Neural and Psychological Predictors of Cognitive Enhancement and Impairment from Neurostimulation.

Modulating the temporoparietal junction (TPJ), especially the right counterpart, shows promises in enhancing social cognitive ability. However, it is ambiguous whether the functional lateralization of TPJ determines people's responsiveness to brain stimulation. Here, this issue is investigated with an individual difference approach. Forty-five participants attended three sessions of transcranial direct current stimulation (tDCS) experiments and one neuroimaging session. The results support the symmetric mechanism of left and right TPJ stimulation. First, the left and right TPJ stimulation effect are comparable in the group-level analysis. Second, the individual-level analysis reveals that a less right-lateralized TPJ is associated with a higher level of responsiveness. Participants could be classified into positive responders showing cognitive enhancement and negative responders showing cognitive impairment due to stimulation. The positive responders show weaker connectivity between bilateral TPJ and the medial prefrontal cortex, which mediates the prediction of offline responsiveness by the lateralization and the social-related trait. These findings call for a better characterization and predictive models for whom tDCS should be used for, and highlight the necessity and feasibility of prestimulation screening.

Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics.

Type 2 diabetes mellitus (T2DM) is well known for its adverse impacts on brain and cognition, which leads to multidimensional cognitive deficits and wildly spread cerebral structure abnormalities. However, existing literatures are mainly focused on patients with advanced age or extended T2DM duration. Therefore, it remains unclear whether and how brain function would be affected at the initial onset stage of T2DM in relatively younger population. In current study, twelve newly diagnosed middle-aged T2DM patients with no previous diabetic treatment history and twelve matched controls were recruited. Brain activations during a working memory task, the digit n-back paradigm (0-, 1- and 2-back), were obtained with functional magnetic resonance imaging and tested by repeated measures ANOVA. Whereas patients performed the n-back task comparably well as controls, significant load-by-group interactions of brain activation were found in the right dorsolateral prefrontal cortex (DLPFC), left middle/inferior frontal gyrus, and left parietal cortex, where patients exhibited hyperactivation in the 2-back, but not the 0-back or 1-back condition compared to controls. Furthermore, the severity of chronic hyperglycemia, estimated by glycosylated hemoglobin (HbA1c) level, was entered into partial correlational analyses with task-related brain activations, while controlling for the real-time influence of glucose, estimated by instant plasma glucose level measured before scanning. Significant positive correlations were found between HbA1c and brain activations in the anterior cingulate cortex and bilateral DLPFC only in patients. Taken together, these findings suggest there might be a compensatory mechanism due to brain inefficiency related to chronic hyperglycemia at the initial onset stage of T2DM.

Resting-state functional connectivity predicts impulsivity in economic decision-making.

Increasing neuroimaging evidence suggests an association between impulsive decision-making behavior and task-related brain activity. However, the relationship between impulsivity in decision-making and resting-state brain activity remains unknown. To address this issue, we used functional MRI to record brain activity from human adults during a resting state and during a delay discounting task (DDT) that requires choosing between an immediate smaller reward and a larger delayed reward. In experiment I, we identified four DDT-related brain networks. The money network (the striatum, posterior cingulate cortex, etc.) and the time network (the medial and dorsolateral prefrontal cortices, etc.) were associated with the valuation process; the frontoparietal network and the dorsal anterior cingulate cortex-anterior insular cortex network were related to the choice process. Moreover, we found that the resting-state functional connectivity of the brain regions in these networks was significantly correlated with participants' discounting rate, a behavioral index of impulsivity during the DDT. In experiment II, we tested an independent group of subjects and demonstrated that this resting-state functional connectivity was able to predict individuals' discounting rates. Together, these findings suggest that resting-state functional organization of the human brain may be a biomarker of impulsivity and can predict economic decision-making behavior.

Rejection of unfair offers can be driven by negative emotions, evidence from modified ultimatum games with anonymity.

