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A major caveat with investigations on schizophrenic patients is the difficulty to control for medication usage across samples as disease-related neural differences may be confounded by medication usage. Following a thorough literature search (632 records identified), we included 37 studies with a total of 740 medicated schizophrenia patients and 367 unmedicated schizophrenia patients. Here, we perform several meta-analyses to assess the neurofunctional differences between medicated and unmedicated schizophrenic patients across fMRI studies to determine systematic regions associated with medication usage. Several clusters identified by the meta-analysis on the medicated group include three right lateralized frontal clusters and a left lateralized parietal cluster, whereas the unmedicated group yielded concordant activity among right lateralized frontal-parietal regions. We further explored the prevalence of activity within these regions across illness duration and task type. These findings suggest a neural compensatory mechanism across these regions both spatially and chronically, offering new insight into the spatial and temporal dynamic neural differences among medicated and unmedicated schizophrenia patients.

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Individuals not only take actions to obtain immediate rewards but also to gain more information to guide future choices. An ideal exploration-exploitation balance is crucial for maximizing reward over the long run. However, the neural signatures of exploration in humans remain unclear. Using quantitative meta-analyses of functional magnetic resonance imaging experiments on exploratory behaviors, we sought to identify the concordant activity pertaining to exploration over a range of experiments. The results revealed that exploration activates concordant brain activity associated with risk (e.g., dorsal medial prefrontal cortex and anterior insula), cognitive control (e.g., dorsolateral prefrontal cortex and inferior frontal gyrus), and motor processing (e.g., premotor cortex). These stereotaxic maps of exploration may indicate that exploration is highly linked to risk processing, but is also specifically associated with regions involved in executive control processes. Although this explanation should be treated as exploratory, these findings support theories positing an important role for the prefrontal-insular-motor cortical network in exploration.

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BACKGROUND: Working memory (WM) is an executive ability that allows one to hold and manipulate information for a short period of time. Schizophrenia and mood disorders are severe psychiatric conditions with overlapping genetic and clinical symptoms. Whilst WM has been suggested as meeting the criteria for being an endophenotype for schizophrenia and mood disorders, it still unclear whether they share overlapping neural circuitry. OBJECTIVE: The n-back task has been widely used to measure WM capacity, such as maintenance, flexible updating, and interference control. Here we compiled studies that included psychiatric populations, i.e., schizophrenia, bipolar disorder and major depressive disorder. METHODS: We performed a coordinate-based meta-analysis that combined 34 BOLD-fMRI studies comparing activity associated with n-back working memory between psychiatric patients and healthy controls. We specifically focused our search using the n-back task to diminish study heterogeneity. RESULTS: All patient groups showed blunted activity in the striatum, anterior insula and frontal lobe. The same brain networks related to WM were compromised in schizophrenia, major depressive disorder and bipolar disorder. CONCLUSION: Our findings support the suggestion of commonal functional abnormalities across schizophrenia and mood disorders related to WM.

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To make adaptive decisions under uncertainty, individuals need to actively monitor the discrepancy between expected outcomes and actual outcomes, known as prediction errors. Reward-based learning deficits have been shown in both depression and schizophrenia patients. For this study, we compiled studies that investigated prediction error processing in depression and schizophrenia patients and performed a series of meta-analyses. In both groups, positive t-maps of prediction error tend to yield striatum activity across studies. The analysis of negative t-maps of prediction error revealed two large clusters within the right superior and inferior frontal lobes in schizophrenia and the medial prefrontal cortex and bilateral insula in depression. The concordant posterior cingulate activity was observed in both patient groups, more prominent in the depression group and absent in the healthy control group. These findings suggest a possible role in dopamine-rich areas associated with the encoding of prediction errors in depression and schizophrenia.

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Abnormal decision making can result in detrimental outcomes of clinical importance, and decision making is strongly linked to neural prediction error signalling. Activation likelihood estimation (ALE) meta-analyses were used to examine the neural correlates of prediction error signals of individuals taking different types of substances and healthy controls with contrast and conjunction analyses. Twenty-eight studies were included in the meta-analysis, representing 424 substance users' individuals and 834 healthy control individuals. Robust brain activity associated with prediction error signals in substance users was found for the bilateral striatum and insula. Healthy control subjects also activated bilateral striatum, midbrain, right insula and right medial-inferior frontal gyrus. Compared with healthy controls, substance users showed blunted activity in the bilateral putamen, right medial-inferior frontal gyrus and insula. The current meta-analysis of cross-sectional findings investigated neural prediction error signals in substance users. PE abnormalities in substance users might be related to poor decision making. In conclusion, the present study helps identify the pathophysiological underpinnings of maladaptive decision making in substance users.

