Dark loops: contagion effects, consistency and chemosocial matrices in psychedelic-assisted therapy trials

What happens when an emerging programme of medical research overlaps with a surging social movement? In this article we draw on the anthropological term ‘chemosociality’ to describe forms of sociality born of shared chemical exposure. Psychedelic administration in the context of recent clinical trials appears to have been particularly chemosocial in nature. We argue that one consequence is that psychedelic-assisted therapy (PAT) clinical research trials tend to breach key assumptions underlying the logic of causal inference used to establish efficacy. We propose the concept of dark loops to describe forms of sociality variously emerging from, and impacting participant experiences in, PAT trials. These dark loops are not recorded, let alone incorporated into the causal pathways in the interpretation of psychedelic trial data to date. We end with three positions which researchers might adopt in response to these issues: chemosocial minimisation where research is designed to attenuate or eliminate the effects of dark loops in trials; chemosocial description where dark loops (and their impacts) are openly and candidly documented and chemosocial valorisation where dark loops are hypothesised to contribute to trial outcomes and actively drawn upon for positive effect. Our goal is to fold in an appreciation of how the increasingly-discussed hype surrounding psychedelic research and therapeutics continues to shape the phenomena under study in complex ways, even as trials become larger and more rigorous in their design

The effects of AMPA receptor blockade on resting magnetoencephalography recordings

The ionotropic N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors of the glutamatergic neurotransmitter system are of fundamental importance to healthy brain function. Neuroimaging studies in humans have previously been conducted using various drugs that interact with N-methyl-D-aspartate glutamate receptors, but no such studies have investigated AMPA receptor signalling. The recent approval of perampanel (Fycompa) for use in humans provides a means to specifically study the role of AMPA receptors in the pharmacological basis of neuroimaging signals. Twenty male subjects participated in this placebo-controlled crossover study that consisted of two study days separated by a minimum two-week washout period. On one occasion participants ingested a 6 mg dose of perampanel, and on the other a placebo. Ten minutes of wakeful rest was recorded before and after each dose using magnetoencephalography. Subjective ratings of intoxication were significantly higher following drug than placebo. Cluster-based randomisation testing of sensor-level magnetoencephalography data showed significant drug-induced increases in low frequency power (1–4 Hz, 4–8 Hz, 8–13 Hz, 13–30 Hz), along with a significant decrease in the high gamma range (50–90 Hz). We also observed selective increases in functional connectivity in the alpha and beta bands. The findings are consistent with preclinical work and are similar to the spectral profile of other anti-epileptic drugs