The rejection of unfair offers can be affected by both negative emotions (e.g. anger and moral disgust) and deliberate cognitive processing of behavioral consequences (e.g. concerns of maintaining social fairness and protecting personal reputation). However, whether negative emotions are sufficient to motivate this behavior is still controversial. With modified ultimatum games, a recent study (Yamagishi T, et al. (2009) Proc Natl Acad Sci USA 106:11520-11523) found that people reject unfair offers even when this behavior increases inequity, and even when they could not communicate to the proposers. Yamagishi suggested that rejection of unfair offers could occur without people's concerning of maintaining social fairness, and could be driven by negative emotions. However, as anonymity was not sufficiently guaranteed in Yamagishi's study, the rejection rates in their experiments may have been influenced by people's concerns of protecting personal reputation (reputational concerns) in addition to negative emotions; thus, it was unclear whether the rejection was driven by negative emotions, or by reputational concerns, or both. In the present study, with specific methods to ensure anonymity, the effect of reputational concerns was successfully ruled out. We found that in a private situation in which rejection could not be driven by reputational concerns, the rejection rates of unfair offers were significantly larger than zero, and in public situations in which rejection rates could be influenced by both negative emotions and reputational concerns, rejection rates were significantly higher than that in the private situation. These results, together with Yamagishi's findings, provided more complete evidence suggesting (a) that the rejection of unfair offers can be driven by negative emotions and (b) that deliberate cognitive processing of the consequences of the behavior can increase the rejection rate, which may benefit social cooperation.

Functional magnetic resource imaging assessment of altered brain function in hypothyroidism during working memory processing.

CONTEXT: Hypothyroidism is related to multiple cognitive deficits including working memory dysfunction, of which the underlying neural correlates were rarely studied. In this study, the impact of hypothyroidism on neural circuits involved in working memory processing was explored by functional magnetic resource imaging (fMRI). DESIGN: Using fMRI, we conducted a longitudinal study investigating alterations of brain function during a working memory task, the four-digit backward recall (BR) and forward recall (FR), in hypothyroid patients and controls. METHODS: fMRI scan was used in 13 female patients at two time points: before and after having been treated with levothyroxine (L-T(4)) for ∼6 months, and 12 matched euthyroid controls were also scanned. Wechsler Memory Scale-Chinese Revision was used to assess the memory states of each participant. RESULTS: The hypothyroid patients showed poorer memory states than that in controls. Furthermore, significant differences of task-induced deactivation (TID, task-dependent decreases in neural activity relative to rest) between patients and controls were found in the bilateral medial prefrontal cortices, posterior cingulate cortices, and left inferior partial lobule (P<0.05). These regions were considered as parts of a task-negative network, namely the default mode network (DMN). Concretely, relative to controls, patients showed diminished TID during BR in contrast to FR. After the L-T(4) treatment, neither the poor memory states nor the alteration of TID was detectable in patients. CONCLUSION: Hypothyroidism is related to alterations of TID within DMN regions during working memory processing. These exploratory findings may imply potential neural correlates in hypothyroidism-related cognitive deficits and their recoveries.

Abnormal brain default-mode network functional connectivity in drug addicts.

BACKGROUND: The default mode network (DMN) is a set of brain regions that exhibit synchronized low frequency oscillations at resting-state, and is believed to be relevant to attention and self-monitoring. As the anterior cingulate cortex and hippocampus are impaired in drug addiction and meanwhile are parts of the DMN, the present study examined addiction-related alteration of functional connectivity of the DMN. METHODOLOGY: Resting-state functional magnetic resonance imaging data of chronic heroin users (14 males, age: 30.1±5.3 years, range from 22 to 39 years) and non-addicted controls (13 males, age: 29.8±7.2 years, range from 20 to 39 years) were investigated with independent component analysis to address their functional connectivity of the DMN. PRINCIPAL FINDINGS: Compared with controls, heroin users showed increased functional connectivity in right hippocampus and decreased functional connectivity in right dorsal anterior cingulate cortex and left caudate in the DMN. CONCLUSIONS: These findings suggest drug addicts' abnormal functional organization of the DMN, and are discussed as addiction-related abnormally increased memory processing but diminished cognitive control related to attention and self-monitoring, which may underlie the hypersensitivity toward drug related cues but weakened strength of cognitive control in the state of addiction.

