Gregory J. DiGirolamo

General and task-specific frontal lobe recruitment in older adults during executive processes: A fMRI investigation of task- switching

Performance deteriorates when subjects must shift between two different tasks relative to performing either task separately. This switching cost is thought to result from executive processes that are not inherent to the component operations of either task when performed alone. Medial and dorsolateral frontal cortices are theorized to subserve these executive processes. Here we show that larger areas of activation were seen in dorsolateral and medial frontal cortex in both younger and older adults during switching than repeating conditions, confirming the role of these frontal brain regions in executive processes. Younger subjects activated these medial and dorsolateral frontal cortices only when switching between tasks; in contrast, older subjects recruited similar frontal regions while performing the tasks in isolation as well as alternating between them. Older adults recruit medial and dorsolateral frontal areas, and the processes computed by these areas, even when no such demands are intrinsic to the current task conditions. This neural recruitment may be useful in offsetting the declines in cognitive function associated with ageing.

Addressing tobacco use disorder in smokers in early remission from alcohol dependence: The case for integrating smoking cessation services in substance use disorder treatment programs

Despite the declining overall rate of cigarette smoking in the general population in the United States, the prevalence of smoking is estimated to be as high as 80% among treatment-seeking alcoholics. The serious adverse health effects of tobacco and heavy alcohol use are synergistic and recent evidence suggests that smoking slows the process of cognitive recovery following alcohol abstinence. In addition, substantial evidence shows that treatment for tobacco dependence does not jeopardize alcohol abstinence. In this paper, we focus on the impact and treatment implications of tobacco dependence among treatment-seeking alcoholics through a review of five areas of research. We begin with brief reviews of two areas of research: studies investigating the genetic and neurobiological vulnerability of comorbid tobacco and alcohol dependence and studies investigating the consequences of comorbid dependence on neurobiological and cognitive functioning. We then review literature on the effects of smoking cessation on drinking urges and alcohol use and the effectiveness of smoking cessation interventions with alcoholic smokers. Finally, we offer recommendations for research with an emphasis on clinical research for enhancing smoking cessation outcomes in this population.

Differential effects of the Müller-Lyer illusion on reflexive and voluntary saccades

Research has produced conflicting evidence as to whether saccade programming is or is not biased by perceptual illusions. However, previous studies have generally not distinguished between effects of illusory percepts on reflexive saccades, programmed automatically in response to an external visual signal, and voluntary saccades, programmed purposively to a location where no signal has occurred. Here we find that voluntary and reflexive saccades are differentially susceptible to the Müller-Lyer illusion; reflexive movements are reliably but modestly affected by the illusion, whereas voluntary movements show an effect similar to that of perceptual judgments. Results suggest that voluntary saccade programming occurs within a non-retinotopic spatial representation similar to that of visual consciousness, whereas reflexive saccade programming occurs within a representation integrating retinotopic and higher level spatial frames. The effects of the illusion on reflexive saccades are not subject to endogenous control, nor are they modulated by the strength of an exogenous target signal.

Differential effects of reward and punishment on conscious and unconscious eye movements

Very little is known about how human movements are influenced by abstract rewards and punishments relevant for human behaviour. The purpose of this study was to expand our knowledge of the behavioural effects of monetary reward and punishment. We introduced a high and low reward and punishment scheme into an antisaccade task where trials were either rewarded for a correct response (+1 or +25p) or punished for an incorrect response (−1 or −25p). The monetary value of the trial was indicated by the go signal, so subjects had to both program the location of the movement and determine the valence in the short interval before the eye movement was executed. We analysed both correct antisaccade responses and prosaccade errors. Importantly, the errors in this task can be either conscious (recognised) or unconscious (unrecognised). Saccades in both high-reward and high-punishment trials were slowed compared to saccades in low-reward and low-punishment trials, respectively. Therefore, unlike moderate rewards only (Blaukopf and DiGirolamo in Exp Brain Res 167:654–659, 2005), combining rewards and punishments and increasing motivation levels leads to a delay in movement execution during high valence trials where all actions are slowed, even errors. However, unconscious errors were differentially affected as they were speeded when punishment was high. We conclude that reward and punishment similarly influence the programming of conscious movements, but the strong saliency for punishment affords unconscious errors immunity from this delay.

Voluntary and reflexive eye movements to illusory lengths

Considerable debate surrounds the extent and manner that motor control is, like perception, susceptible to visual illusions. Using the Brentano version of the Müller-Lyer illusion, we measured the accuracy of voluntary and reflexive eye movements to the endpoints of equal length line segments that appeared different (Experiment 1) and different length line segments that appeared equal (Experiment 3). Voluntary and reflexive saccades were both influenced by the illusion, but the former were more strongly biased and closer to the subjective percept. Experiment 2 demonstrated that these data were the results of the illusion and not centre-of-gravity effects. The representations underlying perception and action interact and this interaction produces biases for actions, particularly voluntary actions.

The automatic extraction and use of information from cues and go signals in an antisaccade task

In a gap antisaccade task that exogenously cues the side that subjects should antisaccade to, subjects find it hard to look away from the suddenly appearing go signal. Surprisingly, subjects are unaware of the majority of the prosaccade errors they make, and these errors remain unrecognised even when corrected by a second saccade requiring twice the amplitude [Fischer B, Weber H (1992) in Exp Brain Res 89:415–424]. This paper presents an extended antisaccade task that investigates what information, if any, subjects extract from redundant cues and go signals. In Exp. 1, multiple saccade locations were introduced and the go signal specified the goal location. A redundant cue appeared, prior to the go signal, in the antisaccade goal location (valid) or in the alternative location on the same side (invalid). In Exp. 2, motivational value was assigned to the go signal. The use of multiple locations showed that subjects automatically extract irrelevant positional information from the cue, which affects the programming of subsequent correct and error saccades. When the cued location was also the goal location, antisaccade reaction times were significantly reduced. The results from Exp. 2 showed that subjects also extract information from the go signal. Errors made to a go signal associated with a higher monetary value were initiated significantly faster than those to a lower monetary value. This study has shown that the visual stimuli used in this antisaccade task do more than initiate orienting sets: Their properties can influence the programming of both accurate actions and errors.

