Mindfulness-oriented recovery enhancement in opioid use disorder: Extended emotional regulation and neural effects and immediate effects of guided meditation in a pilot sample.

OBJECTIVE: Mindfulness-Oriented Recovery Enhancement (MORE) is an efficacious intervention to aid recovery from substance use disorder. This study in a pilot sample of individuals in treatment for opioid use disorder (OUD) characterizes longer-term changes after the MORE intervention and immediate effects of a brief MORE guided meditation session. DESIGN: Twelve female participants in residential treatment for OUD completed an 8-week MORE intervention. Participants completed two sessions: one before and one after the 8-week MORE intervention. Each session included an emotional regulation questionnaire outside an MRI scanner first and then a 10-minute guided MORE meditation inside the scanner during which functional magnetic resonance imaging (fMRI) data were collected. Emotional regulation was measured after 8-weeks of MORE intervention. In addition, functional connectivity (i.e. correlated fMRI signal) between regions in a hypothesized affect regulation network was measured during the meditation state to assess change in brain network function due to 8-weeks of MORE. For each 10-min guided meditation, we also assessed their mood and opioid craving. RESULTS: Nine participants completed all measurements. Participants' emotional regulation difficulty significantly decreased after 8-weeks of MORE intervention. Furthermore, after 8-weeks of MORE, there was significantly increased connectivity between left ventromedial prefrontal cortex and left amygdala and between left ventrolateral prefrontal cortex and left nucleus accumbens captured during a meditation state. In both sessions, positive mood significantly increased after 10-min of guided mediation, however opioid craving was not significantly influenced. CONCLUSIONS: This pilot study characterizes potential benefits of 8-week MORE intervention in improving emotional regulation difficulty and brain function. A 10-min guided MORE meditation may immediately improve mood, with potential to reduce acute stress- or cue-provoked craving. These results warrant future studies with larger sample size.

Efficacy of a Brief Mindfulness Intervention in Underserved Individuals Receiving Inpatient Treatment for Opioid Use Disorder: A Pilot Study.

Introduction A mindfulness intervention is a mind-body complementary health approach that focuses on the relationships between mind, body, brain, and behavior. Mindfulness-Based Stress Reduction (MBSR) and similar mindfulness programs have been shown to decrease drug craving and relapse and improve emotional regulation, stress, pain, and anxiety. To our knowledge, a very limited number of studies have examined its efficacy in individuals from underserved populations. Underserved populations experience disparities in healthcare access, and as a result, see poorer addiction-related outcomes. The goal of this pilot study was to utilize an evidence-based, neuroscience-informed brief mindfulness intervention to improve mental health and decrease substance use behavior in a vulnerable, underserved population in New Jersey suffering from opioid use disorder (OUD). Methods We implemented a brief MBSR intervention in 15 underserved individuals undergoing inpatient medication-assisted treatment (MAT) for OUD. Individuals received weekly intervention sessions lasting one hour over six weeks. Furthermore, they practiced mindfulness for 10 minutes daily. Participants completed pre-and post-mindfulness intervention surveys to examine their mental well-being, drug craving, perceived stress, and emotional regulation. Results Within-subjects t-test results showed that compared to pre-intervention, participants showed significantly decreased perceived stress (t(14) =2.401, p=.015) and significantly decreased difficulty in emotional regulation (t(13) =3.426, p=.002 ) at post-intervention. They also showed significantly decreased drug craving post-intervention (t(14) =5.501, p=.<001). Anxiety decreased post-intervention but was not statistically significant (t(14) =1.582, p=.068). Conclusion This pilot study demonstrates that a brief mindfulness intervention can be effective for underserved individuals with OUD. Consistent with our hypothesis, results showed that a six-week mindfulness intervention could reduce everyday stress, drug craving, and difficulties in emotional regulation. In the future, a large-scale randomized control trial should be conducted with a control group to demonstrate the efficacy of this useful intervention.

Structural MRI and functional connectivity features predict current clinical status and persistence behavior in prescription opioid users.

