Structural and functional cerebral bases of diminished inhibitory control during healthy aging.

Inhibitory control or the ability to refrain from incorrect responses is a critical executive function known to diminish during aging. Imaging studies have elucidated cerebral changes that may underlie the age-related deficits. However, it remains unclear whether the structural and functional changes occur in the same brain regions and whether reduced gray matter volumes (GMV) mediate decreased activation during inhibition. Here, in a sample of 149 participants, we addressed the issues using structural and functional magnetic resonance imaging. Individual's response inhibition was evaluated by the stop signal reaction time (SSRT) in a stop signal task. The results showed that age was associated with prolonged SSRT across participants. Many cortical and subcortical regions demonstrated age-related reduction in GMV and activation to response inhibition. Additionally, age-related diminution in inhibitory control, as indexed by the SSRT, was associated with both shared and distinct morphometric and functional changes. Voxel-based morphometry demonstrated age-related reduction in GMV in the right dorsolateral prefrontal cortex and caudate head as well as bilateral insula, in association with prolonged SSRT. In a contrast of stop success versus go success trials, age was associated with lower activation in the medial and inferior frontal cortex and inferior parietal cortex. Further, reduction in GMV mediated age-related differences in activations only of the medial prefrontal cortex, providing limited evidence for structure function association. Thus, the decline in inhibitory control, as evidenced in the stop signal task, manifest with both shared and distinct structural and functional processes during aging.

The Right Superior Frontal Gyrus and Individual Variation in Proactive Control of Impulsive Response.

A hallmark of cognitive control is the ability to rein in impulsive responses. Previously, we used a Bayesian model to describe trial-by-trial likelihood of the stop signal or p(Stop) and related regional activations to p(Stop) to response slowing in a stop signal task. Here, we characterized the regional processes of conflict anticipation in association with intersubject variation in impulse control in 114 young adults. We computed the stop signal reaction time (SSRT) and a measure of motor urgency, indexed by the reaction time (RT) difference between go and stop error trials or "GoRT - SERT," where GoRT is the go trial RT and SERT is the stop error RT. Motor urgency and SSRT were positively correlated across subjects. A linear regression identified regional activations to p(Stop), each in correlation with SSRT and motor urgency. We hypothesized that shared neural activities mediate the correlation between motor urgency and SSRT in proactive control of impulsivity. Activation of the ventromedial prefrontal cortex, posterior cingulate cortex and right superior frontal gyrus (SFG) during conflict anticipation correlated negatively with the SSRT. Activation of the right SFG also correlated negatively with GoRT - SERT. Therefore, activation of the right SFG was associated with more efficient response inhibition and less motor urgency. A mediation analysis showed that right SFG activation to conflict anticipation mediates the correlation between SSRT and motor urgency bidirectionally. The current results highlight a specific role of the right SFG in translating conflict anticipation to the control of impulsive response, which is consistent with earlier studies suggesting its function in action restraint. SIGNIFICANCE STATEMENT: Individuals vary in impulse control. However, the neural bases underlying individual variation in proactive control of impulsive responses remain unknown. Here, in a large sample of young adults, we showed that activation of the right superior frontal gyrus (SFG) during conflict anticipation is positively correlated with the capacity of inhibitory control and negatively with motor urgency in the stop signal task. Importantly, activity of the right SFG mediates the counteracting processes of inhibitory control and motor urgency across subjects. The results support a unique role of the right SFG in individual variation in cognitive control.

Resting-State Functional Connectivity of the Basal Nucleus of Meynert in Cigarette Smokers: Dependence Level and Gender Differences.