Is the contribution of the amygdala to the sex- and enhancement-related effects of emotional memory time-dependent?

A new focus in the field of emotional memory is the study of sex-related differences. Whether the sex-related lateralization of amygdala function (i.e., the female-left/male-right effect) in the emotional enhancement of memory (EEM) is time-dependent remains unclear. To evaluate this phenomenon, we conducted a two time-point study (20 min vs. 24h) using fMRI and behavioral paradigms. We found that the right amygdala predicted 20-min EEM, while the left amygdala predicted 24-h EEM. The sex-related lateralization of amygdala function was not detected in either the 20-min or the 24-h EEM. Our results further confirm and extend the idea that the amygdala exhibits a lateralized and time-dependent dissociation, occurring even in the 24-h EEM relative to the 20-min EEM. The present and previous studies indicate that sex-related lateralization of amygdala function occurs in the 2- to 3-week EEM, but it does not occur in the 1-week, 24-h, or less than 30-min EEM, suggesting that this effect on emotional memory may also be time-dependent.

Addiction related alteration in resting-state brain connectivity.

It is widely accepted that addictive drug use is related to abnormal functional organization in the user's brain. The present study aimed to identify this type of abnormality within the brain networks implicated in addiction by resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI). With fMRI data acquired during resting state from 14 chronic heroin users (12 of whom were being treated with methadone) and 13 non-addicted controls, we investigated the addiction related alteration in functional connectivity between the regions in the circuits implicated in addiction with seed-based correlation analysis. Compared with controls, chronic heroin users showed increased functional connectivity between nucleus accumbens and ventral/rostral anterior cingulate cortex (ACC), between nucleus accumbens and orbital frontal cortex (OFC), and between amygdala and OFC and reduced functional connectivity between prefrontal cortex and OFC and between prefrontal cortex and ACC. These observations of altered resting-state functional connectivity suggested abnormal functional organization in the addicted brain and may provide additional evidence supporting the theory of addiction that emphasizes enhanced salience value of a drug and its related cues but weakened cognitive control in the addictive state.

Numerical magnitude modulates temporal comparison: an ERP study.

Time is believed to be a part of the generalized magnitude system just like space and quantity. Previous research suggests that time perception can be affected by magnitude in some non-temporal dimensions. Here we address two questions. First, could the influence be caused by an abstract magnitude component without perceptual variables? Second, what are the underlying mechanisms of the influence? Participants compared a pair of durations defined by two Arabic digits in a hundreds of milliseconds range. They performed more accurately when the shorter durations were defined by lower numeric value digits (small digits) and the longer durations were defined by higher value digits (large digits) than they did in the reversed condition. Event-Related Potential (ERP) results showed that the CNVs corresponding to the first duration (CNV1), to the second duration (CNV2) and the N1 were all enhanced when durations marked by small digits than that marked by large ones. Combining the electrophysiological data with the behavioral results, we suggest that digits can modulate performance of temporal comparison at the relatively early stage of perceptual processing. One possible explanation of the current results is that selective temporal attention and subsequent expectation may be involved in this modulation.

Decision-making and prepotent response inhibition functions in excessive internet users.

INTRODUCTION: Excessive Internet use (EIU), also described as Internet addiction or pathological Internet use, has already become a serious social problem around the world. Some researchers consider EIU as a kind of behavioral addiction. However, there are few experimental studies on the cognitive functions of excessive Internet users (EIUers) and limited data are available to compare EIU with other addictive behaviors, such as drug abuse and pathological gambling. METHODS: In the present study, we examined EIUers' functions of decision-making and prepotent response inhibition. Two groups of participants, EIUers and controls, were compared on these two functions by using a Gambling Task and a Go/no-go Task, respectively. RESULTS: Compared with controls, EIUers selected significantly less net decks in the Gambling Task (P=.007). Furthermore, the EIUers made progress in selecting strategy, but more slowly than did the control group (EIUers, chunk 3 > chunk 1, P<.001; controls, chunk 2 > chunk 1, P<.001). Interestingly, EIUers' accuracy during the no-go condition was significantly higher than that of controls (P=.018). CONCLUSION: These results showed some similarities and dissimilarities between EIU and other addictive behaviors such as drug abuse and pathological gambling. The findings from the Gambling Task indicated that EIUers have deficits in decision-making function, which are characterized by a strategy learning lag rather than an inability to learn from task contingencies. EIUers' better performance in the Go/no-go Task suggested some dissociation between mechanisms of decision-making and those of prepotent response inhibition. However, EIUers could hardly suppress their excessive online behaviors in real life. Their ability of inhibition still needs to be further studied with more specific assessments.