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Functional magnetic resonance imaging (fMRI) studies have shown notable age-dependent differences in reward processing. We analyzed data from a total of 554 children, 1,059 adolescents, and 1,831 adults from 70 articles. Quantitative meta-analyses results show that adults engage an extended set of regions that include anterior and posterior cingulate gyri, insula, basal ganglia, and thalamus. Adolescents engage the posterior cingulate and middle frontal gyri as well as the insula and amygdala, whereas children show concordance in right insula and striatal regions almost exclusively. Our data support the notion of reorganization of function over childhood and adolescence and may inform current hypotheses relating to decision-making across age.

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Human decision-making is mainly driven by two fundamental learning processes: a slow, deliberative, goal-directed model-based process that maps out the potential outcomes of all options and a rapid habitual model-free process that enables reflexive repetition of previously successful choices. Although many model-informed neuroimaging studies have examined the neural correlates of model-based and model-free learning, the concordant activity among these two processes remains unclear. We used quantitative meta-analyses of functional magnetic resonance imaging experiments to identify the concordant activity pertaining to model-based and model-free learning over a range of reward-related paradigms. We found that: 1) both processes yielded concordant ventral striatum activity, 2) model-based learning activated the medial prefrontal cortex and orbital frontal cortex, and 3) model-free learning specifically activated the left globus pallidus and right caudate head. Our findings suggest that model-free and model-based decision making engage overlapping yet distinct neural regions. These stereotaxic maps improve our understanding of how deliberative goal-directed and reflexive habitual learning are implemented in the brain.

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Deficits in cognitive function are a major characteristic of schizophrenia. Many functional magnetic resonance imaging (fMRI) studies examine brain correlates of cognitive function in adults with schizophrenia, showing altered implication of associative areas such as the prefrontal cortex and temporal cortex. fMRI studies also examine brain representation of cognitive function in adolescents with early onset schizophrenia and those at risk of the disorder, yet results are often inconsistent. We compile and analyze data from eligible fMRI studies using quantitative meta-analyses to reveal concordant brain activity associated with adolescent relatives of patients with schizophrenia and those with early onset schizophrenia. Results show similar functional hubs of brain activity (eg, precuneus) yet in opposite hemispheres and clusters in ventrolateral rather than dorsolateral prefrontal cortices. Other areas of altered implication include the middle temporal gyrus, insula, and cerebellum. We discuss the findings in reference to the protracted maturation of the prefrontal cortex and possible effects due to the medication status of the two groups.

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Socioeconomic status (SES) is a multidimensional construct that includes not only measures of material wealth, but also education, social prestige, and neighborhood quality. Socioeconomic correlates between wealth and cognitive functions have been well established in behavioral studies. However, functional and structural brain correlates of SES remain unclear. Here, we sought to uncover the most likely neural regions to be affected by low SES, specifically associated with age. Using effect size-seed-based d Mapping, we compiled studies that examined individuals with low SES and performed functional magnetic resonance imaging and voxel-based morphometry meta-analyses. The results revealed that as from early to late age, individuals exposed to low SES are less likely to have sustained executive network activity yet a greater likelihood to enhanced activity within reward-related regions. A similar activity was shown for gray matter volume across early to older age. These findings provide the first quantitative integration of neuroimaging results pertaining to the neural basis of SES. Hypoactivation of the executive network and hyperactivation of the reward network in low SES individuals may support the scarcity hypothesis and animal models of the effects of early adversity.

