Gui Xue

Common Neural Substrates for Inhibition of Spoken and Manual Responses

The inhibition of speech acts is a critical aspect of human executive control over thought and action, but its neural underpinnings are poorly understood. Using functional magnetic resonance imaging and the stop-signal paradigm, we examined the neural correlates of speech control in comparison to manual motor control. Initiation of a verbal response activated left inferior frontal cortex (IFC: Brocas area). Successful inhibition of speech (naming of letters or pseudowords) engaged a region of right IFC (including pars opercularis and anterior insular cortex) as well as presupplementary motor area (pre-SMA); these regions were also activated by successful inhibition of a hand response (i.e., a button press). Moreover, the speed with which subjects inhibited their responses, stop-signal reaction time, was significantly correlated between speech and manual inhibition tasks. These findings suggest a functional dissociation of left and right IFC in initiating versus inhibiting vocal responses, and that manual responses and speech acts share a common inhibitory mechanism localized in the right IFC and pre-SMA.

Greater Neural Pattern Similarity Across Repetitions Is Associated with Better Memory

One, Two, Three, Remember Me When a stimulus (such as a word or a face) is presented for the second, third, or fourth time, do the neural representations differ? And, if they do, are multiply represented stimuli remembered better? These questions and related ones have fascinated psychologists for decades, but only recently has it become feasible to begin tackling them using neuroimaging. Xue et al. (p. 97, published online 9 September) provide evidence that the greater the similarity in the patterns of neural activity during encoding of the item, the greater the likelihood that the item will be remembered. Similarity in neural representations is associated with better memory, as well as conscious cognition. Repeated study improves memory, but the underlying neural mechanisms of this improvement are not well understood. Using functional magnetic resonance imaging and representational similarity analysis of brain activity, we found that, compared with forgotten items, subsequently remembered faces and words showed greater similarity in neural activation across multiple study in many brain regions, including (but not limited to) the regions whose mean activities were correlated with subsequent memory. This result addresses a longstanding debate in the study of memory by showing that successful episodic memory encoding occurs when the same neural representations are more precisely reactivated across study episodes, rather than when patterns of activation are more variable across time.

Functional Dissociations of Risk and Reward Processing in the Medial Prefrontal Cortex

Making a risky decision is a complex process that involves evaluation of both the value of the options and the associated risk level. Yet the neural processes underlying these processes have not so far been clearly identified. Using functional magnetic resonance imaging and a task that simulates risky decisions, we found that the dorsal region of the medial prefrontal cortex (MPFC) was activated whenever a risky decision was made, but the degree of this activity across subjects was negatively correlated with their risk preference. In contrast, the ventral MPFC was parametrically modulated by the received gain/loss, and the activation in this region was positively correlated with an individuals risk preference. These results extend existing neurological evidence by showing that the dorsal and ventral MPFC convey different decision signals (i.e., aversion to uncertainty vs. approach to rewarding outcomes), where the relative strengths of these signals determine behavioral decisions involving risk and uncertainty.

Neural correlates of envisioning emotional events in the near and far future

Being able to envision emotional events that might happen in the future has a clear adaptive value. This study addressed the functional neuroanatomy of this process and investigated whether it is modulated by temporal distance. Participants imagined positive and negative events pertaining to the near future or far future while their brain activity was measured with fMRI. The results demonstrate that the anterior part of the ventromedial prefrontal cortex (vmPFC) was more active in envisioning emotional events in the far future than in the near future, whereas the caudate nucleus was engaged in envisioning emotional (especially positive) situations in the near future. We argue that the anterior part of the vmPFC might assign emotional values to mental representations of future events that pertain to long-term goals. On the other hand, the caudate might support more concrete simulations of action plans to achieve rewarding situations in the near future.

