Yavor Yalachkov

Factors modulating neural reactivity to drug cues in addiction: A survey of human neuroimaging studies

Human neuroimaging studies suggest that neural cue reactivity is strongly associated with indices of drug use, including addiction severity and treatment success. However, little is known about factors that modulate cue reactivity. The goal of this review, in which we survey published fMRI and PET studies on drug cue reactivity in cocaine, alcohol, and tobacco cigarette users, is to highlight major factors that modulate brain reactivity to drug cues. First, we describe cue reactivity paradigms used in neuroimaging research and outline the brain circuits that underlie cue reactivity. We then discuss major factors that have been shown to modulate cue reactivity and review specific evidence as well as outstanding questions related to each factor. Building on previous model-building reviews on the topic, we then outline a simplified model that includes the key modulatory factors and a tentative ranking of their relative impact. We conclude with a discussion of outstanding challenges and future research directions, which can inform future neuroimaging studies as well as the design of treatment and prevention programs.

Brain Regions Related to Tool Use and Action Knowledge Reflect Nicotine Dependence

In addition to reward- and craving-related processes, habitual mechanisms play an important role in addiction. While the dorsal striatum has been proposed to code for the motivational state of habitual drug-seeking actions, the neural underpinnings of the corresponding drug-taking skills and action knowledge remain poorly understood. We used functional magnetic resonance imaging (fMRI) and a behavioral orientation affordance paradigm to investigate the neural and behavioral correlates of automatized drug-taking actions in nicotine dependence. Smokers exhibited higher fMRI activations than nonsmokers when viewing smoking-related but not when viewing control images. These group differences in fMRI activations were located not only in brain regions associated with craving and habitual learning (left ventral and dorsal striatum, dorsolateral prefrontal cortex, insula, uncus, medial frontal gyrus, right subcallosal gyrus, and bilateral parahippocampal gyrus), but also in a network of brain regions which has been strongly implicated in the encoding of action knowledge and tool use skills (bilateral premotor cortex, left superior parietal lobule, and right lateral cerebellum). A behavioral affordance reaction-time task indicated that smokers, but not nonsmokers, showed an automatized responsiveness to smoking paraphernalia similar to everyday objects. Moreover, smokers showed strong intercorrelations between fMRI activations in tool use-related brain regions, behavioral responsiveness to smoking-related cues, and severity of nicotine dependence. Apparently smoking-related action representations in smokers are stored in brain regions typically representing tool use skills and action knowledge. Most importantly, cortical and behavioral correlates of the respective drug-taking skills vary with the individual degree of nicotine dependence.

Functional neuroimaging studies in addiction: Multisensory drug stimuli and neural cue reactivity

Neuroimaging studies on cue reactivity have substantially contributed to the understanding of addiction. In the majority of studies drug cues were presented in the visual modality. However, exposure to conditioned cues in real life occurs often simultaneously in more than one sensory modality. Therefore, multisensory cues should elicit cue reactivity more consistently than unisensory stimuli and increase the ecological validity and the reliability of brain activation measurements. This review includes the data from 44 whole-brain functional neuroimaging studies with a total of 1168 subjects (812 patients and 356 controls). Correlations between neural cue reactivity and clinical covariates such as craving have been reported significantly more often for multisensory than unisensory cues in the motor cortex, insula and posterior cingulate cortex. Thus, multisensory drug cues are particularly effective in revealing brain-behavior relationships in neurocircuits of addiction responsible for motivation, craving awareness and self-related processing.

Sensory and motor aspects of addiction

Research on the psychological and neuronal underpinnings of addiction has concentrated mostly on affective, motivational, learning, and executive processes and the brain regions subserving these functions. In contrast, sensory and motor aspects of addiction have largely been neglected even though they may be highly relevant for the development and preservation of addiction. The aim of the present review is to emphasize the significance of sensory and motor processes for the better understanding and treatment of addiction. We focus on research investigating substance-related addictions and on brain imaging studies in humans that have assessed the contribution of cortical and cerebellar systems to sensory and motor mechanisms of addiction. Activations of sensory and motor brain regions in response to drug-associated cues can predict relapse and correlate with craving, severity of dependence and automatized behavioral reactions towards drug-related stimuli. We propose a model of how sensory and motor processes might be involved in the different stages of addiction.

Sensory modality of smoking cues modulates neural cue reactivity

RationaleBehavioral experiments have demonstrated that the sensory modality of presentation modulates drug cue reactivity.ObjectivesThe present study on nicotine addiction tested whether neural responses to smoking cues are modulated by the sensory modality of stimulus presentation.MethodsWe measured brain activation using functional magnetic resonance imaging (fMRI) in 15 smokers and 15 nonsmokers while they viewed images of smoking paraphernalia and control objects and while they touched the same objects without seeing them.ResultsHaptically presented, smoking-related stimuli induced more pronounced neural cue reactivity than visual cues in the left dorsal striatum in smokers compared to nonsmokers. The severity of nicotine dependence correlated positively with the preference for haptically explored smoking cues in the left inferior parietal lobule/somatosensory cortex, right fusiform gyrus/inferior temporal cortex/cerebellum, hippocampus/parahippocampal gyrus, posterior cingulate cortex, and supplementary motor area.ConclusionsThese observations are in line with the hypothesized role of the dorsal striatum for the expression of drug habits and the well-established concept of drug-related automatized schemata, since haptic perception is more closely linked to the corresponding object-specific action pattern than visual perception. Moreover, our findings demonstrate that with the growing severity of nicotine dependence, brain regions involved in object perception, memory, self-processing, and motor control exhibit an increasing preference for haptic over visual smoking cues. This difference was not found for control stimuli. Considering the sensory modality of the presented cues could serve to develop more reliable fMRI-specific biomarkers, more ecologically valid experimental designs, and more effective cue-exposure therapies of addiction.

