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Biomedical subjects

Steven M Berman

Publications and source records attributed to Steven M Berman.

11 recordsLinked to original sources

Sex differences in regional brain response to aversive pelvic visceral stimuli.

To explore sex differences in the response of seven brain regions to an aversive pelvic visceral stimulus, functional magnetic resonance images were acquired from 13 healthy adults (6 women) during 15 s of cued rectal distension at two pressures: 25 mmHg (uncomfortable), and 45 mmHg (mild pain), as well as during an expectation condition (no distension). Random-effects analyses combining subject data voxelwise found 45-mmHg pressure significantly activated the insular and anterior cingulate cortices in both sexes. In men only, the left thalamus and ventral striatum were also activated. Although all activations appeared more extensive in men, no sex difference attained significance. To explore the presence of deactivations, which are generally cancelled by more numerous activations when subjects are combined for each voxel, the number of activated voxels, number of deactivated voxels, and ratio of deactivated voxels to total voxels affected were assessed via random-effects, mixed-model analyses combining subject data at the region level. Greater insula activation in men compared with women was seen during the expectation condition and during the 25-mmHg distension. Greater deactivations in women were seen in the amygdala (25-mmHg distension) and midcingulate (45-mmHg distension). Women had a significantly higher proportion of deactivated voxels than men in all four subcortical structures during 25-mmHg distension. Greater familiarity of females with physiological pelvic visceral discomfort may have enhanced brain systems that dampen arousal networks during lower levels of discomfort.

Adult↗

P300 development during adolescence: effects of DRD2 genotype.

OBJECTIVE: Young boys at high risk for alcoholism by having a family history of alcoholism (FH+) have lower amplitude of the visual P300 event-related scalp potential. They have also been reported to have a slowing in the rate of P300 amplitude change during adolescence. The present study examined whether the change in P300 amplitude during adolescence in sons of alcoholics and nonalcoholics is affected by D2 dopamine receptor (DRD2) polymorphism. METHODS: P300 was elicited with a visual discrimination task from 71 adolescent sons of alcoholics and social drinkers (Time 1, T1). The task was readministered 2 years later (Time 2, T2). Comparisons were made between boys who had the DRD2 A1 allele (A1+) and boys who did not (A1-), and between boys with one or both parents being alcoholic (FH+) and boys having no alcoholic parents (FH-). RESULTS: Discrimination task accuracy was lowest in the highest risk group (A1+, FH+) at T1, and highest in the lowest risk group (A1-, FH-) at T2, producing a significant interaction of allelic group x family history group x session. Reaction time was faster at T2 than T1, and this effect was larger in FH-boys (125 ms) than FH+boys (40 ms). Overall, the behavioral results suggest mild performance deficits on the discrimination task are associated with higher risk for alcoholism. In both testing sessions, P300 attained larger amplitudes in sons of nonalcoholics than sons of alcoholics. At T2 compared to T1, both the latency and amplitude of the P300 were decreased. However, while the developmental P300 latency effect was equivalent in both the A1+ and A1- allelic groups, the P300 amplitude reduction during adolescence, measured both in response to targets and in target minus non-target subtraction waveforms, was only found in boys with the A1- allele. CONCLUSION: Differences in the developmental course of P300 amplitude over the course of adolescence are dependent on DRD2 polymorphism. SIGNIFICANCE: These results suggest the importance of genetic determinants of the dopaminergic system in understanding the P300 as a risk marker for substance abuse using an integrative developmental perspective.

Adolescent↗

Cerebral metabolic dysfunction and impaired vigilance in recently abstinent methamphetamine abusers.

BACKGROUND: Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. METHODS: We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology. RESULTS: Methamphetamine users had higher error rates than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. CONCLUSIONS: Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.

Adult↗

DRD2 genotypes and substance use in adolescent children of alcoholics.

Research has identified children of alcoholics (COAs) as a population at increased risk for developing substance use problems. Genetic studies support the Al allele of the D2 dopamine receptor gene (DRD2) as a risk marker for alcoholism and substance use disorders. In this study, substance use was assessed in 48 adolescent boys of alcoholics with the DRDR A1(+) allele (A1A1/A1A2 genotypes) or the A1(-) allele (A2A2 genotype). The results revealed that boys with the A1(+) allele tried (p=0.0001) and got intoxicated on alcohol more often (p=0.009) than boys with the A1(-) allele. Boys with the A1(+) allele tried more (p=0.004) and used more substances overall (p=0.008) than boys with the A1(-) allele. Boys with the A1(+) allele developed a tobacco habit more often (p=0.03) and experienced marijuana high at an earlier age (p=0.001) than boys with the A1(-) allele. The best predictors of substance use severity in boys with the A1(+) allele were Psychoticism (p=0.01) and Negative Affect (p=0.04). The results provide support for the DRD2 A1 allele as a marker identifying a subgroup of COAs at high risk for developing substance use problems.

