From brain to body: exploring the connection between altered reward processing and physical fitness in schizophrenia.

Understanding the underlying mechanisms that link psychopathology and physical comorbidities in schizophrenia is crucial since decreased physical fitness and overweight pose major risk factors for cardio-vascular diseases and decrease the patients' life expectancies. We hypothesize that altered reward anticipation plays an important role in this. We implemented the Monetary Incentive Delay task in a MR scanner and a fitness test battery to compare schizophrenia patients (SZ, n = 43) with sex- and age-matched healthy controls (HC, n = 36) as to reward processing and their physical fitness. We found differences in reward anticipation between SZs and HCs, whereby increased activity in HCs positively correlated with overall physical condition and negatively correlated with psychopathology. On the other handy, SZs revealed stronger activity in the posterior cingulate cortex and in cerebellar regions during reward anticipation, which could be linked to decreased overall physical fitness. These findings demonstrate that a dysregulated reward system is not only responsible for the symptomatology of schizophrenia, but might also be involved in physical comorbidities which could pave the way for future lifestyle therapy interventions.

Integration of Prior Expectations and Suppression of Prediction Errors During Expectancy-Induced Pain Modulation: The Influence of Anxiety and Pleasantness.

Pain perception arises from the integration of prior expectations with sensory information. Although recent work has demonstrated that treatment expectancy effects (e.g., placebo hypoalgesia) can be explained by a Bayesian integration framework incorporating the precision level of expectations and sensory inputs, the key factor modulating this integration in stimulus expectancy-induced pain modulation remains unclear. In a stimulus expectancy paradigm combining emotion regulation in healthy male and female adults, we found that participants' voluntary reduction in anticipatory anxiety and pleasantness monotonically reduced the magnitude of pain modulation by negative and positive expectations, respectively, indicating a role of emotion. For both types of expectations, Bayesian model comparisons confirmed that an integration model using the respective emotion of expectations and sensory inputs explained stimulus expectancy effects on pain better than using their respective precision. For negative expectations, the role of anxiety is further supported by our fMRI findings that (1) functional coupling within anxiety-processing brain regions (amygdala and anterior cingulate) reflected the integration of expectations with sensory inputs and (2) anxiety appeared to impair the updating of expectations via suppressed prediction error signals in the anterior cingulate, thus perpetuating negative expectancy effects. Regarding positive expectations, their integration with sensory inputs relied on the functional coupling within brain structures processing positive emotion and inhibiting threat responding (medial orbitofrontal cortex and hippocampus). In summary, different from treatment expectancy, pain modulation by stimulus expectancy emanates from emotion-modulated integration of beliefs with sensory evidence and inadequate belief updating.

Enhanced motor network engagement during reward gain anticipation in fibromyalgia.

Reward motivation is essential in shaping human behavior and cognition. Both reward motivation and reward brain circuits are altered in chronic pain conditions, including fibromyalgia. In this study of fibromyalgia patients, we used a data-driven independent component analysis (ICA) approach to investigate how brain networks contribute to altered reward processing. From females with fibromyalgia (N = 24) and female healthy controls (N = 24), we acquired fMRI data while participants performed a monetary incentive delay (MID) reward task. After analyzing the task-based fMRI data using ICA to identify networks, we analyzed 3 networks of interest: motor network (left), value-driven attention network, and basal ganglia network. Then, we evaluated correlation coefficients between each network timecourse versus a task-based timecourse which modeled gain anticipation. Compared to controls, the fibromyalgia cohort demonstrated significantly stronger correlation between the left motor network timecourse and the gain anticipation timecourse, indicating the left motor network was more engaged with gain anticipation in fibromyalgia. In an exploratory analysis, we compared motor network engagement during early versus late phases of gain anticipation. Across cohorts, greater motor network engagement (i.e., stronger correlation between network and gain anticipation) occurred during the late timepoint, which reflected enhanced motor preparation immediately prior to response. Consistent with the main results, patients exhibited greater engagement of the motor network during both early and late phases compared with healthy controls. Visual-attention and basal ganglia networks revealed similar engagement in the task across groups. As indicated by post-hoc analyses, motor network engagement was positively related to anxiety and negatively related to reward responsiveness. In summary, we identified enhanced reward-task related engagement of the motor network in fibromyalgia using a novel data-driven ICA approach. Enhanced motor network engagement in fibromyalgia may relate to impaired reward motivation, heightened anxiety, and possibly to altered motor processing, such as restricted movement or dysregulated motor planning.