INTRODUCTION: Numerous studies have characterized impaired cerebral functioning in nicotine-addicted individuals. Whereas nicotine interacts with multiple neurotransmitters in cortical and subcortical circuits, it directly targets the cholinergic system, sourced primarily from the basal nucleus of Meynert (BNM). However, no studies have examined how this cholinergic system is influenced by cigarette smoking. Here, we addressed this gap of research. METHODS: Using a dataset from the Functional Connectome Projects, we investigated this issue by contrasting seed-based BNM connectivity of 40 current smokers and 170 age- and gender-matched nonsmokers. We followed our data analytic routines in recent work and examined differences between smokers and nonsmokers in men and women combined as well as separately. RESULTS: Compared to nonsmokers, female but not male smokers demonstrated greater positive BNM connectivity to the supplementary motor area, bilateral anterior insula, and right superior temporal/supramarginal gyri as well as greater negative connectivity to the posterior cingulate cortex and precuneus. Further, BNM connectivity to the supplementary motor area is negatively correlated to the Fagerström Test for Nicotine Dependence score in male but not female smokers. CONCLUSIONS: Along with a previous report of upregulated nicotinic acetylcholine receptor in male but not female smokers, these new findings highlight functional changes of the cholinergic systems in cigarette smokers. The results suggest sex-specific differences in cholinergic dysregulation and a need for multiple imaging modalities to capture the neural markers of nicotine addiction. IMPLICATIONS: Nicotine influences cognition via cholinergic projections of the basal forebrain to the cerebral cortex. This study examined changes in resting-state whole-brain functional connectivity of the BNM in cigarette smokers. The new findings elucidate for the first time sex differences in BNM-cerebral connectivity in cigarette smoking.

Resting-State Functional Connectivity of the Locus Coeruleus in Humans: In Comparison with the Ventral Tegmental Area/Substantia Nigra Pars Compacta and the Effects of Age.

The locus coeruleus (LC) provides the primary noradrenergic inputs to the cerebral cortex. Despite numerous animal studies documenting the functions of the LC, research in humans is hampered by the small volume of this midbrain nucleus. Here, we took advantage of a probabilistic template, explored the cerebral functional connectivity of the LC with resting-state fMRI data of 250 healthy adults, and verified the findings by accounting for physiological noise in another data set. In addition, we contrasted connectivities of the LC and the ventral tegmental area/substantia nigra pars compacta. The results highlighted both shared and distinct connectivity of these 2 midbrain structures, as well as an opposite pattern of connectivity to bilateral amygdala, pulvinar, and right anterior insula. Additionally, LC connectivity to the fronto-parietal cortex and the cerebellum increases with age and connectivity to the visual cortex decreases with age. These findings may facilitate studies of the role of the LC in arousal, saliency responses and cognitive motor control and in the behavioral and cognitive manifestations during healthy and disordered aging. Although the first to demonstrate whole-brain LC connectivity, these findings need to be confirmed with high-resolution imaging.

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

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.

Association of Drinking Problems and Duration of Alcohol Use to Inhibitory Control in Nondependent Young Adult Social Drinkers.

BACKGROUND: Deficits in inhibitory control have been widely implicated in alcohol misuse. However, the literature does not readily distinguish the effects of drinking problems and chronic alcohol use. Here, we examined how years of drinking and the Alcohol Use Disorders Identification Test (AUDIT) score each influences the cerebral responses to inhibitory control in nondependent drinkers. METHODS: Fifty-seven adult drinkers and 57 age- and gender-matched nondrinkers participated in one 40-minute functional magnetic resonance imaging scan of the stop signal task. Data were preprocessed and modeled using SPM8. In a regression model, we contrasted stop and go success trials for individuals and examined activities of response inhibition each in link with the AUDIT score and years of alcohol use in group analyses. We specified the effects of duration of use by contrasting regional activations of drinkers and age-related changes in nondrinkers. In mediation analyses, we investigated how regional activities mediate the relationship between drinking problems and response inhibition. RESULTS: Higher AUDIT score but not years of drinking was positively correlated with prolonged stop signal reaction time (SSRT) and diminished responses in the cerebellum, thalamus, frontal and parietal regions, independent of years of alcohol use. Further, activity of the thalamus, anterior cingulate cortex, and presupplementary motor area significantly mediates the association, bidirectionally, between the AUDIT score and SSRT. The duration of alcohol use was associated with decreased activation in the right inferior frontal gyrus extending to superior temporal gyrus, which was not observed for age-related changes in nondrinkers. CONCLUSIONS: The results distinguished the association of drinking problems and years of alcohol use to inhibitory control in young adult nondependent drinkers. These new findings extend the imaging literature of alcohol misuse and may have implications for treatment to prevent the escalation from social to dependent drinking. More research is needed to confirm age-independent neural correlates of years of alcohol use.

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

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.

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

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 49 years 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.