The Impact of Prior Risk Experiences on Subsequent Risky Decision-Making: The Role of the Insula

Risky decision-making is significantly affected by homeostatic states associated with different prior risk experiences, yet the neural mechanisms have not been well understood. Using functional MRI, we examined how gambling decisions and their underlying neural responses were modulated by prior risk experiences, with a focus on the insular cortex since it has been implicated in interoception, emotion and risky decision-making. Fourteen healthy young participants were scanned while performing a gambling task that was designed to simulate daily-life risk taking. Prior risk experience was manipulated by presenting participants with gambles that they were very likely to accept or gambles that they were unlikely to accept. A probe gamble, which was sensitive to individuals risk preference, was presented to examine the effect of prior risk experiences (Risk vs. Norisk) on subsequent risky decisions. Compared to passing on a gamble (Norisk), taking a gamble, especially winning a gamble (Riskwin), was associated with significantly stronger activation in the insular and dorsal medial prefrontal cortices. Decision making after Norisk was more risky and more likely to recruit activation of the insular and anterior cingulate cortices. This insular activity during decision making predicted the extent of risky decisions both within- and across-subjects, and was also correlated with an individuals personality trait of urgency. These findings suggest that the insula plays an important role in activating representations of homeostatic states associated with the experience of risk, which in turn exerts an influence on subsequent decisions.

Language experience shapes fusiform activation when processing a logographic artificial language: an fMRI training study.

The significant role of the left midfusiform cortex in reading found in recent neuroimaging studies has led to the visual word form area (VWFA) hypothesis. This hypothesis suggests that years of experience reading native language change the visual expertise of this region to be especially sensitive to the visual form of native language. The present study aimed at testing this hypothesis by exploring the role of language experience in shaping the fusiform activation. We designed a logographic artificial language (LAL) using the visual form and pronunciation of Korean Hangul characters (but their correspondence was shuffled) and assigning arbitrary meanings to these characters. Twelve native Chinese Mandarin speakers (6 male and 6 female, 18 to 21 years old) with no prior knowledge of Korean language were trained in the visual form of these characters for 2 weeks, followed by 2 weeks each of phonological and semantic training. Behavioral data indicated that training was effective in increasing the efficiency of visual form processing and establishing the connections among visual form, sounds, and meanings. Imaging data indicated that at the pre-training stage, subjects showed stronger activation in the fusiform regions for LAL than for Chinese across both one-back visual matching task and the passive viewing task. Visual form training significantly decreased the activation of bilateral fusiform cortex and the left inferior occipital cortex, whereas phonological training increased activation in these regions, and the right fusiform remained more active after semantic training. Increased activations after phonological and semantic training were also evident in other regions involved in language processing. These findings thus do not seem to be consistent with the visual-expertise-induced-sensitivity hypothesis about fusiform regions. Instead, our results suggest that visual familiarity, phonological processing, and semantic processing all make significant but different contributions to shaping the fusiform activation.

Engagement of large-scale networks is related to individual differences in inhibitory control.

Understanding which brain regions regulate the execution, and suppression, of goal-directed behavior has implications for a number of areas of research. In particular, understanding which brain regions engaged during tasks requiring the execution and inhibition of a motor response provides insight into the mechanisms underlying individual differences in response inhibition ability. However, neuroimaging studies examining the relation between activation and stopping have been inconsistent regarding the direction of the relationship, and also regarding the anatomical location of regions that correlate with behavior. These limitations likely arise from the relatively low power of voxelwise correlations with small sample sizes. Here, we pooled data over five separate fMRI studies of the Stop-signal task in order to obtain a sufficiently large sample size to robustly detect brain/behavior correlations. In addition, rather than performing mass univariate correlation analysis across all voxels, we increased statistical power by reducing the dimensionality of the data set using independent component analysis and then examined correlations between behavior and the resulting component scores. We found that components reflecting activity in regions thought to be involved in stopping were associated with better stopping ability, while activity in a default-mode network was associated with poorer stopping ability across individuals. These results clearly show a relationship between individual differences in stopping ability in specific activated networks, including regions known to be critical for the behavior. The results also highlight the usefulness of using dimensionality reduction to increase the power to detect brain/behavior correlations in individual differences research.