Neuroimaging-based evidence for sympathetic correlation between brain activity and peripheral vasomotion during pain anticipation.

Anticipation of pain engenders anxiety and fear, potentially shaping pain perception and governing bodily responses such as peripheral vasomotion through the sympathetic nervous system (SNS). Sympathetic innervation of vascular tone during pain perception has been quantified using a peripheral arterial stiffness index; however, its innervation role during pain anticipation remains unclear. This paper reports on a neuroimaging-based study designed to investigate the responsivity and attribution of the index at different levels of anticipatory anxiety and pain perception. The index was measured in a functional magnetic resonance imaging experiment that randomly combined three visual anticipation cues and painful stimuli of two intensities. The peripheral and cerebral responses to pain anticipation and perception were quantified to corroborate bodily responsivity, and their temporal correlation was also assessed to identify the response attribution of the index. Contrasting with the high responsivity across levels of pain sensation, a low responsivity of the index across levels of anticipatory anxiety revealed its specificity across pain experiences. Discrepancies between the effects of perception and anticipation were validated across regions and levels of brain activity, providing a brain basis for peripheral response specificity. The index was also characterized by a 1-s lag in both anticipation and perception of pain, implying top-down innervation of the periphery. Our findings suggest that the SNS responds to pain in an emotion-specific and sensation-unbiased manner, thus enabling an early assessment of individual pain perception using this index. This study integrates peripheral and cerebral hemodynamic responses toward a comprehensive understanding of bodily responses to pain.

Expected events dilate subjective duration in the auditory modality: Effects of predictability and expectation on time perception.

In timing research, repeated stimuli have been shown to have a shortening effect on time perception compared to novel stimuli. This finding had been attributed to repeated stimuli being more expected and, thus, less arousing and/or attended, or eliciting less neuronal activation due to repetition suppression, which results in temporal underestimation. However, more recent studies in the visual domain that disentangled effects of repetition and expectation suggest a more nuanced interpretation. In these studies, repetition led to temporal contraction while expectation caused subjective dilation of time. It was argued that expectations increase the perceptual strength of the stimulus, which leads to temporal overestimation, while repetitions reduce perceptual strength, which then leads to temporal underestimation. In the present study, we sought to further elaborate on these findings using auditory stimuli. In Experiment 1, we used an implicit method to induce expectation and manipulated the probability of stimulus repetition block-wise in a two-stimulus paradigm with auditory tones. Our findings were in line with the recent findings. When repetitions were less frequent, that is, less expected, we found clear evidence for perceived temporal contraction of repetitions. In contrast, when repetitions were more expected, the shortening effect of stimulus repetition on subjective duration disappeared. In Experiment 2, participants explicitly generated expectations about an upcoming tone in a temporal bisection paradigm. In trials, where expectations were fulfilled, presentation durations were perceived longer compared to trials with unfulfilled expectations. Our findings suggest that factors that increase the perceptual strength of a stimulus contribute to subjective temporal dilation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A neural signature for the subjective experience of threat anticipation under uncertainty.

Uncertainty about potential future threats and the associated anxious anticipation represents a key feature of anxiety. However, the neural systems that underlie the subjective experience of threat anticipation under uncertainty remain unclear. Combining an uncertainty-variation threat anticipation paradigm that allows precise modulation of the level of momentary anxious arousal during functional magnetic resonance imaging (fMRI) with multivariate predictive modeling, we train a brain model that accurately predicts subjective anxious arousal intensity during anticipation and test it across 9 samples (total n = 572, both gender). Using publicly available datasets, we demonstrate that the whole-brain signature specifically predicts anxious anticipation and is not sensitive in predicting pain, general anticipation or unspecific emotional and autonomic arousal. The signature is also functionally and spatially distinguishable from representations of subjective fear or negative affect. We develop a sensitive, generalizable, and specific neuroimaging marker for the subjective experience of uncertain threat anticipation that can facilitate model development.

Reward anticipation-related neural activation following cued reinforcement in adults with psychotic psychopathology and biological relatives.

