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Sien Hu

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12 papers

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YNICL Journal 2018 Journal Article

Dynamic network dysfunction in cocaine dependence: Graph theoretical metrics and stop signal reaction time

Yihe Zhang
Sheng Zhang
Jaime S. Ide
Sien Hu
Simon Zhornitsky
Wuyi Wang
Guozhao Dong
Xiaoying Tang

Graphic theoretical metrics have become increasingly popular in characterizing functional connectivity of neural networks and how network connectivity is compromised in neuropsychiatric illnesses. Here, we add to this literature by describing dynamic network connectivities of 78 cocaine dependent (CD) and 85 non-drug using healthy control (HC) participants who underwent fMRI during performance of a stop signal task (SST). Compared to HC, CD showed prolonged stop signal reaction time (SSRT), consistent with deficits in response inhibition. In graph theoretical analysis of dynamic functional connectivity, we examined temporal flexibility and spatiotemporal diversity of 14 networks covering the whole brain. Temporal flexibility quantifies how frequently a brain region interacts with regions of other communities across time, with high temporal flexibility indicating that a region interacts predominantly with regions outside its own community. Spatiotemporal diversity quantifies how uniformly a brain region interacts with regions in other communities over time, with high spatiotemporal diversity indicating that the interactions are more evenly distributed across communities. Compared to HC, CD exhibited decreased temporal flexibility and increased spatiotemporal diversity in the great majority of neural networks. The graph metric measures of the default mode network negatively correlated with SSRT in CD but not HC. The findings are consistent with diminished temporal flexibility and a compensatory increase in spatiotemporal diversity, in association with impairment of a critical executive function, in cocaine addiction. More broadly, the findings suggest that graph theoretical metrics provide new insights for connectivity analyses to elucidate network dysfunction that may elude conventional measures.

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YNICL Journal 2017 Journal Article

Sex differences in the interacting roles of impulsivity and positive alcohol expectancy in problem drinking: A structural brain imaging study

Jaime S. Ide
Simon Zhornitsky
Sien Hu
Sheng Zhang
John H. Krystal
Chiang-shan R. Li

Alcohol expectancy and impulsivity are implicated in alcohol misuse. However, how these two risk factors interact to determine problem drinking and whether men and women differ in these risk processes remain unclear. In 158 social drinkers (86 women) assessed for Alcohol Use Disorder Identification Test (AUDIT), positive alcohol expectancy, and Barratt impulsivity, we examined sex differences in these risk processes. Further, with structural brain imaging, we examined the neural bases underlying the relationship between these risk factors and problem drinking. The results of general linear modeling showed that alcohol expectancy best predicted problem drinking in women, whereas in men as well as in the combined group alcohol expectancy and impulsivity interacted to best predict problem drinking. Alcohol expectancy was associated with decreased gray matter volume (GMV) of the right posterior insula in women and the interaction of alcohol expectancy and impulsivity was associated with decreased GMV of the left thalamus in women and men combined and in men alone, albeit less significantly. These risk factors mediated the correlation between GMV and problem drinking. Conversely, models where GMV resulted from problem drinking were not supported. These new findings reveal distinct psychological factors that dispose men and women to problem drinking. Although mediation analyses did not determine a causal link, GMV reduction in the insula and thalamus may represent neural phenotype of these risk processes rather than the consequence of alcohol consumption in non-dependent social drinkers. The results add to the alcohol imaging literature which has largely focused on dependent individuals and help elucidate alterations in brain structures that may contribute to the transition from social to habitual drinking.

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YNIMG Journal 2016 Journal Article

A dual but asymmetric role of the dorsal anterior cingulate cortex in response inhibition and switching from a non-salient to salient action