Computer games: a double-edged sword?

Excessive computer game playing (ECGP) has already become a serious social problem. However, limited data from experimental lab studies are available about the negative consequences of ECGP on players' cognitive characteristics. In the present study, we compared three groups of participants (current ECGP participants, previous ECGP participants, and control participants) on a Multiple Object Tracking (MOT) task. The previous ECGP participants performed significantly better than the control participants, which suggested a facilitation effect of computer games on visuospatial abilities. Moreover, the current ECGP participants performed significantly worse than the previous ECGP participants. This more important finding indicates that ECGP may be related to cognitive deficits. Implications of this study are discussed.

Verbal working memory deficits in abstinent heroin abusers.

BACKGROUND: A prevailing belief is that opioids tend not to impair cognitive performance in opioid-dependent users. However, the impact of heroin abuse on verbal memory, especially on working memory, is not well studied and the results available are inconsistent. OBJECTIVE: This study was carried out to test the hypothesis that abstinent heroin abusers have intact working memory capacity. METHODS: N-back task and backward digit span task were used to measure the verbal working memory capacity in 28 abstinent heroin abusers and 25 controls matched for age, education level and gender. Forward digit span task was used as a control task to measure short-term memory capacity. RESULTS: Compared with the control subjects, heroin abusers showed normal backward/forward digit spans but significant performance impairment in the n-back task. CONCLUSION: Abstinent heroin abusers have intact short-term memory capacity but impaired verbal working memory capacity.

Binding facilitates attention switching within working memory.

The authors investigated the units of selective attention within working memory. In Experiment 1, a group of participants kept 1 count and 1 location in working memory and updated them repeatedly in random order. Another group of participants were instructed to achieve the same goal by memorizing the verbal and spatial information in an integrative way as a moving digit. The behavioral data showed that switching attention between properties of an integrated working-memory item was faster than switching between respective properties of different items. Experiment 2 demonstrated that this switching facilitation cannot be simply ascribed to the different amount of working-memory items maintained by the two groups of participants. Finally, by adopting a pure verbal task in Experiment 3, the authors observed the same binding facilitation, with the possibility of "location-based selection" excluded. They summarize the observations of all 3 experiments in the study and suggest both a location- and object-based mechanism for attention selection in working memory.

Opposite patterns of hemisphere dominance for early auditory processing of lexical tones and consonants.

In tonal languages such as Mandarin Chinese, a lexical tone carries semantic information and is preferentially processed in the left brain hemisphere of native speakers as revealed by the functional MRI or positron emission tomography studies, which likely measure the temporally aggregated neural events including those at an attentive stage of auditory processing. Here, we demonstrate that early auditory processing of a lexical tone at a preattentive stage is actually lateralized to the right hemisphere. We frequently presented to native Mandarin Chinese speakers a meaningful auditory word with a consonant-vowel structure and infrequently varied either its lexical tone or initial consonant using an odd-ball paradigm to create a contrast resulting in a change in word meaning. The lexical tone contrast evoked a stronger preattentive response, as revealed by whole-head electric recordings of the mismatch negativity, in the right hemisphere than in the left hemisphere, whereas the consonant contrast produced an opposite pattern. Given the distinct acoustic features between a lexical tone and a consonant, this opposite lateralization pattern suggests the dependence of hemisphere dominance mainly on acoustic cues before speech input is mapped into a semantic representation in the processing stream.

fMRI revealed neural substrate for reversible working memory dysfunction in subclinical hypothyroidism.