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The ability to accurately infer one's place with respect to others is crucial for social interactions. Individuals tend to evaluate their own actions and outcomes by comparing themselves to others in either an upward or downward direction. We performed two fMRI meta-analyses on monetary (n = 39; 1,231 participants) and status (n = 23; 572 participants) social comparisons to examine how domain and the direction of comparison can modulate neural correlates of social hierarchy. Overall, both status and monetary downward comparisons activated regions associated with reward processing (striatum) while upward comparisons yielded loss-related activity. These findings provide partial support for the common currency hypothesis in that downward and upward comparisons from both monetary and status domains resemble gains and losses, respectively. Furthermore, status upward and monetary downward comparisons revealed concordant orbitofrontal cortical activity, an area associated with evaluating the value of goals and decisions implicated in both lesion and empirical fMRI studies investigating social hierarchy. These findings may offer new insight into how people relate to individuals with higher social status and how these social comparisons deviate across monetary and social status domains.

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Working memory, a fundamental cognitive function that is highly dependent on the integrity of the prefrontal cortex, is known to show age-related decline across the typical healthy adult lifespan. Moreover, we know from work in neurophysiology that the prefrontal cortex is disproportionately susceptibly to the pathological effects of aging. The n-back task is arguably the most ubiquitous cognitive task for investigating working memory performance. Many functional magnetic resonance imaging (fMRI) studies examine brain regions engaged during performance of the n-back task in adults. The current meta-analyses are the first to examine concordance and age-related changes across the healthy adult lifespan in brain areas engaged when performing the n-back task. We compile data from eligible fMRI articles that report stereotaxic coordinates of brain activity from healthy adults in three age-groups: young (23.57 ±â€¯5.63 years), middle-aged (38.13 ±â€¯5.63 years) and older (66.86 ±â€¯5.70 years) adults. Findings show that the three groups share concordance in the engagement of parietal and cingulate cortices, which have been consistently identified as core areas involved in working memory; as well as the insula, claustrum, and cerebellum, which have not been highlighted as areas involved in working memory. Critically, prefrontal cortex engagement is concordant for young, to a lesser degree for middle-aged adults, and absent in older adults, suggesting a gradual linear decline in concordance of prefrontal cortex engagement. Our results provide important new knowledge for improving methodology and theories of cognition across the lifespan.

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In constantly changing environments, individuals need to overcome old habitual behaviors in order to learn new associations. Neuroimaging studies have focused on prediction errors, reversal errors and reversal switching in the reversal learning paradigm. Due to the inconsistencies of brain functioning across studies, we attempt to shed light on the concordant activity by performing meta-analyses on different components of reversal learning. While all contrasts yielded anterior cingulate and bilateral insulae, specifically prediction errors yielded more concordant activity within the striatum and amygdala, reversal errors yielded more concordant bilateral frontal-parietal activity, and more concordant inferior frontal cortical occurred from reversal switching. These findings suggest that reversal learning is supported by a core saliency network in all aspects of reversal learning as well as other reward and control related regions in distinct stages of this cognitively complex task. Our meta-analyses results provide stereotaxic maps that can be used for further neuroimaging work on adaptive learning.

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The functional role of high beta oscillations (20-35 Hz) during feedback processing has been suggested to reflect unexpected gains. Using a novel gambling task that separates gains and losses across blocks and directly compares reception of monetary rewards to a 'no-reward/punishment' condition with equal probability we aimed to further investigate the role of beta oscillations. When contrasting different feedback conditions across rewards, we found that a late low beta component (12-20 Hz) had increased in power during the omission of rewards relative to the reception of rewards, while no differences were observed during the loss domain. These findings may indicate that late low beta oscillations in the context of feedback processing may respond to omission of gains relative to other potential outcomes. We speculate that late low beta oscillations may operate as a learning mechanism that signals the brain to make future adequate decisions. Overall, our study provides new insights for the role of late low beta oscillations in reward processing.

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Feedback processing is an important aspect of learning. In the human brain, feedback processing is often examined by measuring an event-related potential, the feedback-related negativity component. Typically, the feedback-related negativity component is investigated by directly comparing gain with loss feedback randomized across trials; however, this method does not control for confounds associated with unexpected feedback. For this study we used a blocked design gambling task to investigate the sensitivity of feedback-related negativity to positive and negative feedback separately for gains and losses. While there appeared to be no significant feedback-related negativity in the loss domain, results revealed an enlarged feedback-related negativity during the omission of gains compared to the reception of gains. These findings further support the reward positivity hypothesis which declares that the feedback-related negativity is associated with the processing of outcomes in the context of gains as opposed to losses, irrespective of unexpectedness.

