Rong Ye

Decision-making impairments in breast cancer patients treated with tamoxifen

The selective estrogen receptor modulator tamoxifen (TAM) is most commonly prescribed for patients with hormone-sensitive breast cancer. Although TAM can bind to estrogen receptors in the nervous system, it is unknown whether it acts as an estrogen agonist or antagonist in the human brain. Several studies have reported the negative effects of TAM on cognitive function; however, its effects on decision-making function have not been previously explored. The present study aimed to investigate the decision-making function under ambiguity and risk in breast cancer patients treated with TAM. Participants included breast cancer patients taking TAM (TAM, n=47) and breast cancer patients not taking TAM (non-TAM, n=45) as well as their matched healthy controls (HC, n=50). All participants were given the Iowa Gambling Task (IGT) to assess their decision-making under conditions involving ambiguity, the Game of Dice Task (GDT) to assess their decision-making under conditions involving risk, and a battery of neuropsychological tests. Our results indicated that patients in the TAM group were significantly impaired as assessed by both the IGT and GDT and performed significantly worse on some aspects of various tasks involving memory and information processing. Furthermore, we found that decreased performance on verbal memory testing significantly correlated with IGT performance, and executive dysfunction was associated with poor GDT performance in breast cancer patients undergoing TAM treatment. This study demonstrates that breast cancer patients taking TAM have several decision-making impairments. These findings may support the idea that TAM resulting in cognitive changes plays an antagonistic role in the areas of the brain where estrogen receptors are present, including the prefrontal cortex, hippocampus and amygdala.

Evidence for progressive brain abnormalities in early schizophrenia: a cross-sectional structural and functional connectivity study.

It has long been debated whether a progressive process is involved in schizophrenia. The aim of the current study was to determine whether a progressive process was involved in patients with early schizophrenia, who were drug naive or had received short-term minimal antipsychotic treatment to avoid the distortion through medication effects. Twenty-eight patients with schizophrenia with illness-duration of up to 3 years and twenty-six matched healthy controls were recruited. Structural and functional brain networks were examined based on diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). The intergroup differences and correlation with illness duration in the patient group were surveyed. The schizophrenic patients showed lower fractional anisotropy (FA) values in the corpus callosum and corona radiata. Negative correlations of illness duration with FA values were observed in similar regions. During functional analysis, reduced functional connectivity between bilateral temporoparietal-junction (TPJ) and the posterior cingulate cortex (PCC) were found in the default mode network (DMN) in schizophrenic patients. In addition, the left TPJ showed gradually weaker functional connectivity with PCC and the medial prefrontal cortex (MPFC) in DMN as the duration of schizophrenia increased. The results suggested that early in the disease process patients have decreased connectivity in both structural and functional networks and that the weaker structural and functional connectivity negatively correlated with illness duration, which provided evidence for progressive brain abnormalities in early schizophrenia.

Dissociation of decision making under ambiguity and decision making under risk in breast cancer patients receiving adjuvant chemotherapy: a neuropsychological study.

There is evidence that women with breast cancer show a cognitive impairment after having undergone chemotherapy treatment; this cognitive impairment may result in behavioral deficits. However, the neural mechanism of this cognitive impairment remains unclear. The present study investigated the neural basis of the cognitive impairment caused by chemotherapy treatment by exploring the decision-making function of the executive subcomponents under ambiguity and risk in breast cancer survivors. Participants included breast cancer patients who had undergone chemotherapy (CT, N=63) or patients who did not undergo chemotherapy (non-CT, N=62), as well as matched healthy controls (HC, N=61). All participants were examined using the Iowa Gambling Task (IGT) to assess their decision-making under ambiguity, the Game of Dice Task (GDT) to assess their decision-making under risk and neuropsychological background tests. Our results indicated that during the IGT test, the chemotherapy-treated breast cancer patients selected from the disadvantageous decks with a higher frequency than the non-treated breast cancer patients or healthy controls, whereas all three groups performed at the same level when performing the GDT. The CT group demonstrated significantly lower scores in several cognitive tasks, including attention, memory, executive functions and cognitive processing, when compared with the other two groups. In addition, within the CT group, significant correlations were found between the IGT performance and information processing, as well as with working memory. This study demonstrated that breast cancer survivors treated with chemotherapy may have selective reductions in IGT performance but unimpaired GDT performance and that these deficits may result from dysfunctions in the limbic loop rather than in the dorsolateral prefrontal loop.

