Increased random exploration in schizophrenia is associated with inflammation.

One aspect of goal-directed behavior, which is known to be impaired in patients with schizophrenia (SZ), is balancing between exploiting a familiar choice with known reward value and exploring a lesser known, but potentially more rewarding option. Despite its relevance to several symptom domains of SZ, this has received little attention in SZ research. In addition, while there is increasing evidence that SZ is associated with chronic low-grade inflammation, few studies have investigated how this relates to specific behaviors, such as balancing exploration and exploitation. We therefore assessed behaviors underlying the exploration-exploitation trade-off using a three-armed bandit task in 45 patients with SZ and 19 healthy controls (HC). This task allowed us to dissociate goal-unrelated (random) from goal-related (directed) exploration and correlate them with psychopathological symptoms. Moreover, we assessed a broad range of inflammatory proteins in the blood and related them to bandit task behavior. We found that, compared to HC, patients with SZ showed reduced task performance. This impairment was due to a shift from exploitation to random exploration, which was associated with symptoms of disorganization. Relative to HC, patients with SZ showed a pro-inflammatory blood profile. Furthermore, high-sensitivity C-reactive protein (hsCRP) positively correlated with random exploration, but not with directed exploration or exploitation. In conclusion, we show that low-grade inflammation in patients with SZ is associated with random exploration, which can be considered a behavioral marker for disorganization. hsCRP may constitute a marker for severity of, and a potential treatment target for maladaptive exploratory behaviors.

Dissociable mechanisms govern when and how strongly reward attributes affect decisions.

Theories and computational models of decision-making usually focus on how strongly different attributes are weighted in choice, for example, as a function of their importance or salience to the decision-maker. However, when different attributes affect the decision process is a question that has received far less attention. Here, we investigated whether the timing of attribute consideration has a unique influence on decision-making by using a time-varying drift diffusion model and data from four separate experiments. Experimental manipulations of attention and neural activity demonstrated that we can dissociate the processes that determine the relative weighting strength and timing of attribute consideration. Thus, the processes determining either the weighting strengths or the timing of attributes in decision-making can independently adapt to changes in the environment or goals. Quantifying these separate influences of timing and weighting on choice improves our understanding and predictions of individual differences in decision behaviour.

Functional neuroanatomy of gesture-speech integration in children varies with individual differences in gesture processing.

Gesture is an integral part of children's communicative repertoire. However, little is known about the neurobiology of speech and gesture integration in the developing brain. We investigated how 8- to 10-year-old children processed gesture that was essential to understanding a set of narratives. We asked whether the functional neuroanatomy of gesture-speech integration varies as a function of (1) the content of speech, and/or (2) individual differences in how gesture is processed. When gestures provided missing information not present in the speech (i.e., disambiguating gesture; e.g., "pet" + flapping palms = bird), the presence of gesture led to increased activity in inferior frontal gyri, the right middle temporal gyrus, and the left superior temporal gyrus, compared to when gesture provided redundant information (i.e., reinforcing gesture; e.g., "bird" + flapping palms = bird). This pattern of activation was found only in children who were able to successfully integrate gesture and speech behaviorally, as indicated by their performance on post-test story comprehension questions. Children who did not glean meaning from gesture did not show differential activation across the two conditions. Our results suggest that the brain activation pattern for gesture-speech integration in children overlaps with-but is broader than-the pattern in adults performing the same task. Overall, our results provide a possible neurobiological mechanism that could underlie children's increasing ability to integrate gesture and speech over childhood, and account for individual differences in that integration.

Dopamine Receptor-Specific Contributions to the Computation of Value.

Dopamine is thought to play a crucial role in value-based decision making. However, the specific contributions of different dopamine receptor subtypes to the computation of subjective value remain unknown. Here we demonstrate how the balance between D1 and D2 dopamine receptor subtypes shapes subjective value computation during risky decision making. We administered the D2 receptor antagonist amisulpride or placebo before participants made choices between risky options. Compared with placebo, D2 receptor blockade resulted in more frequent choice of higher risk and higher expected value options. Using a novel model fitting procedure, we concurrently estimated the three parameters that define individual risk attitude according to an influential theoretical account of risky decision making (prospect theory). This analysis revealed that the observed reduction in risk aversion under amisulpride was driven by increased sensitivity to reward magnitude and decreased distortion of outcome probability, resulting in more linear value coding. Our data suggest that different components that govern individual risk attitude are under dopaminergic control, such that D2 receptor blockade facilitates risk taking and expected value processing.

