Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were rested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 mu g/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggestinga primary involvement of the 5-HT1A receptor in the observed defecit. Based on physiological and pharmacological data,we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

CFD modelling of the fast pyrolysis of an in-flight cellulosic particle subjected to convective heat transfer

The pyrolysis of a freely moving cellulosic particle inside a 41.7mgs -1 source continuously fed fluid bed reactor subjected to convective heat transfer is modelled. The Lagrangian approach is adopted for the particle tracking inside the reactor, while the flow of the inert gas is treated with the standard Eulerian method for gases. The model incorporates the thermal degradation of cellulose to char with simultaneous evolution of gases and vapours from discrete cellulosic particles. The reaction kinetics is represented according to the Broido–Shafizadeh scheme. The convective heat transfer to the surface of the particle is solved by two means, namely the Ranz–Marshall correlation and the limit case of infinitely fast external heat transfer rates. The results from both approaches are compared and discussed. The effect of the different heat transfer rates on the discrete phase trajectory is also considered.

Data-Driven Motion Detection and Characterization in PET Brain Scans Using List Mode

Head motion during a Positron Emission Tomography (PET) brain scan can considerably degrade image quality. External motion-tracking devices have proven successful in minimizing this effect, but the associated time, maintenance, and workflow changes inhibit their widespread clinical use. List-mode PET acquisition allows for the retroactive analysis of coincidence events on any time scale throughout a scan, and therefore potentially offers a data-driven motion detection and characterization technique. An algorithm was developed to parse list-mode data, divide the full acquisition into short scan intervals, and calculate the line-of-response (LOR) midpoint average for each interval. These LOR midpoint averages, known as “radioactivity centroids,” were presumed to represent the center of the radioactivity distribution in the scanner, and it was thought that changes in this metric over time would correspond to intra-scan motion.

Several scans were taken of the 3D Hoffman brain phantom on a GE Discovery IQ PET/CT scanner to test the ability of the radioactivity to indicate intra-scan motion. Each scan incrementally surveyed motion in a different degree of freedom (2 translational and 2 rotational). The radioactivity centroids calculated from these scans correlated linearly to phantom positions/orientations. Centroid measurements over 1-second intervals performed on scans with ~1mCi of activity in the center of the field of view had standard deviations of 0.026 cm in the x- and y-dimensions and 0.020 cm in the z-dimension, which demonstrates high precision and repeatability in this metric. Radioactivity centroids are thus shown to successfully represent discrete motions on the submillimeter scale. It is also shown that while the radioactivity centroid can precisely indicate the amount of motion during an acquisition, it fails to distinguish what type of motion occurred.

Single particle motion of polymeric, colloidal, and biological materials

Small particles and their dynamics are of widespread interest due both to their unique properties and their ubiquity. Here, we investigate several classes of small particles: colloids, polymers, and liposomes. All these particles, due to their size on the order of microns, exhibit significant similarity in that they are large enough to be visualized in microscopes, but small enough to be significantly influenced by thermal (or Brownian) motion. Further, similar optical microscopy and experimental techniques are commonly employed to investigate all these particles. In this work, we develop single particle tracking techniques, which allow thorough characterization of individual particle dynamics, observing many behaviors which would be overlooked by methods which time or ensemble average. The various particle systems are also similar in that frequently, the signal-to-noise ratio represented a significant concern. In many cases, development of image analysis and particle tracking methods optimized to low signal-to-noise was critical to performing experimental observations. The simplest particles studied, in terms of their interaction potentials, were chemically homogeneous (though optically anisotropic) hard-sphere colloids. Using these spheres, we explored the comparatively underdeveloped conjunction of translation and rotation and particle hydrodynamics. Developing off this, the dynamics of clusters of spherical colloids were investigated, exploring how shape anisotropy influences the translation and rotation respectively. Transitioning away from uniform hard-sphere potentials, the interactions of amphiphilic colloidal particles were explored, observing the effects of hydrophilic and hydrophobic interactions upon pattern assembly and inter-particle dynamics. Interaction potentials were altered in a different fashion by working with suspensions of liposomes, which, while homogeneous, introduce the possibility of deformation. Even further degrees of freedom were introduced by observing the interaction of particles and then polymers within polymer suspensions or along lipid tubules. Throughout, while examination of the trajectories revealed that while by some measures, the averaged behaviors accorded with expectation, often closer examination made possible by single particle tracking revealed novel and unexpected phenomena.

Particle dynamics and airflow patterns in a ventilated two-zone enclosure

Understanding the transport mechanisms of aerosol particles in enclosures has broad ramifications in the context of cleaning strategies, and health risk assessment (e. g., occupational exposure). This paper addresses airflow pattern and aerosol transport mechanism in a ventilated two-zone enclosure with the outlet (exhaust location) situated at different locations. A numerical approach that combines a Eulerian simulation of turbulent flow with a Lagrangian particle-tracking algorithm is used. Simulations are carried out using solid suspensions with different sizes (1 to 100 micron) and densities (240 and 2300 kg/m3). The effect of location of the outlet (exhaust) on airflow patterns and aerosol dynamics is analyzed and quantified.