Cue-induced craving in patients with cocaine use disorder predicts cognitive control deficits toward cocaine cues

INTRODUCTION Cue-induced craving is a clinically important aspect of cocaine addiction influencing ongoing use and sobriety. However, little is known about the relationship between cue-induced craving and cognitive control toward cocaine cues. While studies suggest that cocaine users have an attentional bias toward cocaine cues, the present study extends this research by testing if cocaine use disorder patients (CDPs) can control their eye movements toward cocaine cues and whether their response varied by cue-induced craving intensity. METHODS Thirty CDPs underwent a cue exposure procedure to dichotomize them into high and low craving groups followed by a modified antisaccade task in which subjects were asked to control their eye movements toward either a cocaine or neutral drug cue by looking away from the suddenly presented cue. The relationship between breakdowns in cognitive control (as measured by eye errors) and cue-induced craving (changes in self-reported craving following cocaine cue exposure) was investigated. RESULTS CDPs overall made significantly more errors toward cocaine cues compared to neutral cues, with higher cravers making significantly more errors than lower cravers even though they did not differ significantly in addiction severity, impulsivity, anxiety, or depression levels. Cue-induced craving was the only specific and significant predictor of subsequent errors toward cocaine cues. CONCLUSION Cue-induced craving directly and specifically relates to breakdowns of cognitive control toward cocaine cues in CDPs, with higher cravers being more susceptible. Hence, it may be useful identifying high cravers and target treatment toward curbing craving to decrease the likelihood of a subsequent breakdown in control.

Memantine improves buprenorphine/naloxone treatment for opioid dependent young adults

BACKGROUND Opioid use disorders are considered a serious public health problem among young adults. Current treatment is limited to long-term opioid substitution therapy, with high relapse rates after discontinuation. This study evaluated the co-administration of memantine to brief buprenorphine pharmacotherapy as a treatment alternative. METHODS 13-week double-blind placebo-controlled trial evaluating 80 young adult opioid dependent participants treated with buprenorphine/naloxone 16-4mg/day and randomized to memantine (15mg or 30mg) or placebo. Primary outcomes were a change in the weekly mean proportion of opioid use, and cumulative abstinence rates after rapid buprenorphine discontinuation on week 9. RESULTS Treatment retention was not significantly different between groups. The memantine 30mg group was significantly less likely to relapse and to use opioids after buprenorphine discontinuation. Among participants abstinent on week 8, those in the memantine 30mg group (81.9%) were significantly less likely to relapse after buprenorphine was discontinued compared to the placebo group (30%) (p<0.025). Also, the memantine 30mg group had significantly reduced opioid use (mean=0, SEM±0.00) compared to the placebo group (mean=0.33, SEM±0.35; p<0.004) during the last 2 weeks of study participation. CONCLUSIONS Memantine 30mg significantly improved short-term treatment with buprenorphine/naloxone for opioid dependent young adults by reducing relapse and opioid use after buprenorphine discontinuation. Combined short-term treatment with buprenorphine/naloxone may be an effective alternative treatment to long-term methadone or buprenorphine maintenance in young adults.

Reward, context, and human behaviour.

Animal models of reward processing have revealed an extensive network of brain areas that process different aspects of reward, from expectation and prediction to calculation of relative value. These results have been confirmed and extended in human neuroimaging to encompass secondary rewards more unique to humans, such as money. The majority of the extant literature covers the brain areas associated with rewards whilst neglecting analysis of the actual behaviours that these rewards generate. This review strives to redress this imbalance by illustrating the importance of looking at the behavioural outcome of rewards and the context in which they are produced. Following a brief review of the literature of reward-related activity in the brain, we examine the effect of reward context on actions. These studies reveal how the presence of reward vs. reward and punishment, or being conscious vs. unconscious of reward-related actions, differentially influence behaviour. The latter finding is of particular importance given the extent to which animal models are used in understanding the reward systems of the human mind. It is clear that further studies are needed to learn about the human reaction to reward in its entirety, including any distinctions between conscious and unconscious behaviours. We propose that studies of reward entail a measure of the animals (human or nonhuman) knowledge of the reward and knowledge of its own behavioural outcome to achieve that reward.

Breakdowns of eye movement control toward smoking cues in young adult light smokers

BACKGROUND Many studies suggest that dependent smokers have a preference or attentional bias toward smoking cues. The purpose of this study was to test the ability of infrequent non-dependent light smokers to control their eye movements by look away from smoking cues. Poor control in the lightest of smokers would suggest nicotine cue-elicited behavior occurring even prior to nicotine dependency as measured by daily smoking. METHODS 17 infrequent non-dependent light smokers and 17 lifetime non-smokers performed an antisaccade task (look away from suddenly appearing cue) on smoking, alcohol, neutral, and dot cues. RESULTS The light smokers, who were confirmed light smokers and non-dependent (MFaegerström Dependency Score=0.35), were significantly worse at controlling their eye movements to smoking cues relative to both neutral cues (p<.04) and alcohol cues (p<.02). Light smokers made significantly more errors to smoking cues than non-smokers (p<.004). CONCLUSIONS These data suggest that prior to developing clinical symptoms of severe dependence or progressing to heavier smoking (e.g., daily smoking), the lightest of smokers are showing a specific deficit in control of nicotine cue-elicited behavior.