) for psychosis. Methods: To further elucidate this issue, we assessed resting-state EEG data of 63 ARMS patients and 29 healthy controls (HC). Twenty-three ARMS patients later made a transition to psychosis (ARMS-T) and 40 did not (ARMS-NT). CSD and lagged phase synchronization of neural oscillations across brain areas were assessed using eLORETA and their relationships to neurocognitive deficits and clinical symptoms were analyzed using linear mixed-effects models. Results: ARMS-T patients showed higher gamma activity in the medial prefrontal cortex compared to HC, which was associated with abstract reasoning abilities in ARMS-T. Furthermore, in ARMS-T patients lagged phase synchronization of beta oscillations decreased more over Euclidian distance compared to ARMS-NT and HC. Finally, this steep spatial decrease of phase synchronicity was most pronounced in ARMS-T patients with high positive and negative symptoms scores. Conclusions: These results indicate that patients who will later make the transition to psychosis are characterized by impairments in localized and synchronized neural oscillations providing new insights into the pathophysiological mechanisms of schizophrenic psychoses and may be used to improve the prediction of psychosi

Alpha oscillations underlie working memory abnormalities in the psychosis high-risk state

Working memory (WM) functioning, known to be modulated by neural oscillations, is impaired in schizophrenic psychoses. It remains unclear whether in the psychosis high-risk state, WM encoding is altered or whether patients are impaired at shielding their WM against distractors. We employed single-trial analyses of neurophysiological and behavioral data recorded during a WM paradigm, designed to include predictable distractors, on 18 patients with an at-risk mental state for psychosis (ARMS, 26.1±5.45 years) and 21 healthy controls (HCs, 25.5±3.95 years). Strong distractors were associated with reduced WM accuracy (p=0.036), but only ARMS patients required more processing time for strong distractors (p=0.002). Increased parieto-occipital alpha amplitude preceding distractor presentations was associated with enhanced accuracy only in HCs (p=0.009). During encoding, increased intertrial alpha phase locking values were associated with increased performance. Reduced shielding mechanisms against distractors in ARMS patients could lead to defective WM maintenance, which may result in significant confusion that may contribute to the formation of psychotic symptoms

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine

Recently, the Amazonian plant medicine “ayahuasca”—containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous β-carboline alkaloids, such as harmine—has been suggested to exhibit beneficial effects in patients with affective and other mental health disorders. Although ayahuasca ingestion is considered safe, its pharmacokinetics/pharmacodynamics and tolerability profile pose some challenges and may limit the clinical applicability in vulnerable patient populations. While overdosing and the admixture of intolerable plant constituents may explain some of the common adverse reactions, the peroral route of administration may represent another relevant source of gastro-intestinal intolerabilities and unpredictable pharmacokinetics across users. To overcome these challenges, the present work aimed at creating ayahuasca-analogue formulations with improved pharmacokinetics and tolerability profiles. To this end, we developed peroral formulas and compared them with parenteral formulas specifically designed to circumvent the gastro-intestinal tract. In more detail, peroral administration of a capsule (containing purified DMT and harmine) was tested against a combined administration of an oromucosal harmine tablet and an intranasal DMT spray at two dose levels in an open-label within-subject study in 10 healthy male subjects. Pharmacokinetic and pharmacodynamic profiles were assessed by means of continuous blood sampling, vital sign monitoring, and psychometric assessments. Common side effects induced by traditional herbal ayahuasca such as nausea, vomiting, and diarrhea were significantly attenuated by our DMT/harmine formulations. While all preparations were well tolerated, the combined buccal/intranasal administration of harmine and DMT yielded substantially improved pharmacokinetic profiles, indicated by significantly reduced variations in systemic exposure. In conclusion, the combined buccal/intranasal administration of harmine and DMT is an innovative approach that may pave the way towards a safe, rapid-acting, and patient-oriented administration of DMT/harmine for the treatment of affective disorders.Clinical Trial Registration:clinicaltrials.gov, identifier NCT0471633

Gamma-hydroxybutyrate increases brain resting-state functional connectivity of the salience network and dorsal nexus in humans

According to the triple network hypothesis the brain is equipped with three core neurocognitive networks: the default mode (DMN), the salience (SN), and the central executive (CEN) network. Moreover, the so called dorsal nexus, has met growing interest as it is a hub region connecting these three networks. Assessment of resting-state functional connectivity (rsFC) of these networks enables the elucidation of drug-induced brain alterations. Gamma-hydroxybutyrate (GHB) is a GHB/GABA-B receptor agonist that induces a paradoxical state of mixed stimulation and sedation at moderate doses, which makes it a valuable tool to investigate neural signatures of subjective drug effects. Employing a placebo-controlled, double-blind, randomized, cross-over design, we assessed the effects of GHB (35 mg/kg p. o.) in 19 healthy male subjects on DMN-, SN-, CEN-, and dorsal nexus-rsFC measured by functional magnet resonance imaging and applying independent component as well as seed-based analyses, while subjective drug effects were investigated using visual analog scales (VAS). Subjectively, GHB increased VAS ratings of a general drug effect, stimulation, and sedation. Intrinsic DMN-, and CEN-rsFC remained largely unchanged under GHB, but the drug increased SN-DMN-rsFC and SN-dorsal nexus-rsFC, while dorsal nexus-rsFC was reciprocally increased to both the SN (right anterior insula) and to the CEN (right middle frontal gyrus). Increased sedation significantly predicted the observed SN-dorsal nexus-rsFC. In conclusion, GHB generates a unique stimulant/sedative subjective state that is paralleled by a complex pattern of increased functional connectivity encompassing all three core neurocognitive networks of the brain, while increased SN-dorsal nexus-rsFC was demonstrated to be a potential signature of the sedative component of the drug effect