Leanne Trick

Withdrawal-associated increases and decreases in functional neural connectivity associated with altered emotional regulation in alcoholism

Alcoholic patients who have undergone multiple detoxifications/relapses show altered processing of emotional signals. We performed functional magnetic resonance imaging during performance of implicit and explicit versions of a task in which subjects were presented with morphs of fearful facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n=12) or singly detoxified patients (SDTx; n=17), and social drinker controls (n=31). Alcoholic patients were less able than controls to recognize fearful expressions, and showed lower activation in prefrontal areas, including orbitofrontal cortex and insula, which mediate emotional processing. The decrease in activation was greater in MDTx patients who also showed decreased connectivity between insula and prefrontal areas, and between amygdala and globus pallidus. In the explicit condition, the strength of connectivity between insula and areas involved in regulation of emotion (inferior frontal cortex and frontal pole) was negatively correlated with both the number of detoxifications and dependency (measured by the severity of alcohol dependency (SADQ) and control over drinking score (Impaired Control questionnaire, ICQ)). In contrast, increased connectivity was found between insula and the colliculus neuronal cluster, and between amygdala and stria terminalis bed nucleus. In the implicit condition, number of detoxifications and ICQ score correlated positively with connectivity between amygdala and prefrontal cortical areas involved in attentional and executive processes. Repeated episodes of detoxification from alcohol are associated with altered function both in fear perception pathways and in cortical modulation of emotions. Such changes may confer increased sensitivity to emotional stress and impaired social competence, contributing to relapse.

Unique Brain Areas Associated with Abstinence Control Are Damaged in Multiply Detoxified Alcoholics

Background The ability to abstain from drinking, despite incentives to imbibe, is essential to recovery from alcoholism. Methods We used an incentive conflict task to investigate ability to abstain from responding during presentations of incentive cues. Both alcoholic (n = 23) and healthy subjects (n = 22) were required to withhold responding during the simultaneous presentation of two visual stimuli in which the individual presentation allowed responding for monetary reward. Brain structures activated during performance of the task were studied using functional magnetic resonance imaging in healthy volunteers (n = 8), and changes in gray matter volume were studied in a separate group of patients (n = 29) compared with control subjects (n = 31) in regions of interest identified on functional magnetic resonance imaging. Results Abstinent alcoholic patients were severely impaired on the incentive conflict task. The impairment was greater in patients with experience of several versus a single detoxification. Healthy volunteers, during the same incentive conflict task, showed distinct patterns of brain activation (including gyrus rectus, ventromedial prefrontal cortex, and superior frontal gyrus). Reduction of gray matter volume in ventromedial prefrontal cortex and superior frontal gyrus of patients was more extensive in those with multiple detoxifications. Conclusions Performance deficits in alcoholics are associated with withdrawal-induced impairments in prefrontal subfields, which are exacerbated following repeated episodes of detoxification. Detoxification thus compromises functional and structural integrity of prefrontal cortex and may thus impair the ability to control future drinking. Performance in the incentive conflict task is a sensitive biomarker for such deficits.

Exaggerated waiting impulsivity associated with human binge drinking, and high alcohol consumption in mice

There are well-established links between impulsivity and alcohol use in humans and animal models; however, whether exaggerated impulsivity is a premorbid risk factor or a consequence of alcohol intake remains unclear. In a first approach, human young (18–25 years) social binge and non-binge drinkers were tested for motor impulsivity and attentional abilities in a human version of the Five-Choice Serial Reaction Time Task (Sx-5CSRTT), modeled on the rodent 5CSRTT. Participants completed four variants of the Sx-5CSRT, in addition to being screened for impulsive traits (BIS-11 questionnaire) and impulsive behavior (by means of the Delay Discounting Questionnaire, Two-Choice Impulsivity Paradigm (TCIP), Stop Signal Reaction Time, and Time Estimation Task). Using a second approach, we compared one of these impulsivity measures, 5CSRTT performance, in two inbred strains of mice known to differ in alcohol intake. Compared with non-bingers (NBD; n=22), binge drinkers (BD, n=22) showed robust impairments in attention and premature responding when evaluated under increased attentional load, in addition to presenting deficits in decision making using the TCIP. The best predictors for high binge drinking score were premature responding in the Sx-5CSRTT, trait impulsivity in the BIS-11, and decision making in the TCIP. Alcohol-naïve C57BL/6J (B6) mice (alcohol preferring) were more impulsive in the 5CSRTT than DBA2/J (D2) mice (alcohol averse); the degree of impulsivity correlated with subsequent alcohol consumption. Homologous measures in animal and human studies indicate increased premature responding in young social BD and in the ethanol-preferring B6 strain of mice.

