Associative Visuomotor Learning Using Transcranial Magnetic Stimulation Induces Stimulus-Response Interference.

Classical conditioning states that the systematic co-occurrence of a neutral stimulus with an unconditioned stimulus can cause the neutral stimulus to, over time, evoke the same response as the unconditioned stimulus. On a neural level, Hebbian learning suggests that this type of learning occurs through changes in synaptic plasticity when two neurons are simultaneously active, resulting in increased connectivity between them. Inspired by associative learning theories, we here investigated whether the mere co-activation of visual stimuli and stimulation of the primary motor cortex using TMS would result in stimulus-response associations that can impact future behavior. During a learning phase, we repeatedly paired the presentation of a specific color (but not other colors) with a TMS pulse over the motor cortex. Next, participants performed a two-alternative forced-choice task where they had to categorize simple shapes and we studied whether the shapes' task-irrelevant color (and its potentially associated involuntary motor activity) affected the required motor response. Participants showed more errors on incongruent trials for stimuli that were previously paired with high intensity TMS pulses, but only when tested on the same day. Using a drift diffusion model for conflict tasks, we further demonstrate that this interference occurred early, and gradually increased as a function of associated TMS intensity. Taken together, our findings show that the human brain can learn stimulus-response associations using externally induced motor cortex stimulation. Although we were inspired by the Hebbian learning literature, future studies should investigate whether Hebbian or other learning processes were also what brought about this effect.

The gene environment aetiology of freezing and its relationship with internalizing symptoms during adolescence.

BACKGROUND: The freezing response is a universal response to threat, linked to attentive immobility and action preparation. It is relevant for acute stress coping in animals and humans, and subtle deviations in toddler freezing duration (absence of, or excessively long reactions) have been linked to higher risk for internalizing symptoms in adolescence. Yet, while individual freezing tendencies are relatively stable throughout life, little is known about their gene-environment aetiology. METHODS: We investigated the heritability of toddler freezing in the Quebec Newborn Twin Study (QNTS; n=508 twins) by fitting behavioural genetic models to video-coded freezing responses during a robot confrontation. Furthermore, we examined the predictive associations between toddler freezing and internalizing symptoms (anxiety and depressive symptoms), as they unfold during adolescence (ages 12-19 years) using linear mixed-effects models. FINDINGS: Freezing was found to be moderately heritable (45% of the variance accounted for by genetic factors). The remaining variance was explained by unique environmental factors, including measurement error. No significant contribution of shared environmental factors was noted. Additionally, shorter freezing was associated with more internalizing symptoms in adolescence at trend level, a pattern that was significant for depressive but not anxiety symptoms. INTERPRETATION: Freezing is an adaptive coping mechanism in early childhood, which is partly driven by genetic factors. Crucially, the absence or shorter duration of these behaviours may signal vulnerability to depressive problems later in life. FUNDING: Canadian Institutes of Health Research and Research Fund of Quebec-Health and Society and Culture. Consolidator grant from the European Research Council (ERC_CoG-2017_772337).