Missing motoric manipulations: rethinking the imaging of the ventral striatum and dopamine in human reward

Human neuroimaging studies of natural rewards and drugs of abuse frequently assay the brain’s response to stimuli that, through Pavlovian learning, have come to be associated with a drug’s rewarding properties. This might be characterized as a ‘sensorial’ view of the brain’s reward system, insofar as the paradigms are designed to elicit responses to a reward’s (drug’s) sight, aroma, or flavor. A different field of research nevertheless suggests that the mesolimbic dopamine system may also be critically involved in the motor behaviors provoked by such stimuli. This brief review and commentary surveys some of the preclinical data supporting this more “efferent” (motoric) view of the brain’s reward system, and discusses what such findings might mean for how human brain imaging studies of natural rewards and drugs of abuse are designed

Semiparametric Estimation of Task-Based Dynamic Functional Connectivity on the Population Level

Dynamic functional connectivity (dFC) estimates time-dependent associations between pairs of brain region time series as typically acquired during functional MRI. dFC changes are most commonly quantified by pairwise correlation coefficients between the time series within a sliding window. Here, we applied a recently developed bootstrap-based technique (Kudela et al., 2017) to robustly estimate subject-level dFC and its confidence intervals in a task-based fMRI study (24 subjects who tasted their most frequently consumed beer and Gatorade as an appetitive control). We then combined information across subjects and scans utilizing semiparametric mixed models to obtain a group-level dFC estimate for each pair of brain regions, flavor, and the difference between flavors. The proposed approach relies on the estimated group-level dFC accounting for complex correlation structures of the fMRI data, multiple repeated observations per subject, experimental design, and subject-specific variability. It also provides condition-specific dFC and confidence intervals for the whole brain at the group level. As a summary dFC metric, we used the proportion of time when the estimated associations were either significantly positive or negative. For both flavors, our fully-data driven approach yielded regional associations that reflected known, biologically meaningful brain organization as shown in prior work, as well as closely resembled resting state networks (RSNs). Specifically, beer flavor-potentiated associations were detected between several reward-related regions, including the right ventral striatum (VST), lateral orbitofrontal cortex, and ventral anterior insular cortex (vAIC). The enhancement of right VST-vAIC association by a taste of beer independently validated the main activation-based finding (Oberlin et al., 2016). Most notably, our novel dFC methodology uncovered numerous associations undetected by the traditional static FC analysis. The data-driven, novel dFC methodology presented here can be used for a wide range of task-based fMRI designs to estimate the dFC at multiple levels-group-, individual-, and task-specific, utilizing a combination of well-established statistical methods

A morphospace of functional configuration to assess configural breadth based on brain functional networks

The best approach to quantify human brain functional reconfigurations in response to varying cognitive demands remains an unresolved topic in network neuroscience. We propose that such functional reconfigurations may be categorized into three different types: i) Network Configural Breadth, ii) Task-to-Task transitional reconfiguration, and iii) Within-Task reconfiguration. In order to quantify these reconfigurations, we propose a mesoscopic framework focused on functional networks (FNs) or communities. To do so, we introduce a 2D network morphospace that relies on two novel mesoscopic metrics, Trapping Efficiency (TE) and Exit Entropy (EE), which capture topology and integration of information within and between a reference set of FNs. In this study, we use this framework to quantify the Network Configural Breadth across different tasks. We show that the metrics defining this morphospace can differentiate FNs, cognitive tasks and subjects. We also show that network configural breadth significantly predicts behavioral measures, such as episodic memory, verbal episodic memory, fluid intelligence and general intelligence. In essence, we put forth a framework to explore the cognitive space in a comprehensive manner, for each individual separately, and at different levels of granularity. This tool that can also quantify the FN reconfigurations that result from the brain switching between mental states.Comment: main article: 24 pages, 8 figures, 2 tables. supporting information: 11 pages, 5 figure

