Goal-Directed and Habitual Control in Human Substance Use: State of the Art and Future Directions.

Theories of addiction posit a deficit in goal-directed behavior and an increased propensity toward habitual actions in individuals with substance use disorders. Control over drug intake is assumed to shift from goal-directed to automatic or habitual motivation as the disorder progresses. Several diagnostic criteria reflect the inability to pursue goals regarding reducing or controlling drug use and performing social or occupational functions. The current review gives an overview of the mechanisms underlying the goal-directed and habitual systems in humans, and the existing paradigms that aim to evaluate them. We further summarize the current state of research on habitual and goal-directed functioning in individuals with substance use disorders. Current evidence of alterations in addiction and substance use are mixed and need further investigation. Increased habitual responding has been observed in more severely affected groups with contingency degradation and some outcome devaluation tasks. Reduced model-based behavior has been mainly observed in alcohol use disorder and related to treatment outcomes. Motor sequence learning tasks might provide a promising new approach to examine the development of habitual behavior. In the final part of the review, we discuss possible implications and further developments regarding the influence of contextual factors, such as state and trait variations, and recent advances in task design.

Distal Functional Connectivity of Known and Emerging Cortical Targets for Therapeutic Noninvasive Stimulation.

Noninvasive stimulation is an emerging modality for the treatment of psychiatric disorders, including addiction. A crucial element in effective cortical target selection is its distal influence. We approached this question by examining resting-state functional connectivity patterns in known and potential stimulation targets in 145 healthy adults. We compared connectivity patterns with distant regions of particular relevance in the development and maintenance of addiction. We used stringent Bonferroni-correction for multiple comparisons. We show how the anterior insula, dorsal anterior cingulate, and ventromedial prefrontal cortex had opposing functional connectivity with striatum compared to the dorsomedial prefrontal cortex. However, the dorsolateral prefrontal cortex, the currently preferred target, and the presupplementary motor area had strongest negative connections to amygdala and hippocampus. Our findings highlight differential and opposing influences as a function of cortical site, underscoring the relevance of careful cortical target selection dependent on the desired effect on subcortical structures. We show the relevance of dorsal anterior cingulate and ventromedial prefrontal cortex as emerging cortical targets, and further emphasize the anterior insula as a potential promising target in addiction treatment, given its strong connections to ventral striatum, putamen, and substantia nigra.

Distraction towards contextual alcohol cues and craving are associated with levels of alcohol use among youth.

BACKGROUND: Controlling drinking behaviour requires the ability to block out distracting alcohol cues in situations in which drinking is inappropriate or harmful. However, at present few studies have investigated whether distraction and response inhibition to contextual alcohol cues are related to alcohol use in adolescents and young adults. We aimed to investigate whether tendencies towards distraction and failures of response inhibition in the presence of contextual alcohol cues, and alcohol craving were associated with higher levels of alcohol consumption, beyond what could be explained by demographic variables. METHODS: To test this, 108 participants (Mean age = 21.7, range = 16-27), whom were both drinkers and non-drinkers performed a modified Go/NoGo task tailored to measure distraction and response inhibition in the presence of alcohol cues relative to neutral stimuli. Alcohol craving was assessed using a visual analogue scale of craving for different types of alcohol cues. Levels of alcohol use and problematic alcohol use were assessed using a self-report measure of number of drinking days in the previous month and the Alcohol Use Disorders Identification Test. Data were analysed using sequential multiple regression using a zero-inflated negative binomial distribution model. RESULTS: Drinking days correlated with distraction but not response inhibition to contextual alcohol cues. Sequential regression analyses revealed that the inclusion of distraction bias accounted for 11% additional variance (significant) in alcohol use, in addition to that explained by demographics alone (17%). Craving for alcohol explained an additional 30% variance (significant) in alcohol use. CONCLUSIONS: The results reported here support the idea that both biased distraction towards alcohol cues and alcohol craving are associated with preceding drinking days, but not necessarily drinking status. Further studies are warranted that address whether cognitive distraction to alcohol-related cues cause or is an effect of alcohol use among youth.

The involuntary nature of binge drinking: goal directedness and awareness of intention.

