Altered impulse control in alcohol dependence: neural measures of stop signal performance.

BACKGROUND: Altered impulse control has been implicated in the shaping of habitual alcohol use and eventual alcohol dependence. We sought to identify the neural correlates of altered impulse control in 24 abstinent patients with alcohol dependence (PAD), as compared to 24 demographics matched healthy control subjects (HC). In particular, we examined the processes of risk taking and cognitive control as the neural endophenotypes of alcohol dependence. METHODS: To this end, functional magnetic resonance imaging (fMRI) was conducted during a stop signal task (SST), in which a procedure was used to elicit errors in the participants. The paradigm allowed trial-by-trial evaluation of response inhibition, error processing, and post-error behavioral adjustment. Furthermore, by imposing on the subjects to be both fast and accurate, the SST also introduced a distinct element of risk, which participants may or may not avert during the task. Brain imaging data were analyzed with Statistical Parametric Mapping in covariance analyses accounting for group disparity in general performance. RESULTS: The results showed that, compared to HC, PAD demonstrated longer go trial reaction time (RT) and higher stop success rate (SS%). HC and PAD were indistinguishable in stop signal reaction time (SSRT) and post-error slowing (PES). In a covariance analysis accounting for go trial RT and SS%, HC showed greater activity in the left dorsolateral prefrontal cortex than PAD, when subjects with short and long SSRT were contrasted. By comparing PAD and HC directly during stop errors (SE), as contrasted with SS, we observed greater activity in PAD in bilateral visual and frontal cortices. Compared to HC, PAD showed less activation of the right dorsolateral prefrontal cortex during PES, an index of post-error behavioral adjustment. Furthermore, PAD who showed higher alcohol urge at the time of the fMRI were particularly impaired in dorsolateral prefrontal activation, as compared to those with lower alcohol urge. Finally, compared to HC subjects, PAD showed less activity in cortical and subcortical structures including putamen, insula, and amygdala during risk-taking decisions in the SST. CONCLUSION: These preliminary results provided evidence for altered neural processing during impulse control in PAD. These findings may provide a useful neural signature in the evaluation of treatment outcomes and development of novel pharmacotherapy for alcohol dependence.

Decreased amygdala activation during risk taking in non-dependent habitual alcohol users: A preliminary fMRI study of the stop signal task.

BACKGROUND AND OBJECTIVES: Habitual alcohol use is prodromal to alcohol dependence. It has been suggested that impairment in impulse control contributes to habitual drinking. Little is known whether neural processes associated with impulse control is altered in non-dependent social drinkers. The current preliminary study combined functional magnetic resonance imaging and the stop signal task (SST) to address this issue. METHODS: We compared non-dependent non/light (n = 12) and moderate/heavy (n = 9) young adult alcohol drinkers in a SST, in which they were required to exercise inhibitory control during the stop trials and were engaged in a speed/accuracy trade-off during trial-to-trial go responses. Our previous studies identified neural correlates of inhibitory control and risk taking during the SST ( [10] , [11] ). Furthermore, alcohol dependent patients showed altered brain activation both during inhibitory control and risk taking, compared to healthy controls ( [12] ). RESULTS: We showed that moderate/heavy alcohol drinkers were decreased in amygdala activation during risk taking, while indistinguishable in neural measures of inhibitory control, when compared to non/light drinkers. CONCLUSIONS AND SIGNIFICANCE: Altered amygdala activation during risk taking may be a key neural process underlying early habitual alcohol use and a potential marker mediating transition to alcohol dependence.

Neural correlates of impulse control during stop signal inhibition in cocaine-dependent men.