Prescription opioid use disorder (POUD) has reached epidemic proportions in the United States, raising an urgent need for diagnostic biological tools that can improve predictions of disease characteristics. The use of neuroimaging methods to develop such biomarkers have yielded promising results when applied to neurodegenerative and psychiatric disorders, yet have not been extended to prescription opioid addiction. With this long-term goal in mind, we conducted a preliminary study in this understudied clinical group. Univariate and multivariate approaches to distinguishing between POUD (n = 26) and healthy controls (n = 21) were investigated, on the basis of structural MRI (sMRI) and resting-state functional connectivity (restFC) features. Univariate approaches revealed reduced structural integrity in the subcortical extent of a previously reported addiction-related network in POUD subjects. No reliable univariate between-group differences in cortical structure or edgewise restFC were observed. Contrasting these mixed univariate results, multivariate machine learning classification approaches recovered more statistically reliable group differences, especially when sMRI and restFC features were combined in a multi-modal model (classification accuracy = 66.7%, p < .001). The same multivariate multi-modal approach also yielded reliable prediction of individual differences in a clinically relevant behavioral measure (persistence behavior; predicted-to-actual overlap r = 0.42, p = .009). Our findings suggest that sMRI and restFC measures can be used to reliably distinguish the neural effects of long-term opioid use, and that this endeavor numerically benefits from multivariate predictive approaches and multi-modal feature sets. This can serve as theoretical proof-of-concept for future longitudinal modeling of prognostic POUD characteristics from neuroimaging features, which would have clearer clinical utility.

Neural responses to negative events and subsequent persistence behavior differ in individuals recovering from opioid use disorder compared to controls.

Background: Negative emotion is associated with substance craving and use in individuals recovering from substance use disorders, including prescription opioid use disorder (POUD). Decisions to abandon or persist towards a goal after negative emotion-eliciting events, and neural responses that shape such decisions, may be important in maintaining recovery from POUD.Objectives: We examined differences in neural responses to negative events and subsequent persistence decisions in individuals recovering from POUD without a history of a substance use disorder. Methods: 20 individuals with POUD (POUD group: 4 females, abstinent 2-3 weeks after admission to an inpatient treatment facility post-detoxification, no other substance use disorder), and 20 individuals with no substance use history (control group: 6 females) completed a persistence-after-setbacks task during functional magnetic resonance imaging. Participants advanced along a path toward a reward; after encountering each negative event (i.e., progress-erasing setback), participants made decisions to persist or abandon the path. Persistence decision rates were compared between groups and blood-oxygen-level-dependent signal to negative events was analyzed within a striatum region of interest (ROI) as well as whole-brain.Results: The POUD group persisted less (t(38) = 2.293, p = .028, d = .725) and showed lower striatum (left ventral putamen) signal to negative events compared to the control group (p < .05, corrected for striatum ROI).Conclusions: In POUD, neural and behavioral responses to negative events differ from controls. These differences are a target for research to address whether POUD treatment increases persistence and striatum responses to negative events and improves recovery outcomes.

Modeling Causal Relationships among Brain Areas in the Mesocorticolimbic System during Resting-State in Cocaine Users Utilizing a Graph Theoretic Approach.

OBJECTIVE: While effective connectivity (EC, causal interaction) between brain areas has been investigated in chronic users of cocaine as they view cocaine pictures cues, no study has examined EC while they take part in a resting-state scan. This resting-state fMRI study aims to investigate the causal interaction among brain areas in the mesocorticolimbic system (MCLS), which is involved in reward and motivation, in cocaine users (vs. controls). METHOD: Twenty cocaine users and 17 healthy controls finished a structural and a resting-state scan. Mean voxel-based time series data were obtained from brain regions of interest (ROIs) from the MCLS, and were input into a Bayesian search algorithm called IMaGES. RESULTS: The causal interaction pattern was different between the two groups. The feed-forward pattern found in cocaine smokers, between 7 ROIs of the MCLS during resting-state [ventral tegmental area (VTA)→hippocampus (HIPP)→ventral striatum (VenStri)→orbital frontal cortex (OFC), medial frontal cortex (MFC), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC)], was absent in controls. That is, the subcortical VenStri area had a causal influence on four cortical brain areas only in cocaine users. CONCLUSIONS: During the resting-state scan, the VTA of cocaine smokers abstinent for at least 72 hours, but not controls, begins causal connections to limbic, midbrain, and frontal regions in the MCLS in a feed-forward manner. Following replication, further studies may assess if changes over time in EC during resting-state predict cocaine treatment efficacy and outcome.

Effective Connectivity within the Mesocorticolimbic System during Resting-State in Cocaine Users.