Independent component analysis of functional networks for response inhibition: Inter-subject variation in stop signal reaction time.

Cognitive control is a critical executive function. Many studies have combined general linear modeling and the stop signal task (SST) to delineate the component processes of cognitive control. For instance, by contrasting stop success (SS) and stop error (SE) trials in the SST, investigators examined regional responses to stop signal inhibition. In contrast to this parameterized approach, independent component analysis (ICA) elucidates brain networks subserving cognitive control. In our earlier work of 59 adults performing the SST during fMRI, we characterized six independent components (ICs). However, none of these ICs correlated with stop signal performance, raising questions about their behavioral validity. Here, in a larger sample (n = 100), we identified and explored 23 ICs for correlation with the stop signal reaction time (SSRT), a measure of the efficiency of response inhibition. At a corrected threshold (P < 0.0005), a paracentral lobule-midcingulate network and a left inferior parietal-supplementary motor-somatomotor network showed a positive correlation between SE beta weight and SSRT. In contrast, a midline cerebellum-thalamus-pallidum network showed a negative correlation between SE beta weight and SSRT. These findings suggest that motor preparation and execution prolongs the SSRT, likely via an interaction between the go and stop processes as suggested by the race model. Behaviorally, consistent with this hypothesis, the difference in G and SE reaction times is positively correlated with SSRT across subjects. These new results highlight the importance of cognitive motor regions in response inhibition and support the utility of ICA in uncovering functional networks for cognitive control in the SST.

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

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.

Neural bases of individual variation in decision time.

People make decisions by evaluating existing evidence against a threshold or level of confidence. Individuals vary widely in response times even when they perform a simple task in the laboratory. We examine the neural bases of this individual variation by combining computational modeling and brain imaging of 64 healthy adults performing a stop signal task. Behavioral performance was modeled by an accumulator model that describes the process of information growth to reach a threshold to respond. In this model, go trial reaction time (goRT) is jointly determined by the information growth rate, threshold, and movement time (MT). In a linear regression of activations in successful go and all stop (Go+Stop) trials against goRT across participants, the insula, supplementary motor area (SMA), pre-SMA, thalamus including the subthalamic nucleus (STN), and caudate head respond to increasing goRT. Among these areas, the insula, SMA, and thalamus including the STN respond to a slower growth rate, the caudate head responds to an elevated threshold, and the pre-SMA responds to a longer MT. In the regression of Go+Stop trials against the stop signal reaction time (SSRT), the pre-SMA shows a negative correlation with SSRT. These results characterize the component processes of decision making and elucidate the neural bases of a critical aspect of inter-subject variation in human behavior. These findings also suggest that the pre-SMA may play a broader role in response selection and cognitive control rather than simply response inhibition in the stop signal task.

The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults.

By blocking dopamine and norepinephrine transporters, methylphenidate affects cognitive performance and regional brain activation in healthy individuals as well as those with neuropsychiatric disorders. Resting-state connectivity evaluates the functional integrity of a network of brain regions. Here, we examined how methylphenidate effects resting-state functional connectivity of the dorsal striatum and thalamus, areas each with dense dopaminergic and noradrenergic innervations, as well as global cerebral connectivity. We administered a single, oral dose (45 mg) to 24 healthy adults and compared resting-state connectivity to 24 demographically matched adults who did not receive any medication. The results showed that methylphenidate alters seed-based and global connectivity between the thalamus/dorsal striatum with primary motor cortex, amygdala/hippocampus and frontal executive areas (p < 0.05, corrected). Specifically, while methylphenidate at this dosage enhances connectivity to the motor cortex and memory circuits, it dampens prefrontal cortical connectivity perhaps by increasing catecholaminergic signalling past the 'optimal' level. These findings advance our understanding of a critical aspect of the multifaceted effects of methylphenidate on brain functions. The results may also facilitate future studies of the aetiology and treatment of neurological and psychiatric disorders that implicate catecholaminergic dysfunction.

Error processing and gender-shared and -specific neural predictors of relapse in cocaine dependence.