BACKGROUND: Schizophrenia is associated with hypoactivation of reward sensitive brain areas during reward anticipation. However, it is unclear whether these neural functions are similarly impaired in other disorders with psychotic symptomatology or individuals with genetic liability for psychosis. If abnormalities in reward sensitive brain areas are shared across individuals with psychotic psychopathology and people with heightened genetic liability for psychosis, there may be a common neural basis for symptoms of diminished pleasure and motivation. METHODS: We compared performance and neural activity in 123 people with a history of psychosis (PwP), 81 of their first-degree biological relatives, and 49 controls during a modified Monetary Incentive Delay task during fMRI. RESULTS: PwP exhibited hypoactivation of the striatum and anterior insula (AI) during cueing of potential future rewards with each diagnostic group showing hypoactivations during reward anticipation compared to controls. Despite normative task performance, relatives demonstrated caudate activation intermediate between controls and PwP, nucleus accumbens activation more similar to PwP than controls, but putamen activation on par with controls. Across diagnostic groups of PwP there was less functional connectivity between bilateral caudate and several regions of the salience network (medial frontal gyrus, anterior cingulate, AI) during reward anticipation. CONCLUSIONS: Findings implicate less activation and connectivity in reward processing brain regions across a spectrum of disorders involving psychotic psychopathology. Specifically, aberrations in striatal and insular activity during reward anticipation seen in schizophrenia are partially shared with other forms of psychotic psychopathology and associated with genetic liability for psychosis.

Blunted Neurobehavioral Loss Anticipation Predicts Relapse to Stimulant Drug Use.

BACKGROUND: Patients with stimulant use disorder experience high rates of relapse. While neurobehavioral mechanisms involved in initiating drug use have been studied extensively, less research has focused on relapse. METHODS: To assess motivational processes involved in relapse and diagnosis, we acquired functional magnetic resonance imaging responses to nondrug (monetary) gains and losses in detoxified patients with stimulant use disorder (n = 68) and community control participants (n = 42). In a prospective multimodal design, we combined imaging of brain function, brain structure, and behavior to longitudinally track subsequent risk for relapse. RESULTS: At the 6-month follow-up assessment, 27 patients remained abstinent, but 33 had relapsed. Patients with blunted anterior insula (AIns) activity during loss anticipation were more likely to relapse, an association that remained robust after controlling for potential confounds (i.e., craving, negative mood, years of use, age, and gender). Lower AIns activity during loss anticipation was associated with lower self-reported negative arousal to loss cues and slower behavioral responses to avoid losses, which also independently predicted relapse. Furthermore, AIns activity during loss anticipation was associated with the structural coherence of a tract connecting the AIns and the nucleus accumbens, as was functional connectivity between the AIns and nucleus accumbens during loss processing. However, these neurobehavioral responses did not differ between patients and control participants. CONCLUSIONS: Taken together, the results of the current study show that neurobehavioral markers predicted relapse above and beyond conventional self-report measures, with a cross-validated accuracy of 72.7%. These findings offer convergent multimodal evidence that implicates blunted avoidance motivation in relapse to stimulant use and may therefore guide interventions targeting individuals who are most vulnerable to relapse.

Lack of effect of methamphetamine on reward-related brain activity in healthy adults.

INTRODUCTION: Stimulant drugs are thought to alter processing of rewarding stimuli. However, the mechanisms by which they do this are not fully understood. METHOD: In this study we used EEG to assess effects of single doses of methamphetamine (MA) on neural responses during anticipation and receipt of reward in healthy volunteers. Healthy young men and women (N = 28) completed three sessions in which they received placebo, a low MA dose (10 mg) or a higher MA dose (20 mg) under double blind conditions. Subjective and cardiovascular measures were obtained, and EEG was used to assess brain activity during an electrophysiological version of the Monetary Incentive Delay (eMID) task. RESULTS: EEG measures showed expected patterns during anticipation and receipt of reward, and MA produced its expected effects on mood and cardiovascular function. However, MA did not affect EEG responses during either anticipation or receipt of rewards. CONCLUSIONS: These findings suggest that the effects of MA on EEG signals of reward processing are subtle, and not related to the drug's effects on subjective feelings of well-being. The findings contribute to our understanding of the neural effects of MA during behaviors related to reward.

Skill and experience impact neural activity during global and local biological motion processing.

