Riding the techwave in an era of change

Learn how innovation is finding its way within the healthcare sector and get a grip on the latest technological developments. Based on insights from 77 stakeholders within the Dutch healthcare system, including healthcare professionals, entrepreneurs, researchers, consultants, policy makers, and input from 80 healthcare consumers this book helps you to understand: • the technologies with the highest implementation potential in the healthcare

Catecholamine-mediated increases in neural gain improve the precision of cortical representations

Neurophysiological evidence suggests that neuromodulators, such as norepinephrine and dopamine, increase neural gain in target brain areas. Computational models and prominent theoretical frameworks indicate that this should enhance the precision of neural representations, but direct empirical evidence for this hypothesis is lacking. In two functional MRI studies, we examine the effect of baseline catecholamine levels (as indexed by pupil diameter and manipulated pharmacologically) on the precision of object representations in the human ventral temporal cortex using angular dispersion, a powerful, multivariate metric of representational similarity (precision). We first report the results of computational model simulations indicating that increasing catecholaminergic gain should reduce the angular dispersion, and thus increase the precision, of object representations from the same category, as well as reduce the angular dispersion of object representations from distinct categories when distinct-category representations overlap. In Study 1 (N = 24), we show that angular dispersion covaries with pupil diameter, an index of baseline catecholamine levels. In Study 2 (N = 24), we manipulate catecholamine levels and neural gain using the norepinephrine transporter blocker atomoxetine and demonstrate consistent, causal effects on angular dispersion and brain-wide functional connectivity. Despite the use of very different methods of examining the effect of baseline catecholamine levels, our results show a striking convergence and demonstrate that catecholamines increase the precision of neural representations

Catecholaminergic neuromodulation shapes intrinsic MRI functional connectivity in the human brain

The brain commonly exhibits spontaneous (i.e., in the absence of a task) fluctuations in neural activity that are correlated across brain regions. It has been established that the spatial structure, or topography, of these intrinsic correlations is in part determined by the fixed anatomical connectivity between regions. However, it remains unclear which factors dynamically sculpt this topography as a function of brain state. Potential candidate factors are subcortical catecholaminergic neuromodulatory systems, such as the locus ceruleus-norepinephrine system, which send diffuse projections to most parts of the forebrain. Here, we systematically characterized the effects of endogenous central neuromodulation on correlated fluctuations during rest in the human brain. Using a double-blind placebo-controlled crossover design, we pharmacologically increased synaptic catecholamine levels by administering atomoxetine, an NE transporter blocker, and examined the effects on the strength and spatial structure of resting-state MRI functional connectivity. First, atomoxetine reduced the strength of inter-regional correlations across three levels of spatial organization, indicating that catecholamines reduce the strength of functional interactions during rest. Second, this modulatory effect on intrinsic correlations exhibited a substantial degree of spatial specificity: the decrease in functional connectivity showed an anterior-posterior gradient in the cortex, depended on the strength of baseline functional connectivity, and was strongest for connections between regions belonging to distinct resting-state networks. Thus, catecholamines reduce intrinsic correlations in a spatially heterogeneous fashion. We conclude that neuromodulation is an important factor shaping the topography of intrinsic functional connectivity

Noradrenergic regulation of cognitive flexibility:No effects of stress, transcutaneous vagus nerve stimulation, and atomoxetine on task-switching in humans

Cognitive flexibility allows us to adaptively switch between different responsibilities in important domains of our daily life. Previous work has elucidated the neurochemical basis underlying the ability to switch responses to a previously nonreinforced exemplar and to switch between attentional sets. However, the role of neuromodulators in task switching, the ability to rapidly switch between two or more cognitive tasks afforded by the same stimuli, is still poorly understood. We attempted to fill this gap by manipulating norepinephrine levels using stress manipulation (Study 1a,n= 48; between-group design), transcutaneous vagus nerve stimulation at two different intensities (Study 1b,n= 48; sham-controlled between-group design), and pharmacological manipulation (Study 2,n= 24; double-blind crossover design), all of which increased salivary cortisol measures. Participants repeatedly switched between two cognitive tasks (classifying a digit as high/low [Task 1] or as odd/even [Task 2]), depending on the preceding cue. On each trial, a cue indicated the task to be performed. The cue-stimulus interval was varied to manipulate the time to prepare for the switch. Participants showed typical switch costs, which decreased with the time available for preparation. None of the manipulations modulated the size of the switch costs or the preparation effect, as supported by frequentist and Bayesian model comparisons. Task-switching performance reflects a complex mix of cognitive control and bottom-up dynamics of task-set representations. Our findings suggest that norepinephrine does not affect either of these aspects of cognitive flexibility