Binge drinking represents a public health issue and is a known risk factor in the development of alcohol use disorders. Previous studies have shown behavioural as well as neuroanatomical alterations associated with binge drinking. Here, we address the question of the automaticity or involuntary nature of the behaviour by assessing goal-directed behaviour and intentionality. In this study, we used a computational two-step task, designed to discern between model-based/goal-directed and model-free/habitual behaviours, and the classic Libet clock task, to study intention awareness, in a sample of 31 severe binge drinkers (BD) and 35 matched healthy volunteers. We observed that BD had impaired goal-directed behaviour in the two-step task compared with healthy volunteers. In the Libet clock task, BD showed delayed intention awareness. Further, we demonstrated that alcohol use severity, as reflected by the alcohol use disorders identification test, correlated with decreased conscious awareness of volitional intention in BD, although it was unrelated to performance on the two-step task. However, the time elapsed since the last drinking binge influenced the model-free scores, with BD showing less habitual behaviour after longer abstinence. Our findings suggest that the implementation of goal-directed strategies and the awareness of volitional intention are affected in current heavy alcohol users. However, the modulation of these impairments by alcohol use severity and abstinence suggests a state effect of alcohol use in these measures and that top-down volitional control might be ameliorated with alcohol use cessation.

Reward Sensitivity and Waiting Impulsivity: Shift towards Reward Valuation away from Action Control.

Background: Impulsivity and reward expectancy are commonly interrelated. Waiting impulsivity, measured using the rodent 5-Choice Serial Reaction Time task, predicts compulsive cocaine seeking and sign (or cue) tracking. Here, we assess human waiting impulsivity using a novel translational task, the 4-Choice Serial Reaction Time task, and the relationship with reward cues. Methods: Healthy volunteers (n=29) performed the monetary incentive delay task as a functional MRI study where subjects observe a cue predicting reward (cue) and wait to respond for high (£5), low (£1), or no reward. Waiting impulsivity was tested with the 4-Choice Serial Reaction Time task. Results: For high reward prospects (£5, no reward), greater waiting impulsivity on the 4-CSRT correlated with greater medial orbitofrontal cortex and lower supplementary motor area activity to cues. In response to high reward cues, greater waiting impulsivity was associated with greater subthalamic nucleus connectivity with orbitofrontal cortex and greater subgenual cingulate connectivity with anterior insula, but decreased connectivity with regions implicated in action selection and preparation. Conclusion: These findings highlight a shift towards regions implicated in reward valuation and a shift towards compulsivity away from higher level motor preparation and action selection and response. We highlight the role of reward sensitivity and impulsivity, mechanisms potentially linking human waiting impulsivity with incentive approach and compulsivity, theories highly relevant to disorders of addiction.

Brain network of semantic integration in sentence reading: insights from independent component analysis and graph theoretical analysis.

A set of cortical and sub-cortical brain structures has been linked with sentence-level semantic processes. However, it remains unclear how these brain regions are organized to support the semantic integration of a word into sentential context. To look into this issue, we conducted a functional magnetic resonance imaging (fMRI) study that required participants to silently read sentences with semantically congruent or incongruent endings and analyzed the network properties of the brain with two approaches, independent component analysis (ICA) and graph theoretical analysis (GTA). The GTA suggested that the whole-brain network is topologically stable across conditions. The ICA revealed a network comprising the supplementary motor area (SMA), left inferior frontal gyrus, left middle temporal gyrus, left caudate nucleus, and left angular gyrus, which was modulated by the incongruity of sentence ending. Furthermore, the GTA specified that the connections between the left SMA and left caudate nucleus as well as that between the left caudate nucleus and right thalamus were stronger in response to incongruent vs. congruent endings.

Magneto- and electroencephalographic manifestations of reward anticipation and delivery.

The monetary incentive delay task was used to characterize reward anticipation and delivery with concurrently acquired evoked magnetic fields, EEG potentials and EEG/MEG oscillatory responses, obtaining a precise portrayal of their spatiotemporal evolution. In the anticipation phase, differential activity was most prominent over midline electrodes and parieto-occipital sensors. Differences between non-reward- and reward-predicting cues were localized in the cuneus and later in the dorsal PCC, suggesting a modulation by potential reward information during early visual processing, followed by a coarse emotional evaluation of the cues. Oscillatory analysis revealed increased theta power after non-reward cues over fronto-central sites. In the beta range, power decreased with the magnitude of the potential reward and increased with reaction time, probably reflecting the influence of the striatal response to potential reward on the sensorimotor cortex. At reward delivery, negative prediction errors led to a larger mediofrontal negativity. The spatiotemporal evolution of reward processing was modulated by prediction error: whereas differences were located in PCC and putamen in the prediction error comparison, in the case of expected outcomes they were located in PCC, ACC and parahippocampal gyrus. In the oscillatory realm, theta power was largest following rewards and, in the case of non-rewards, was largest when these were unexpected. Higher beta activity following rewards was also observed in both modalities, but MEG additionally showed a significant power decrease for this condition over parieto-occipital sensors. Our results show how visual, limbic and striatal structures are involved in the different stages of reward anticipation and delivery, and how theta and beta oscillations have a prominent role in the processing of these stimuli.