Objective: Although effective connectivity between brain regions has been examined in cocaine users during tasks, no effective connectivity study has been conducted on cocaine users during resting-state. In the present functional magnetic resonance imaging study, we examined effective connectivity in resting-brain, between the brain regions within the mesocorticolimbic dopamine system, implicated in reward and motivated behavior, while the chronic cocaine users and controls took part in a resting-state scan by using a spectral Dynamic causal modeling (spDCM) approach. Method: As part of a study testing cocaine cue reactivity in cocaine users (Ray et al., 2015b), 20 non-treatment seeking cocaine-smoking (abstinent for at least 3 days) and 17 control participants completed a resting state scan and an anatomical scan. A mean voxel-based time series data extracted from four key brain areas (ventral tegmental area, VTA; nucleus accumbens, NAc; hippocampus, medial frontal cortex) within the mesocorticolimbic dopamine system during resting-state from the cocaine and control participants were used as input to the spDCM program to generate spDCM analysis outputs. Results: Compared to the control group, the cocaine group had higher effective connectivity from the VTA to NAc, hippocampus and medial frontal cortex. In contrast, the control group showed a higher effective connectivity from the medial frontal cortex to VTA, from the NAc to medial frontal cortex, and on the hippocampus self-loop. Conclusions: The present study is the first to show that during resting-state in abstaining cocaine users compared to controls, the VTA initiates an enhanced effective connectivity to NAc, hippocampus and medial frontal cortex areas within the mesocorticolimbic dopamine system, the brain's reward system. Future studies of effective connectivity analysis during resting-state may eventually be used to monitor treatment outcome.

Drinkers' memory bias for alcohol picture cues in explicit and implicit memory tasks.

BACKGROUND: Alcohol cues can bias attention and elicit emotional reactions, especially in drinkers. Yet, little is known about how alcohol cues affect explicit and implicit memory processes, and how memory for alcohol cues is affected by acute alcohol intoxication. METHODS: Young adult participants (N=161) were randomly assigned to alcohol, placebo, or control beverage conditions. Following beverage consumption, they were shown neutral, emotional and alcohol-related pictures cues. Participants then completed free recall and repetition priming tasks to test explicit and implicit memory, respectively, for picture cues. Average blood alcohol concentration for the alcohol group was 74±13mg/dl when memory testing began. Two mixed linear model analyses were conducted to examine the effects of beverage condition, picture cue type, and their interaction on explicit and implicit memory. RESULTS: Picture cue type and beverage condition each significantly affected explicit recall of picture cues, whereas only picture cue type significantly influenced repetition priming. Individuals in the alcohol condition recalled significantly fewer pictures than those in other conditions, regardless of cue type. Both free recall and repetition priming were greater for emotional and alcohol-related cues compared to neutral picture cues. No interaction effects were detected. CONCLUSIONS: Young adult drinkers showed enhanced explicit and implicit memory processing of alcohol cues compared to emotionally neutral cues. This enhanced processing for alcohol cues was on par with that seen for positive emotional cues. Acute alcohol intoxication did not alter this preferential memory processing for alcohol cues over neutral cues.

Modeling Causal Relationship Between Brain Regions Within the Drug-Cue Processing Network in Chronic Cocaine Smokers.

The cues associated with drugs of abuse have an essential role in perpetuating problematic use, yet effective connectivity or the causal interaction between brain regions mediating the processing of drug cues has not been defined. The aim of this fMRI study was to model the causal interaction between brain regions within the drug-cue processing network in chronic cocaine smokers and matched control participants during a cocaine-cue exposure task. Specifically, cocaine-smoking (15M; 5F) and healthy control (13M; 4F) participants viewed cocaine and neutral cues while in the scanner (a Siemens 3 T magnet). We examined whole brain activation, including activation related to drug-cue processing. Time series data extracted from ROIs determined through our General Linear Model (GLM) analysis and prior publications were used as input to IMaGES, a computationally powerful Bayesian search algorithm. During cocaine-cue exposure, cocaine users showed a particular feed-forward effective connectivity pattern between the ROIs of the drug-cue processing network (amygdala → hippocampus → dorsal striatum → insula → medial frontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex) that was not present when the controls viewed the cocaine cues. Cocaine craving ratings positively correlated with the strength of the causal influence of the insula on the dorsolateral prefrontal cortex in cocaine users. This study is the first demonstration of a causal interaction between ROIs within the drug-cue processing network in cocaine users. This study provides insight into the mechanism underlying continued substance use and has implications for monitoring treatment response.