Sedation and antihistamines: an update. Review of inter-drug differences using proportional impairment ratios

The use of antihistamines (AHs) has been associated with cognitive and psychomotor impairments, largely caused by the sedative properties of many of these drugs. Due to the ambulant nature of the population using AHs, it is important to evaluate these effects using standardised methodology and psychometric tests. A previous extensive review of the literature collated the results of studies of H1 receptor antagonists to determine the extent to which a particular AH produced impairments on a battery of psychometric tests by calculating a proportional impairment ratio for each AH.

Next‐day cognition, psychomotor function, and driving‐related skills following nighttime administration of eszopiclone

To evaluate next‐day driving ability, as assessed by brake reaction time (BRT), and cognitive/psychomotor function following nighttime administration of 3 mg eszopiclone.

Prediction and Uncertainty in Human Pavlovian to Instrumental Transfer.

Attentional capture and behavioral control by conditioned stimuli have been dissociated in animals. The current study assessed this dissociation in humans. Participants were trained on a Pavlovian schedule in which 3 visual stimuli, A, B, and C, predicted the occurrence of an aversive noise with 90%, 50%, or 10% probability, respectively. Participants then went on to separate instrumental training in which a key-press response canceled the aversive noise with a .5 probability on a variable interval schedule. Finally, in the transfer phase, the 3 Pavlovian stimuli were presented in this instrumental schedule and were no longer differentially predictive of the outcome. Observing times and gaze dwell time indexed attention to these stimuli in both training and transfer. Aware participants acquired veridical outcome expectancies in training--that is, A > B > C, and these expectancies persisted into transfer. Most important, the transfer effect accorded with these expectancies, A > B > C. By contrast, observing times accorded with uncertainty--that is, they showed B > A = C during training, and B < A = C in the transfer phase. Dwell time bias supported this association between attention and uncertainty, although these data showed a slightly more complicated pattern. Overall, the study suggests that transfer is linked to outcome prediction and is dissociated from attention to conditioned stimuli, which is linked to outcome uncertainty.

Impaired fear recognition and attentional set-shifting is associated with brain structural changes in alcoholic patients

Alcoholic patients with multiple detoxifications/relapses show cognitive and emotional deficits. We performed structural magnetic resonance imaging and examined performance on a cognitive flexibility task (intra‐extradimensional set shift and reversal; IED). We also presented subjects with fearful, disgust and anger facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n = 12) or singly detoxified patients (SDTx; n = 17) and social drinker controls (n = 31). Alcoholic patients were less able than controls to change their behavior in accordance with the changing of the rules in the IED and they were less accurate in recognizing fearful expressions in particular. They also showed lower gray matter volume compared with controls in frontal brain areas, including inferior frontal cortex (IFC) and insula that mediate emotional processing, inferior parietal lobule and medial frontal cortex that mediate attentional and motor planning processes, respectively. Impairments in performance and some of the regional decreases in gray matter were greater in MDTx. Gray matter volume in IFC in patients was negatively correlated with the number of detoxifications, whereas inferior parietal lobule was negatively correlated with the control over drinking score (impaired control over drinking questionnaire). Performance in IED was also negatively correlated with gray matter volume in IFC/BA47, whereas recognition of fearful faces was positively correlated with the IFC gray matter. Repeated episodes of detoxification from alcohol, related to severity of dependency, are coupled with altered brain structure in areas of emotional regulation, attention and motor planning. Such changes may confer increased inability to switch behavior according to environmental demands and social incompetence, contributing to relapse.