Evaluation Of Soft-tissue Lesions With (18)f-fdg Pet/ct: Initial Results Of A Prospective Trial.

Although MRI is utilized for planning the resection of soft-tissue tumors, it is not always capable of differentiating benign from malignant lesions. The risk of local recurrence of soft-tissue sarcomas is increased when biopsies are performed before resection and by inadequate resections. PET associated with computed tomography using fluorodeoxyglucose labeled with fluorine-18 ((18)F-FDG PET/CT) may help differentiate between benign and malignant tumors, thus avoiding inadequate resections and making prior biopsies unnecessary. The purpose of this study was to evaluate the usefulness of (18)F-FDG PET/CT in differentiating benign from malignant solid soft-tissue lesions. Patients with solid lesions of the limbs or abdominal wall detected by MRI were submitted to (18)F-FDG PET/CT. The maximum standardized uptake value (SUVmax) cutoff was determined to differentiate malignant from benign tumors. Regardless of the (18)F-FDG PET/CT results all patients underwent biopsy and surgery. MRI was performed in 54 patients, and 10 patients were excluded because of purely lipomatose or cystic lesions. (18)F-FDG PET/CT was performed in the remaining 44 patients. Histopathology revealed 26 (59%) benign and 18 (41%) malignant soft-tissue lesions. A significant difference in SUVmax was observed between benign and malignant soft-tissue lesions. The SUVmax cutoff of 3.0 differentiated malignant from benign lesions with 100% sensitivity, 83.3% specificity, 89.6% accuracy, 78.3% positive predictive value, and 100% negative predictive value. (18)F-FDG PET/CT seems to be able to differentiate benign from malignant soft-tissue lesions with good accuracy and very high negative predictive value. Incorporating (18)F-FDG PET/CT into the diagnostic algorithm of these patients may prevent inadequate resections and unnecessary biopsies.

Anticipation of pain enhances the nociceptive transmission and functional connectivity within pain network in rats

Background: Expectation is a very potent pain modulator in both humans and animals. There is evidence that pain transmission neurons are modulated by expectation preceding painful stimuli. Nonetheless, few studies have examined the influence of pain expectation on the pain-related neuronal activity and the functional connectivity within the central nociceptive network. Results: This study used a tone-laser conditioning paradigm to establish the pain expectation in rats, and simultaneously recorded the anterior cingulate cortex (ACC), the medial dorsal thalamus (MD), and the primary somatosensory cortex (SI) to investigate the effect of pain expectation on laser-induced neuronal responses. Cross-correlation and partial directed coherence analysis were used to determine the functional interactions within and between the recorded areas during nociceptive transmission. The results showed that under anticipation condition, the neuronal activity to the auditory cue was significantly increased in the ACC area, whereas those to actual noxious stimuli were enhanced in all the recorded areas. Furthermore, neuronal correlations within and between these areas were significantly increased under conditions of expectation compared to those under non-expectation conditions, indicating an enhanced synchronization of neural activity within the pain network. In addition, information flow from the medial (ACC and MD) to the lateral (SI cortex) pain pathway increased, suggesting that the emotion-related neural circuits may modulate the neuronal activity in the somatosensory pathway during nociceptive transmission. Conclusion: These results demonstrate that the nociceptive processing in both medial and lateral pain systems is modulated by the expectation of pain.

Orbitofrontal Cortex Volumes in Medication Naive Children with Major Depressive Disorder: A Magnetic Resonance Imaging Study

Objectives: Adults with major depressive disorder (MDD) are reported to have reduced orbitofrontal cortex (OFC) volumes, which could be related to decreased neuronal density. We conducted a study on medication naive children with MDD to determine whether abnormalities of OFC are present early in the illness course. Methods: Twenty seven medication naive pediatric Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) MDD patients (mean age +/- SD = 14.4 +/- 2.2 years; 10 males) and 26 healthy controls (mean age +/- SD = 14.4 +/- 2.4 years; 12 males) underwent a 1.5T magnetic resonance imaging (MRI) with 3D spoiled gradient recalled acquisition. The OFC volumes were compared using analysis of covariance with age, gender, and total brain volume as covariates. Results: There was no significant difference in either total OFC volume or total gray matter OFC volume between MDD patients and healthy controls. Exploratory analysis revealed that patients had unexpectedly larger total right lateral (F = 4.2, df = 1, 48, p = 0.05) and right lateral gray matter (F = 4.6, df = 1, 48, p = 0.04) OFC volumes compared to healthy controls, but this finding was not significant following statistical correction for multiple comparisons. No other OFC subregions showed a significant difference. Conclusions: The lack of OFC volume abnormalities in pediatric MDD patients suggests the abnormalities previously reported for adults may develop later in life as a result of neural cell loss.