Coupling electrophysiological and hemodynamic responses to errors.

Performance errors are associated with distinct electrophysiological and hemodynamic signatures: a fronto-central error-related negativity (ERN) is seen in the event-related potentials and a network of activations including medio-frontal, parietal, and insular cortex is revealed by functional magnetic resonance imaging. We used simultaneous electroencephalography and functional magnetic resonance imaging (fMRI) to characterize the relationship between the electrophysiological and hemodynamic responses to errors. Participants performed a modified Flanker task. When analyzed independently, we found the ERN and hemodynamic activations in dorsal anterior cingulate cortex, superior frontal gyrus, precentral gyrus, inferior frontal gyrus, and inferior parietal lobule. fMRI-informed dipole modeling and joint independent component analysis (ICA) were used to couple electrophysiological and hemodynamic data. Both techniques revealed a temporal evolution of the areas found in the fMRI analysis, with the right hemisphere activations peaking before the left hemisphere. However, joint ICA added information, revealing a number of cortical and subcortical areas that had not been shown with parametric mapping. This technique also uncovered how these areas evolve over time. All together, these analyses provide a more detailed picture of the spatiotemporal dynamics of the processing of performance errors.

Temporal dynamics of reward processing revealed by magnetoencephalography.

Monetary gains and losses in gambling situations are associated with a distinct electroencephalographic signature: in the event-related potentials (ERPs), a mediofrontal feedback-related negativity (FRN) is seen for losses, whereas oscillatory activity shows a burst of in the θ-range for losses and in the ß-range for gains. We used whole-head magnetoencephalography to pinpoint the magnetic counterparts of these effects in young healthy adults and explore their evolution over time. On each trial, participants bet on one of two visually presented numbers (25 or 5) by button-press. Both numbers changed color: if the chosen number turned green (red), it indicated a gain (loss) of the corresponding sum in Euro cent. For losses, we found the magnetic correlate of the FRN extending between 230 and 465 ms. Source localization with low-resolution electromagnetic tomography indicated a first generator in posterior cingulate cortex with subsequent activity in the anterior cingulate cortex. Importantly, this effect was sensitive to the magnitude of the monetary loss (25 cent > 5 cent). Later activation was also found in the right insula. Time-frequency analysis revealed a number of oscillatory components in the theta, alpha, and high-beta/low-gamma bands associated to gains, and in the high-beta band, associated to the magnitude of the loss. All together, these effects provide a more fine-grained picture of the temporal dynamics of the processing of monetary rewards and losses in the brain.

Addictions NeuroImaging Assessment (ANIA): Towards an integrative framework for alcohol use disorder.

Alcohol misuse and addiction are major international public health issues. Addiction can be characterized as a disorder of aberrant neurocircuitry interacting with environmental, genetic and social factors. Neuroimaging in alcohol misuse can thus provide a critical window into underlying neural mechanisms, highlighting possible treatment targets and acting as clinical biomarkers for predicting risk and treatment outcomes. This neuroimaging review on alcohol misuse in humans follows the Addictions Neuroclinical Assessment (ANA) that proposes incorporating three functional neuroscience domains integral to the neurocircuitry of addiction: incentive salience and habits, negative emotional states, and executive function within the context of the addiction cycle. Here we review and integrate multiple imaging modalities focusing on underlying cognitive processes such as reward anticipation, negative emotionality, cue reactivity, impulsivity, compulsivity and executive function. We highlight limitations in the literature and propose a model forward in the use of neuroimaging as a tool to understanding underlying mechanisms and potential clinical applicability for phenotyping of heterogeneity and predicting risk and treatment outcomes.

Electrophysiology of goal-directed versus habitual control during outcome devaluation.

Dual-system accounts posit that instrumental behavior is controlled by both a goal-directed and a habitual system. In this study, we aimed to identify the electrophysiological components associated with goal-directed versus habitual performance using an outcome devaluation procedure. Datasets from 35 healthy participants were analyzed. Behaviorally, in line with previous research, participants displayed sensitivity to outcome devaluation, a hallmark of goal-directed control. Electrophysiologically, decreased N2 and increased error-related negativity (ERN) amplitudes were associated with slips of action in conditions that could potentially engage both the goal-directed and habitual systems. These amplitude differences were more pronounced in participants that displayed more sensitivity to devaluation. Furthermore, we show how specific neurophysiological learning signals, namely ERN and feedback-locked P3, could predict subsequent sensitivity to devaluation. Our findings indicate that the N2 and ERN components can be used as indices of goal-directed versus habitual control, and emphasize the importance of the ERN as an electrophysiological trait in the context of goal-directed behavior.