The dopaminergic reward system underpins gender differences in social preferences.

Women are known to have stronger prosocial preferences than men, but it remains an open question as to how these behavioural differences arise from differences in brain functioning. Here, we provide a neurobiological account for the hypothesized gender difference. In a pharmacological study and an independent neuroimaging study, we tested the hypothesis that the neural reward system encodes the value of sharing money with others more strongly in women than in men. In the pharmacological study, we reduced receptor type-specific actions of dopamine, a neurotransmitter related to reward processing, which resulted in more selfish decisions in women and more prosocial decisions in men. Converging findings from an independent neuroimaging study revealed gender-related activity in neural reward circuits during prosocial decisions. Thus, the neural reward system appears to be more sensitive to prosocial rewards in women than in men, providing a neurobiological account for why women often behave more prosocially than men.

Transcranial Stimulation over Frontopolar Cortex Elucidates the Choice Attributes and Neural Mechanisms Used to Resolve Exploration-Exploitation Trade-Offs.

Optimal behavior requires striking a balance between exploiting tried-and-true options or exploring new possibilities. Neuroimaging studies have identified different brain regions in humans where neural activity is correlated with exploratory or exploitative behavior, but it is unclear whether this activity directly implements these choices or simply reflects a byproduct of the behavior. Moreover, it remains unknown whether arbitrating between exploration and exploitation can be influenced with exogenous methods, such as brain stimulation. In our study, we addressed these questions by selectively upregulating and downregulating neuronal excitability with anodal or cathodal transcranial direct current stimulation over right frontopolar cortex during a reward-learning task. This caused participants to make slower, more exploratory or faster, more exploitative decisions, respectively. Bayesian computational modeling revealed that stimulation affected how much participants took both expected and obtained rewards into account when choosing to exploit or explore: Cathodal stimulation resulted in an increased focus on the option expected to yield the highest payout, whereas anodal stimulation led to choices that were less influenced by anticipated payoff magnitudes and were more driven by recent negative reward prediction errors. These findings suggest that exploration is triggered by a neural mechanism that is sensitive to prior less-than-expected choice outcomes and thus pushes people to seek out alternative courses of action. Together, our findings establish a parsimonious neurobiological mechanism that causes exploration and exploitation, and they provide new insights into the choice features used by this mechanism to direct decision-making.

Computational modeling of resting-state activity demonstrates markers of normalcy in children with prenatal or perinatal stroke.

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children.

Frontal and temporal contributions to understanding the iconic co-speech gestures that accompany speech.

In everyday conversation, listeners often rely on a speaker's gestures to clarify any ambiguities in the verbal message. Using fMRI during naturalistic story comprehension, we examined which brain regions in the listener are sensitive to speakers' iconic gestures. We focused on iconic gestures that contribute information not found in the speaker's talk, compared with those that convey information redundant with the speaker's talk. We found that three regions-left inferior frontal gyrus triangular (IFGTr) and opercular (IFGOp) portions, and left posterior middle temporal gyrus (MTGp)--responded more strongly when gestures added information to nonspecific language, compared with when they conveyed the same information in more specific language; in other words, when gesture disambiguated speech as opposed to reinforced it. An increased BOLD response was not found in these regions when the nonspecific language was produced without gesture, suggesting that IFGTr, IFGOp, and MTGp are involved in integrating semantic information across gesture and speech. In addition, we found that activity in the posterior superior temporal sulcus (STSp), previously thought to be involved in gesture-speech integration, was not sensitive to the gesture-speech relation. Together, these findings clarify the neurobiology of gesture-speech integration and contribute to an emerging picture of how listeners glean meaning from gestures that accompany speech.

Interhemispheric functional connectivity following prenatal or perinatal brain injury predicts receptive language outcome.