Altered Functional Connectivity Strength in Abstinent Chronic Cocaine Smokers Compared to Healthy Controls.

Past research involving cocaine and resting-state functional connectivity (RSFC) has shown altered functional connectivity within the frontal and between the frontal and other cortical and subcortical brain regions in chronic users of cocaine. However, there have been discrepancies in literature regarding the relationship between RSFC between brain regions and cocaine use behavior. This study explored the RSFC between brain regions in cocaine smokers abstinent from cocaine use for 72 h and healthy controls. Also, the relationship between RSFC between brain regions and various cocaine use measures (cocaine use duration; frequency, and money spent on cocaine/week) was examined. Twenty chronic cocaine users and 17 controls completed a resting-state scan and an anatomical MPRAGE scan. Group independent component analysis performed on functional magnetic resonance imaging data identified 13 ICs pertaining to distinct resting-state networks, and group-level differences were examined. To examine inter-network functional connectivity between brain regions, these 13 ICs were divided into 61 distinct regions of interest (ROIs). Correlations were calculated between 61 ROI time series. For the ROI pairs that significantly differed from controls in connectivity strength, correlations were computed between connectivity strength and cocaine use measures. Results showed an enhanced RSFC within the sensory motor cortex and the left frontal-parietal network in cocaine users than controls. An increased inter-network RSFC between frontal-temporal and frontal-parietal brain regions, and a decreased RSFC between parietal-parietal, occipital-limbic, occipital-occipital, and occipital-parietal brain regions was found in cocaine users. This study demonstrated that intra-network connectivity strength of sensory motor cortex was negatively correlated with years of cocaine use. Inter-network connectivity strength between occipital-limbic brain regions was positively correlated with years of cocaine use, while connectivity strength within occipital brain regions was negatively related to cocaine use frequency and money spent on cocaine per week in abstinent cocaine users.

Memory for drug-related visual stimuli in young adult, cocaine-dependent polydrug users.

BACKGROUND AND OBJECTIVES: Implicit (unconscious) and explicit (conscious) memory associations with drugs have been examined primarily using verbal cues. However, drug seeking, drug use behaviors, and relapse in chronic cocaine and other drug users are frequently triggered by viewing substance-related visual cues in the environment. We thus examined implicit and explicit memory for drug picture cues to understand the relative extent to which conscious and unconscious memory facilitation of visual drug cues occurs during cocaine dependence. METHODS: Memory for drug-related and neutral picture cues was assessed in 14 inpatient cocaine-dependent polydrug users and a comparison group of 21 young adults with limited drug experience (n = 35). Participants completed picture cue exposure, free recall and recognition tasks to assess explicit memory, and a repetition priming task to assess implicit memory. RESULTS: Drug cues, compared to neutral cues, were better explicitly recalled and implicitly primed, and especially so in the cocaine group. In contrast, neutral cues were better explicitly recognized, and especially in the control group. CONCLUSION: Certain forms of explicit and implicit memory for drug cues were enhanced in cocaine users compared to controls when memory was tested a short time following cue exposure. Enhanced unconscious memory processing of drug cues in chronic cocaine users may be a behavioral manifestation of heightened drug cue salience that supports drug seeking and taking. There may be value in expanding intervention techniques to utilize cocaine users' implicit memory system.

Negative mood and alcohol problems are related to respiratory dynamics in young adults.

This study examined the relationship of negative affect and alcohol use behaviors to baseline respiration and respiratory response to emotional challenge in young adults (N = 138, 48 % women). Thoracic-to-abdominal ratio, respiratory frequency and variability, and minute volume ventilation were measured during a low-demand baseline task, and emotional challenge (viewing emotionally-valenced, emotionally-neutral, and alcohol-related pictures). Negative mood and alcohol problems principal components were generated from self-report measures of negative affect and mood, alcohol use, and use-related problems. The negative mood component was positively related to a thoracic bias when measured throughout the study (including baseline and picture exposure). There was generally greater respiratory activity in response to the picture cues, although not specifically in response to the content (emotional or alcohol-related) of the picture cues. The alcohol problems component was positively associated with respiratory reactivity to picture cues, when baseline breathing patterns were controlled. Self-report arousal data indicated that higher levels of negative mood, but not alcohol problems, were associated with greater arousal ratings overall. However, those with alcohol problems reported greater arousal to alcohol cues, compared to emotionally neutral cues. These results are consistent with theories relating negative affect and mood to breathing patterns as well as the relationship between alcohol problems and negative emotions, suggesting that the use of respiratory interventions may hold promise for treating problems involving negative affect and mood, as well as drinking problems.