Deficits in cognitive control are implicated in cocaine dependence. Previously, combining functional magnetic resonance imaging and a stop signal task, we demonstrated altered cognitive control in cocaine-dependent individuals. However, the clinical implications of these cross-sectional findings and, in particular, whether the changes were associated with relapse to drug use, were not clear. In a prospective study, we recruited 97 treatment-seeking individuals with cocaine dependence to perform the stop signal task during functional magnetic resonance imaging and participate in follow-up assessments for 3 months, during which time cocaine use was evaluated with timeline follow back and ascertained by urine toxicology tests. Functional magnetic resonance imaging data were analysed using general linear models as implemented in Statistical Parametric Mapping 8, with the contrast 'stop error greater than stop success trials' to index error processing. Using voxelwise analysis with logistic and Cox regressions, we identified brain activations of error processing that predict relapse and time to relapse. In females, decreased error-related activations of the thalamus and dorsal anterior cingulate cortex predicted relapse and an earlier time to relapse. In males, decreased error-related activations of the dorsal anterior cingulate cortex and left insula predicted relapse and an earlier time to relapse. These regional activations were validated with data resampling and predicted relapse with an average area under the curve of 0.849 in receiver operating characteristic analyses. These findings provide direct evidence linking deficits in cognitive control to clinical outcome in a moderate-sized cohort of cocaine-dependent individuals. These results may provide a useful basis for future studies to examine how psychosocial factors interact with cognitive control to determine drug use and to evaluate the efficacy of pharmacological or behavioural treatment in remediating deficits of cognitive control in cocaine addicts.

Gray matter volume correlates of global positive alcohol expectancy in non-dependent adult drinkers.

Alcohol use and misuse is known to involve structural brain changes. Numerous imaging studies have examined changes in gray matter (GM) volumes in dependent drinkers, but there is little information on whether non-dependent drinking is associated with structural changes and whether these changes are related to psychological factors-such as alcohol expectancy-that influence drinking behavior. We used voxel-based morphometry (VBM) to examine whether the global positive scale of alcohol expectancy, as measured by the Alcohol Expectancy Questionnaire-3, is associated with specific structural markers and whether such markers are associated with drinking behavior in 113 adult non-dependent drinkers (66 women). Alcohol expectancy is positively correlated with GM volume of left precentral gyrus (PCG) in men and women combined and bilateral superior frontal gyri (SFG) in women, and negatively correlated with GM volume of the right ventral putamen in men. Furthermore, mediation analyses showed that the GM volume of PCG mediate the correlation of alcohol expectancy and the average number of drinks consumed per occasion and monthly total number of drinks in the past year. When recent drinking was directly accounted for in multiple regressions, GM volume of bilateral dorsolateral prefrontal cortices correlated positively with alcohol expectancy in the combined sample. To our knowledge, these results are the first to identify the structural brain correlates of alcohol expectancy and its mediation of drinking behaviors. These findings suggest that more studies are needed to investigate increased GM volume in the frontal cortices as a neural correlate of alcohol expectancy.

Displacement of Abdominal Organs Into the Thoracic Cavity: A Rare Case of Adult Bochdalek Hernia.

Congenital diaphragmatic hernias are primarily found in infants and have a high mortality rate due to neonatal respiratory distress. The most common type of congenital diaphragmatic hernia is Bochdalek hernia, which occurs in the posterolateral diaphragm, with the left side being the most commonly affected. However, congenital diaphragmatic hernias are extremely rare in adults and are often misdiagnosed due to their subtle symptoms. Therefore, we suggest that a contrast-enhanced CT scan should be used for early screening and diagnosis in all patients with sudden severe pain or recurrent ambiguous symptoms in the chest and abdomen. This case report presents a rare occurrence of Bochdalek hernia in an adult male. The patient experienced nonspecific abdominal symptoms after eating. The hernia resulted in the displacement of the left kidney, the transverse colon of the splenic flexure, and most of the stomach into the thoracic cavity. This displacement led to atelectasis of the left lung, which reached three-fifths of its capacity. The patient underwent successful treatment using a combination of laparoscopy and open surgery. Follow-up CT scans conducted two weeks, three months, and one year later revealed a stable condition with no complications.

Development and Application of a Novel Machine Learning Model Predicting Pancreatic Cancer-Specific Mortality.

