Methylphenidate as a treatment option for substance use disorder: a transdiagnostic perspective

A transition in viewing mental disorders from conditions defined as a set of unique characteristics to one of the quantitative variations on a collection of dimensions allows overlap between disorders. The overlap can be utilized to extend to treatment approaches. Here, we consider the overlap between attention-deficit/hyperactivity disorder and substance use disorder to probe the suitability to use methylphenidate as a treatment for substance use disorder. Both disorders are characterized by maladaptive goal-directed behavior, impaired cognitive control, hyperactive phasic dopaminergic neurotransmission in the striatum, prefrontal hypoactivation, and reduced frontal cortex gray matter volume/density. In addition, methylphenidate has been shown to improve cognitive control and normalize associated brain activation in substance use disorder patients and clinical trials have found methylphenidate to improve clinical outcomes. Despite the theoretical basis and promising, but preliminary, outcomes, many questions remain unanswered. Most prominent is whether all patients who are addicted to different substances may equally profit from methylphenidate treatment

Impact of filgotinib on pain control in the phase 3 FINCH studies

Objective This post hoc analysis of the FINCH 1–3 (NCT02889796, NCT02873936 and NCT02886728) studies assessed specific effects of filgotinib on pain control and their relationship with other aspects of efficacy in patients with rheumatoid arthritis (RA). Methods Assessments included: residual pain responses of ≤10 and ≤20 mm on a 100 mm visual analogue scale (VAS); the proportion of patients who achieved VAS pain responses in addition to remission or low disease activity by Disease Activity Score-28 with C-reactive protein (DAS28-CRP) or Clinical Disease Activity Index (CDAI) criteria. Results Across studies, filgotinib reduced pain from week 2, with responses sustained throughout the studies. In FINCH 1, at week 24, 35.8%, 25.0%, 24.6% and 11.6% of patients in the filgotinib 200 mg, filgotinib 100 mg, adalimumab and placebo arms (each plus methotrexate) achieved VAS pain ≤20 mm in addition to DAS28-CRP remission; 26.3%, 17.9%, 17.2% and 7.6% achieved VAS pain ≤10 mm in addition to DAS28-CRP remission. A similar pattern was seen for CDAI remission. Time during which VAS pain was ≤10 or ≤20 mm was longest with filgotinib 200 mg and comparable between adalimumab and filgotinib 100 mg. Similar findings were reported for filgotinib in FINCH 2 and 3. Conclusion In all RA populations studied, pain improvements occurred from week 2 and were sustained over time. In FINCH 1, filgotinib 100 mg provided similar pain amelioration to adalimumab, whereas filgotinib 200 mg resulted in greater pain improvement and higher proportion of patients with residual pain ≤10 or ≤20 mm and meeting DAS28-CRP remission criteria

Percussion Convocation

Program listing performers and works performe

Logic and Value in Wittgenstein's Philosophy

In Tractatus Logico‐Philosophicus (TLP), Wittgenstein gave ethics the same semantic status as logic. This paper first investigates this claim from the perspective of Wittgenstein’s lifelong semantic framework. This reveals that ethical sentences are meaningless expressions, which can only be used to ostensively point out conditions of meaningfulness. Secondly, the paper assesses the implications of this conclusion for understanding the seven cryptic remarks on value and ethics in TLP. Using the connection between will and value in TLP and will and sentence interpretation in Philosophical Investigations, it is suggested that Wittgenstein held lifelong views on value and ethic

PFCTEXD - Striatum

Distributed and interconnected representation of different task context in striatum and lateral PFC

Task-specific subnetworks extend from prefrontal cortex to striatum

Functional magnetic resonance imaging (fMRI) studies on the dynamic representation of task content focus preferentially on the cerebral cortex. However, neurophysiological studies report coding of task-relevant features also by neurons in the striatum, suggesting basal ganglia involvement in cognitive decision-making. Here we use fMRI data to show that also in humans the striatum is an integrated part of the cognitive brain network. Twelve participants performed 3 cognitive tasks in the scanner, i.e., the Eriksen flanker task, a 2-back matching spatial working memory task, and a response scheme switching task. First, we use region of interest-based multivariate pattern classification to demonstrate that each task reliably induces a unique activity pattern in the striatum and in the lateral prefrontal cortex. We show that the three tasks can also be distinguished in putamen, caudate nucleus and ventral striatum alone. We additionally establish that the contribution of striatum to cognition is not sensitive to habituation or learning. Secondly, we use voxel-to-voxel functional connectivity to establish that voxels in the lateral prefrontal cortex and in the striatum that prefer the same task show significantly stronger functional coupling than voxel pairs in these remote structures that prefer different tasks. These results suggest that striatal neurons form subnetworks with cognition-related regions of the prefrontal cortex. These remote neuron populations are interconnected via functional couplings that exceed the time of execution of the specific tasks

Functional connectivity of task context representations in prefrontal nodes of the multiple demand network

