Biomedical subjects

K I Bolla

Publications and source records attributed to K I Bolla.

At least 19 recordsLinked to original sources

PubMed2003

Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task.

Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with (15)O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence.

Adult↗

PubMed2002

Dose-related neurocognitive effects of marijuana use.

BACKGROUND: Although about 7 million people in the US population use marijuana at least weekly, there is a paucity of scientific data on persistent neurocognitive effects of marijuana use. OBJECTIVE: To determine if neurocognitive deficits persist in 28-day abstinent heavy marijuana users and if these deficits are dose-related to the number of marijuana joints smoked per week. METHODS: A battery of neurocognitive tests was given to 28-day abstinent heavy marijuana abusers. RESULTS: As joints smoked per week increased, performance decreased on tests measuring memory, executive functioning, psychomotor speed, and manual dexterity. When dividing the group into light, middle, and heavy user groups, the heavy group performed significantly below the light group on 5 of 35 measures and the size of the effect ranged from 3.00 to 4.20 SD units. Duration of use had little effect on neurocognitive performance. CONCLUSIONS: Very heavy use of marijuana is associated with persistent decrements in neurocognitive performance even after 28 days of abstinence. It is unclear if these decrements will resolve with continued abstinence or become progressively worse with continued heavy marijuana use.

Adolescent↗

PubMed2001

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with neurobehavioral test scores in South Korean lead workers.

The authors performed a cross-sectional study to evaluate associations between blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead and measures of neurobehavioral and peripheral nervous system function among 803 lead-exposed workers and 135 unexposed controls in South Korea. The workers and controls were enrolled in the study between October 1997 and August 1999. Central nervous system function was assessed with a modified version of the World Health Organization Neurobehavioral Core Test Battery. Peripheral nervous system function was assessed by measuring pinch and grip strength and peripheral vibration thresholds. After adjustment for covariates, the signs of the beta coefficients for blood lead were negative for 16 of the 19 tests and blood lead was a significant predictor of worse performance on eight tests. On average, for the eight tests that were significantly associated with blood lead levels, an increase in blood lead of 5 microg/dl was equivalent to an increase of 1.05 years in age. In contrast, after adjustment for covariates, tibia lead level was not associated with neurobehavioral test scores. Associations with DMSA-chelatable lead were similar to those for blood lead. In these currently exposed workers, blood lead was a better predictor of neurobehavioral performance than was tibia or DMSA-chelatable lead, mainly in the domains of executive abilities, manual dexterity, and peripheral motor strength.

Adult↗

PubMed2000

Past adult lead exposure is associated with longitudinal decline in cognitive function.

OBJECTIVE: To determine whether adults with past exposure to neurotoxicants have progressive declines in cognitive function years after exposure has ceased, and whether tibia lead is a predictor of the magnitude of change. METHODS: A total of 535 former organolead manufacturing workers with a mean age of 55.6 years, a mean duration of 16 years since last occupational lead exposure, and low blood lead levels at the first study visit and 118 controls were evaluated with neurobehavioral tests two to four times over 4 years. "Peak" tibia lead levels, estimated from current levels measured by X-ray fluorescence, were used to predict changes in cognitive function over time. RESULTS: In former lead workers, peak tibia lead ranged from -2.2 to 98.7 microg Pb/g bone mineral. Compared to controls, former lead workers performed worse over time for three tests of visuo-constructive ability and verbal memory and learning (p < 0.05). In former lead workers, peak tibia lead predicted declines for six tests of verbal memory and learning, visual memory, executive ability, and manual dexterity (p < 0.05 for four tests and < 0.10 for two additional tests). On average, for these six tests, an increase of 15.7 microg/g of peak tibia lead was equivalent in its effects on annual test decline to 5 more years of age at baseline. CONCLUSIONS: These are the first data to suggest that cognitive function can progressively decline due to past occupational exposures to a neurotoxicant.

Adult↗

PubMed2000

Differential effects of cocaine and cocaine alcohol on neurocognitive performance.