Altered impulse control is associated with substance use disorders, including cocaine dependence. We sought to identify the neural correlates of impulse control in abstinent male patients with cocaine dependence (PCD). Functional magnetic resonance imaging (fMRI) was conducted during a stop signal task that allowed trial-by-trial evaluation of response inhibition. Fifteen male PCD and 15 healthy control (HC) subjects, matched in age and years of education, were compared. Stop signal reaction time (SSRT) was derived on the basis of a horse race model. By comparing PCD and HC co-varied for stop success rate, task-related frustration rating, and post-error slowing, we isolated the neural substrates of response inhibition, independent of attentional monitoring (of the stop signal) and post-response processes including affective responses and error monitoring. Using region of interest analysis, we found no differences between HC and PCD who were matched in stop signal performance in the pre-supplementary motor area (pre-SMA) previously shown to be associated with SSRT. However, compared with HC, PCD demonstrated less activation of the rostral anterior cingulate cortex (rACC), an area thought to be involved in the control of stop signal inhibition. The magnitude of rACC activation also correlated negatively with the total score and the impulse control subscore of the Difficulty in Emotion Regulation Scale in PCD. The current study thus identified the neural correlates of altered impulse control in PCD independent of other cognitive processes that may influence stop signal performance. Relative hypoactivation of the rACC during response inhibition may represent a useful neural marker of difficulties in impulse control in abstinent cocaine-dependent men who are at risk of relapse.

Fiber bundle length and cognition: a length-based tractography MRI study.

Executive function (EF) and cognitive processing speed (CPS) are two cognitive performance domains that decline with advanced age. Reduced EF and CPS are known to correlate with age-related frontal-lobe volume loss. However, it remains unclear whether white matter microstructure in these regions is associated with age-related decline in EF and/or CPS. We utilized quantitative tractography metrics derived from diffusion-tensor MRI to investigate the relationship between the mean fiber bundle lengths (FBLs) projecting to different lobes, and EF/CPS performance in 73 healthy aging adults. We measured aspects of EF and CPS with the Trail Making Test (TMT), Color-Word Interference Test, Letter-Number Sequencing (L-N Seq), and Symbol Coding. Results revealed that parietal and occipital FBLs explained a significant portion of variance in EF. Frontal, temporal, and occipital FBLs explained a significant portion of variance in CPS. Shorter occipital FBLs were associated with poorer performance on the EF tests TMT-B and CWIT 3. Shorter frontal, parietal, and occipital FBLs were associated with poorer performance on L-N Seq and Symbol Coding. Shorter frontal and temporal FBLs were associated with lower performance on CPS tests TMT-A and CWIT 1. Shorter FBLs were also associated with increased age. Results suggest an age-related FBL shortening in specific brain regions related to poorer EF and CPS performance among older adults. Overall, results support both the frontal aging hypothesis and processing speed theory, suggesting that each mechanism is contributing to age-related cognitive decline.

Verbal memory declines more rapidly with age in HIV infected versus uninfected adults.

OBJECTIVES: In the current era of effective antiretroviral treatment, the number of older adults living with HIV is rapidly increasing. This study investigated the combined influence of age and HIV infection on longitudinal changes in verbal and visuospatial learning and memory. METHOD: In this longitudinal, case-control design, 54 HIV seropositive and 30 seronegative individuals aged 40-74 years received neurocognitive assessments at baseline visits and again one year later. Assessment included tests of verbal and visuospatial learning and memory. Linear regression was used to predict baseline performance and longitudinal change on each test using HIV serostatus, age, and their interaction as predictors. Multivariate analysis of variance (MANOVA) was used to assess the effects of these predictors on overall baseline performance and overall longitudinal change. RESULTS: The interaction of HIV and age significantly predicted longitudinal change in verbal memory performance, as did HIV status, indicating that although the seropositive group declined more than the seronegative group overall, the rate of decline depended on age such that greater age was associated with a greater decline in this group. The regression models for visuospatial learning and memory were significant at baseline, but did not predict change over time. HIV status significantly predicted overall baseline performance and overall longitudinal change. CONCLUSIONS: This is the first longitudinal study focused on the effects of age and HIV on memory. Findings suggest that age and HIV interact to produce larger declines in verbal memory over time. Further research is needed to gain a greater understanding of the effects of HIV on the aging brain.

Gender Differences in Cognitive Control: an Extended Investigation of the Stop Signal Task.