Noradrenergic regulation of cognitive flexibility: No effects of stress, transcutaneous vagus nerve stimulation, and atomoxetine on task-switching in humans

Cognitive flexibility allows us to adaptively switch between different responsibilities in important domains of our daily life. Previous work has elucidated the neurochemical basis underlying the ability to switch responses to a previously nonreinforced exemplar and to switch between attentional sets. However, the role of neuromodulators in task switching, the ability to rapidly switch between two or more cognitive tasks afforded by the same stimuli, is still poorly understood. We attempted to fill this gap by manipulating norepinephrine levels using stress manipulation (Study 1a,n= 48; between-group design), transcutaneous vagus nerve stimulation at two different intensities (Study 1b,n= 48; sham-controlled between-group design), and pharmacological manipulation (Study 2,n= 24; double-blind crossover design), all of which increased salivary cortisol measures. Participants repeatedly switched between two cognitive tasks (classifying a digit as high/low [Task 1] or as odd/even [Task 2]), depending on the preceding cue. On each trial, a cue indicated the task to be performed. The cue-stimulus interval was varied to manipulate the time to prepare for the switch. Participants showed typical switch costs, which decreased with the time available for preparation. None of the manipulations modulated the size of the switch costs or the preparation effect, as supported by frequentist and Bayesian model comparisons. Task-switching performance reflects a complex mix of cognitive control and bottom-up dynamics of task-set representations. Our findings suggest that norepinephrine does not affect either of these aspects of cognitive flexibility

Quantifying the contrast of the human locus coeruleus in vivo at 7 Tesla MRI.

The locus coeruleus is a small brainstem nucleus which contains neuromelanin cells and is involved in a number of cognitive functions such as attention, arousal and stress, as well as several neurological and psychiatric disorders. Locus coeruleus imaging in vivo is generally performed using a T1-weighted turbo spin echo MRI sequence at 3 Tesla (T). However, imaging at high magnetic field strength can increase the signal-to-noise ratio and offers the possibility of imaging at higher spatial resolution. Therefore, in the present study we explored the possibility of visualizing the locus coeruleus at 7T. To this end, twelve healthy volunteers participated in three scanning sessions: two with 3T MRI and one with 7T MRI. The volumes of the first 3T session were used to segment the locus coeruleus, whereas the volumes of the second 3T and the 7T session were used to quantify the contrast of the locus coeruleus with several reference regions across eight different structural sequences. The results indicate that several of the 7T sequences provide detectable contrast between the locus coeruleus and surrounding tissue. Of the tested sequences, a T1-weighted sequence with spectral presaturation inversion recovery (SPIR) seems the most promising method for visualizing the locus coeruleus at ultra-high field MRI. While there is insufficient evidence to prefer the 7T SPIR sequence over the 3T TSE sequence, the isotropic voxels at 7T are an important advantage when visualizing small structures such as the locus coeruleus

Transcutaneous Vagus Nerve Stimulation Enhances Post-error Slowing

FSW - Self-regulation models for health behavior and psychopathology - ou

In vivo visualization of the locus coeruleus in humans: quantifying the test-retest reliability

The locus coeruleus (LC) is a brainstem nucleus involved in important cognitive functions. Recent developments in neuroimaging methods and scanning protocols have made it possible to visualize the human LC in vivo by utilizing a T1-weighted turbo spin echo (TSE) scan. Despite its frequent use and its application as a biomarker for tracking the progress of monoaminergic-related neurodegenerative diseases, no study to date has investigated the reproducibility and inter-observer variability of LC identification using this TSE scan sequence. In this paper, we aim to quantify the test-retest reliability of LC imaging by assessing stability of the TSE contrast of the LC across two independent scan sessions and by quantifying the intra- and inter-rater reliability of the TSE scan. Additionally, we created a probabilistic LC atlas which can facilitate the spatial localization of the LC in standardized (MNI) space. Seventeen healthy volunteers participated in two scanning sessions with a mean intersession interval of 2.8 months. We found that for intra-rater reliability the mean Dice coefficient ranged between 0.65 and 0.74, and inter-rater reliability ranged between 0.54 and 0.64, showing moderate reproducibility. The mean LC contrast was 13.9% (SD 3.8) and showed scan-rescan stability (ROI approach: ICC = 0.63; maximum intensity approach: ICC = 0.53). We conclude that localization and segmentation of the LC in vivo are a challenging but reliable enterprise although clinical or longitudinal studies should be carried out carefully