The effects of acute inflammation on cognitive functioning and emotional processing in humans: A systematic review of experimental studies

OBJECTIVE The cognitive neuropsychological model of depression proposes that negative biases in the processing of emotionally salient information have a central role in the development and maintenance of depression. We have conducted a systematic review to determine whether acute experimental inflammation is associated with changes to cognitive and emotional processing that are thought to cause and maintain depression. METHODS We identified experimental studies in which healthy individuals were administered an acute inflammatory challenge (bacterial endotoxin/vaccination) and standardised tests of cognitive function were performed. RESULTS Fourteen references were identified, reporting findings from 12 independent studies on 345 participants. Methodological quality was rated strong or moderate for 11 studies. Acute experimental inflammation was triggered using a variety of agents (including endotoxin from E. coli, S. typhi, S. abortus Equi and Hepatitis B vaccine) and cognition was assessed over hours to months, using cognitive tests of i) attention/executive functioning, ii) memory and iii) social/emotional processing. Studies found mixed evidence that acute experimental inflammation caused changes to attention/executive functioning (2 of 6 studies showed improvements in attention executive function compared to control), changes in memory (3 of 5 studies; improved reaction time: reduced memory for object proximity: poorer immediate and delayed memory) and changes to social/emotional processing (4 of 5 studies; reduced perception of emotions, increased avoidance of punishment/loss experiences, and increased social disconnectedness). CONCLUSIONS Acute experimental inflammation causes negative biases in social and emotional processing that could explain observed associations between inflammation and depression.

The association of perseverative negative thinking with depression, anxiety and emotional distress in people with long term conditions: A systematic review

OBJECTIVE Depression is common in people with long term conditions, and is associated with worse medical outcomes. Previous research shows perseverative negative thinking (e.g. worry, rumination) predicts subsequent depression and worse medical outcomes, suggesting interventions targeting perseverative negative thinking could improve depression and medical outcomes. Previous studies recruited healthy individuals, however. This review aimed to determine the temporal relationship and strength of prospective association of perseverative negative thinking with depression, anxiety and emotional distress in people with long term conditions. METHOD Four electronic databases were searched for studies including standardised measures of perseverative negative thinking and depression, anxiety or emotional distress, and which presented prospective associations. Findings were narratively synthesized. RESULTS Thirty studies were identified in a range of long term conditions. Perseverative negative thinking and subsequent depression, anxiety or emotional distress were significantly correlated in the majority of studies (bivariate r=0.23 to r=0.73). 25 studies controlled for confounders, and in 15 perseverative negative thinking predicted subsequent depression, anxiety or emotional distress. Results varied according to condition and study quality. Six of 7 studies found bivariate associations between depression, anxiety or emotional distress and subsequent perseverative negative thinking, though 2 studies controlling for key covariates found no association. Few studies assessed the impact of perseverative negative thinking on medical outcomes. CONCLUSION Strongest evidence supported perseverative negative thinking predicting subsequent depression, anxiety and emotional distress in people with long term conditions. Further prospective research is warranted to clarify the association of perseverative negative thinking with subsequent poor medical outcomes.

The association between perseverative negative cognitive processes and negative affect in people with long term conditions: a protocol for systematic review and meta-analysis

BackgroundDepression is common in people with long term conditions (LTCs) and is associated with worse medical outcomes. Understanding the mechanisms underpinning this relationship could help predict who is at increased risk of adverse medical outcomes, and lead to the development of novel interventions. Perseverative negative cognitive processes, such as worry and rumination, involve repetitive and frequent thoughts about oneself and one’s concerns. These processes have been associated with negative affect, and also adverse medical outcomes. The results of prospective studies, which would allow causal inferences to be drawn, are more equivocal however. Furthermore, the majority of studies have been conducted in physically healthy individuals, and we do not know to what extent these findings will generalise to people with LTCs.Methods/designElectronic databases will be searched using a search strategy including controlled vocabulary and text words related to perseverative negative cognitive processes (such as worry and rumination) and negative affect (including depression and anxiety). Records will be hand-searched for terms related to LTCs. Citation and bibliography searching will be conducted, and authors of included studies will be contacted to identify unpublished studies. Studies will be included if they contain a standardised measure of the prospective association between perseverative negative cognitive processes and negative affect, or vice versa, in people with LTCs. Narrative and meta-analytic methods will be used to synthesize the data collected.DiscussionThis review will identify and synthesise studies of the prospective association between perseverative negative cognitive processes and negative affect among people with LTCs. The findings will help to identify whether worry and rumination could cause depression and anxiety in people with LTCs, and might indicate whether perseverative negative cognitive processes are appropriate targets for treatment.