Association of structural brain imaging markers with alcoholism incorporating structural connectivity information: a regularized statistical approach

poster abstractAbstract: Brain imaging studies collect multiple imaging data types, but most analyses are done for each modality separately. Statistical methods that simultaneously utilize and combine multiple data types can instead provide a more holistic view of brain function. Here we model associations between alcohol abuse phenotypes and imaging data while incorporating prior scientific knowledge. Specifically, we utilize cortical thickness and integrated rectified mean curvature measures obtained by FreeSurfer software [1] to predict the alcoholism-related phenotypes while incorporating prior information from the structural connectivity between cortical regions. The sample consisted of 148 young (21-35 years) social-to-heavy drinking male subjects from several alcoholism risk studies [2,3,4]. Structural connectivity model [5] was used to estimate the density of connections between 66 cortical regions based on Desikan-Killiany atlas [6]. We employed a functional linear model with a penalty operator to quantify the relative contributions of imaging markers obtained from high resolution structural MRI (cortical thickness and curvature) as predictors of drinking frequency and risk-relevant personality traits, while co-varying for age. Model parameters were estimated by a unified approach directly incorporating structural connectivity information into the estimation by exploiting the joint eigenproperties of the predictors and the penalty operator [7]. We found that the best predictive imaging markers of the Alcohol Use Disorders Identification Test (AUDIT) score were the average thickness of left frontal pole (-), right transverse temporal gyrus (+), left inferior parietal lobule (+), right supramarginal gyrus (-), right rostral middle frontal gyrus (+), right precentral gyrus (+), left superior parietal lobule (-), left lateral orbitofrontal cortex (+), left rostral middle frontal gyrus (+), left postcentral gyrus (+) and left supramarginal gyrus (-), where (+) denotes positive and (-) negative association. In summary, the use of structural connectivity information allowed the incorporation of different modalities in associating cortical measures and alcoholism risk

An fMRI Study of Responses to Sexual Stimuli as a Function of Gender and Sensation Seeking: A Preliminary Analysis

Although sexual cues produce stronger neural activation in men than in women, mechanisms underlying this differential response are unclear. We examined the relationship of sensation seeking and the brain’s response to sexual stimuli across gender in 27 subjects (14 men, M = 25.2 years, SD = 3.6, 85.2% Caucasian) who underwent functional magnetic resonance imaging (fMRI) while viewing sexual and nonsexual images. Whole-brain corrected significant clusters of regional activation were extracted and associated with gender, sensation seeking, and sexual behaviors. Men responded more to sexual than nonsexual images in the anterior cingulate/medial prefrontal cortex (ACC/mPFC), anterior insula/lateral orbitofrontal cortex, bilateral amygdala, and occipital regions. Sensation seeking related positively to ACC/mPFC (r = 0.65, p = 0.01) and left amygdala (r = 0.66, p = 0.01) response in men alone, with both of these correlations being significantly larger in men than in women (ps < 0.03). The relationship between brain responses and self-reported high-risk and low-risk sexual behaviors showed interesting, albeit nonsignificant, gender-specific trends. These findings suggest the relationship between sexual responsivity, sensation seeking, and sexual behavior is gender specific. This study indicates a need to identify the gender-specific mechanisms that underlie sexual responsivity and behaviors. In addition, it demonstrates that the nature of stimuli used to induce positive mood in imaging and other studies should be carefully considered

A preliminary study of the human brain response to oral sucrose and its association with recent drinking

BACKGROUND: A preference for sweet tastes has been repeatedly shown to be associated with alcohol preference in both animals and humans. In this study, we tested the extent to which recent drinking is related to blood oxygen level-dependent (BOLD) activation from an intensely sweet solution in orbitofrontal areas known to respond to primary rewards. METHODS: Sixteen right-handed, non-treatment-seeking, healthy volunteers (mean age: 26 years; 75% male) were recruited from the community. All underwent a taste test using a range of sucrose concentrations, as well as functional magnetic resonance imaging (fMRI) during pseudorandom, event-driven stimulation with water and a 0.83 M concentration of sucrose in water. RESULTS: [Sucrose > water] provoked a significant BOLD activation in primary gustatory cortex and amygdala, as well as in the right ventral striatum and in bilateral orbitofrontal cortex. Drinks/drinking day correlated significantly with the activation as extracted from the left orbital area (r = 0.52, p = 0.04 after correcting for a bilateral comparison). Using stepwise multiple regression, the addition of rated sucrose liking accounted for significantly more variance in drinks/drinking day than did left orbital activation alone (multiple R = 0.79, p = 0.002). CONCLUSIONS: Both the orbitofrontal response to an intensely sweet taste and rated liking of that taste accounted for significant variance in drinking behavior. The brain response to sweet tastes may be an important phenotype of alcoholism risk