OBJECTIVE: To investigate the dose-related effects of cocaine with or without alcohol use on the CNS by measuring performance on neurobehavioral tests. BACKGROUND: Chronic use of cocaine is associated with persistent decrements in cognitive function that are most pronounced in heavy users. Specific neurobehavioral deficits in areas such as executive function and impulsivity would make it difficult for the cocaine abuser to discontinue using drugs. Because alcohol is often used in conjunction with cocaine, the CNS effects of alcohol when taken with cocaine deserve further investigation. METHOD: The authors evaluated the dose-related effects of cocaine and alcohol use on performance in a variety of neuropsychological tests after 1 to 3 days of abstinence and again after 4 weeks of abstinence. Fifty-six chronic cocaine abusers who had used cocaine during the past 24 to 48 hours volunteered to perform a battery of neuropsychological tests on two separate occasions during a period of enforced abstinence. In addition to using cocaine, most of the volunteers consumed alcohol. Approximately half of the participants consumed more than 10 alcohol-containing drinks per week. RESULTS: After controlling for the effects of age, sex, and intelligence on performance, the authors found dose-related associations between neurobehavioral performance and cocaine dose and alcohol dose. When the influences of cocaine and alcohol on neurobehavioral performance were taken separately, cocaine and alcohol each selectively affected performance on different neurobehavioral tests after 1 to 3 days of abstinence, with these effects persisting after 4 weeks of abstinence. CONCLUSION: The concomitant use of cocaine and alcohol may have additive negative effects on the brain as compared to the use of only one of these two substances.

Adult↗

PubMed1999

Neurobehavioral function and tibial and chelatable lead levels in 543 former organolead workers.

OBJECTIVE: To evaluate the associations between tibial lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and neurobehavioral function in former organolead manufacturing workers with past exposure to organic and inorganic lead. METHODS: Data were collected from 543 subjects with a mean age of 58 years and an average of 17.8 years since last lead exposure. Years since last exposure to lead was used to estimate tibial lead levels in the year of last occupational lead exposure, termed "peak tibial lead." Current tibial lead levels, measured by x-ray fluorescence, were extrapolated back using a clearance half-time of lead in tibia of 27 years, assuming first-order clearance from tibia. RESULTS: Peak tibial lead levels ranged from -2.2 to 105.9 microg Pb/g bone mineral, and DMSA-chelatable lead levels were between 1.2 and 136 microg. After adjustment for confounding variables, peak tibial lead was a significant negative predictor of performance on the Wechsler Adult Intelligence Scale-Revised vocabulary subtest (p = 0.02), serial digit learning test (p = 0.04), Rey Auditory-Verbal Learning Test (immediate recall and recognition, p = 0.03 for each), Trail Making Test B (p = 0.03), finger tapping (dominant hand [p = 0.02] and nondominant hand [p < 0.01]), Purdue pegboard (dominant hand, nondominant hand, both hands, and assembly, p < 0.01 for each), and Stroop Test (p < 0.01). Moreover, with one exception, average neurobehavioral test scores were poorer at higher peak tibial lead levels. DMSA-chelatable lead was only significantly associated with choice reaction time (p = 0.01). CONCLUSION: Peak tibial lead was consistently associated with poorer neurobehavioral test scores, particularly in the domains of manual dexterity, executive ability, verbal intelligence, and verbal memory.

Adult↗

PubMed1999

Dose-related neurobehavioral effects of chronic cocaine use.

Although cocaine use is a significant public health problem, there is a paucity of scientific data on long-term neurobehavioral effects. This study examined the dose-related association between chronic cocaine use and neurobehavioral performance. A battery of neuropsychological tests was administered to 30 abstinent chronic cocaine abusers and 21 non-drug-using control subjects matched for age, education, and intelligence. After controlling for age, education, and intellectual ability, greater use of cocaine (grams per week) was associated with larger decrements on tests measuring executive functioning, visuoperception, psychomotor speed, and manual dexterity. These results suggest that chronic cocaine use is associated with persistent decrements in cognitive function that are most pronounced in heavy users. Knowledge of specific cognitive processing deficits in chronic cocaine users would be useful for designing individually tailored drug treatment programs.

Adult↗

PubMed1998

The neuropsychiatry of chronic cocaine abuse.

This review integrates findings from neuropsychological, PET, and MRI studies in human subjects and neurochemical findings in animals to make inferences about neuropsychiatric consequences of chronic abuse of cocaine. It also aims to develop insights into brain-behavioral relationships that may explain the perpetuation of addictive behaviors. Such insights promise to lead to a better understanding of the neuropsychiatry of cocaine abuse and to promote the development of more efficacious treatments. The authors present evidence suggesting that cocaine abusers have specific dysfunction of executive functions (decision making, judgment) and that this behavior is associated with dysfunction of specific prefrontal brain regions, the orbitofrontal cortex, and anterior cingulate gyrus. Suggestions for future research and treatment are also discussed.

