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1.  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.
PMCID: PMC2930251  PMID: 20729530
2.  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.
PMCID: PMC2930252  PMID: 20729527
3.  Implicit Memory for Object Locations Depends on Reactivation of Encoding-Related Brain Regions 
Human brain mapping  2011;32(1):32-50.
This study explored the correspondence between implicit memory and the reactivation of encoding-related brain regions. By using a classification method, we examined whether reactivation reflects only the similarities between study and test or voxels at the reactivated regions are diagnostic of facilitation in the implicit memory task. A simple detection task served as incidental encoding of object–location pairings. A subsequent visual search task served as the indirect (implicit) test of memory. Subjects did not know that their memory would be tested. Half of the subjects were unaware that some stimuli in the search task are the same as those that had appeared during the detection task. Another group of subjects was made aware of this relationship at the onset of the visual search task. Memory performance was superior for the study-test aware, compared to study-test unaware, subjects. Brain reactivation was calculated using a conjunction analysis implemented through overlaying the neural activity at encoding and testing. The conjunction analysis revealed that implicit memory in both groups of subjects was associated with reactivation of parietal and occipital brain regions. We were able to classify study-test aware and study-test unaware subjects based on the per-voxel reactivation values representing the neural dynamics between encoding and test. The classification results indicate that neural dynamics between encoding and test accounts for the differences in implicit memory. Overall, our study demonstrates that implicit memory performance requires and depends upon reactivation of encoding-related brain regions.
PMCID: PMC3065329  PMID: 21157878
implicit memory; incidental learning; reactivation; object locations; fMRI; SMLR classifier
4.  Investigation of Crohn’s Disease Risk Loci in Ulcerative Colitis Further Defines Their Molecular Relationship 
Gastroenterology  2008;136(2):523-9.e3.
Background & Aims
Identifying shared and disease-specific susceptibility loci for Crohn’s disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD.
We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls.
Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 × 10-8; odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD.
Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis.
PMCID: PMC2675137  PMID: 19068216
5.  Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn’s disease 
Nature genetics  2008;40(6):710-712.
We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn’s disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn’s disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.
PMCID: PMC2719289  PMID: 18438406

Results 1-5 (5)