Project description:The ability to reproduce visually presented actions has been studied through neuropsychological observations of patients with ideomotor apraxia. These studies include attempts to understand the neural basis of action reproduction based on lesion-symptom mapping in different patient groups. While there is a convergence of evidence that areas in the parietal and frontal lobes within the left hemisphere are involved in the imitation of a variety of actions, questions remain about whether the results generalize beyond the imitation of tool use and whether the presence of a strong grasp component of the action is critical. Here we used voxel-based lesion-symptom mapping to assess the neural substrates of imitating meaningful (familiar, MF) and meaningless (unfamiliar, ML) tool-related (transitive) and non-tool related (intransitive) actions. The analysis showed that the left parietal cortex was involved in the imitation of transitive gestures, regardless of whether they were meaningful or not. In addition there was poor reproduction of meaningless actions (both transitive and intransitive) following damage of the right frontal cortex. These findings suggest a role of right frontal regions in processing of unfamiliar actions.
Project description:Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system-level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.
Project description:We investigate the feasibility of inferring the choices people would make (if given the opportunity) based on their neural responses to the pertinent prospects when they are not engaged in actual decision making. The ability to make such inferences is of potential value when choice data are unavailable, or limited in ways that render standard methods of estimating choice mappings problematic. We formulate prediction models relating choices to "non-choice" neural responses and use them to predict out-of-sample choices for new items and for new groups of individuals. The predictions are sufficiently accurate to establish the feasibility of our approach.
Project description:Prosocial behaviors are hypothesized to require socio-cognitive and empathic abilities-engaging brain regions attributed to the mentalizing and empathy brain networks. Here, we tested this hypothesis with a coordinate-based meta-analysis of 600 neuroimaging studies on prosociality, mentalizing and empathy (∼12,000 individuals). We showed that brain areas recruited by prosocial behaviors only partially overlap with the mentalizing (dorsal posterior cingulate cortex) and empathy networks (middle cingulate cortex). Additionally, the dorsolateral and ventromedial prefrontal cortices were preferentially activated by prosocial behaviors. Analyses on the functional connectivity profile and functional roles of the neural patterns underlying prosociality revealed that in addition to socio-cognitive and empathic processes, prosocial behaviors further involve evaluation processes and action planning, likely to select the action sequence that best satisfies another person's needs. By characterizing the multidimensional construct of prosociality at the neural level, we provide insights that may support a better understanding of normal and abnormal social cognition (e.g., psychopathy).
Project description:Hard decisions between equally valued alternatives can result in preference changes, meaning that subsequent valuations for chosen items increase and decrease for rejected items. Previous research suggests that this phenomenon is a consequence of cognitive dissonance reduction after the decision, induced by the mismatch between initial preferences and decision outcomes. In contrast, this functional magnetic resonance imaging and eye-tracking study with male and female human participants found that preferences are already updated online during the process of decision-making. Preference changes were predicted from activity in left dorsolateral prefrontal cortex and precuneus while making hard decisions. Fixation durations during this phase predicted both choice outcomes and subsequent preference changes. These preference adjustments became behaviorally relevant only for choices that were remembered and were in turn associated with hippocampus activity. Our results suggest that preferences evolve dynamically as decisions arise, potentially as a mechanism to prevent stalemate situations in underdetermined decision scenarios.SIGNIFICANCE STATEMENT Most theories of decision-making assume that we always choose the best option available, based on a set of stable preferences. However, what happens for hard decisions when the available options are preferred equally? We show that in such stalemate situations, decision-makers adjust their preferences dynamically during the process of decision-making, and these preference adjustments are predicted by a left prefrontal-parietal network. We also show that eye movements during decision-making are predictive of the magnitude of the upcoming value change. Our results suggest that preferences are dynamic, adjusted every time a hard decision is made, prompting a re-evaluation of existing frameworks of decision-making.
