Stimulating human prefrontal cortex increases reward learning.

Work in computational psychiatry suggests that mood disorders may stem from aberrant reinforcement learning processes. Specifically, it has been proposed that depressed individuals believe that negative events are more informative than positive events, resulting in higher learning rates from negative outcomes (Pulcu and Browning, 2019). In this proof-of-concept study, we investigated whether transcranial direct current stimulation (tDCS) applied to dorsolateral prefrontal cortex, as commonly used in depression treatment trials, might change learning rates for affective outcomes. Healthy adults completed an established reinforcement learning task (Pulcu and Browning, 2017) in which the information content of reward and loss outcomes was manipulated by varying the volatility of stimulus-outcome associations. Learning rates on the tasks were quantified using computational models. Stimulation over dorsolateral prefrontal cortex (DLPFC) but not motor cortex (M1) increased learning rates specifically for reward outcomes. The effects of prefrontal tDCS were cognitive state-dependent: tDCS applied during task performance increased learning rates for wins; tDCS applied before task performance decreased both win and loss learning rates. A replication study confirmed the key finding that tDCS to DLPFC during task performance increased learning rates specifically for rewards. Taken together, these findings demonstrate the potential of tDCS for modulating computational parameters of reinforcement learning that are relevant to mood disorders.

Estimating premorbid intelligence in people living with dementia: a systematic review.

OBJECTIVES: In diagnosing dementia, estimating premorbid functioning is critical for accurate detection of the presence and severity of cognitive decline. However, which assessments of premorbid intelligence are most suitable for use in clinical practice is not well established. Here, we systematically evaluate the validity of instruments for measuring premorbid intelligence in people living with dementia. DESIGN AND SETTING: In this systematic review, electronic databases (EMBASE, PsycINFO, MEDLINE, CINAHL, and AMED) were searched to identify studies reporting on objective measures of premorbid intelligence in dementia. Participants from included studies were recruited from local communities and clinical settings. PARTICIPANTS: A total of 1082 patients with dementia and 2587 healthy controls were included in the review. MEASUREMENTS: The literature search resulted in 13 eligible studies describing 19 different instruments. The majority of instruments (n = 14) consisted of language-based measures, with versions of the National Adult Reading Test (NART) being most commonly investigated. RESULTS: Preliminary evidence suggested comparable performance of patients with mild dementia and healthy controls on word reading tasks in English, Portuguese, Swedish, and Japanese. In moderate dementia, however, the performance was significantly impaired on most verbal tasks. There was a lack of reliability and validity testing of available instruments, with only one of the included studies reporting psychometric properties within the patient group. CONCLUSIONS: The results demonstrate that there is a wide range of tools available for estimating premorbid intelligence in dementia, with cautious support for the potential of word reading tasks across different languages in individuals with mild dementia. However, the review highlights the urgent need for extensive assessments of the psychometric properties of these tasks in dementia. We propose that further longitudinal research and assessments of nonverbal measures are necessary to validate these instruments and enhance diagnostic procedures for people living with dementia worldwide.

Inducing Affective Learning Biases with Cognitive Training and Prefrontal tDCS: A Proof-of-Concept Study.

BACKGROUND: Cognitive models of mood disorders emphasize a causal role of negative affective biases in depression. Computational work suggests that these biases may stem from a belief that negative events have a higher information content than positive events, resulting in preferential processing of and learning from negative outcomes. Learning biases therefore represent a promising target for therapeutic interventions. In this proof-of-concept study in healthy volunteers, we assessed the malleability of biased reinforcement learning using a novel cognitive training paradigm and concurrent transcranial direct current stimulation (tDCS). METHODS: In two studies, young healthy adults completed two sessions of negative (n = 20) or positive (n = 20) training designed to selectively increase learning from loss or win outcomes, respectively. During training active or sham tDCS was applied bilaterally to dorsolateral prefrontal cortex. Analyses tested for changes both in learning rates and win- and loss-driven behaviour. Potential positive/negative emotional transfer of win/loss learning was assessed by a facial emotion recognition task and mood questionnaires. RESULTS: Negative and positive training increased learning rates for losses and wins, respectively. With negative training, there was also a trend for win (but not loss) learning rates to decrease over successive task blocks. After negative training, there was evidence for near transfer in the form of an increase in loss-driven choices when participants performed a similar (untrained) task. There was no change in far transfer measures of emotional face processing or mood. tDCS had no effect on any aspect of behaviour. DISCUSSION AND CONCLUSIONS: Negative training induced a mild negative bias in healthy adults as reflected in loss-driven choice behaviour. Prefrontal tDCS had no effect. Further research is needed to assess if this training procedure can be adapted to enhance learning from positive outcomes and whether effects translate to affective disorders.

Splenial white matter integrity is associated with memory impairments in posterior cortical atrophy.

Posterior cortical atrophy is an atypical form of Alzheimer's disease characterized by visuospatial impairments and predominant tissue loss in the posterior parieto-occipital and temporo-occipital cortex. Whilst episodic memory is traditionally thought to be relatively preserved in posterior cortical atrophy, recent work indicates that memory impairments form a common clinical symptom in the early stages of the disease. Neuroimaging studies suggest that memory dysfunction in posterior cortical atrophy may originate from atrophy and functional hypoconnectivity of parietal cortex. The structural connectivity patterns underpinning these memory impairments, however, have not been investigated. This line of inquiry is of particular interest, as changes in white matter tracts of posterior cortical atrophy patients have been shown to be more extensive than expected based on posterior atrophy of grey matter. In this cross-sectional diffusion tensor imaging MRI study, we examine the relationship between white matter microstructure and verbal episodic memory in posterior cortical atrophy. We assessed episodic memory performance in a group of posterior cortical atrophy patients (n = 14) and a group of matched healthy control participants (n = 19) using the Free and Cued Selective Reminding Test with Immediate Recall. Diffusion tensor imaging measures were obtained for 13 of the posterior cortical atrophy patients and a second control group of 18 healthy adults. Patients and healthy controls demonstrated similar memory encoding performance, indicating that learning of verbal information was preserved in posterior cortical atrophy. However, retrieval of verbal items was significantly impaired in the patient group compared with control participants. As expected, tract-based spatial statistics analyses showed widespread reductions of white matter integrity in posterior cortical regions of patients compared with healthy adults. Correlation analyses indicated that poor verbal retrieval in the patient group was specifically associated with microstructural damage of the splenium of the corpus callosum. Post-hoc tractography analyses in healthy controls demonstrated that this splenial region was connected to thalamic radiations and the retrolenticular part of the internal capsule. These results provide insight into the brain circuits that underlie memory impairments in posterior cortical atrophy. From a cognitive perspective, we propose that the association between splenial integrity and memory dysfunction could arise indirectly via disruption of attentional processes. We discuss implications for the clinical phenotype and development of therapeutic aids for cognitive impairment in posterior cortical atrophy.