No abstract

Learning to articulate novel combinations of phonemes that form new words through a small number of auditory exposures is crucial for development of language and our capacity for fluent speech, yet the underlying neural mechanisms are largely unknown. We used functional magnetic resonance imaging to reveal repetition-suppression effects accompanying such learning and reflecting discrete changes in brain activity due to stimulus-specific fine-tuning of neural representations. In an event-related design, subjects were repeatedly exposed to auditory pseudowords, which they covertly repeated. Covert responses during scanning and postscanning overt responses showed evidence of learning. An extensive set of regions activated bilaterally when listening to and covertly repeating novel pseudoword stimuli. Activity decreased, with repeated exposures, in a subset of these areas mostly in the left hemisphere, including premotor cortex, supplementary motor area, inferior frontal gyrus, superior temporal cortex, and cerebellum. The changes most likely reflect more efficient representation of the articulation patterns of these novel words in two connected systems, one involved in the perception of pseudoword stimuli (in the left superior temporal cortex) and one for processing the output of speech (in the left frontal cortex). Both of these systems contribute to vocal learning.

One contribution of 15 to a theme issue 'Controlling brain activity to alter perception, behaviour and society'. The way in which emotion is represented and processed in the human brain is an expanding area of research and has key implications for how we understand and potentially treat affective disorders such as depression. Characterizing the effects of pharmacological manipulations of key neurotransmitter systems can also help reveal the neurochemical underpinnings of emotional processing and how common antidepressant drugs may work in the treatment of depression and anxiety. This approach has revealed that depression is associated with both neural and behavioural biases towards negative over positive stimuli. Evidence from pharmacological challenge studies suggests that antidepressant treatment acts to normalize these biases early on in treatment, resulting in patients experiencing the world in a more positive way, improving their mood over time. This model is supported by evidence from both pharmacological and non-pharmacological interventions. The unique perspective on antidepressant treatment offered by this approach provides some insights into individual response to treatment, as well as novel approaches to drug development.

Lithium is one of the most effective mood stabilizing medications in bipolar disorder.This study was designed to test whether lithium administration may stabilize mood via effects on reward processing. It was hypothesized that lithium administration would modulate reward processing in the striatum and affect both anticipation and outcome computations. Thirty-seven healthy human participants (18 males, 33 with suitable fMRI data) received 11 (+/-1) days of lithium carbonate or placebo intervention (double-blind), after which they completed the Monetary Incentive Delay task while fMRI data were collected. The Monetary Incentive Delay task is a robust task with excellent test-retest reliability and is well suited to investigate different phases of reward processing within the caudate and nucleus accumbens. To test for correlations with prediction error signals a Rescorla-Wagner reinforcement-learning model was applied. Lithium administration enhanced activity in the caudate during reward anticipation compared to placebo. In contrast, lithium administration reduced caudate and nucleus accumbens activity during reward outcome. This latter effect seems related to learning as reward prediction errors showed a positive correlation with caudate and nucleus accumbens activity during placebo, which was absent after lithium administration. Lithium differentially modulates the anticipation relative to the learning of rewards. This suggests that lithium might reverse dampened reward anticipation while reducing overactive reward updating in patients with bipolar disorder. This specific effect of lithium suggests that a targeted modulation of reward learning may be a viable approach for novel interventions in bipolar disorder.