Clinical Study of Hypocalcemia following Thyroid Surgery

NEED FOR STUDY: Post-thyroidectomy hypocalcemia is a serious early complication. Estimates indicate that transient hypocalcemia incidence of 9.2% and permanent hypocalcemia incidence of 0.5%. Hypocalcemia may occur secondarily to surgical trauma, devascularization, unintentional removal of parathyroid glands, reoperation2. Even after meticulously performed procedures, some temporary parathyroid dysfunction may occur2. Surgery extension has been seen as a risk factor, as in total thyroidectomy there is potential blood supply involvement resulting from bilateral surgical manipulation. However, other factors are related to the chosen surgical procedure and its impact on devascularization or accidental removal of the parathyroid glands. The recommended surgical strategy is meticulous dissection and preservation of the parathyroid glands and their blood supply. The best way to avoid accidental excision is properly identifying the parathyroid glands. Risk of complication is higher when fewer than three glands are identified during surgery. Depending upon the extent of parathyroid damage, postoperative hypocalcemia may be transient, resolving within a few months, or permanent, requiring lifelong oral or intravenous calcium supplementation3. This study aims to prospectively study and analyze the incidence and possible causes of hypocalcemia following thyroid surgery. REVIEW OF LITERATURE: Postoperative hypocalcemia ia a common complication after thyroidectomy. permanent hypocalcemia is rare, The incidence of transient and permanent hypocalcemia was 9.2%, and 0.5%, respectively. Yon seon kim et al concluded in their study that the number of preserved parathyroid glands is the most important factor for predicting permanent hypocalcemia and found that only one functional parathyroid gland was needed to avoid permanent hypocalcemia. Even if all the parathyroid glands cannot be completely accounted for, the surgeon should make an attempt at identifying and preserving parathyroid glands without damaging their blood supply. Rogerio aparecido dedivitis et al recommended that parathyroid glands are spared based on careful dissection of the gland’s blood pedicle. Permanent hypoparathyroidism occurs exclusively when fewer than three parathyroid glands are identified during surgery. Other authors consider that the iden-tification and sparing of at least two glands may result in higher rates of permanent hypoparathyroidism. Randall L. Baldassarre et al concluded in their study that Postoperative hypocalcemiaoccurred in 5.5% (n = 6, 605) of all thyroidectomy patients before discharge. Patients undergoing total thyroidectomy had a postoperative hypocalcemia incidence of 9.0%, compared with 1.9% following unilateral thyroid lobectomy. OBJECTIVES OF THE STUDY: 1. To determine the incidence of hypocalcemia following thyroid surgery. 2. To study the prevalence of post thyroidectomy hypocalcemia in response to age 3. To study the various clinical presentations of post thyroidectomy hypocalcemia 4. Post thyroidectomy hypocalcemia related with various pathological conditions of thyroid 5. To correlate the serum calcium level with clinical diagnosis 6. To study the time of presentation of post thyroidectomy hypocalcemia 7. Post thyroidectomy related with surgical procedure SOURCE OF DATA : All patients undergoing thyroidectomy surgeries (Minimum of 50 cases) from August 2014 to July 2015 at Tirunelveli Medical College Hospital,Tirunelveli. METHODS OF COLLECTION OF DATA: Data will be collected from the patients undergoing total thyroidectomies by meticulous history taking, careful clinical examination, appropriate radiological, haematological investigations including serum calcium and serum albumin, operative findings and follow-up of the cases will be done after surgery for post-operative hypocalcemia. A. Sample: Minimum of 50 cases B. Study Design: Prospective study C. Statistical Method : Data collected will be analyzed using descriptive statistical principles (like mean, proportions and percentages) D. Inclusion Criteria : Patient aged more than 12 yrs including both genter with clinically and pathologically diagnosed thyroid swellings undergoing thyroidectomy surgery E. Exclusion Criteria : 1. Patients undergoing hemithyroidectomy/lobectomy. 2. Primary parathyroid pathologies. 3. Age < 12 years. 4. previous irradiation to neck 5. patient already on calcium supplementation. Does the study require any investigation or intervention to be conducted on patients or animals specify? No investigations will be done on animals. Study will be done on patients after taking their informed consent. Investigations: Investigations only on patients with their consent. 1. Routine blood investigations like hemoglobin, bleeding time, clotting time 2. Blood sugar levels 3. Renal parameters : Blood urea, Serum creatinine 4. Serum electrolytes including total Calcium and ionised Calcium (pre-operative and post-operative) 5. Serum Albumin 6. Liver function tests 7. Thyroid function tests: T3, T4, TSH, free T3 & T4. 8. Neck radiograph 9. Chest radiograph 10. FNAC 11. post operative histo pathological analysis. CONCLUSION: From our study we concluded that post thyroidectomy transient hypocalcaemia is a frequent complication which can be prevented with preoperative preparation of patients with extreme caution and peroperative meticulous dissection, prompt identification of parathyroids and postoperative frequent monitoring of serum calcium and early treatment can prevent significant morbidity. Parathyroid autotransplantation should be considered in accidental injury to parathyroids during the procedure. Resurgeries of thyroid should be done with extreme caution. For treating patients more than 50 years surgeon should careful in preventing hypocalcaemia. While doing surgeries for malignant and toxic lesions for thyroid, the surgeon should consider total thyroidectomy as not only a thyroid removing surgery but also a surgery done to preserve parathyroids. For small scale hospitals serial monitoring of serum calcium levels preoperatively and postoperatively combined with careful monitoring of signs. and symptoms of hypocalcemia is a efficient and cost effective tool to detect post thyroidectomy hypocalcemia

High-frequency brain activity and muscle artifacts in MEG/EEG: A review and recommendations

In recent years high-frequency brain activity in the gamma-frequency band (30–80 Hz) and above has become the focus of a growing body of work in MEG/EEG research. Unfortunately, high-frequency neural activity overlaps entirely with the spectral bandwidth of muscle activity (~20–300 Hz). It is becoming appreciated that artifacts of muscle activity may contaminate a number of non-invasive reports of high-frequency activity. In this review, the spectral, spatial, and temporal characteristics of muscle artifacts are compared with those described (so far) for high-frequency neural activity. In addition, several of the techniques that are being developed to help suppress muscle artifacts in MEG/EEG are reviewed. Suggestions are made for the collection, analysis, and presentation of experimental data with the aim of reducing the number of publications in the future that may contain muscle artifacts