During biological motion perception, individuals with perceptual experience learn to use more global processing, simultaneously extracting information from multiple body segments. Less experienced observers may use more local processing of individual body segments. The parietal lobe (e.g., alpha and beta power) has been shown to be critical to global and local static stimulus perception. Therefore, in this paper, we examined how skill impacts motion processing by assessing behavioral and neural responses to degrading global or local motion information for soccer penalty kicks. Skilled (N = 21) and less skilled (N = 19) soccer players anticipated temporally occluded videos of penalty kicks under normal, blurred (degraded local information), or spatially occluded (hips-only; degraded global information) viewing conditions. EEG was used to measure parietal alpha and beta power. Skilled players outperformed less skilled players, albeit both skill groups were less accurate in the blurred and hips-only conditions. Skilled performers showed significant decreases in bilateral parietal beta power in the hips-only condition, suggesting a greater reliance on global motion information under normal viewing conditions. Additionally, the hips-only condition elicited significantly greater beta relative to alpha power (beta - alpha), lower beta power, and lower alpha power than the control condition for both skill groups, suggesting spatial occlusion elicited a shift towards more local processing. Our novel findings demonstrate that skill and experience impact how motion is processed.

Brain dynamics of visual anticipation during spatial occlusion tasks in expert tennis players.

Stimulus identification and action outcome understanding for a rapid and accurate response selection, play a fundamental role in racquet sports. Here, we investigated the neurodynamics of visual anticipation in tennis manipulating the postural and kinematic information associated with the body of opponents by means of a spatial occlusion protocol. Event Related Potentials (ERPs) were evaluated in two groups of professional tennis players (N = 37) with different levels of expertise, while they observed pictures of opponents and predicted the landing position as fast and accurately as possible. The observed action was manipulated by deleting different body districts of the opponent (legs, ball, racket and arm, trunk). Full body image (no occlusion) was used as control condition. The worst accuracy and the slowest response time were observed in the occlusion of trunk and ball. The former was associated with a reduced amplitude of the ERP components likely linked to body processing (the N1 in the right hemisphere) and visual-motor integration awareness (the pP1), as well as with an increase of the late frontal negativity (the pN2), possibly reflecting an effort by the insula to recover and/or complete the most correct sensory-motor representation. In both occlusions, a decrease in the pP2 may reflect an impairment of decisional processes upon action execution following sensory evidence accumulation. Enhanced amplitude of the P3 and the pN2 components were found in more experienced players, suggesting a greater allocation of resources in the process connecting sensory encoding and response execution, and sensory-motor representation.

Mothers exhibit higher neural activity in gaining rewards for their children than for themselves.

Are people willing to exert greater effort to obtain rewards for their children than they are for themselves? Although previous studies have demonstrated that social distance influences neural responses to altruistic reward processing, the distinction between winning rewards for oneself and winning them for one's child is unclear. In the present study, a group of 31 mothers performed a monetary incentive delay task in which cue-induced reward anticipations of winning a reward for themselves, their children and donation to a charity program were manipulated trial-wise, followed by performance-contingent feedback. Behaviorally, the anticipation of winning a reward for their children accelerated participants' responses. Importantly, the electroencephalogram results revealed that across the reward anticipation and consumption phases, the child condition elicited comparable or higher brain responses of participants than the self condition did. The source localization results showed that participants' reward anticipations for their children were associated with more activation in the social brain regions, compared to winning a reward for themselves or a charity donation. Overall, these findings advance our understanding of the neural mechanisms of altruistic reward processing and suggest that the priority of winning a reward for one's child may transcend the limits of the self-advantage effect in reward processing.

Prediction during language comprehension: what is next?

Prediction is often regarded as an integral aspect of incremental language comprehension, but little is known about the cognitive architectures and mechanisms that support it. We review studies showing that listeners and readers use all manner of contextual information to generate multifaceted predictions about upcoming input. The nature of these predictions may vary between individuals owing to differences in language experience, among other factors. We then turn to unresolved questions which may guide the search for the underlying mechanisms. (i) Is prediction essential to language processing or an optional strategy? (ii) Are predictions generated from within the language system or by domain-general processes? (iii) What is the relationship between prediction and memory? (iv) Does prediction in comprehension require simulation via the production system? We discuss promising directions for making progress in answering these questions and for developing a mechanistic understanding of prediction in language.