Project description:Recent studies suggest that psychopathy may be associated with dysfunction in the neural circuitry supporting both threat- and reward-related processes. However, these studies have involved small samples and often focused on extreme groups. Thus, it is unclear to what extent current findings may generalize to psychopathic traits in the general population. Furthermore, no studies have systematically and simultaneously assessed associations between distinct psychopathy facets and both threat- and reward-related brain function in the same sample of participants. Here, we examined the relationship between threat-related amygdala reactivity and reward-related ventral striatum (VS) reactivity and variation in four facets of self-reported psychopathy in a sample of 200 young adults. Path models indicated that amygdala reactivity to fearful facial expressions is negatively associated with the interpersonal facet of psychopathy, whereas amygdala reactivity to angry facial expressions is positively associated with the lifestyle facet. Furthermore, these models revealed that differential VS reactivity to positive versus negative feedback is negatively associated with the lifestyle facet. There was suggestive evidence for gender-specific patterns of association between brain function and psychopathy facets. Our findings are the first to document differential associations between both threat- and reward-related neural processes and distinct facets of psychopathy and thus provide a more comprehensive picture of the pattern of neural vulnerabilities that may predispose to maladaptive outcomes associated with psychopathy.
Project description:Memories involving the hippocampus can take several days to consolidate, challenging efforts to uncover the neuronal signatures underlying this process. Using calcium imaging in freely moving mice, we tracked the hippocampal dynamics underlying memory formation across a ten-day contextual fear conditioning (CFC) task. We found that cell turnover between the conditioning chamber and a neutral arena even prior to learning predicted the accuracy of subsequent memory recall the next day. Following learning, context-specific place field remapping correlated with memory performance. To causally test whether these hippocampal dynamics support memory consolidation, we induced amnesia in a group of mice by pharmacologically blocking protein synthesis immediately following learning. We found that halting protein synthesis following learning paradoxically accelerated cell turnover and also arrested learning-related remapping, paralleling the absence of remapping observed in untreated mice that exhibited poor memory expression. Finally, coordinated neural activity that emerged following learning was dependent on intact protein synthesis and predicted memory-related freezing behavior. We conclude that context-specific place field remapping and the development of coordinated ensemble activity require protein synthesis and underlie contextual fear memory consolidation.
Project description:Cytosine methylation is an important epigenetic mark, but how the distinctive patterns of DNA methylation arise remains elusive. For the first time, we systematically investigated how these patterns can be imparted by the inherent enzymatic preferences of mammalian de novo DNA methyltransferases in vitro and the extent to which this applies in cells. In a biochemical experiment, we subjected a wide variety of DNA sequences to methylation by DNMT3A or DNMT3B and then applied deep bisulfite sequencing to quantitatively determine the sequence preferences for methylation. The data show that DNMT3A prefers CpG and non-CpG sites followed by a 3'-pyrimidine, whereas DNMT3B favors a 3'-purine. Overall, we show that DNMT3A has a sequence preference for a TNC[G/A]CC context, while DNMT3B prefers TAC[G/A]GC. We extended our finding using publicly available data from mouse Dnmt1/3a/3b triple-knockout cells in which reintroduction of either DNMT3A or DNMT3B expression results in the acquisition of the same enzyme specific signature sequences observed in vitro. Furthermore, loss of DNMT3A or DNMT3B in human embryonic stem cells leads to a loss of methylation at the corresponding enzyme specific signatures. Therefore, the global DNA methylation landscape of the mammalian genome can be fundamentally determined by the inherent sequence preference of de novo methyltransferases.
Project description:Most teenage fears subside with age, a change that may reflect brain maturation in the service of refined fear learning. Whereas adults clearly demarcate safe situations from real dangers, attenuating fear to the former but not the latter, adolescents' immaturity in prefrontal cortex function may limit their ability to form clear-cut threat categories, allowing pervasive fears to manifest. Here we developed a discrimination learning paradigm that assesses the ability to categorize threat from safety cues to test these hypotheses on age differences in neurodevelopment. In experiment 1, we first demonstrated the capacity of this paradigm to generate threat/safety discrimination learning in both adolescents and adults. Next, in experiment 2, we used this paradigm to compare the behavioral and neural correlates of threat/safety discrimination learning in adolescents and adults using functional MRI. This second experiment yielded three sets of findings. First, when labeling threats online, adolescents reported less discrimination between threat and safety cues than adults. Second, adolescents were more likely than adults to engage early-maturing subcortical structures during threat/safety discrimination learning. Third, adults' but not adolescents' engagement of late-maturing prefrontal cortex regions correlated positively with fear ratings during threat/safety discrimination learning. These data are consistent with the role of dorsolateral regions during category learning, particularly when differences between stimuli are subtle [Miller EK, Cohen JD (2001) Annu Rev Neurosci 24:167-202]. These findings suggest that maturational differences in subcortical and prefrontal regions between adolescent and adult brains may relate to age-related differences in threat/safety discrimination.