Supplying Data for an RDF Based Content Management System

Personalized Internet Services have become an important topic of research and study. The concept of personalization is possible only with a system that can integrate and deliver data that are present in large number of repositories. An 'e-Travel system' being developed by the 'Agent Lab' group aims to provide personalized services to its customers in the travel domain. The main objective of this thesis was to propose an architecture for the content management system (CMS), which is an integral part of the e-Travel system. CMS's responsibilities include gathering and integrating data from varied sources (Web pages, Relational Databases, RDF dumps). In this attempt, many existing architectures for CMS were studied. Most of these architectures were based on either lazy (on demand) or eager (data warehousing) approach for data integration. Studies and requirements proved that an ideal architecture will be the one in which some data is pre fetched, processed, integrated (using a global ontology) and stored in the database, while other data, when not present in the database, is fetched and processed upon user queries. As a result, an architecture that uses Resource Description Framework (RDF) for representing the travel domain was developed. This architecture was implemented using Jena - a Java framework for building Semantic Web applications. The functionality of this architecture was studied with the help of 'Verified Content Providers' - sources of data that are considered reliable and whose structures and topologies are known beforehand. 'Time Adaptive' capability built within the architecture determined how often these sources are visited in search of updated content.Computer Science Departmen

Decreased directed functional connectivity in the psychedelic state

Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the large-scale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data

Mu suppression – a good measure of the human mirror neuron system?

Mu suppression has been proposed as a signature of the activity of the human mirror neuron system. However the mu frequency band (8-13 Hz) overlaps with the alpha frequency band, which is sensitive to attentional fluctuation, and thus mu suppression could potentially be confounded by changes in attentional engagement. The specific baseline against which mu suppression is assessed may be crucial, yet there is little consistency in how this is defined. We examined mu suppression in 61 typical adults, the largest mu suppression study so far conducted. We compared different methods of baselining, and examined activity at central and occipital electrodes, to both biological (hands) and non-biological (kaleidoscope) moving stimuli, to investigate the involvement of attention and alpha activity in mu suppression. We also examined changes in beta power, another candidate index of mirror neuron system engagement. We observed strong mu suppression restricted to central electrodes when participants performed hand movements, demonstrating that mu is indeed responsive to the activity of the motor cortex. However, when we looked for a similar signature of mu suppression to passively observed stimuli, the baselining method proved to be crucial. Selective suppression for biological vs non-biological stimuli was seen at central electrodes only when we used a within-trial baseline based on a static stimulus: this method greatly reduced trial-by-trial variation in the suppression measure compared with baselines based on blank trials presented in separate blocks. Even in this optimal condition, 16-21% of participants showed no mu suppression. Changes in beta power also did not match our predicted pattern for mirror neuron system engagement, and did not seem to offer a better measure than mu. Our conclusions are in contrast to those of a recent meta-analysis, which concluded that mu suppression is a valid means to examine mirror neuron activity. We argue that mu suppression can be used to index the human mirror neuron system, but the effect is weak and unreliable and easily confounded with alpha suppression

Arterial CO2 fluctuations modulate neuronal rhythmicity: Implications for MEG and fMRI studies of resting-state networks

A fast emerging technique for studying human resting state networks (RSNs) is based on spontaneous temporal fluctuations in neuronal oscillatory power, as measured by magnetoencephalography. However, it has been demonstrated recently that this power is sensitive to modulations in arterial CO2 concentration. Arterial CO2 can be modulated by natural fluctuations in breathing pattern, as might typically occur during the acquisition of an RSN experiment. Here, we demonstrate for the first time the fine-scale dependence of neuronal oscillatory power on arterial CO2 concentration, showing that reductions in alpha, beta, and gamma power are observed with even very mild levels of hypercapnia (increased arterial CO2). We use a graded hypercapnia paradigm and participant feedback to rule out a sensory cause, suggesting a predominantly physiological origin. Furthermore, we demonstrate that natural fluctuations in arterial CO2, without administration of inspired CO2, are of a sufficient level to influence neuronal oscillatory power significantly in the delta-, alpha-, beta-, and gamma-frequency bands. A more thorough understanding of the relationship between physiological factors and cortical rhythmicity is required. In light of these findings, existing results, paradigms, and analysis techniques for the study of resting-state brain data should be revisited

Peak visual gamma frequency is modified across the healthy menstrual cycle

Fluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABAA receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females’ mid‐luteal phase when progesterone and estradiol are highest, and early follicular phase when progesterone and estradiol are lowest. Significantly higher (∼5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modeling, these changes were linked to stronger self‐inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition, the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma‐band oscillations