A subset of regions in the lateral and medial prefrontal cortex and the anterior insula increase their activity level whenever a cognitive task becomes more demanding, regardless of the specific nature of this demand. During execution of a task, these areas and the surrounding cortex temporally encode aspects of the task context in spatially distributed patterns of activity. It is not clear whether these patterns reflect underlying anatomical subnetworks that still exist when task execution has finished. We use fMRI in 12 participants performing alternating blocks of three cognitive tasks to address this question. A first data set is used to define multiple demand regions in each participant. A second dataset from the same participants is used to determine multiple demand voxel assemblies with a preference for one task over the others. We then show that these voxels remain functionally coupled during execution of non-preferred tasks and that they exhibit stronger functional connectivity during rest. This indicates that the assemblies of task preference sharing voxels reflect patterns of underlying anatomical connections. Moreover, we show that voxels preferring the same task have more similar whole brain functional connectivity profiles that are consistent across participants. This suggests that voxel assemblies differ in patterns of input-output connections, most likely reflecting task demand-specific information exchange

Improved intersubject colocalization of functional activations by nonlinear fitting of individual contrast maps to a functional atlas

A comparison of activation maps obtained with fMRI reveals substantial inter-individual variability in the anatomical location of activated areas. In group studies functional data are smoothed with a Gaussian kernel to increase the functional overlap between activated areas from different subjects. We present an alternative approach to increase this overlap, based on non-linear deformations of individual contrast maps to a sample-specific minimal deformation target. Functional images were obtained from six adult subjects passively viewing a short stimulus sequence. The stimuli were organized in a blocked design with three conditions: static objects, faces and moving natural scenes. All functional images were spatially normalized to the standard MNI template. Individual statistical maps were calculated, contrasting each of the three conditions with a fixation condition. Deformation fields resulting from viscous fluid registrations between these individual contrast maps were obtained to create sample-specific minimal deformation targets for the three contrasts. For each subject we then calculated the average deformation needed to register each contrast map with its associated target. This subject-specific deformation field was subsequently applied to all functional images for that specific subject. This procedure does increase the inter-subject overlap in activated areas, as evidenced by a comparison between the results of fixed-effects group analyses on the deformed and on the undeformed functional images. The analysis on the functionally deformed images yields about one third more activated clusters than the analysis on the functionally undeformed images (33 versus 24). With functionally deformed images the contrast between moving scenes and fixation reveals a number of areas that are not significantly activated with functionally undeformed images: hMT/V5, the frontal eye fields (FEF) and both the anterior and lateral dorsal intraparietal sulcus regions (DIPSA and DIPSL). We believe the enhanced functional overlap generated by this functional atlas fitting paradigm improves the analysis of functional group data. Moreover, this paradigm provides a means for a direct mapping of a functional brain atlas to individual contrast maps. As such, it may enable automated labeling of functional areas and as such provide a valuable diagnostic tool for functional patient studies.status: publishe

Task-specific subnetworks extend from prefrontal cortex to striatum

Functional magnetic resonance imaging (fMRI) studies on the dynamic representation of task content focus preferentially on the cerebral cortex. However, neurophysiological studies report coding of task-relevant features also by neurons in the striatum, suggesting basal ganglia involvement in cognitive decision-making. Here we use fMRI data to show that also in humans the striatum is an integrated part of the cognitive brain network. Twelve participants performed 3 cognitive tasks in the scanner, i.e., the Eriksen flanker task, a 2-back matching spatial working memory task, and a response scheme switching task. First, we use region of interest-based multivariate pattern classification to demonstrate that each task reliably induces a unique activity pattern in the striatum and in the lateral prefrontal cortex. We show that the three tasks can also be distinguished in putamen, caudate nucleus and ventral striatum alone. We additionally establish that the contribution of striatum to cognition is not sensitive to habituation or learning. Secondly, we use voxel-to-voxel functional connectivity to establish that voxels in the lateral prefrontal cortex and in the striatum that prefer the same task show significantly stronger functional coupling than voxel pairs in these remote structures that prefer different tasks. These results suggest that striatal neurons form subnetworks with cognition-related regions of the prefrontal cortex. These remote neuron populations are interconnected via functional couplings that exceed the time of execution of the specific tasks

Vandenbussche E: Optotype and grating visual acuity in patients with ocular and cerebral visual impairment. Invest Ophthalmol Vis Sci 2004

PURPOSE. To investigate the discrepancy between grating and optotype visual acuity in children with visual impairment due to brain and/or ocular abnormalities. METHODS. Better eye acuity at 114 cm was studied in 81 patients (ages, 5-24 years) attending special schools for the visually handicapped. Fourteen patients had a brain abnormality, 48 had an ocular disorder, and 19 had both. Three acuity tasks were administered: detecting gratings in one of two positions, discriminating the orientation of single gratings, and discriminating the orientation of uncrowded Landolt-C optotypes. The three paradigms were similar in stimulus contrast, luminance, presentation mode, and psychophysical procedure. RESULTS. Overall, grating acuity was better than optotype acuity, and the disparity increased with poorer optotype acuity. The largest discrepancies occurred in patients with brain abnormality, but disparities were also large in patients with optic nerve disorder. In patients with ocular and brain abnormality, grating acuities were only mildly better and not different from patients with only ocular abnormality. Grating orientation and grating detection tasks yielded similar thresholds, except in patients with cerebral visual impairment and with optic nerve disorder, whose grating detection acuity was better than grating orientation acuity. CONCLUSIONS. Grating-to-optotype acuity superiority is typically large in visual disorders involving the brain. The closely matched test paradigms point to stimulus characteristics as the explanation. However, because the discrepancy decreased with grating orientation acuity instead of grating detection acuity, the complexity of the response required also plays a role. (Invest Ophthalmol Vis Sci