Governing coordination: Behavioural principles and neural correlates

The coordination of movement is governed by a coalition of constraints. The expression of these constraints ranges from the concrete—the restricted range of motion offered by the mechanical configuration of our muscles and joints; to the abstract—the difficulty that we experience in combining simple movements into complex rhythms. We seek to illustrate that the various constraints on coordination are complementary and inclusive, and the means by which their expression and interaction are mediated systematically by the integrative action of the central nervous system (CNS). Beyond identifying the general principles at the behavioural level that govern the mutual interplay of constraints, we attempt to demonstrate that these principles have as their foundation specific functional properties of the cortical motor systems. We propose that regions of the brain upstream of the motor cortex may play a significant role in mediating interactions between the functional representations of muscles engaged in sensorimotor coordination tasks. We also argue that activity in these ldquosupramotorrdquo regions may mediate the stabilising role of augmented sensory feedback.

Prefrontal cortex involvement in selective letter generation: A functional magnetic resonance imaging study

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

An exploration of varieties of visual attention: ERP findings

A set of five tasks was designed to examine dynamic aspects of visual attention: selective attention to color, selective attention to pattern, dividing and switching attention between color and pattern, and selective attention to pattern with changing target. These varieties of visual attention were examined using the same set of stimuli under different instruction sets; thus differences between tasks cannot be attributed to differences in the perceptual features of the stimuli. ERP data are presented for each of these tasks. A within-task analysis of different stimulus types varying in similarity to the attended target feature revealed that an early frontal selection positivity (FSP) was evident in selective attention tasks, regardless of whether color was the attended feature. The scalp distribution of a later posterior selection negativity (SN) was affected by whether the attended feature was color or pattern. The SN was largely unaffected by dividing attention across color and pattern. A large widespread positivity was evident in most conditions, consisting of at least three subcomponents which were differentially affected by the attention conditions. These findings are discussed in relation to prior research and the time course of visual attention processes in the brain. (C) 1999 Elsevier Science B.V. All rights reserved.

Relationships between movement initiation times and movement-related cortical potentials in Parkinson's disease

Movement-related cortical potentials recorded from the scalp reveal increasing cortical activity occurring prior to voluntary movement. Studies of set-related cortical activity recorded from single neurones within premotor and supplementary motor areas in monkeys suggest that such premovement activity may act to prime activity of appropriate motor units in readiness to move, thereby facilitating the movement response. Such a role of early stage premovement activity in movement-related cortical potentials was investigated by examining the relationship between premovement cortical activity and movement initiation or reaction times. Parkinson's disease and control subjects performed a simple button-pressing reaction time task and individual movement-related potentials were averaged for responses with short compared with long reaction times. For Parkinson's disease subjects but not for the control subjects, early stage premovement cortical activity was significantly increased in amplitude for faster reaction times, indicating that there is indeed a relationship between premovement cortical activity amplitude and movement initiation or reaction times. In support of studies of set-related cortical activity in monkeys, it is therefore suggested that early stage premovement activity reflects the priming of appropriate motor units of primary motor cortex, thereby reducing movement initiation or reaction times. (C) 1999 Elsevier Science B.V. All rights reserved.

MDMA (Ecstasy) neurotoxicity: assessing and communicating the risks

MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine analogue that produces euphoric and stimulant effects and a feeling of closeness towards others.1 and 2 For more than a decade, MDMA (colloquially known as “Ecstasy” or “E”) has been widely used by young adults as a dance-party drug. The usual recreational oral dose is 1-2 tablets (each containing about 60-120 mg of MDMA) a standard oral dose of 0·75–4·00 mg per kg in 60–80 kg people. MDMA is typically used once fortnightly or less because tolerance to the effects of MDMA develops rapidly. More frequent use requires larger doses to achieve the desired effects, but this increases the prevalence of unpleasant side-effects.3 A number of deaths have occurred as a result of malignant hyperthermia or idiosyncractic reactions to the drug, but these have been rare.4 MDMA is perceived by many users to be a safe drug.1 Few report the craving associated with opiates or cocaine3 and most MDMA users are aware of only mild and transient disruptions of functioning.3 and 5 AC Parrott and J Lasky, Ecstasy (MDMA) effects upon mood and cognition: before, during and after a Saturday night dance, Psychopharmacology 139 (1998), pp. 261–268. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (174)5 The perceived safety of MDMA is at odds with animal evidence of MDMA neurotoxicity, an increasing prevalence of hazardous patterns of use among recreational MDMA users, and emerging evidence of neurotoxicity among heavier MDMA users.

Finite element modelling of three-dimensional convection problems in fluid-saturated porous media heated from below

We use the finite element method to model three-dimensional convective pore-fluid flow in fluid-saturated porous media when they are heated from below. In particular, we employ the particle-tracking technique to mimic the trajectories of particles in three-dimensional fluid flow problems. The related numerical results demonstrated that: (1) The progressive asymptotic approach procedure, which was previously developed for the finite element modelling of two-dimensional convective pore-fluid flow problems, is equally applicable to the finite element modelling of three-dimensional convective pore-fluid flow in fluid-saturated porous media heated from below. (2) The perturbation of gravity at different planes has a significant effect on the pattern of three-dimensional convective pore-fluid flow and therefore, may influence the pattern of orebody formation and mineralization in three-dimensional hydrothermal systems. Copyright (C) 2001 John Wiley & Sons, Ltd.