The Neural Substrates of Visual Perceptual Learning of Words: Implications for the Visual Word Form Area Hypothesis

It remains under debate whether the fusiform visual word form area (VWFA) is specific to visual word form and whether visual expertise increases its sensitivity (Xue et al., 2006; Cohen et al., 2002). The present study examined three related issues: (1) whether the VWFA is also involved in processing foreign writing that significantly differs from the native one, (2) the effect of visual word form training on VWFA activation after controlling the task difficulty, and (3) the transfer of visual word form learning. Eleven native English speakers were trained, during five sessions, to judge whether two subsequently flashed (100-msec duration with 200-msec interval) foreign characters (i.e., Korean Hangul) were identical or not. Visual noise was added to the stimuli to manipulate task difficulty. In functional magnetic resonance imaging scans before and after training, subjects performed the task once with the same noise level (i.e., parameter-matched scan) and once with noise level changed to match performance from pretraining to posttraining (i.e., performance-matched scan). Results indicated that training increased the accuracy in parameter-matched condition but remained constant in performance-matched condition (because of increasing task difficulty). Pretraining scans revealed stronger activation for English words than for Korean characters in the left inferior temporal gyrus and the left inferior frontal cortex, but not in the VWFA. Visual word form training significantly decreased the activation in the bilateral middle and left posterior fusiform when either parameters or performance were matched and for both trained and new items. These results confirm our conjecture that the VWFA is not dedicated to words, and visual expertise acquired with training reduces rather than increases its activity.

Serotonin transporter gene-linked polymorphic region (5-HTTLPR) influences decision making under ambiguity and risk in a large Chinese sample

Risky decision making is a complex process that involves weighing the probabilities of alternative options that can be desirable, undesirable, or neutral. Individuals vary greatly in how they make decisions either under ambiguity and/or under risk. Such individual differences may have genetic bases. Based on previous studies on the genetic basis of decision making, two decision making tasks [i.e., the Iowa Gambling Task (IGT) and Loss Aversion Task (LAT)] were used to test the effect of 5-HTTLPR polymorphism on decision making under ambiguity and under risk in a large Han Chinese sample (572 college students, 312 females). Basic intelligence and memory tests were also included to control for the influence of basic cognitive abilities on decision making. We found that 5-HTTLPR polymorphism significantly influenced performance in both IGT and LAT. After controlling for intelligence and memory abilities, subjects homozygous for s allele had lower IGT scores than l carriers in the first 40 trials of the IGT task. They also exhibited higher loss aversion than l carriers in the LAT task. Moreover, the effects of 5-HTTLPR were stronger for males than for females. These results extend the literature on the important role of emotion in decision making under ambiguity and risk, and shed additional lights on how decision making is influenced by culture as well as sex differences. Combining our results with existing literature, we propose that these effects might be mediated by a neural circuitry that comprises the amygdala, ventromedial prefrontal cortex, and insular cortex. Understanding the genetic factors affecting decision making in healthy subjects may allow us to better identify at-risk individuals, and better target the development of new potential treatments for specific disorders such as schizophrenia, addiction, and depression.

Abnormal Affective Decision Making Revealed in Adolescent Binge Drinkers Using a Functional Magnetic Resonance Imaging Study

The goal of this study was to investigate the neural correlates of affective decision making, as measured by the Iowa Gambling Task (IGT), which are associated with adolescent binge drinking. Fourteen adolescent binge drinkers (16-18 years of age) and 14 age-matched adolescents who had never consumed alcohol--never drinkers--were recruited from local high schools in Chengdu, China. Questionnaires were used to assess academic performance, drinking experience, and urgency. Brain regions activated by the IGT performance were identified with functional magnetic resonance imaging. Results showed that, compared to never drinkers, binge drinkers performed worse on the IGT and showed higher activity in the subcomponents of the decision-making neural circuitry implicated in the execution of emotional and incentive-related behaviors, namely, the left amygdala and insula bilaterally. Moreover, measures of the severity of drinking problems in real life, as well as high urgency scores, were associated with increased activity within the insula, combined with decreased activity within the orbitofrontal cortex. These results suggest that hyperreactivity of a neural system implicated in the execution of emotional and incentive-related behaviors can be associated with socially undesirable behaviors, such as binge drinking, among adolescents. These findings have social implications because they potentially reveal underlying neural mechanisms for making poor decisions, which may increase an individuals risk and vulnerability for alcoholism.