Memory for emotional picture cues during acute alcohol intoxication.

OBJECTIVE: Memory affects behavior by allowing events to be anticipated and goals to be planned based on previous experiences. Emotional memory, in particular, is thought to play a central role in behavior in general and in drinking behavior in particular. Alcohol intoxication has been shown to disrupt intentional, conscious memory, but not unintentional, implicit memory for neutral stimuli; however, its effects on emotional memory are not well understood. This study examined whether alcohol intoxication affected memory for emotionally valenced stimuli by testing explicit recall and implicit repetition priming of emotional picture cues. METHOD: Participants were 36 young adults (21-24 years old, 16 women) who received an alcohol, placebo, or no-alcohol beverage. Both cue exposure and memory testing occurred after beverage consumption (i.e., during intoxication for the alcohol group). RESULTS: Alcohol intoxication impaired explicit recall of all cue types but did not impair implicit repetition priming. Emotionally negative and positive cues were more often recalled compared with neutral cues across all beverage groups, and emotionally negative cues demonstrated more priming than emotionally positive or neutral cues in all beverage groups. CONCLUSIONS: Alcohol intoxication disrupted effortful recall of all cues, although the relative memory advantage of emotionally valenced over-neutral stimuli remained even after drinking. The effects of alcohol on unintentional memory priming were not statistically significant, but the effects of emotionally negative cues were. Further research is needed to better understand alcohol intoxication and emotional valence effects on memory processes during implicit memory tasks and the possibility that negative mood facilitates memory priming of negative emotional stimuli.

Cocaine, Appetitive Memory and Neural Connectivity.

This review examines existing cognitive experimental and brain imaging research related to cocaine addiction. In section 1, previous studies that have examined cognitive processes, such as implicit and explicit memory processes in cocaine users are reported. Next, in section 2, brain imaging studies are reported that have used chronic users of cocaine as study participants. In section 3, several conclusions are drawn. They are: (a) in cognitive experimental literature, no study has examined both implicit and explicit memory processes involving cocaine related visual information in the same cocaine user, (b) neural mechanisms underlying implicit and explicit memory processes for cocaine-related visual cues have not been directly investigated in cocaine users in the imaging literature, and (c) none of the previous imaging studies has examined connectivity between the memory system and craving system in the brain of chronic users of cocaine. Finally, future directions in the field of cocaine addiction are suggested.

fMRI BOLD response of high-risk college students (Part 2): during memory priming of alcohol, marijuana and polydrug picture cues.

AIMS: This study examined brain activity using functional magnetic resonance imaging (fMRI) and reaction time (RT) during an implicit repetition priming memory task involving alcohol, polydrug, marijuana and emotional picture cues. METHODS: Participants were 5 male and 5 female high-risk college students who had just participated in a cue exposure study (Ray et al., this issue). fMRI and RT data were collected while participants made decisions about previously seen and new picture cues. RESULTS: Both behavioral RT and brain imaging data revealed strong memory priming for drug and alcohol cues. Neurologically, a repetition priming effect (suppression in neural activity for repeated cues) was observed in response to alcohol cues in the left prefrontal, bilateral occipital, and bilateral occipitotemporal regions, as well as right insula and right precuneus (Z ranged from 3.03 to 3.31 P < 0.05). Polydrug cues elicited priming in the occipital and temporal areas, and marijuana cues in the occipital area. CONCLUSIONS: Prefrontal and insular cortex involvement both in reactivity to alcohol cues (Ray et al., this issue) and subsequent implicit memory processing of these cues, as found in this study, suggests their potential role in the maintenance of high-risk alcohol use behaviors.

fMRI BOLD response in high-risk college students (Part 1): during exposure to alcohol, marijuana, polydrug and emotional picture cues.