Visuohaptic convergence in a corticocerebellar network

The processing of visual and haptic inputs, occurring either separately or jointly, is crucial for everyday‐life object recognition, and has been a focus of recent neuroimaging research. Previously, visuohaptic convergence has been mostly investigated with matching‐task paradigms. However, much less is known about visuohaptic convergence in the absence of additional task demands. We conducted two functional magnetic resonance imaging experiments in which subjects actively touched and/or viewed unfamiliar object stimuli without any additional task demands. In addition, we performed two control experiments with audiovisual and audiohaptic stimulation to examine the specificity of the observed visuohaptic convergence effects. We found robust visuohaptic convergence in bilateral lateral occipital cortex and anterior cerebellum. In contrast, neither the anterior cerebellum nor the lateral occipital cortex showed any involvement in audiovisual or audiohaptic convergence, indicating that multisensory convergence in these regions is specifically geared to visual and haptic inputs. These data suggest that in humans the lateral occipital cortex and the anterior cerebellum play an important role in visuohaptic processing even in the absence of additional task demands.

Involvement of action-related brain regions in nicotine addiction

The study of Wagner et al. (J Neurosci 31: 894-898, 2011) reveals the neural correlates of spontaneously activated action representations in smokers when subjects watch movie characters smoke. We stress the importance of differentiating how these representations are activated: while the anterior intraparietal sulcus and inferior frontal gyrus are part of the mirror neuron system of smokers, the middle frontal gyrus, premotor cortex, and superior parietal lobule represent the smoking-related tool use skills and action knowledge activated by smoking paraphernalia.

Smoking experience modulates the cortical integration of vision and haptics

Human neuroplasticity of multisensory integration has been studied mainly in the context of natural or artificial training situations in healthy subjects. However, regular smokers also offer the opportunity to assess the impact of intensive daily multisensory interactions with smoking-related objects on the neural correlates of crossmodal object processing. The present functional magnetic resonance imaging study revealed that smokers show a comparable visuo-haptic integration pattern for both smoking paraphernalia and control objects in the left lateral occipital complex, a region playing a crucial role in crossmodal object recognition. Moreover, the degree of nicotine dependence correlated positively with the magnitude of visuo-haptic integration in the left lateral occipital complex (LOC) for smoking-associated but not for control objects. In contrast, in the left LOC non-smokers displayed a visuo-haptic integration pattern for control objects, but not for smoking paraphernalia. This suggests that prolonged smoking-related multisensory experiences in smokers facilitate the merging of visual and haptic inputs in the lateral occipital complex for the respective stimuli. Studying clinical populations who engage in compulsive activities may represent an ecologically valid approach to investigating the neuroplasticity of multisensory integration.

The compulsive habit of cars

The car dependence of people living in contemporary cities is a major concern for policy makers, who often find it difficult to persuade people into more sustainable transport modes. By contrast, recent insights from neuroscience have shown that a broad spectrum of behaviors can become habitual and, thus, resistant to change. Here, we outline the potential of collaboration between neuroscience and human geography aiming at a better understanding of habits that determine everyday commuting routines.

Automatized smoking-related action schemata are reflected by reduced fMRI activity in sensorimotor brain regions of smokers

In the later stages of addiction, automatized processes play a prominent role in guiding drug-seeking and drug-taking behavior. However, little is known about the neural correlates of automatized drug-taking skills and drug-related action knowledge in humans. We employed functional magnetic resonance imaging (fMRI) while smokers and non-smokers performed an orientation affordance task, where compatibility between the hand used for a behavioral response and the spatial orientation of a priming stimulus leads to shorter reaction times resulting from activation of the corresponding motor representations. While non-smokers exhibited this behavioral effect only for control objects, smokers showed the affordance effect for both control and smoking-related objects. Furthermore, smokers exhibited reduced fMRI activation for smoking-related as compared to control objects for compatible stimulus-response pairings in a sensorimotor brain network consisting of the right primary motor cortex, supplementary motor area, middle occipital gyrus, left fusiform gyrus and bilateral cingulate gyrus. In the incompatible condition, we found higher fMRI activation in smokers for smoking-related as compared to control objects in the right primary motor cortex, cingulate gyrus, and left fusiform gyrus. This suggests that the activation and performance of deeply embedded, automatized drug-taking schemata employ less brain resources. This might reduce the threshold for relapsing in individuals trying to abstain from smoking. In contrast, the interruption or modification of already triggered automatized action representations require increased neural resources.