Correction to: Mapping anticipatory anhedonia: an fMRI study.

The image of the Figure 2b in Figure 2 in the published article was incorrect and the authors would like to correct them. The original article has been corrected.

Mapping anticipatory anhedonia: an fMRI study.

Anhedonia-broadly defined as loss of interest and/or an inability to experience pleasure-is an important feature of several psychiatric disorders. Research into the clinical presentation and neurobiology of this symptom has identified components related to motivation, learning, anticipation, and experience of pleasure as important constructs that inform therapeutic interventions. The experimental study of anhedonia is largely based on incentive processing paradigms, most often with monetary rewards, though studies have also used pleasantness ratings of various stimuli. However, linking an individual's own system of reinforcers and ability to enjoy them with anhedonia and neural activity remains comparatively under-explored. A previous study of participants with major depressive disorder (MDD) and healthy controls found that activity word ratings correlated with measures of anhedonia, depression, and motivation. The present study collected functional magnetic resonance imaging (fMRI) images in healthy controls while they rated activity words and pictures showing activities in order to identify networks differentially responsive to subjective decisions about the appetitive value of activities. The study sought to measure individually-relevant hedonic capacity as demonstrated by correlations between task measures and anticipatory anhedonia ratings. Ratings of potential pleasure were associated with neural activity in areas previously identified as relevant to pleasure and reward processing, such as anterior and posterior cingulate, middle frontal areas, and dorsal and ventral striatum. Although the study included only healthy controls, the results demonstrate a link between anhedonia measures, behavior, and brain responses and also test a paradigm that could be used to study anhedonia in clinical populations.

Effects of Ketamine on Brain Activity During Emotional Processing: Differential Findings in Depressed Versus Healthy Control Participants.

BACKGROUND: In the search for novel treatments for depression, ketamine has emerged as a unique agent with rapid antidepressant effects. Experimental tasks involving emotional processing can be used during functional magnetic resonance imaging scanning to investigate ketamine's effects on brain function in major depressive disorder (MDD). This study examined ketamine's effects on functional magnetic resonance imaging activity during an emotional processing task. METHODS: A total of 33 individuals with treatment-resistant MDD and 24 healthy control participants (HCs) took part in this double-blind, placebo-controlled crossover study. Participants received ketamine and placebo infusions 2 weeks apart, and functional magnetic resonance imaging scans were conducted at baseline and 2 days after each infusion. Blood oxygen level-dependent signal was measured during an emotional processing task, and a linear mixed-effects model was used to analyze differences in activation among group, drug, and task-specific factors. RESULTS: A group-by-drug interaction was observed in several brain regions, including a right frontal cluster extending into the anterior cingulate cortex and insula. Participants with MDD had greater activity than HCs after placebo infusion but showed lower activity after ketamine infusion, which was similar to the activity in HCs after placebo. A group-by-drug-by-task condition interaction was also found, which showed further differences that varied between implicit and explicit emotional conditions. CONCLUSIONS: The main results indicate that ketamine had differential effects on brain activity in participants with MDD versus HCs. The pattern of activation in participants with MDD after ketamine infusion resembled the activation in HCs after placebo infusion, suggesting a normalization of function during emotional processing. The findings contribute to a better understanding of ketamine's actions in the brain.

Functional Imaging of the Implicit Association of the Self With Life and Death.

OBJECTIVE: A critical need exists to identify objective markers of suicide ideation. One potential suicide risk marker is the Suicide Implicit Association Task (S-IAT), a behavioral task that uses differential reaction times to compare the implicit association between the self and death to the implicit association between the self and life. Individuals with a stronger association between the self and death on the S-IAT are more likely to attempt suicide in the future. To better understand the neural underpinnings of the implicit association between self and either life or death, a functional magnetic resonance imaging (fMRI) version of the S-IAT was adapted and piloted in healthy volunteers. METHOD: An fMRI version of the S-IAT was administered to 28 healthy volunteers (ages 18-65, 14F/14M). RESULTS: Behavioral results were comparable to those seen in non-scanner versions of the task. The task was associated with patterns of neural activation in areas relevant to emotional processing, specifically the insula and right ventrolateral prefrontal cortex. CONCLUSIONS: Performance on the S-IAT fMRI task may reflect scores obtained outside of the scanner. In future evaluations, this task could help assess whether individuals at increased risk of suicide display a different pattern of neural activation in response to self/death and self/life stimuli.