Dissociation of neural substrates of response inhibition to negative information between implicit and explicit facial go/nogo tasks: evidence from an electrophysiological study

Background Although ample evidence suggests that emotion and response inhibition are interrelated at the behavioral and neural levels, neural substrates of response inhibition to negative facial information remain unclear. Thus we used event-related potential (ERP) methods to explore the effects of explicit and implicit facial expression processing in response inhibition. Methods We used implicit (gender categorization) and explicit emotional Go/Nogo tasks (emotion categorization) in which neutral and sad faces were presented. Electrophysiological markers at the scalp and the voxel level were analyzed during the two tasks. Results We detected a task, emotion and trial type interaction effect in the Nogo-P3 stage. Larger Nogo-P3 amplitudes during sad conditions versus neutral conditions were detected with explicit tasks. However, the amplitude differences between the two conditions were not significant for implicit tasks. Source analyses on P3 component revealed that right inferior frontal junction (rIFJ) was involved during this stage. The current source density (CSD) of rIFJ was higher with sad conditions compared to neutral conditions for explicit tasks, rather than for implicit tasks. Conclusions The findings indicated that response inhibition was modulated by sad facial information at the action inhibition stage when facial expressions were processed explicitly rather than implicitly. The rIFJ may be a key brain region in emotion regulation.

Decision-making impairments in patients with Wilson's disease

Wilsons disease (WD) causes deposition of copper, mainly in the basal ganglia. One consequence of deposition seems to be impairment of executive functions, which could cause problems in decision making. In 30 WD patients and 30 healthy controls (HCs), we examined decision making under risk in the Game of Dice Task, and we assessed working memory and executive functions. WD patients exhibited a greater preference for disadvantageous choices than did HCs. Reduced decision-making performance was closely correlated to lower executive functions. Decision-making deficits of WD might be associated with frontostriatal loops, which are involved in executive functions and feedback processing.

How does emotional context modulate response inhibition in alexithymia: electrophysiological evidence from an ERP study.

Background Alexithymia, characterized by difficulties in identifying and describing feelings, is highly indicative of a broad range of psychiatric disorders. Several studies have also discovered the response inhibition ability impairment in alexithymia. However, few studies on alexithymic individuals have specifically examined how emotional context modulates response inhibition procedure. In order to investigate emotion cognition interaction in alexithymia, we analyzed the spatiao-temporal features of such emotional response inhibition by the approaches of event-related potentials and neural source-localization. Method The study participants included 15 subjects with high alexithymia scores on the 20-item Toronto Alexithymia Scale (alexithymic group) and 15 matched subjects with low alexithymia scores (control group). Subjects were instructed to perform a modified emotional Go/Nogo task while their continuous electroencephalography activities were synchronously recorded. The task includes 3 categories of emotional contexts (positive, negative and neutral) and 2 letters (“M” and “W”) centered in the screen. Participants were told to complete go and nogo actions based on the letters. We tested the influence of alexithymia in this emotional Go/Nogo task both in behavioral level and related neural activities of N2 and P3 ERP components. Results We found that negatively valenced context elicited larger central P3 amplitudes of the Nogo–Go difference wave in the alexithymic group than in the control group. Furthermore, source-localization analyses implicated the anterior cingulate cortex (ACC) as the neural generator of the Nogo-P3. Conclusion These findings suggest that difficulties in identifying feelings, particularly in negative emotions, is a major feature of alexithymia, and the ACC plays a critical role in emotion-modulated response inhibition related to alexithymia.