Men and women show important differences in clinical conditions in which deficits in cognitive control are implicated. We used functional magnetic resonance imaging to examine gender differences in the neural processes of cognitive control during a stop-signal task. We observed greater activation in men, compared to women, in a wide array of cortical and sub-cortical areas, during stop success (SS) as compared to stop error (SE). Conversely, women showed greater regional brain activation during SE > SS, compared to men. Furthermore, compared to women, men engaged the right inferior parietal lobule to a greater extent during post-SE go compared to post-go go trials. Women engaged greater posterior cingulate cortical activation than men during post-SS slowing in go trial reaction time (RT) but did not differ during post-SE slowing in go trial RT. These findings extended our previous results of gender differences in regional brain activation during response inhibition. The results may have clinical implications by, for instance, helping initiate studies to understand why women are more vulnerable to depression while men are more vulnerable to impulse control disorders.

Subcortical processes of motor response inhibition during a stop signal task.

Previous studies have delineated the neural processes of motor response inhibition during a stop signal task, with most reports focusing on the cortical mechanisms. A recent study highlighted the importance of subcortical processes during stop signal inhibition in 13 individuals and suggested that the subthalamic nucleus (STN) may play a role in blocking response execution (Aron and Poldrack, 2006. Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. J Neurosci 26, 2424-2433). Here in a functional magnetic resonance imaging (fMRI) study we replicated the finding of greater activation in the STN during stop (success or error) trials, compared to go trials, in a larger sample of subjects (n=30). However, since a contrast between stop and go trials involved processes that could be distinguished from response inhibition, the role of subthalamic activity during stop signal inhibition remained to be specified. To this end we followed an alternative strategy to isolate the neural correlates of response inhibition (Li et al., 2006a. Imaging response inhibition in a stop signal task--neural correlates independent of signal monitoring and post-response processing. J Neurosci 26, 186-192). We compared individuals with short and long stop signal reaction time (SSRT) as computed by the horse race model. The two groups of subjects did not differ in any other aspects of stop signal performance. We showed greater activity in the short than the long SSRT group in the caudate head during stop successes, as compared to stop errors. Caudate activity was positively correlated with medial prefrontal activity previously shown to mediate stop signal inhibition. Conversely, bilateral thalamic nuclei and other parts of the basal ganglia, including the STN, showed greater activation in subjects with long than short SSRT. Thus, fMRI delineated contrasting roles of the prefrontal-caudate and striato-thalamic activities in mediating motor response inhibition.

Neural correlates of post-error slowing during a stop signal task: a functional magnetic resonance imaging study.

The ability to detect errors and adjust behavior accordingly is essential for maneuvering in an uncertain environment. Errors are particularly prone to occur when multiple, conflicting responses are registered in a situation that requires flexible behavioral outputs; for instance, when a go signal requires a response and a stop signal requires inhibition of the response during a stop signal task (SST). Previous studies employing the SST have provided ample evidence indicating the importance of the medial cortical brain regions in conflict/error processing. Other studies have also related these regional activations to postconflict/error behavioral adjustment. However, very few studies have directly explored the neural correlates of postconflict/error behavioral adjustment. Here we employed an SST to elicit errors in approximately half of the stop trials despite constant behavioral adjustment of the observers. Using functional magnetic resonance imaging, we showed that prefrontal loci including the ventrolateral prefrontal cortex are involved in post-error slowing in reaction time. These results delineate the neural circuitry specifically involved in error-associated behavioral modifications.

Greater activation of the "default" brain regions predicts stop signal errors.

Previous studies have provided evidence for a role of the medial cortical brain regions in error processing and post-error behavioral adjustment. However, little is known about the neural processes that precede errors. Here in an fMRI study we employ a stop signal task to elicit errors approximately half of the time despite constant behavioral adjustment of the observers (n=40). By comparing go trials preceding a stop error and those preceding a stop success, we showed that (at p<0.05, corrected for multiple comparisons) the activation of midline brain regions including bilateral precuneus and posterior cingulate cortices, perigenual anterior cingulate cortices and transverse frontopolar gyri precedes errors during the stop signal task. Receiver operating characteristic (ROC) analysis based on the signal detection theory showed that the activity in these three regions predicts errors with an accuracy between 0.81 and 0.85 (area under the ROC curve). Broadly supporting the hypothesis that deactivation of the default mode circuitry is associated with mental effort in a cognitive task, the current results further indicate that greater activity of these brain regions can precede performance errors.