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Identifying facial expressions is crucial for social interactions. Functional neuroimaging studies show that a set of brain areas, such as the fusiform gyrus and amygdala, become active when viewing emotional facial expressions. The majority of functional magnetic resonance imaging (fMRI) studies investigating face perception typically employ static images of faces. However, studies that use dynamic facial expressions (e.g., videos) are accumulating and suggest that a dynamic presentation may be more sensitive and ecologically valid for investigating faces. By using quantitative fMRI meta-analysis the present study examined concordance of brain regions associated with viewing dynamic facial expressions. We analyzed data from 216 participants that participated in 14 studies, which reported coordinates for 28 experiments. Our analysis revealed bilateral fusiform and middle temporal gyri, left amygdala, left declive of the cerebellum and the right inferior frontal gyrus. These regions are discussed in terms of their relation to models of face processing.

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The n-back task is likely the most popular measure of working memory for functional magnetic resonance imaging (fMRI) studies. Despite accumulating neuroimaging studies with the n-back task and children, its neural representation is still unclear. fMRI studies that used the n-back were compiled, and data from children up to 15 years (n = 260) were analyzed using activation likelihood estimation. Results show concordance in frontoparietal regions recognized for their role in working memory as well as regions not typically highlighted as part of the working memory network, such as the insula. Findings are discussed in terms of developmental methodology and potential contribution to developmental theories of cognition.

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Performance in the attentional blink task has been demonstrated to be directly influenced by alpha and beta neural oscillatory activity. In two experiments we stimulated the right parietal cortex and left frontal cortex with transcranial alternating current stimulation. For the first experiment we targeted only the right parietal cortex and found a non-significant increase in performance from 20 Hz stimulation. In the second experiment we applied two stimulators to the right parietal and left frontal cortex and found a significant increase in performance from 20 Hz tACS with a phase difference of 180°. Since low intensity stimulation has been shown to inhibit cortical excitability, and anti-phasic stimulation has been hypothesized to decrease presynaptic activation in one region and drive postsynaptic spikes in the other, we suggest that low intensity anti-phasic 20 Hz stimulation inhibited the parietal cortex, thereby disinhibiting the frontal cortex. This visual attention mechanism supposedly reduces processing of distractor stimuli and enhances processing of target stimuli. This study reveals that the frontal-parietal visual attention network may be modulated with low intensity 20 Hz anti-phase tACS.

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A phenomenon termed negative priming is defined as an increase in reaction time and/or decrease in performance during instances in which current target stimuli are employed as distractor stimuli in the previous trial. A recent qualitative review on negative priming reported neural regions of interest underlined by activity within the right middle frontal gyrus and left middle temporal gyrus; however, these areas of interest have not been tested and supported by using coordinate-based, quantitative meta-analysis. We compiled functional magnetic resonance imaging studies that examined neural correlates of priming tasks using perceptual, conceptual and lexical primes. Effect-size signed differential mapping was used to perform a neuroimaging meta-analysis on the negative priming effect. Results from fourteen studies (245 participants; 85 foci) show concordance across studies in the right middle frontal gyrus and the left superior temporal gyrus, as suggested by the previous review; however, results also yielded concordance within the anterior cingulate cortex. Our data support the extant hypothesis and offer new insights into the neural mechanisms of the negative priming effect.

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In this study, we investigated the effect of transcranial alternating current stimulation (tACS) on voluntary risky decision making and executive control in humans. Stimulation was delivered online at 5 Hz (θ), 10 Hz (α), 20 Hz (ß), and 40 Hz (γ) on the left and right frontal area while participants performed a modified risky decision-making task. This task allowed participants to voluntarily select between risky and certain decisions associated with potential gains or losses, while simultaneously measuring the cognitive control component (voluntary switching) of decision making. The purpose of this experimental design was to test whether voluntary risky decision making and executive control can be modulated with tACS in a frequency-specific manner. Our results revealed a robust effect of a 20-Hz stimulation over the left prefrontal area that significantly increased voluntary risky decision making, which may suggest a possible link between risky decision making and reward processing, underlined by ß-oscillatory activity.

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[This corrects the article on p. 305 in vol. 10, PMID: 27445674.].