Precise prognostication is vital for guiding treatment decisions in people diagnosed with pancreatic cancer. Existing models depend on predetermined variables, constraining their effectiveness. Our objective was to explore a novel machine learning approach to enhance a prognostic model for predicting pancreatic cancer-specific mortality and, subsequently, to assess its performance against Cox regression models. Datasets were retrospectively collected and analyzed for 9,752 patients diagnosed with pancreatic cancer and with surgery performed. The primary outcomes were the mortality of patients with pancreatic carcinoma at one year, three years, and five years. Model discrimination was assessed using the concordance index (C-index), and calibration was assessed using Brier scores. The Survival Quilts model was compared with Cox regression models in clinical use, and decision curve analysis was done. The Survival Quilts model demonstrated robust discrimination for one-year (C-index 0.729), three-year (C-index 0.693), and five-year (C-index 0.672) pancreatic cancer-specific mortality. In comparison to Cox models, the Survival Quilts models exhibited a higher C-index up to 32 months but displayed inferior performance after 33 months. A subgroup analysis was conducted, revealing that within the subset of individuals without metastasis, the Survival Quilts models showcased a significant advantage over the Cox models. In the cohort with metastatic pancreatic cancer, Survival Quilts outperformed the Cox model before 24 months but exhibited a weaker performance after 25 months. This study has developed and validated a novel machine learning-based Survival Quilts model to predict pancreatic cancer-specific mortality that outperforms the Cox regression model.

Pathologic complete response of hepatoid adenocarcinoma of the stomach after chemo-immunotherapy: A rare case report and literature review.

Background: Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant subtype of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. We present an exceedingly rare case of complete response after chemo-immunotherapy. Case Description: A 48-year-old woman with highly elevated serum alpha-fetoprotein (AFP) level was found to have HAS verified by pathological examination based on gastroscopy. Computed tomography scan was done and TNM staging of the tumor was T4aN3aMx. Programmed cell death ligand-1 (PD-L1) immunohistochemistry was performed, revealing a negative PD-L1 expression. Chemo-immunotherapy including oxaliplatin plus S-1 and PD-1 inhibitor terelizumab was given to this patient for 2 months until the serum AFP level decreased from 748.5 to 12.9 ng/mL and the tumor shrank. D2 radical gastrectomy was then performed and histopathology of the resected specimen revealed that the cancerous cells had disappeared. Pathologic complete response (pCR) was achieved and no evidence of recurrence has been found after 1 year of follow-up. Conclusions: We, for the first time, reported an HAS patient with negative PD-L1 expression who achieved pCR from the combined chemotherapy and immunotherapy. Although no consensus has been reached regarding the therapy, it might provide a potential effective management strategy for HAS patient.

Sex differences in the effects of trait anxiety and age on resting-state functional connectivities of the amygdala.

Background: Numerous studies characterized how resting-state functional connectivities (rsFCs) of the amygdala were disrupted in emotional disorders and varied with emotional traits, including anxiety. With trait anxiety known to diminish with age, a critical issue concerns disambiguating the effects of age and anxiety on amygdala rsFCs in studying the neural bases of individual differences in anxiety. Methods: Two-hundred adults (83 women) 19-85 years of age underwent fMRI and assessment for trait anxiety. Amygdala rsFC correlates were identified using multiple regression with age and anxiety in the same model for all and separately in men and women. The rsFC correlates were examined for age-anxiety interaction. Results: Anxiety was negatively correlated with amygdala-temporooccipital gyri rsFC in all and in men alone. In women, amgydala rsFC with the thalamus/pallidum, angular/supramarginal gyri, inferior temporal gyrus, and posterior insula correlated positively and rsFC with calcarine cortex and caudate correlated negatively with anxiety. We also observed sex differences in age correlation of amgydala-posterior cingulate cortex/precuneus and -insula/temporoparietal rsFCs, with stronger associations in women. In women alone, anxiety and age interacted to determine amygdala rsFC with the thalamus/pallidum, calcarine cortex, and caudate, with older age associated with stronger correlation between anxiety and the rsFCs. Limitations: The findings need to be validated in an independent sample and further explored using task-based data. Conclusion: Highlighting anxiety- and age- specific as well as interacting correlates of amygdala rsFCs and sex differences in the correlates, the findings may shed light on the neural markers of anxiety.

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

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 ± 4 years), 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.

Cerebral correlates of skin conductance responses in a cognitive task.

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.