Adolescent↗

Impaired performance in a test of decision-making by opiate-dependent tobacco smokers.

This study tested whether opiate dependence, tobacco smoking, or their combination accompanied impaired performance on the gambling task (GT), which tests decision-making. GT previously detected impairments in patients with lesions of the ventromedial prefrontal cortex and in substance abusers. Four groups were matched on demographic characteristics and intelligence: methadone-maintained smokers (n = 9) and nonsmokers (n = 9), and control (i.e., not opiate-dependent) smokers (n = 9) and nonsmokers (n = 10). The Wisconsin Card Sorting Task (WCST) was administered to test whether differences in GT performance reflected generalized deficits in prefrontal cortical function. While there were no significant group differences on the WCST, groups differed significantly on GT performance (F(3,31) = 2.95, P = 0.048), controlling for depressive symptom ratings and childhood attention deficit hyperactivity disorder. Methadone-maintained smokers (but not nonsmokers) performed more poorly than either of the two control groups (P = 0.007 versus smokers; P = 0.024 versus nonsmokers). In a planned analysis of methadone-maintained subjects, smokers scored more poorly on GT than nonsmokers (F(1,18) = 5.64, P = 0.032) and had more treatment failures (67% heroin use during the last 30 days versus 20%). The findings suggest that among opiate-dependent individuals, tobacco smoking may be a marker for a more severe form of substance abuse disorder, reflecting impaired decision-making, as modeled by GT.

Adult↗

Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers.

BACKGROUND: Mood disturbances in methamphetamine (MA) abusers likely influence drug use, but the neurobiological bases for these problems are poorly understood. OBJECTIVE: To assess regional brain function and its possible relationships with negative affect in newly abstinent MA abusers. DESIGN: Two groups were compared by measures of mood and cerebral glucose metabolism ([18F]fluorodeoxyglucose positron emission tomography) during performance of a vigilance task. SETTING: Participants were recruited from the general community to a research center. PARTICIPANTS: Seventeen abstaining (4-7 days) MA abusers (6 women) were compared with 18 control subjects (8 women). MAIN OUTCOME MEASURES: Self-reports of depressive symptoms and anxiety were measured, as were global and relative glucose metabolism in the orbitofrontal, cingulate, lateral prefrontal, and insular cortices and the amygdala, striatum, and cerebellum. RESULTS: Abusers of MA provided higher self-ratings of depression and anxiety than control subjects and differed significantly in relative regional glucose metabolism: lower in the anterior cingulate and insula and higher in the lateral orbitofrontal area, middle and posterior cingulate, amygdala, ventral striatum, and cerebellum. In MA abusers, self-reports of depressive symptoms covaried positively with relative glucose metabolism in limbic regions (eg, perigenual anterior cingulate gyrus and amygdala) and ratings of state and trait anxiety covaried negatively with relative activity in the anterior cingulate cortex and left insula. Trait anxiety also covaried negatively with relative activity in the orbitofrontal cortex and positively with amygdala activity. CONCLUSIONS: Abusers of MA have abnormalities in brain regions implicated in mood disorders. Relationships between relative glucose metabolism in limbic and paralimbic regions and self-reports of depression and anxiety in MA abusers suggest that these regions are involved in affective dysregulation and may be an important target of intervention for MA dependence.

Adult↗

Differential associations of sex and D2 dopamine receptor (DRD2) genotype with negative affect and other substance abuse risk markers in children of alcoholics.

Children of alcoholics have increased risk for substance abuse problems. Self-medication of negative affect may be one developmental path to future substance abuse. Because the 146 young (adolescent) children of alcoholics in the current sample had not used enough abused substances to study substance use directly, the relation of substance abuse risk markers to negative affect was assessed. Because the D2 dopamine receptor (DRD2) A1 allele has been associated with alcoholism and other substance use disorders, negative affect, measured by the Beck Depression Inventory (BDI), was determined in four groups of children: boys and girls with the A1+ allele (A1A1 and A1A2 genotypes) and with the A1- allele (A2A2 genotype). The other risk markers were stress, low amplitude of the P300 evoked potential, poor visuospatial functioning, novelty seeking (NS), and harm avoidance (HA). Stress was correlated with BDI scores in all groups. In contrast, low P300 was associated with BDI scores only in boys with the A1+ allele (P = .04), NS was associated with BDI scores only in girls with the A1+ allele (P = .02), and HA was associated with BDI scores only in boys with the A1- allele (P = .01). In addition, boys with the A1+ allele had lower BDI (P = .05) and HA (P = .005) scores than the respective scores for boys with the A1- allele. Girls with the A1- allele had lower HA scores compared with scores for boys with the A1- allele (P = .02). Girls with the A1+ allele had lower visuospatial functioning than that of boys with the A1+ allele (P<.001). Results indicate that both sex and DRD2 genotype modify associations between negative affect and other substance abuse risk markers.