Aged↗

PubMed1998

Memory impairment in abstinent MDMA ("Ecstasy") users.

BACKGROUND: Methylenedioxymethamphetamine (MDMA, or "Ecstasy") is a popular recreational drug of abuse that is known to damage brain serotonergic neurons in animals and possibly humans. Few functional consequences of MDMA-induced serotonin (5-HT) neurotoxicity have been identified, either in animals or humans. This study sought to determine whether individuals with a history of extensive MDMA use showed evidence of memory impairment, because brain serotonin has been implicated in mnemonic function. METHOD: The authors compared 24 abstinent MDMA users and 24 control subjects on several standardized tests of memory, after matching subjects for age, gender, educational level, and vocabulary score (a surrogate of verbal intelligence). The authors also explored correlations between changes in memory function and decrements in CSF 5-hydroxyindoleacetic acid (5-HIAA), which serves as a marker of central 5-HT neural function. RESULTS: Greater use of MDMA (total milligrams per month) was associated with greater impairment in immediate verbal memory (p < 0.02) and delayed visual memory (p < 0.06). Furthermore, lower vocabulary scores were associated with stronger dose-related effects, with men having greater dose-related deficits than women. Lastly, lower concentrations of CSF 5-HIAA were associated with poorer memory performance. CONCLUSION: Abstinent MDMA users have impairment in verbal and visual memory. The extent of memory impairment correlates with the degree of MDMA exposure and the reduction in brain 5-HT, as indexed by CSF 5-HIAA.

Adult↗

PubMed1997

Simple visual reaction time in organolead manufacturing workers: comparison of different methods of modeling lead exposure and reaction time.

In March 1990, 222 organolead manufacturing workers and 62 nonexposed referents were administered a neurobehavioral test battery that included simple visual reaction time (SVRT). SVRT was measured over 44 trials with interstimulus intervals ranging from 1 to 10 sec in a random but fixed order for all study subjects. Different measures of lead exposure and dose (e.g., recent and cumulative exposure based on personal sampling data, exposed/nonexposed status, recent blood lead and zinc protoporphyrin levels, and peak and cumulative urine lead levels) were examined as predictors of several different parameters of SVRT (e.g., mean, median, truncated mean, and standard deviation of SVRT over 44 trials). The association varied, depending on the measures used for SVRT and lead exposure and dose. In linear regression analyses, the strongest and most consistent associations of lead exposure and dose were observed with the standard deviation of SVRT. In assessing the different exposure measures, strong and consistent associations were observed with blood lead levels at the time of SVRT testing, but not with recent or cumulative exposure measures. That is, stronger associations were observed with measures of relatively recent internal dose (i.e., blood lead level) than with cumulative measures (i.e., cumulative exposure). Future studies using SVRT should consider parameters of SVRT that have not been commonly used to date, such as the standard deviation of the SVRT.

Adult↗

PubMed1996

Chronic cocaine use as a neuropsychiatric syndrome: a model for debate.

In humans, chronic cocaine abuse is associated with changes in the central nervous system (CNS). Neuropathological changes include cerebrovascular events, EEG abnormalities, vasculitis, seizures, and decrements in neurobehavioral performance. The acute administration of cocaine is associated with acute psychotic episodes and paranoid states while withdrawal from the drug is often associated with depressed mood. The mechanistic basis of these behavioral states is not known. Given the structural and functional changes associated with cocaine use, we propose that the chronic heavy use of cocaine may result in a neuropsychiatric syndrome which might be associated with neuropsychological changes that are not obvious during routine clinical evaluation of drug-using individuals. This disconnection syndrome, because of its sublety, might have deleterious effects on both acute and long-term therapeutic interventions with these subjects. An approach which deals with cocaine abuse as a neuropsychiatric disorder might be more beneficial to the long-term goal of treating these patients. This approach entails a neurobehavioral evaluation which will be comprised of a thorough neurological and psychiatric examination, neuropsychological testing, and imaging studies. The results of this evaluation would provide a more rational basis for cognitive and/or pharmacological therapies.

Cocaine↗

PubMed1996

Neuropsychological evaluation for detecting alterations in the central nervous system after chemical exposure.