Cognitive impairments have been found in thyroid hormone-related diseases (e.g. hyperthyroidism and hypothyroidism) for a long time. However, whether and how subclinical hypothyroidism (SCH) causes any deficits in brain functions, and whether a hormone-replacement treatment is necessary for SCH patients, still remain controversial subjects. In the present study, functional MRI (fMRI) was used to measure brain functions by asking euthyroid subjects, hyperthyroid patients and SCH patients to perform the widely used digit n-back working memory task. After having been treated with l-thyroxine for approximately 6 months, the SCH patients were asked to do the same fMRI experiment. The hypothyroid and SCH patients scored significantly lower in the 2-back task than either the hyperthyroid patients or the euthyroid subjects (P < 0.012). The fMRI showed that a common frontoparietal network, including bilateral middle/inferior frontal gyri (M/IFG), bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor areas (PreMA), the supplementary motor area/anterior cingulate cortex (SMA/ACC) and bilateral parietal areas (PA), was activated by the n-back task in all the subjects. Further quantitative analysis showed that the load effect of blood oxygen level-dependent (BOLD) response appeared in all the five regions of interest (ROIs) in the euthyroid and hyperthyroid subjects. In the pre-treatment SCH patients, however, the load effect of BOLD response was only found in the PA and PreMA, but not in other frontal cortex ROIs [general linear model (GLM), F < 2.6, P > 0.1]. After an approximately 6 month treatment with LT4, the SCH patients exhibited the same load effects in all five ROIs as the euthyroid subjects (GLM, F > 6, P < 0.05) along with an improvement of performance in n-back task. These results suggest that working memory (but not other memory functions) is impaired in SCH patients, mainly as far as disorders of the frontoparietal network were concerned. Both the memory performance and frontal executive functions were improved after an l-thyroxine-replacement treatment.

Backward inhibition in a task of switching attention within verbal working memory.

Three experiments were conducted to examine the backward inhibition effect in attention switching within verbal working memory. Experiment one showed significant backward inhibition effect in a "tri-count task". Experiment two suggested that the effect was not due to a perceptual inhibition on the previously presented figure. Experiment three excluded the sequential expectancy explanation for this inhibition effect. Our results suggest that attention switching between working memory items is accompanied by inhibition of the previously attended working memory item. The findings are discussed in respect to the account of the executive function.

Behavioral and functional MRI study of attention shift in human verbal working memory.

The tripartite model of memory proposed the requirement of attentional switching when accessing different items in working memory [J. Exp. Psychol. Learn. Mem. Cogn. 27 (2001) 817]. This internal focus of attention is limited to just one item and the switching process is time-consuming [Mem. Cogn. 26 (1998) 263]. In the current study, given a three-digit list stored in working memory, we found that it took longer to shift attention in the direction of "Upstream" than "Downstream", and that each shift was a "single step" process. To investigate the neural basis of this type of attention switching, we performed a functional MRI study. The results revealed that at least three important brain areas are involved, including the left dorsal lateral prefrontal cortex, the cingulate gyrus, and the medial occipital cortex. These areas all showed greater activation in the attention shift condition compared to control conditions of no (or decreased) attention shift requirements. In addition, the hemodynamic activities in these areas are highly correlated, suggesting a strong functional connectivity between them. Taken together with evidence from several recent investigations, our results suggest that these areas each play an important and specific role in collaboratively supporting the function of attention shift in working memory.

Functional comparison of primacy, middle and recency retrieval in human auditory short-term memory: an event-related fMRI study.

Primacy and recency effects refer to the better performance or shorter response time on the first and last items than the middle ones of a memory list. In order to investigate its neural basis in auditory short-term memory, event-related fMRI was used to measure brain activities when subject was recalling the first, the last, or the middle items. Recalling the middle item was associated with more extensive activation in the left parietal and visual cortex, basal ganglia, and dorsal cerebellum. Recalling items from different serial positions also resulted in different activation time courses in the bilateral primary auditory cortex, left prefrontal cortex and left premotor cortex. These data indicate that the auditory cortex may serve as a transient storage or the auditory input buffer, which seems to play an important role in the primacy and recency effects.