Adolescent↗

Complementary hemispheric specialization for word and accent detection.

When we hear a familiar word pronounced in a foreign accent, which parts of the brain identify the word and which identify the accent? Here we present converging evidence from PET blood flow, event-related scalp potentials, and behavioral responses during dichotic listening, showing homologous and complementary hemispheric specialization for word and accent detection. Accuracy of detecting target words was greater when stimuli were presented to the right ear, indicating left hemisphere specialization, with no ear advantage for detecting target accents. Detection of words also produced increased blood flow in a left frontal area associated with motor and phonetic processing, and a left temporal area associated with semantic memory. Homologous areas of the right hemisphere, together with right prefrontal and precuneus regions, showed increased blood flow during detection of accents. Separate analyses for each detection task indicated that voxels whose activity maximally correlated with accuracy were in the left hemisphere for word detection, but in the right hemisphere for accent detection. Voxels whose activity maximally correlated with inaccuracy were in the opposite hemisphere for both tasks, strengthening the interpretation that between-task differences in brain activation are related to lateralized specializations for task performance. ERP waveforms and reaction times suggested that greater left hemisphere activation during word detection preceded greater right hemisphere activation during accent detection. The results are interpreted as supporting left hemisphere specialization for extraction of the linguistic, phonetic, and semantic information contained in speech, and right hemisphere specialization for pragmatics, the social context of linguistic communication.

Adult↗

Condition-specific deactivation of brain regions by 5-HT3 receptor antagonist Alosetron.

BACKGROUND & AIMS: The 5-HT3 receptor (5-HT3R) antagonist Alosetron (Alos) reduces the symptoms of female patients with diarrhea-predominant irritable bowel syndrome (IBS); yet, the mechanism(s) underlying this effect remains incompletely understood. We determined the effect of Alos on regional cerebral blood flow (rCBF) in the absence and presence of rectal or sigmoid stimulation to evaluate 2 hypothesized mechanisms of therapeutic action: peripheral antinociception and inhibition of emotional motor system (EMS) regions in the brain. METHODS: Forty-nine nonconstipated irritable bowel syndrome (IBS) patients (26 female) received H(2)(15)O positron emission tomography (PET) brain scans before a randomized, placebo-controlled, 3-week trial with Alos (1-4 mg twice daily). PET scans were repeated after treatment in 37 completers. We assessed rCBF during baseline, rectal distention, and anticipation of undelivered rectal distention. The 3 conditions were repeated after a series of noxious sigmoid distentions. Rectal (45 mm Hg) and sigmoid (60 mm Hg) distentions were performed with a computer-controlled barostat device. RESULTS: Alos treatment, as compared with placebo, improved IBS symptoms and reduced rCBF in 5-HT3R containing regions of the EMS, but not in areas activated by pain. Reduction of rCBF appeared greatest in the absence of visceral stimulation, and was partially reversed by rectal or sigmoid distention. Symptom improvement across sessions was significantly correlated with rCBF decreases in the 5-HT3R-rich amygdala, ventral striatum, and dorsal pons. CONCLUSIONS: Reduction in IBS symptoms correlated with a drug-induced reduction in the activity of central autonomic networks mediating emotional expression that was maximal in the absence of nociceptive input.

Adult↗

Enhanced preattentive central nervous system reactivity in irritable bowel syndrome.

OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder characterized by enhanced perceptual sensitivity and hypervigilance toward afferent signals from the viscera. We hypothesize that the increased responsiveness of IBS patients is a generalized phenomenon applying to stimuli other than visceral and attempt to demonstrate increased responsiveness to sounds as measured by the P1 scalp potential. METHODS: Event-related potentials were recorded from IBS patients and control subjects in an auditory task requiring detection of rare pitch targets in a designated ear. Visual words served as targets in an additional block. RESULTS: Compared to control subjects, IBS patients displayed a robust increase in the amplitude of the P1 scalp potential elicited by both attended and unattended sounds. CONCLUSIONS: Enhanced P1 indicates preattentive central nervous system dishabituation in response to repeated sounds. A generalized preattentive increase in central nervous system reactivity may be a feature that IBS shares with several anxiety disorders that frequently co-occur in these patients.

Acoustic Stimulation↗