The effect of frontoparietal paired associative stimulation on decision-making and working memory.

Previous single-site neurostimulation experiments have unsuccessfully attempted to shift decision-making away from habitual control, a fast, inflexible cognitive strategy, towards goal-directed control, a flexible, though computationally expensive strategy. We employed a dual-target neurostimulation approach in 30 healthy participants, using cortico-cortical paired associative stimulation (ccPAS) to target two key nodes: lateral prefrontal cortex (LPFC) and intraparietal sulcus (IPS), to test whether decision-making can be artificially shifted from habitual toward goal-directed control. Participants received three active stimulations, delivered at least six days apart (each involving 100 paired pulses over the IPS and LPFC, varying the interstimulus interval): two interventional, time-relevant ccPAS (10 msec interval) and one control, non-time-relevant ccPAS (100 msec interval). Following stimulation, participants completed a sequential learning task, measuring goal-directed/habitual control, and a working memory task. IPS→LPFC ccPAS (stimulating IPS, then LPFC with a 10 msec interval) shifted decision-making from habitual toward goal-directed control, compared to control ccPAS. There was no effect of LPFC→IPS ccPAS, nor an effect of any PAS condition on working memory. Previous studies have shown ccPAS effects outside the motor domain targeting prefrontal regions on response inhibition, attentional bias, and alpha asymmetry. The present study measures the behavioural effects of parietal-prefrontal PAS, focusing on a highly complex decision-making task and working memory. If confirmed in larger studies, this would be the first instance of neurostimulation successfully shifting decision-making from habitual to goal-directed control, putatively via inducing long-term potentiation between the IPS and LPFC. However, we found no effect in the other direction (LPFC→IPS ccPAS), and no effect on working memory overall. PAS is a relatively new neuromodulatory technique in the cognitive arsenal, and this study could help guide future approaches in healthy and disordered decision-making.

Neural processing of food and monetary rewards is modulated by metabolic state.

In humans, food is considered a powerful primary reinforcer, whereas money is a secondary reinforcer, as it gains a value through learning experience. Here, we aimed to identify the neural regions supporting the processing of food-related reinforcers, relate it to the neural underpinnings of monetary reinforcers, and explore their modulation by metabolic state (hunger vs satiety). Twenty healthy male participants were tested in two experimental sessions, once hungry and once satiated, using functional magnetic resonance imaging. Participants performed an associative learning task, receiving food or monetary rewards (in the form of images) on separate blocks. Irrespective of incentive type, both food and monetary rewards engaged ventral striatum, medial orbitofrontal cortex and amygdala, regions that have been previously associated with reward processing. Food incentives additionally engaged the opercular part of the inferior frontal gyrus and the insula, collectively known as a primary gustatory cortex. Moreover, in response to negative feedback (here, reward omission), robust activation was observed in anterior insula, supplementary motor area and lateral parts of the prefrontal cortex, including middle and inferior frontal gyrus. Furthermore, the interaction between metabolic state and incentive type resulted in supramarginal gyrus (SMG) activity, among other motor and sensory-related regions. Finally, functional connectivity analysis showed correlation in the hungry state between the SMG and mesolimbic regions, including the hippocampus, midbrain and cingulate areas. Also, the interaction between metabolic state and incentive type revealed coupling between SMG and ventral striatum. Whereas general purpose reward-related regions process incentives of different kinds, the current results suggest that the SMG might play a key role in integrating the information related to current metabolic state and available incentive type.

Event-related potentials and neural oscillations dissociate levels of cognitive control.

Recent models of human behavior suggest a hierarchical organization of cognitive control processes. These models assume that different sub-goals of cognitive control processes are nested in each other, such that higher-level sub-goals can only be accomplished when lower-level sub-goals have been realized. While the neuroanatomical localization of this organizational principle has already been successfully tested, the exact temporal nature remains to be explored. The present study applied event-related potentials (ERPs) and investigated neural oscillations during performance of three different nested cognitive control tasks. Results demonstrated a parametric modulation of the P300 component as well as beta-band (13-25Hz) oscillations as a function of different levels of cognitive control. Moreover, conditions requiring flexible updating of information exhibited similar alpha-band (8-13Hz) oscillations, which differed from the condition without flexible updating (low-level). These results suggest dissociable mechanisms of flexible information updating and complexity of cognitive control processes indexed by different oscillatory effects.

Increase in Beta-Band Activity during Preparation for Overt Speech in Patients with Parkinson's Disease.

