The distinction between letter strings that form words and those that look and sound plausible but are not meaningful is a basic one. Decades of functional neuroimaging experiments have used this distinction to isolate the neural basis of lexical (word-level) semantics, associated with areas such as the middle temporal, angular, and posterior cingulate gyri that overlap the default-mode network. In two functional magnetic resonance imaging (fMRI) experiments, a different set of findings emerged when word stimuli were used that were less familiar (measured by word frequency) than those typically used. Instead of activating default-mode network areas often associated with semantic processing, words activated task-positive areas such as the inferior prefrontal cortex and supplementary motor area, along with multi-functional ventral occipito-temporal cortices related to reading, while nonwords activated default-mode areas previously associated with semantics. Effective connectivity analyses of fMRI data on less familiar words showed activation driven by task-positive and multi-functional reading-related areas, while highly familiar words showed bottom-up activation flow from occipito-temporal cortex. These findings suggest functional neuroimaging correlates of semantic processing are less stable than previously assumed, with factors such as word frequency influencing the balance between task-positive, reading-related, and default-mode networks. More generally, this suggests results of contrasts typically interpreted in terms of semantic content may be more influenced by factors related to task difficulty than is widely appreciated.

Studies of the neural substrates of semantic (word meaning) processing have typically focused on semantic manipulations, with less consideration for potential differences in difficulty across conditions. While the idea that particular brain regions can support multiple functions is widely accepted, studies of specific cognitive domains rarely test for co-location with other functions. Here we start with standard univariate analyses comparing words to meaningless nonwords, replicating our recent finding that this contrast can activate task-positive regions for words, and default-mode regions in the putative semantic network for nonwords, pointing to difficulty effects. Critically, this was followed up with a multivariate analysis to test whether the same areas activated for meaningless nonwords contained semantic information sufficient to distinguish high- from low-imageability words. Indeed, this classification was performed reliably better than chance at 75% accuracy. This is compatible with two non-exclusive interpretations. Numerous areas in the default-mode network are task-negative in the sense of activating for less demanding conditions, and the same areas contain information supporting semantic cognition. Therefore, while areas of the default mode network have been hypothesized to support semantic cognition, we offer evidence that these areas can respond to both domain-general difficulty effects, and to specific aspects of semantics.

Previous research has demonstrated behavioral and neural differences associated with experiencing adversity. However, adversity is unlikely to be a monolithic construct, and we expect that examining effects of more specific components such as exposure to violence in the home community will yield more concretely interpretable results. Here we account for effects of low socioeconomic status (SES) to examine the specific effects of exposure to violence on functional connectivity between brain areas known to be related to emotion regulation and working memory. Decreased resting state functional connectivity for individuals exposed to high compared to low levels of violence during childhood was predicted for two sets of areas: (1) bilateral amygdala with anterior medial regions involved in cognitive control of emotion, and (2) the right dorsolateral prefrontal cortex (dlPFC) with frontal and parietal regions implicated in working memory. Consistent with our predictions, increasing exposure to violence was related to decreased resting state functional connectivity between the right amygdala and anterior cingulate cortex, even after accounting for SES. Also after accounting for SES, exposure to violence was related to reductions in connectivity between the right dlPFC and frontal regions, but not with parietal regions typically associated with working memory. Overall, this pattern suggests increased exposure to violence in childhood is associated with reduced connectivity among key areas of the circuitry involved in emotion regulation and cognitive control, but not working memory. These results offer insight into the neural underpinnings of behavioral outcomes associated with exposure to violence, laying the foundation for ultimately designing interventions to address the effects of such exposure.

Although much is known about the cognitive and neural basis of establishing letter-sound mappings in learning word forms, relatively little is known about what makes for the most effective feedback during this process. We sought to determine the neural basis by which elaborative feedback (EF), which contains both reward-related and content-specific information, may be more helpful than feedback containing only one kind of information (simple positive feedback, PF) or the other (content feedback, CF) in learning orthography-phonology (spelling-sound) mappings for novel letter strings. Compared to CF, EF activated the ventromedial prefrontal cortex, implicated in reward processing. Compared to PF, EF activated the posterior middle temporal, superior temporal, and supramarginal gyri-regions implicated in orthography-phonology conversion. In the same comparison, EF also activated the left fusiform gyrus/visual word form area-implicated in orthographic processing. Also EF, but not CF or PF, modulated activity in the caudate nucleus. In a postscan questionnaire, EF and PF were rated as more pleasant than CF, suggesting that modulation of the caudate for EF may be due to the coupling of reward and skill content. These findings suggest the enhanced effectiveness of EF may be due to concurrent activation of reward-related and task-relevant brain regions.

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Depression is more prevalent among autistic adults than neurotypical adults, yet risk factors are incompletely understood in this population. Some research groups have focused on relationships between negative repetitive thinking and depression in the autistic population, which may explain elevated prevalence rates in line with general population findings on rumination and internalizing disorders. Little is known about associations between depression and more prototypical repetitive cognitions and/or behaviors characteristic of autism (i.e., insistence on sameness [IS] and repetitive sensorimotor [RSM] behaviors). Therefore, the present study aimed to examine associations between IS, RSM behaviors, and depressive symptoms in 762 autistic adults, and whether observed effects are confounded by additional factors (e.g., demographic factors, trait neuroticism). To test if greater IS scores were associated with greater depressive symptoms on the BDI-II, a Bayesian linear regression was conducted with BDI-II scores (dependent variable) regressed on age, gender, educational level, RSM scores, and IS scores (independent variables). To test the effects of neuroticism on observed relationships, a second regression was conducted that included all predictors from the baseline model and neuroticism. Standardized regression coefficients were tested against an interval null hypothesis of [−0.1, 0.1] to assess for practical significance. Results indicated that IS exhibited a moderate positive relationship with depressive symptoms, while RSM behaviors provided only a slight increase in predictive ability. However in the second model, neuroticism exhibited a strong positive relationship with depressive symptoms, completely attenuating the effect of IS. Associations between RSM behaviors and depressive symptoms did not meet our criteria for practical significance, particularly when neuroticism was added to the model. Neither RSM nor IS moderated the effect of neuroticism on depression. The findings from this study add to the literature on risk factors in the pathway to depression in autism, and suggest opportunities for clinical translation to screening and intervention efforts. Screening for IS in autistic individuals is a common diagnostic practice in clinical and research settings that may be leveraged to also identify those at higher risk for depression, and increasing flexibility in daily life may promote emotional regulation and distress tolerance.