Temporally specific patterns of neural activity in interconnected corticolimbic structures during reward anticipation.

Functional neuroimaging studies indicate that interconnected parts of the subcallosal anterior cingulate cortex (ACC), striatum, and amygdala play a fundamental role in affect in health and disease. Yet, although the patterns of neural activity engaged in the striatum and amygdala during affective processing are well established, especially during reward anticipation, less is known about subcallosal ACC. Here, we recorded neural activity in non-human primate subcallosal ACC and compared this with interconnected parts of the basolateral amygdala and rostromedial striatum while macaque monkeys performed reward-based tasks. Applying multiple analysis approaches, we found that neurons in subcallosal ACC and rostromedial striatum preferentially signal anticipated reward using short bursts of activity that form temporally specific patterns. By contrast, the basolateral amygdala uses a mixture of both temporally specific and more sustained patterns of activity to signal anticipated reward. Thus, dynamic patterns of neural activity across populations of neurons are engaged in affect, especially in subcallosal ACC.

Aberrant reward dynamics in depression with anticipatory anhedonia.

OBJECTIVE: Previous studies have shown that anticipatory anhedonia is linked to abnormal reward processing. The present study aimed to explore the underlying neural mechanism of the influence of anticipatory anhedonia symptoms on reward processing. METHODS: Electrophysiological activities in the anticipatory and consummatory phase were recorded during the Monetary Incentive Delay (MID) task in 24 depressed high anticipatory anhedonia (HAA) patients, 25 depressed low anticipatory anhedonia (LAA) patients, and 29 healthy controls (HC). RESULTS: We suggested a significant condition × group interaction effect on feedback-related negativity (FRN) amplitudes during the consummatory phase, a smaller FRN in reward cue trails compared with neutral cue trail was revealed in the HC and LAA group, but such reward-related effect was not found in the HAA group. In addition, we found significant correlations between FRN, fb-P3 and cue-N1, cue-N2 in the HC group, besides, significant correlations between FRN, fb-P3 and cue-P2 was also revealed in the HC and LAA group. However, no significant correlation was found in HAA patients. CONCLUSIONS: Our results suggest that the link between the anticipatory and consummatory phase was interrupted in depressed HAA patients, which may be driven by the aberrant consummatory reward processing. SIGNIFICANCE: The current study is the first one to demonstrate the influence of anticipatory anhedonia symptom on the association between anticipatory and consummatory phase of reward process.

The neural correlates of continuous feedback processing.

Feedback processing is commonly studied by analyzing the brain's response to discrete rather than continuous events. Such studies have led to the hypothesis that rapid phasic midbrain dopaminergic activity tracks reward prediction errors (RPEs), the effects of which are measurable at the scalp via electroencephalography (EEG). Although studies using continuous feedback are sparse, recent animal work suggests that moment-to-moment changes in reward are tracked by slowly ramping midbrain dopaminergic activity. Some have argued that these ramping signals index state values rather than RPEs. Our goal here was to develop an EEG measure of continuous feedback processing in humans, then test whether its behavior could be accounted for by the RPE hypothesis. Participants completed a stimulus-response learning task in which a continuous reward cue gradually increased or decreased over time. A regression-based unmixing approach revealed EEG activity with a topography and time course consistent with the stimulus-preceding negativity (SPN), a scalp potential previously linked to reward anticipation and tonic dopamine release. Importantly, this reward-related activity depended on outcome expectancy: as predicted by the RPE hypothesis, activity for expected reward cues was reduced compared to unexpected reward cues. These results demonstrate the possibility of using human scalp-recorded potentials to track continuous feedback processing, and test candidate hypotheses of this activity.

Reward processing in schizophrenia and its relation to Mu opioid receptor availability and negative symptoms: A [11C]-carfentanil PET and fMRI study.