Early brain injury alters both structural and functional connectivity between the cerebral hemispheres. Despite increasing knowledge on the individual hemispheric contributions to recovery from such injury, we know very little about how their interactions affect this process. In the present study, we related interhemispheric structural and functional connectivity to receptive language outcome following early left hemisphere stroke. We used functional magnetic resonance imaging to study 14 people with neonatal brain injury, and 25 age-matched controls during passive story comprehension. With respect to structural connectivity, we found that increased volume of the corpus callosum predicted good receptive language outcome, but that this is not specific to people with injury. In contrast, we found that increased posterior superior temporal gyrus interhemispheric functional connectivity during story comprehension predicted better receptive language performance in people with early brain injury, but worse performance in typical controls. This suggests that interhemispheric functional connectivity is one potential compensatory mechanism following early injury. Further, this pattern of results suggests refinement of the prevailing notion that better language outcome following early left hemisphere injury relies on the contribution of the contralesional hemisphere (i.e., the "right-hemisphere-take-over" theory). This pattern of results was also regionally specific; connectivity of the angular gyrus predicted poorer performance in both groups, independent of brain injury. These results present a complex picture of recovery, and in some cases, such recovery relies on increased cooperation between the injured hemisphere and homologous regions in the contralesional hemisphere, but in other cases, the opposite appears to hold.

Brain signal variability relates to stability of behavior after recovery from diffuse brain injury.

Variability or noise is an unmistakable feature of neural signals; however such fluctuations have been regarded as not carrying meaningful information or as detrimental for neural processes. Recent empirical and computational work has shown that neural systems with a greater capacity for information processing are able to explore a more varied dynamic repertoire, and the hallmark of this is increased irregularity or variability in the neural signal. How this variability in neural dynamics affects behavior remains unclear. Here, we investigated the role of variability of magnetoencephalography signals in supporting healthy cognitive functioning, measured by performance on an attention task, in healthy adults and in patients with traumatic brain injury. As an index of variability, we calculated multiscale entropy, which quantifies the temporal predictability of a time series across progressively more coarse time scales. We found lower variability in traumatic brain injury patients compared to controls, arguing against the idea that greater variability reflects dysfunctional neural processing. Furthermore, higher brain signal variability indicated improved behavioral performance for all participants. This relationship was statistically stronger for people with brain injury, demonstrating that those with higher brain signal variability were also those who had recovered the most cognitive ability. Rather than impede neural processing, cortical signal variability within an optimal range enables the exploration of diverse functional configurations, and may therefore play a vital role in healthy brain function.

Brain activity patterns uniquely supporting visual feature integration after traumatic brain injury.

Traumatic brain injury (TBI) patients typically respond more slowly and with more variability than controls during tasks of attention requiring speeded reaction time. These behavioral changes are attributable, at least in part, to diffuse axonal injury (DAI), which affects integrated processing in distributed systems. Here we use a multivariate method sensitive to distributed neural activity to compare brain activity patterns of patients with chronic phase moderate to-severe TBI to those of controls during performance on a visual feature integration task assessing complex attentional processes that has previously shown sensitivity to TBI. The TBI patients were carefully screened to be free of large focal lesions that can affect performance and brain activation independently of DAI. The task required subjects to hold either one or three features of a Target in mind while suppressing responses to distracting information. In controls, the multi-feature condition activated a distributed network including limbic, prefrontal, and medial temporal structures. TBI patients engaged this same network in the single-feature and baseline conditions. In multi-feature presentations, TBI patients alone activated additional frontal, parietal, and occipital regions. These results are consistent with neuroimaging studies using tasks assessing different cognitive domains, where increased spread of brain activity changes was associated with TBI. Our results also extend previous findings that brain activity for relatively moderate task demands in TBI patients is similar to that associated with of high task demands in controls.

Left hemisphere regions are critical for language in the face of early left focal brain injury.

A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we used functional magnetic resonance imaging to examine brain activity during category fluency in participants who had sustained pre- or perinatal left hemisphere stroke (n = 25) and in neurologically normal siblings (n = 27). In typically developing children, performance of a category fluency task elicits strong involvement of left frontal and lateral temporal regions and a lesser involvement of right hemisphere structures. In our cohort of atypically developing participants with early stroke, expressive and receptive language skills correlated with activity in the same left inferior frontal regions that support language processing in neurologically normal children. This was true independent of either the amount of brain injury or the extent that the injury was located in classical cortical language processing areas. Participants with bilateral activation in left and right superior temporal-inferior parietal regions had better language function than those with either predominantly left- or right-sided unilateral activation. The advantage conferred by left inferior frontal and bilateral temporal involvement demonstrated in our study supports a strong predisposition for typical neural language organization, despite an intervening injury, and argues against models suggesting that the right hemisphere fully accommodates language function following early injury.