Investigating subtypes of reward processing deficits as trait markers for depression

Background: Anhedonia, the loss of pleasure in usually enjoyable activities, is a central feature of major depressive disorder (MDD). The aim of the present study was to examine whether young people at a familial risk of depression display signs of anticipatory, motivational or consummatory anhedonia, which would indicate that these deficits may be trait markers for MDD. Methods: The study was completed by 22 participants with a family history of depression (FH+) and 21 controls (HC). Anticipatory anhedonia was assessed by asking participants to rate their anticipated liking of pleasant and unpleasant foods which they imagined tasting when cued with images of the foods. Motivational anhedonia was measured by requiring participants to perform key presses to obtain pleasant chocolate taste rewards or to avoid unpleasant apple tastes. Additionally, physical consummatory anhedonia was examined by instructing participants to rate the pleasantness of the acquired tastes. Moreover, social consummatory anhedonia was investigated by asking participants to make preference-based choices between neutral facial expressions, genuine smiles, and polite smiles. Results: It was found that the FH+ group’s anticipated liking of unpleasant foods was significantly lower than that of the control group. By contrast, no group differences in the pleasantness ratings of the actually experienced tastes or in the amount of performed key presses were observed. However, controls preferred genuine smiles over neutral expressions more often than they preferred polite smiles over neutral expressions, while this pattern was not seen in the FH+ group. Conclusion: These findings suggest that FH+ individuals demonstrate an altered anticipatory response to negative stimuli and show signs of social consummatory anhedonia, which may be trait markers for depression

Examining Mechanisms of Childhood Cognitive Control

Childhood cognitive control is an important predictor for positive development, yet interventions seeking to improve it have provided mixed results. This is partly due to lack of clarity surrounding mechanisms of cognitive control, notably the role of inhibition and context monitoring. Here we use a randomized controlled trial to causally test the contributions of inhibition and context monitoring to cognitive control in childhood. Sixty children aged 6 to 9-years were assigned to three groups training either inhibition, context monitoring group or response speed using a gamified, highly variable and maximally adaptive training protocol. Whereas all children improved in the targeted cognitive functions over the course of training, pre-post data show that only the inhibition group improved on cognitive control. These findings serve as a first step in demonstrating the promise inhibition-based cognitive control interventions may hold

In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans

Not context monitoring but inhibition plays a privileged role in childhood cognitive control

Childhood cognitive control is an important predictor for positive development, yet interventions seeking to improve it have provided mixed results. This is partly due to lack of clarity surrounding mechanisms of cognitive control, notably the role of inhibition and context monitoring. Here we use a randomized controlled trial to causally test the contributions of inhibition and context monitoring to cognitive control in childhood. Sixty children aged 6 to 9-years were assigned to three groups training either inhibition, context monitoring group or response speed using a gamified, highly variable and maximally adaptive training protocol. Whereas all children improved in the targeted cognitive functions over the course of training, pre-post data show that only the inhibition group improved on cognitive control. These data support a privileged role of inhibition in cognitive control during childhood. Further, gamified and maximally adaptive interventions hold promise for improving cognitive control at developmental periods of heightened plasticity

Choline-containing metabolite spectrum.

<p>Spectral patterns for the metabolites CHO, PHC and GPC simulated using VeSPA (<a href="https://scion.duhs.duke.edu/vespa/project" target="_blank">https://scion.duhs.duke.edu/vespa/project</a>). Metabolites were simulated at a field strength of 3T (main field 123.25MHz) using a PRESS pulse sequence (TE1 = 20ms, TE2 = 10ms).</p

Choline-containing metabolite amplitude changes in synthetic data.

<p>Amplitudes of choline (CHO, red) and the combined phosphocholine/glycerophosphocholine peak (PHC/GPC, blue) estimated using the MOD_CHOsep (top) and MOD_CHOglobal (bottom) models in synthetic data. Estimated levels of CHO (red) and PHC/GPC (blue) show an increase in line with the simulated levels of CHO and PHC. Also shown are the levels of NAA and CRE and GPC (right panel). Note that the bottom panel shows combined amplitudes for choline-containing compounds as the MOD_CHOglobal model does not differentiate between CHO and other choline-containing metabolites.</p

Overview of trial and MRS acquisition timing.

<p>Trial timing (top): Each trial had a total length of 5s and begun with a short onset jitter of 0–0.29 s, followed by a cue (0.5s) and a jittered inter stimulus interval (ISI) of 0.8 to 1.3s. The stimuli were presented for 0.5s followed by a maximum response interval of 2.2s and an inter trial interval (ITI) of 0.2 to 0.5s. MRS acquisition (bottom): We collected two MRS acquisitions for each trial (2.5s)—an early epoch, covering the cue, the attention shift phase and part of the stimuli, and a late epoch covering the rest of the trial.</p

Sum of MRS voxels over all subjects.

<p>For better visualization the MRS voxel masks were transformed to MNI space. All subjects contributed to coordinates with the highest overlap, including the average center coordinate (MNI -18, -72, 42) (yellow color).</p