Speech impairment is a frequent and often serious symptom of Parkinson's disease (PD), characterized by a disorder of phonation, articulation and prosody. While research on the pathogenesis of the prominent limb motor symptoms has made considerable progress in recent years, the pathophysiology of PD speech impairment is still incompletely understood. To investigate the neural correlates of speech production in PD, EEG was recorded in 14 non-demented patients with idiopathic PD and preserved verbal fluency on regular dopaminergic medication (8 women; mean age ± SD: 69.5 ± 8.0 years). The control group consisted of 15 healthy age-matched individuals (7 women; age: 69.7 ± 7.0 years). All participants performed a visually-cued, overt speech production task; required utterances were papapa and pataka. During the preparatory phase of speech production, in a time window of 200-400 ms after presentation of the visual cue, ß-power was significantly increased in PD patients compared to healthy controls. Previous research has shown that the physiological decrease of ß-power preceding limb movement onset is delayed and smaller in PD patients off medication and normalizes under dopaminergic treatment. By contrast, our study demonstrates that ß-power during preparation for speech production is higher in patients on dopaminergic therapy than controls. Thus, our results suggest that the mechanisms that regulate ß-activity preceding limb movement and speech production differ in PD. The pathophysiological role of this increase in ß-power during speech preparation needs to be determined.

Event-related EEG responses to anticipation and delivery of monetary and social reward.

Monetary and a social incentive delay tasks were used to characterize reward anticipation and delivery with electroencephalography. During reward anticipation, N1, P2 and P3 components were modulated by both prospective reward value and incentive type (monetary or social), suggesting distinctive allocation of attentional and motivational resources depending not only on whether rewards or non-rewards were cued, but also on the monetary and social nature of the prospective outcomes. In the delivery phase, P2, FRN and P3 components were also modulated by levels of reward value and incentive type, illustrating how distinctive affective and cognitive processes were attached to the different outcomes. Our findings imply that neural processing of both reward anticipation and delivery can be specific to incentive type, which might have implications for basic as well as translational research. These results are discussed in the light of previous electrophysiological and neuroimaging work using similar tasks.

Performance monitoring during associative learning and its relation to obsessive-compulsive characteristics.

Neural responses to performance errors and external feedback have been suggested to be altered in obsessive-compulsive disorder. In the current study, an associative learning task was used in healthy participants assessed for obsessive-compulsive symptoms by the OCI-R questionnaire. The task included a condition with equivocal feedback that did not inform about the participants' performance. Following incorrect responses, an error-related negativity and an error positivity were observed. In the feedback phase, the largest feedback-related negativity was observed following equivocal feedback. Theta and beta oscillatory components were found following incorrect and correct responses, respectively, and an increase in theta power was associated with negative and equivocal feedback. Changes over time were also explored as an indicator for possible learning effects. Finally, event-related potentials and oscillatory components were found to be uncorrelated with OCI-R scores in the current non-clinical sample.

Parafoveal N400 effect during sentence reading.

Research has suggested that during reading, parafoveal information pertaining to the next word in a line might be, at least partially, processed. We used event-related brain potentials (ERPs) to examine this issue. Volunteers read sentences presented word-by-word at fixation with each word flanked bilaterally on its right by the next word in the sentence and on its left by the preceding word. Infrequently, the right flanker was replaced by a word that was semantically incongruous with the ongoing sentence context. N400 amplitudes to the critical triads were smaller when the right flanker was contextually congruent than incongruent, indicating that parafoveal information was extracted and quickly and incrementally integrated within the evolving sentence representation.

Emotional and cognitive aspects of empathy and their relation to social cognition--an fMRI-study.

The present functional magnetic resonance imaging (fMRI) study sought to characterize neural processes related to aspects of empathy and social cognition. It has been hypothesized previously that merely observing emotions in others automatically activates associated representations of the emotional state in the observer. We tested this prediction by presenting drawings depicting either one or two persons in an emotionally charged or neutral situation. Importantly and in contrast to previous imaging studies on empathy or social cognition, we did not instruct participants to assess the depicted persons' feelings or thoughts, but told them to simply watch the pictures to be able to perform a memory task unrelated to the main experimental question. This novel design allowed us to assess automatically elicited empathy-related effects (contrasting emotional and neutral situations) and to compare them with automatic social cognitive processes (contrasting stimuli with two persons vs. one person). We observed empathy-related increased hemodynamic responses in areas previously shown to be related to emotion processing (ventromedial and ventrolateral prefrontal cortex, PFC) and to social cognitive processes (superior temporal sulcus, STS, and medial PFC). The medial PFC activation was negatively correlated with participants' predisposition to feel distressed in emotional social situations, suggesting that interindividual differences in these higher-order functions might also impact empathic responses in social interactions.