Ketamine normalizes brain activity during emotionally valenced attentional processing in depression.

Background: An urgent need exists for faster-acting pharmacological treatments in major depressive disorder (MDD). The glutamatergic modulator ketamine has been shown to have rapid antidepressant effects, but much remains unknown about its mechanism of action. Functional MRI (fMRI) can be used to investigate how ketamine impacts brain activity during cognitive and emotional processing. Methods: This double-blind, placebo-controlled, crossover study of 33 unmedicated participants with MDD and 26 healthy controls (HCs) examined how ketamine affected fMRI activation during an attentional bias dot probe task with emotional face stimuli across multiple time points. A whole brain analysis was conducted to find regions with differential activation associated with group, drug session, or dot probe task-specific factors (emotional valence and congruency of stimuli). Results: A drug session by group interaction was observed in several brain regions, such that ketamine had opposite effects on brain activation in MDD versus HC participants. Additionally, there was a similar finding related to emotional valence (a drug session by group by emotion interaction) in a large cluster in the anterior cingulate and medial frontal cortex. Conclusions: The findings show a pattern of brain activity in MDD participants following ketamine infusion that is similar to activity observed in HCs after placebo. This suggests that ketamine may act as an antidepressant by normalizing brain function during emotionally valenced attentional processing. Clinical trial: NCT#00088699: https://www.clinicaltrials.gov/ct2/show/NCT00088699.

Interaction of childhood urbanicity and variation in dopamine genes alters adult prefrontal function as measured by functional magnetic resonance imaging (fMRI).

Brain phenotypes showing environmental influence may help clarify unexplained associations between urban exposure and psychiatric risk. Heritable prefrontal fMRI activation during working memory (WM) is such a phenotype. We hypothesized that urban upbringing (childhood urbanicity) would alter this phenotype and interact with dopamine genes that regulate prefrontal function during WM. Further, dopamine has been hypothesized to mediate urban-associated factors like social stress. WM-related prefrontal function was tested for main effects of urbanicity, main effects of three dopamine genes-catechol-O-methyltransferase (COMT), dopamine receptor D1 (DRD1), and dopamine receptor D2 (DRD2)-and, importantly, dopamine gene-by-urbanicity interactions. For COMT, three independent human samples were recruited (total n = 487). We also studied 253 subjects genotyped for DRD1 and DRD2. 3T fMRI activation during the N-back WM task was the dependent variable, while childhood urbanicity, dopamine genotype, and urbanicity-dopamine interactions were independent variables. Main effects of dopamine genes and of urbanicity were found. Individuals raised in an urban environment showed altered prefrontal activation relative to those raised in rural or town settings. For each gene, dopamine genotype-by-urbanicity interactions were shown in prefrontal cortex-COMT replicated twice in two independent samples. An urban childhood upbringing altered prefrontal function and interacted with each gene to alter genotype-phenotype relationships. Gene-environment interactions between multiple dopamine genes and urban upbringing suggest that neural effects of developmental environmental exposure could mediate, at least partially, increased risk for psychiatric illness in urban environments via dopamine genes expressed into adulthood.

Sex differences in verbal working memory performance emerge at very high loads of common neuroimaging tasks.

Working memory (WM) supports a broad range of intelligent cognition and has been the subject of rich cognitive and neural characterization. However, the highest ranges of WM have not been fully characterized, especially for verbal information. Tasks developed to test multiple levels of WM demand (load) currently predominate brain-based WM research. These tasks are typically used at loads that allow most healthy participants to perform well, which facilitates neuroimaging data collection. Critically, however, high performance at lower loads may obscure differences that emerge at higher loads. A key question not yet addressed at high loads concerns the effect of sex. Thoroughgoing investigation of high-load verbal WM is thus timely to test for potential hidden effects, and to provide behavioral context for effects of sex observed in WM-related brain structure and function. We tested 111 young adults, matched on genotype for the WM-associated COMT-Val108/158Met polymorphism, on three classic WM tasks using verbal information. Each task was tested at four WM loads, including higher loads than those used in previous studies of sex differences. All tasks loaded on a single factor, enabling comparison of verbal WM ability at a construct level. Results indicated sex effects at high loads across tasks and within each task, such that males had higher accuracy, even among groups that were matched for performance at lower loads.