Biology subjects

Bosch, J. E.

Publications and source records attributed to Bosch, J. E..

6 recordsLinked to original sources

bioRxiv2025

Basal forebrain and neural correlates of self-regulation traits in sustained attention

Self-regulation is a human trait consistently associated with success in both academic and professional settings and to better mental health. Based on previous findings, we used functional imaging data in a sustained attention task to test three hypotheses on neural substrates associated with individual differences in self-regulation. The first linked higher self-regulation and cognitive control, predicting modulation of recruitment of prefrontal substrates. The second, originating in the animal literature, suggests increased recruitment of cholinergic substrates in the basal forebrain. The third predicted higher modulation of reward-sensitive regions in the brainstem in less regulated individuals for differences in reward levels during the task. The second hypothesis was confirmed by our study, which also provided suggestive evidence for the third hypothesis. Our data suggest that one mechanism of higher self-regulation in humans may ensue from greater activity in the cholinergic system to sustain attention during a cognitively simple task.

neuroscience↗

bioRxiv2024

Cognitive effort and reward. Functional imaging of time on task and the involvement of dopaminergic and cholinergic substrates

Neuroimaging studies have identified the neural substrates associated with sustained cognitive efforts and control and their modulation by rewards. Different lines of evidence implicate the prefrontal cortex (especially the anterior cingulate cortex, ACC), dopaminergic, and cholinergic substrates in this modulation. We studied here the activity of these substrates at increasing time on task (requiring increasing levels of cognitive effort) in trials within blocks with differing reward levels. In the cortex, while peaking in the ACC, activity associated with time on task was extensive, also including activity decrements outside the default mode network, primarily involving motor and somatosensory regions. Information about reward levels was carried in the ventral striatum, consistent with its motivational role, but did not reflect trade-offs with increasing efforts during time on task. Instead, the ventral tegmental area and parts of the basal forebrain (BF) corresponding to the cholinergic Ch4 nuclei increased in activity with time on task and were sensitive to reward levels. This BF activity is consistent with a cholinergic role in driving compensatory efforts modulated by reward levels. These findings identify the BF as a neuroimaging phenotype associated with sustaining task sets and cognitive efforts.

neuroscience↗

bioRxiv2020

Genetic polymorphism of CYP2C19 and subcortical variability in the human adult brain

Pharmacogenetic studies have shown involvement of cytochrome P450 enzymes in the metabolism of psychotropic drugs. However, expression and activity on endogenous substrates in the brain may underlie a constitutive role of these enzymes beyond drug metabolism. CYP2C19, which is expressed in the human fetal brain during neurodevelopment, shows affinity for endogenous compounds including monoaminergic neurotransmitters, steroid hormones, and endocannabinoids. In this study (N=608), we looked at the genetic polymorphism of CYP2C19 and its potential associations with structural phenotypes of subcortical brain volume with structural imaging. Using two independent volume estimation techniques, we found converging evidence for a positive association between CYP2C19 activity scores, as inferred from the genotype, and basal ganglia and hippocampal volume. This association was present only in female individuals, raising the possibility that effects on brain morphology may arise through a mechanism involving the metabolism of estrogen steroids.

neuroscience↗

bioRxiv2019

Choosing between personal values: The Pavlovian substrates of intrinsic preferences

Several brain circuits interact in computing the value of choices between options, as when we express our preference between a set of available consumer goods. Here, we used a procedure developed in functional neuroimaging studies of consumer choice to identify the neural substrates activated by choosing between values that, when put into practice, can give meaning to ones life, such as achievement, community, tradition, or religion, and are unrelated to material needs or financial security. In a first sample (N=18), instead of the neural substrates usually associated with choice between consumer goods, we found activation of the amygdala, a limbic system structure which presides over assignment of values to stimuli according to immediate affective experience and promotes responses according to their association with potential rewards. This unexpected finding was replicated in a second independent sample (N=18). These results are consistent with views arguing for the existential nature of values that give meaning to ones life here and now, in contrast to maximizing long-term utility.

neuroscience↗

bioRxiv2019

Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity

The polymorphic drug-metabolizing enzyme CYP2D6, which is responsible for the metabolism of most psychoactive compounds, is expressed not only in the liver, but also in the brain. The effects of its marked genetic polymorphism on the individual capacity to metabolize drugs are well known, but its role in metabolism of neural substrates affecting behavior personality or cognition, suggested by its CNS expression, is a long-standing unresolved issue. To verify earlier findings suggesting a potential effect on attentional processes, we collected functional imaging data while N=415 participants performed a simple task in which the reward for correct responses varied. CYP2D6 allelic variants predicting higher levels of enzymatic activity level were positively associated with cortical activity in occipito-parietal areas as well as in a right lateralized network known to be activated by spatial attentional tasks. Reward-related modulation of activity in cortical areas was more pronounced in poor metabolizers. In conjunction with effects on reaction times, our findings provide evidence for reduced cognitive efficiency in rapid metabolizers compared to poor metabolizers in on-task attentional processes manifested through differential recruitment of a specific neural substrate.

pharmacology and toxicology↗

bioRxiv2019

Signals of anticipation of reward and of mean reward rates in the human brain

Theoretical models of dopamine function stemming from reinforcement learning theory have emphasized the importance of prediction errors, which signal changes in the expectation of impending rewards. Much less is known about the effects of mean reward rates, which may be of motivational significance due to their role in computing the optimal effort put into exploiting reward opportunities. Here, we used a reinforcement learning model to design three functional neuroimaging studies and disentangle the effects of changes in reward expectations and mean reward rates, showing recruitment of specific regions in the brainstem regardless of prediction errors. While changes in reward expectations activated ventral striatal areas as in previous studies, mean reward rates preferentially modulated the substantia nigra/ventral tegmental area, deep layers of the superior colliculi, and a posterior pontomesencephalic region. These brainstem structures may work together to set motivation and attentional efforts levels according to perceived reward opportunities.

neuroscience↗