How does gaze direction affect facial processing in social anxiety? —An ERP study

Previous behavioral studies have demonstrated an effect of eye gaze direction on the processing of emotional expressions in adults with social anxiety. However, specific brain responses to the interaction between gaze direction and facial expressions in social anxiety remain unclear. The present study aimed to explore the time course of such interaction using event-related potentials (ERPs) in participants with social anxiety. High socially anxious individuals and low socially anxious individuals were asked to identify the gender of angry or neutral faces with direct or averted gaze while their behavioral performance and electrophysiological data were monitored. We found that identification of angry faces with direct but not averted gaze elicited larger N2 amplitude in high socially anxious individuals compared to low socially anxious individuals, while identification of neutral faces did not produce any gaze modulation effect. Moreover, the N2 was correlated with increased anxiety severity upon exposure to angry faces with direct gaze. Therefore, our results suggest that gaze direction modulates the processing of threatening faces in social anxiety. The N2 component elicited by angry faces with direct gaze could be a state-dependent biomarker of social anxiety and may be an important reference biomarker for social anxiety diagnosis and intervention.

External Error Monitoring in Subclinical Obsessive-Compulsive Subjects: Electrophysiological Evidence from a Gambling Task

Background Feedback-related negativity (FRN) is believed to be an important electrophysiology index of “external” negative feedback processing. Previous studies on FRN in obsessive-compulsive (OC) individuals are scarce and controversial. In these studies, anxiety symptoms were not evaluated in detail. However, OC disorders have a number of radical differences from anxiety disorders. It is necessary to study FRN and its neuroanatomical correlates in OC individuals without anxious symptoms. Methods A total of 628 undergraduate students completed an OC questionnaire. We chose 14 students who scored in the upper 10% and 14 students who scored in the lowest 10% without anxiety symptoms as a subclinical OC group (SOC) and a low obsessive-compulsive group (LOC). The students all performed the revised Iowa Gambling Task. We used the event-related potentials (ERP) and standardized low-resolution brain electromagnetic tomography (sLORETA) to track external negative feedback processing and its substrate in the brain. Results Our study revealed poorer decision-making ability and greater FRN amplitudes in SOC subjects compared with LOC controls. The SOC subjects displayed anterior prefrontal cortex (aPFC) hyperactivation during the loss feedback condition. Specifically, we found an intercorrelation of current source density during the loss condition between the dorsal anterior cingulate cortex (dACC) and aPFC in the LOC subjects but not in the SOC group. Conclusions Our results support the notion that overactive external feedback error processing may reflect a candidate endophenotype of OC. We also provide important information on the dysfunction in the interaction between aPFC and dACC in populations with OC. Nevertheless, the findings support that OC may be distinguished from other anxiety disorders using a new electrophysiology perspective.

The neural substrates of response inhibition to negative information across explicit and implicit tasks in GAD patients: electrophysiological evidence from an ERP study

Background: It has been established that the inability to inhibit a response to negative stimuli is the genesis of anxiety. However, the neural substrates of response inhibition to sad faces across explicit and implicit tasks in general anxiety disorder (GAD) patients remain unclear. Methods: Electrophysiological data were recorded when subjects performed two modified emotional go/no-go tasks in which neutral and sad faces were presented: one task was explicit (emotion categorization), and the other task was implicit (gender categorization). Results: In the explicit task, electrophysiological evidence showed decreased amplitudes of no-go/go difference waves at the N2 interval in the GAD group compared to the control group. However, in the implicit task, the amplitudes of no-go/go difference waves at the N2 interval showed a reversed trend. Source localization analysis on no-go/N2 components revealed a decreased current source density (CSD) in the right dorsal lateral prefrontal cortex in GAD individuals relative to controls. In the implicit task, the left superior temporal gyrus and the left inferior parietal lobe showed enhanced activation in GAD individuals and may compensate for the dysfunction of the right dorsal lateral prefrontal cortex. Conclusion: These findings indicated that the processing of response inhibition to socially sad faces in GAD individuals was interrupted in the explicit task. However, this processing was preserved in the implicit task. The neural substrates of response inhibition to sad faces were dissociated between implicit and explicit tasks.