Peter Manza
Sien Hu
Herta H. Chao
Sheng Zhang
Hoi-Chung Leung
Chiang-shan R. Li

Response inhibition and salience detection are among the most studied psychological constructs of cognitive control. Despite a growing body of work, how inhibition and salience processing interact and engage regional brain activations remains unclear. Here, we examined this issue in a stop signal task (SST), where a prepotent response needs to be inhibited to allow an alternative, less dominant response. Sixteen adult individuals performed two versions of the SST each with 25% (SST25) and 75% (SST75) of stop trials. We posited that greater regional activations to the infrequent trial type in each condition (i. e. , to stop as compared to go trials in SST25 and to go as compared to stop trials in SST75) support salience detection. Further, successful inhibition in stop trials requires attention to the stop signal to trigger motor inhibition, and the stop signal reaction time (SSRT) has been used to index the efficiency of motor response inhibition. Therefore, greater regional activations to stop as compared to go success trials in association with the stop signal reaction time (SSRT) serve to expedite response inhibition. In support of an interactive role, the dorsal anterior cingulate cortex (dACC) increases activation to salience detection in both SST25 and SST75, but only mediates response inhibition in SST75. Thus, infrequency response in the dACC supports motor inhibition only when stopping has become a routine. In contrast, although the evidence is less robust, the pre-supplementary motor area (pre-SMA) increases activity to the infrequent stimulus and supports inhibition in both SST25 and SST75. These findings clarify a unique role of the dACC and add to the literature that distinguishes dACC and pre-SMA functions in cognitive control.

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YNICL Journal 2016 Journal Article

Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis

Sheng Zhang
Sien Hu
Rajita Sinha
Marc N. Potenza
Robert T. Malison
Chiang-shan R. Li

Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence.

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YNICL Journal 2016 Journal Article

Power spectrum scale invariance as a neural marker of cocaine misuse and altered cognitive control

Jaime S. Ide
Sien Hu
Sheng Zhang
Lilianne R. Mujica-Parodi
Chiang-shan R. Li

BACKGROUND: Magnetic resonance imaging (MRI) has highlighted the effects of chronic cocaine exposure on cerebral structures and functions, and implicated the prefrontal cortices in deficits of cognitive control. Recent investigations suggest power spectrum scale invariance (PSSI) of cerebral blood oxygenation level dependent (BOLD) signals as a neural marker of cerebral activity. We examined here how PSSI is altered in association with cocaine misuse and impaired cognitive control. METHODS: Eighty-eight healthy (HC) and seventy-five age and gender matched cocaine dependent (CD) adults participated in functional MRI of a stop signal task (SST). BOLD images were preprocessed using standard procedures in SPM, including detrending, band-pass filtering (0.01-0.25 Hz), and correction for head motions. Voxel-wise PSSI measures were estimated by a linear fit of the power spectrum with a log-log scale. In group analyses, we examined differences in PSSI between HC and CD, and its association with clinical and behavioral variables using a multiple regression. A critical component of cognitive control is post-signal behavioral adjustment, which is compromised in cocaine dependence. Therefore, we examined the PSSI changes in association with post-signal slowing (PSS) in the SST. RESULTS: Compared to HC, CD showed decreased PSS and PSSI in multiple frontoparietal regions. PSSI was positively correlated with PSS in HC in multiple regions, including the left inferior frontal gyrus (IFG) and right supramarginal gyrus (SMG), which showed reduced PSSI in CD. CONCLUSIONS: These findings suggest disrupted connectivity dynamics in the fronto-parietal areas in association with post-signal behavioral adjustment in cocaine addicts. These new findings support PSSI as a neural marker of impaired cognitive control in cocaine addiction.

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YNIMG Journal 2015 Journal Article

Anticipating conflict: Neural correlates of a Bayesian belief and its motor consequence

Sien Hu
Jaime S. Ide
Sheng Zhang
Chiang-shan R. Li

Previous studies have examined the neural correlates of proactive control using a variety of behavioral paradigms; however, the neural network relating the control process to its behavioral consequence remains unclear. Here, we applied a dynamic Bayesian model to a large fMRI data set of the stop signal task to address this issue. By estimating the probability of the stop signal – p(Stop) – trial by trial, we showed that higher p(Stop) is associated with prolonged go trial reaction time (RT), indicating proactive control of motor response. In modeling fMRI signals at trial and target onsets, we distinguished activities of proactive control, prediction error, and RT slowing. We showed that the anterior pre-supplementary motor area (pre-SMA) responds specifically to increased stop signal likelihood, and its activity is correlated with activations of the posterior pre-SMA and bilateral anterior insula during prolonged response times. This directional link is also supported by Granger causality analysis. Furthermore, proactive control, prediction error, and time-on-task are each mapped to distinct areas in the medial prefrontal cortex. Together, these findings dissect regional functions of the medial prefrontal cortex in cognitive control and provide system level evidence associating conflict anticipation with its motor consequence.