BACKGROUND: Reward processing deficits are a core feature of schizophrenia and are thought to underlie negative symptoms. Pre-clinical evidence suggests that opioid neurotransmission is linked to reward processing. However, the contribution of Mu Opioid Receptor (MOR) signalling to the reward processing abnormalities in schizophrenia is unknown. Here, we examined the association between MOR availability and the neural processes underlying reward anticipation in patients with schizophrenia using multimodal neuroimaging. METHOD: 37 subjects (18 with Schizophrenia with moderate severity negative symptoms and 19 age and sex-matched healthy controls) underwent a functional MRI scan while performing the Monetary Incentive Delay (MID) task to measure the neural response to reward anticipation. Participants also had a [11C]-carfentanil PET scan to measure MOR availability. RESULTS: Reward anticipation was associated with increased neural activation in a widespread network of brain regions including the striatum. Patients with schizophrenia had both significantly lower MOR availability in the striatum as well as striatal hypoactivation during reward anticipation. However, there was no association between MOR availability and striatal neural activity during reward anticipation in either patient or controls (Pearson's Correlation, controls df = 17, r = 0.321, p = 0.18, patients df = 16, r = 0.295, p = 0.24). There was no association between anticipation-related neural activation and negative symptoms (r = -0.120, p = 0.14) or anhedonia severity (social r = -0.365, p = 0.14 physical r = -0.120, p = 0.63). CONCLUSIONS: Our data suggest reduced MOR availability in schizophrenia might not underlie striatal hypoactivation during reward anticipation in patients with established illness. Therefore, other mechanisms, such as dopamine dysfunction, warrant further investigation as treatment targets for this aspect of the disorder.

Comparing monetary gain and loss in the monetary incentive delay task: EEG evidence.

What is more effective to guide behavior: The desire to gain or the fear to lose? Electroencephalography (EEG) studies have yielded inconsistent answers. In a systematic exploration of the valence and magnitude parameters in monetary gain and loss processing, we used time-domain and time-frequency-domain analyses to uncover the underlying neural processes. A group of 24 participants performed a monetary incentive delay (MID) task in which cue-induced anticipation of a high or low magnitude of gain or loss was manipulated trial-wise. Behaviorally, the anticipation of both gain and loss expedited responses, with gain anticipation producing greater facilitation than loss anticipation. Analyses of cue-locked P2 and P3 components revealed the significant valence main effect and valence × magnitude interaction: amplitude differences between high and low incentive magnitudes were larger with gain vs. loss cues. However, the contingent negative variation component was sensitive to incentive magnitude but did not vary with incentive valence. In the feedback phase, the RewP component exhibited reversed patterns for gain and loss trials. Time-frequency analyses revealed a large increase in delta/theta-ERS oscillatory activity in high- vs. low-magnitude conditions and a large decrease of alpha-ERD oscillatory activity in gain vs. loss conditions in the anticipation stage. In the consumption stage, delta/theta-ERS turned out stronger for negative than positive feedback, especially in the gain condition. Overall, our study provides new evidence for the neural oscillatory features of monetary gain and loss processing in the MID task, suggesting that participants invested more attention under gain and high-magnitude conditions vs. loss and low-magnitude conditions.

Neural bases of reward anticipation in healthy individuals with low, mid, and high levels of schizotypy.

A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior.

What's in Stock? Drug drought anticipation during COVID-19 among people who use drugs and service providers.

BACKGROUND: As with other areas of life, drug markets have been impacted by the COVID-19 pandemic and related restrictions. This article examines how structurally vulnerable people who use drugs (PWUD) experienced and adapted to changes in street drug markets caused by lockdown measures. METHODS: The article builds on ethnographic fieldwork in two Danish cities in 2020, including in-depth interviews with 22 PWUD, and interviews with 20 service providers, including low-threshold service providers and outreach workers. RESULTS: The most consistently reported effect of lockdown measures on local drug markets related to increases in cannabis prices. Accounts of changes in drug availability varied greatly, with some participants reporting changing availability while others described the situation as similar to pre-lockdown conditions. Rather than a long-term drug shortage, changes reported by participants related to the anticipated disruption of local markets and drug scarcity, restrictions in access to cash and sellers seeking to capitalize on the crisis. CONCLUSION: Although no long-term drug scarcity was seen, the anticipation of a shortage was sufficient to impact on local drug market dynamics. Heterogeneity in PWUDs' experiences of access to drug markets during lockdown can to some degree be explained in terms of their varied embeddedness in social networks. While local markets proved resilient to lockdown measures, PWUD less embedded in social networks were more vulnerable to shifts in drug availability and to sellers' over-pricing of drugs.