AIM: This functional magnetic resonance imaging (fMRI) study examined reactivity to alcohol, polydrug, marijuana and emotional picture cues in students who were referred to a college alcohol and drug assistance program. METHODS: The fMRI data of 10 participants (5 females; 5 males) were collected while they viewed standardized emotional and appetitive cues. RESULTS: Positive and negative emotional cues produced greater activity than neutral cues in the expected brain areas. Compared with neutral cues, alcohol cues produced greater brain activation in the right insula, left anterior cingulate, left caudate and left prefrontal cortex (Z = 2.01, 1.86, 1.82, 1.81, respectively; P < 0.05). Drug cues produced significantly greater left prefrontal activity compared with neutral cues, with polydrug cues activating the right insula and marijuana cues activating left anterior cingulate. CONCLUSIONS: Students at-risk for alcohol abuse showed neural reactivity to alcohol cues in four brain regions, which is consistent with their greater use of alcohol. Insula activation to appetitive cues may be an early marker of risk for progression to alcohol/drug abuse.

Gender differences in acute alcohol effects on self-regulation of arousal in response to emotional and alcohol-related picture cues.

Basic mechanisms through which men and women self-regulate arousal have received little attention in human experimental addiction research, although stress-response-dampening and craving theories suggest an important role of emotional arousal in motivating alcohol use. This study examined gender differences in the effects of acute alcohol intoxication on psychophysiological and self-reported arousal in response to emotionally negative, positive, and neutral, and alcohol-related, picture cues. Thirty-six social drinkers (16 women) were randomly assigned to an alcohol, placebo, or control beverage group and exposed to picture cues every 10 s (0.1 Hz presentation frequency). Psychophysiological arousal was assessed via a 0.1-Hz heart rate variability (HRV) index. A statistically significant beverage group-by-gender interaction effect on psychophysiological, but not self-reported, arousal was found. The 0.1-Hz HRV responses to picture cues were suppressed by alcohol only in men. This gender-specific suppression pattern did not differ significantly across picture cue types. There were no significant gender differences in the placebo or control group. Greater dampening of arousal by alcohol intoxication in men, compared with women, may contribute to men's greater tendency to use alcohol to cope with stress.

Heart rate variability response to alcohol, placebo, and emotional picture cue challenges: effects of 0.1-Hz stimulation.

Heart rate variability (HRV) supports emotion regulation and is reduced by alcohol. Based on the resonance properties of the cardiovascular system, a new 0.1-Hz methodology was developed to present emotional stimuli and assess HRV reaction in participants (N=36) randomly assigned to an alcohol, placebo, or control condition. Blocked picture cues (negative, positive, neutral) were presented at a rate of 5 s on, 5 s off (i.e., 0.1-Hz frequency). SDNN, pNN50, and HF HRV were reduced by alcohol, compared to the placebo and control. The 0.1-Hz HRV index was diminished by alcohol and placebo, suggesting that autonomic regulation can be affected by cognitive expectancy. The 0.1-Hz HRV index and pNN50 detected changes in arousal during emotional compared to neutral cues, and the 0.1-Hz HRV index was most sensitive to negative valence. The 0.1-Hz HRV methodology may be useful for studying the intersection of cognition, emotion, and autonomic regulation.

An investigation of time course of category and semantic priming.

Low semantically similar exemplars in a category demonstrate the category-priming effect through priming of the category (i.e., exemplar-category-exemplar), whereas high semantically similar exemplars in the same category demonstrate the semantic-priming effect (i.e., direct activation of one high semantically similar exemplar by another). The author asked whether the category- and semantic-priming effects are based on a common memory process. She examined this question by testing the time courses of category- and semantic-priming effects. She tested participants on either category- or semantic-priming paradigm at 2 different time intervals (6 min and 42 min) by using a lexical decision task using exemplars from categories. Results showed that the time course of category priming was different from that of semantic priming. The author concludes that these 2 priming effects are based on 2 separate memory processes.

Two routes for activation in the priming of categorical coordinates.

The authors operationalized category priming as participants' recognition facilitation of nonstudied, low semantically similar exemplars by studied exemplars in a category. The existing literature either does not examine the effect of studied exemplars on nonstudied exemplars in a category or fails to show an appreciable amount of category priming. In 2 experiments, the authors demonstrated a unique process to account for the category priming effect and distinguish it from the semantic priming effect, facilitation of semantically similar exemplars, in the context of a category. In Experiment 1A, the authors used a multidimensional scaling technique to examine participants' internal structure of different categories. In Experiment 1B, the authors used a lexical decision task that used these internal structures to show that semantic encoding of category exemplars causes activation of existing category knowledge in memory. Consequently, participants easily recognized nonstudied, low semantically similar exemplars in a category. However, recognition facilitation between high semantically similar exemplars did not require category knowledge activation.