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YNICL Journal 2015 Journal Article

Conflict anticipation in alcohol dependence — A model-based fMRI study of stop signal task

Sien Hu
Jaime S. Ide
Sheng Zhang
Rajita Sinha
Chiang-shan R. Li

BACKGROUND: Our previous work characterized altered cerebral activations during cognitive control in individuals with alcohol dependence (AD). A hallmark of cognitive control is the ability to anticipate changes and adjust behavior accordingly. Here, we employed a Bayesian model to describe trial-by-trial anticipation of the stop signal and modeled fMRI signals of conflict anticipation in a stop signal task. Our goal is to characterize the neural correlates of conflict anticipation and its relationship to response inhibition and alcohol consumption in AD. METHODS: Twenty-four AD and 70 age and gender matched healthy control individuals (HC) participated in the study. fMRI data were pre-processed and modeled with SPM8. We modeled fMRI signals at trial onset with individual events parametrically modulated by estimated probability of the stop signal, p(Stop), and compared regional responses to conflict anticipation between AD and HC. To address the link to response inhibition, we regressed whole-brain responses to conflict anticipation against the stop signal reaction time (SSRT). RESULTS: Compared to HC (54/70), fewer AD (11/24) showed a significant sequential effect - a correlation between p(Stop) and RT during go trials - and the magnitude of sequential effect is diminished, suggesting a deficit in proactive control. Parametric analyses showed decreased learning rate and over-estimated prior mean of the stop signal in AD. In fMRI, both HC and AD responded to p(Stop) in bilateral inferior parietal cortex and anterior pre-supplementary motor area, although the magnitude of response increased in AD. In contrast, HC but not AD showed deactivation of the perigenual anterior cingulate cortex (pgACC). Furthermore, deactivation of the pgACC to increasing p(Stop) is positively correlated with the SSRT in HC but not AD. Recent alcohol consumption is correlated with increased activation of the thalamus and cerebellum in AD during conflict anticipation. CONCLUSIONS: The current results highlight altered proactive control that may serve as an additional behavioral and neural marker of alcohol dependence.

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YNIMG Journal 2015 Journal Article

The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood

Peter Manza
Sheng Zhang
Sien Hu
Herta H. Chao
Hoi-Chung Leung
Chiang-shan R. Li

The basal ganglia nuclei are critical for a variety of cognitive and motor functions. Much work has shown age-related structural changes of the basal ganglia. Yet less is known about how the functional interactions of these regions with the cerebral cortex and the cerebellum change throughout the lifespan. Here, we took advantage of a convenient sample and examined resting state functional magnetic resonance imaging data from 250 adults 18 to 49years of age, focusing specifically on the caudate nucleus, pallidum, putamen, and ventral tegmental area/substantia nigra (VTA/SN). There are a few main findings to report. First, with age, caudate head connectivity increased with a large region of ventromedial prefrontal/medial orbitofrontal cortex. Second, across all subjects, pallidum and putamen showed negative connectivity with default mode network (DMN) regions such as the ventromedial prefrontal cortex and posterior cingulate cortex, in support of anti-correlation of the “task-positive” network (TPN) and DMN. This negative connectivity was reduced with age. Furthermore, pallidum, posterior putamen and VTA/SN connectivity to other TPN regions, such as somatomotor cortex, decreased with age. These results highlight a distinct effect of age on cerebral functional connectivity of the dorsal striatum and VTA/SN from young to middle adulthood and may help research investigating the etiologies or monitoring outcomes of neuropsychiatric conditions that implicate dopaminergic dysfunction.

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YNICL Journal 2014 Journal Article

Error-related functional connectivity of the thalamus in cocaine dependence

Sheng Zhang
Sien Hu
Sarah R. Bednarski
Emily Erdman
Chiang-shan R. Li

Error processing is a critical component of cognitive control, an executive function that has been widely implicated in substance misuse. In previous studies we showed that error related activations of the thalamus predicted relapse to drug use in cocaine addicted individuals (Luo et al., 2013). Here, we investigated whether the error-related functional connectivity of the thalamus is altered in cocaine dependent patients (PCD, n = 54) as compared to demographically matched healthy individuals (HC, n = 54). The results of a generalized psychophysiological interaction analysis showed negative thalamic connectivity with the ventral medial prefrontal cortex (vmPFC), in the area of perigenual and subgenual anterior cingulate cortex, in HC but not PCD (p < 0.05, corrected, two-sample t test). This difference in functional connectivity was not observed for task-residual signals, suggesting that it is specific to task-related processes during cognitive control. Further, the thalamic-vmPFC connectivity is positively correlated with the amount of cocaine use in the prior month for female but not for male PCD. These findings add to recent literature and provide additional evidence for circuit-level biomarkers of cocaine dependence.