Involvement of the left anterior insula and frontopolar gyrus in odor discrimination

Discriminating between successively presented odors requires brief storage of the first odor's perceptual trace, which then needs to be subsequently compared to the second odor in the pair. This study explores the cortical areas involved in odor discrimination and compares them with findings from studies of working‐memory, traditionally investigated with n‐back paradigms. Sixteen right‐handed subjects underwent H2 15O positron emission tomography during counterbalanced conditions of odorless sniffing, repeated single odor detection, multiple odor detection, and conscious successive discrimination between odor pairs. Eight odorants were delivered using a computer‐controlled olfactometer through a birhinal nasal cannula. Conscious successive odor discrimination evoked significantly greater activity in the left anterior insula and frontopolar gyrus when compared to reported sensory detection of the identical odors. Additional activation was found in the left lateral orbital/inferior frontal and middle frontal gyri when discrimination was compared to the odorless condition. The left anterior insula is likely involved in the evaluation of odor properties. Consistent with other studies, frontopolar and middle frontal gyrus activation is more likely related to working memory during odor discrimination

Pairing Neutral Cues with Alcohol Intoxication: New Findings in Executive and Attention Networks

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. Objectives: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian conditioned stimuli in fMRI when subjects were not intoxicated. Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day two, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS−, and an irrelevant symbol. Results: CS+ elicited stronger activation than CS− in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS−] activation. Delay-tolerant choice and [CS+ > CS−] activation in right inferior parietal cortex were positively related. Conclusions: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations

Negative urgency and ventromedial prefrontal cortex responses to alcohol cues: FMRI evidence of emotion-based impulsivity

BACKGROUND: Recent research has highlighted the role of emotion-based impulsivity (negative and positive urgency personality traits) for alcohol use and abuse, but has yet to examine how these personality traits interact with the brain's motivational systems. Using functional magnetic resonance imaging (fMRI), we tested whether urgency traits and mood induction affected medial prefrontal responses to alcohol odors (AcO). METHODS: Twenty-seven social drinkers (mean age = 25.2, 14 males) had 6 fMRI scans while viewing negative, neutral, or positive mood images (3 mood conditions) during intermittent exposure to AcO and appetitive control (AppCo) aromas. RESULTS: Voxel-wise analyses (p AppCo] activation throughout medial prefrontal cortex (mPFC) and ventromedial PFC (vmPFC) regions. Extracted from a priori mPFC and vmPFC regions and analyzed in Odor (AcO, AppCo) × Mood factorial models, AcO activation was greater than AppCo in left vmPFC (p AppCo] activation. Negative urgency also mediated the relationship between vmPFC activation and both (i) subjective craving and (ii) problematic drinking. CONCLUSIONS: The trait of negative urgency is associated with neural responses to alcohol cues in the vmPFC, a region involved in reward value and emotion-guided decision-making. This suggests that negative urgency might alter subjective craving and brain regions involved in coding reward value

Brain Connectivity-Informed Regularization Methods for Regression

One of the challenging problems in brain imaging research is a principled incorporation of information from different imaging modalities. Frequently, each modality is analyzed separately using, for instance, dimensionality reduction techniques, which result in a loss of mutual information. We propose a novel regularization method to estimate the association between the brain structure features and a scalar outcome within the linear regression framework. Our regularization technique provides a principled approach to use external information from the structural brain connectivity and inform the estimation of the regression coefficients. Our proposal extends the classical Tikhonov regularization framework by defining a penalty term based on the structural connectivity-derived Laplacian matrix. Here, we address both theoretical and computational issues. The approach is first illustrated using simulated data and compared with other penalized regression methods. We then apply our regularization method to study the associations between the alcoholism phenotypes and brain cortical thickness using a diffusion imaging derived measure of structural connectivity. Using the proposed methodology in 148 young male subjects with a risk for alcoholism, we found a negative associations between cortical thickness and drinks per drinking day in bilateral caudal anterior cingulate cortex, left lateral OFC, and left precentral gyrus