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YNIMG Journal 2014 Journal Article

Resting state functional connectivity of the basal nucleus of Meynert in humans: In comparison to the ventral striatum and the effects of age

Chiang-shan R. Li
Jaime S. Ide
Sheng Zhang
Sien Hu
Herta H. Chao
Laszlo Zaborszky

The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer's disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, supplementary motor area and pre-supplementary motor area, a network of brain regions that respond to salient stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS showed stronger positive connectivity with the ventral caudate and medial orbitofrontal cortex, areas implicated in reward processing and motivated behavior. Furthermore, the BNM and VS each showed extensive negative connectivity with visual and lateral prefrontal cortices. Together, the distinct cerebral functional connectivities support the role of the BNM in arousal, saliency responses and cognitive motor control and the VS in reward related behavior. Considering the importance of BNM in age-related cognitive decline, we explored the effects of age on BNM and VS connectivities. BNM connectivity to the visual and somatomotor cortices decreases while connectivity to subcortical structures including the midbrain, thalamus, and pallidum increases with age. These findings of age-related changes of cerebral functional connectivity of the BNM may facilitate research of the neural bases of cognitive decline in health and illness.

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YNIMG Journal 2012 Journal Article

Cerebral correlates of skin conductance responses in a cognitive task

Sheng Zhang
Sien Hu
Herta H. Chao
Xi Luo
Olivia M. Farr
Chiang-shan R. Li

Changes in physiological arousal frequently accompany cognitive performance. Many studies sought to identify the neural correlates of heightened arousal as indexed by skin conductance responses (SCR). However, the observed regional activations may be confounded by task events. We addressed this issue by recording SCR in 25 adults performing a stop signal task (SST) during functional magnetic resonance imaging. We compared only go trials with high and low SCR in order to isolate the event-independent processes. Furthermore, we distinguished go trials that followed another go, a stop success, or a stop error trial to examine whether the neural activities are contingent on the local context in which changes in SCR occurred. The results showed that the supplementary motor area responded to increased SCR irrespective of the preceding trial. The dorsal anterior cingulate cortex increased activation to heightened arousal most significantly in response to stop errors. The medial prefrontal cortex increased activation to SCR following a stop error but decreased activation following a go or stop success trial. These new findings specify the regional activations that accompany changes in physiological arousal during the SST and support distinct processes for the changes that occur under different local contexts. In particular, the MPFC shows opposing responses by increasing activation to changes in arousal evoked by salient stimuli and decreasing activation to the control of arousal.

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YNIMG Journal 2012 Journal Article

Decreased saliency processing as a neural measure of Barratt impulsivity in healthy adults

Olivia M. Farr
Sien Hu
Sheng Zhang
Chiang-shan R. Li

Cognitive control is necessary to navigating through an uncertain world. With the stop signal task (SST), we measure how cognitive control functions in a controlled environment. There has been conflicting evidence on whether trait impulsivity might reflect differences in cognitive control during the SST. While some studies find that trait impulsivity relates to measures of response inhibition, such as the stop signal reaction time (SSRT), other studies do not. Here, in 92 young adult participants (58 females; age 25±4years), we examined whether trait impulsivity, measured by the Barratt impulsivity scale (BIS-11), is associated with differences in performance and regional brain activations for the component processes of cognitive control during the SST. Across participants, trait impulsivity showed a trend-level correlation with SSRT (F(1. 90)=3. 18, p<. 07; Pearson regression). In simple regressions, activation of the right anterior dorsal insula and middle frontal cortex (MFC) during stop as compared to go trials negatively correlated with motor and non-planning impulsivity score. Using the generalized form of psychophysiological interaction (gPPI), we showed that functional connectivity of the right insula and MFC with the left dorsolateral prefrontal cortex and bilateral visual areas were also negatively correlated with impulsivity. None of the other component processes of cognitive control, including response inhibition, error processing, post-error slowing, were significantly related to Barratt impulsivity. These results suggest that trait impulsivity as measured by BIS-11 may have distinct effects on saliency processing in adult individuals.

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