Individuals with multiple chemical sensitivity (MCS) report decreased attention/concentration, memory loss, disorientation, confusion, fatigue, depression, irritability, decreased libido, sleep disturbances, headaches, and weakness. These neurobehavioral symptoms represent possible alterations in the central nervous system (CNS). The evaluation of neurobehavioral functioning using neuropsychological techniques provides an indirect method for determining the integrity of the CNS. However, caution must be used in interpreting neuropsychological test results, since this technique is extremely sensitive but is not specific. Clinically significant aberrant test performance may be noted after chemical exposure as well as with other diseases of the CNS. In addition, neuropsychiatric conditions such as anxiety and depression are often manifested as cognitive difficulties that are similar in pattern to the cognitive dysfunction caused by toxic chemicals. Herein, limitations and cautions in the interpretations of neuropsychological test results are discussed.

Anxiety↗

PubMed1996

Neurobehavioral performance in multiple chemical sensitivities.

Individuals with Multiple Chemical Sensitivities (MCS) frequently report difficulties in attention/concentration, memory and accuracy and speed of problem solving. We evaluated neurobehavioral functioning in 35 chemically exposed patients referred to our Occupational and Environmental Neurology Clinic. Of these 35 patients, 17 presented with symptoms of MCS and 16 patients reported no symptoms of MCS. In addition, we used a group of 126 healthy controls for comparison. The performance of the MCS group was not significantly different from that of the control group on tests of verbal learning and memory, executive functioning, and psychomotor functioning. The MCS group performed below the control group on a test of visual learning and memory, but this performance was similar to the group with chemical exposure and no MCS. Therefore, performance on objective neurobehavioral tests did not confirm the most frequently reported subjective complaints of patients with MCS. These results suggests that patients with symptoms of MCS do not have compromised central nervous system functioning.

Adult↗

PubMed1996

Clinical evaluation of 58 organolead manufacturing workers.

Fifty-eight workers were evaluated at a university-based occupational health clinic for potential health effects related to organic and inorganic lead exposures. The clinical evaluation included a history, physical, and laboratory examination, and in a subset of workers, neurobehavioral tests and nerve conduction studies. Workers reported symptoms that predominantly involved the central and peripheral nervous systems. Findings for which no alternative medical explanations could be found included neurobehavioral abnormalities (18 of 39 workers) and sensorimotor polyneuropathies (11 of 31 workers). The clinical presentation and evaluation of workers exposed to organic lead are discussed.

Adult↗

PubMed1995

Comparison of neurobehavioral function in workers exposed to a mixture of organic and inorganic lead and in workers exposed to solvents.

The neurobehavioral effects of lead (organic and inorganic) and organic solvents were compared in 386 U.S. workers (52 reference, 190 lead, and 144 solvent workers). The association between neurobehavioral test performance and duration of exposure to lead or solvents was also examined and compared. The neurobehavioral test battery consisted of examiner and computer-administered neurobehavioral tests, a test of olfactory function, and questionnaires that assessed neuropsychiatric symptoms. Adjusted mean differences on the neurobehavioral test scores were estimated by comparing the exposed group to the referent group using linear regression and adjusting for premorbid intellectual ability, age, and race. Both lead and solvents were associated with diminished neurobehavioral performance in all neurobehavioral areas tested. Specifically, while lead and solvent exposure had the same magnitude of adverse effects on tests of manual dexterity, lead exposure was associated with greater adverse effects on memory and learning tests but with less adverse effects on executive/motor tests and on a test of olfaction than solvent exposure. An elevated number of neuropsychiatric symptoms was reported by 7% of the referent group, 43% of the lead group, and 15% of the solvent group. For exposure duration of < or = 10 years, more neurobehavioral decrements were found in the solvent group relative to the lead group. However, for exposure duration of > or = 18 years, the lead group showed more decrements than the solvent group. Overall, these data suggest differences in neurobehavioral functioning between the lead (organic and inorganic) and solvent exposed workers examined in this study.

Adult↗

PubMed1995

Cumulative exposure to inorganic lead and neurobehavioural test performance in adults: an epidemiological review.

OBJECTIVES: To evaluate the current evidence that cumulative exposure to inorganic lead is associated with decreased performance in neurobehavioural tests in adults. METHODS: 21 unique studies were reviewed from 28 published manuscripts. An algorithm was developed to determine the usefulness of each study on the basis of exposure assessment, control of confounding variables, methods of subject selection, test conditions, and data analysis. Highest emphasis was placed on the use of cumulative measures of exposure or absorption. RESULTS: Only three studies used a measure of cumulative exposure to or absorption of lead, and two others used duration of exposure as a surrogate for cumulative exposure. All other studies used a measure that did not adequately estimate cumulative exposure to lead, most often current blood lead concentration. 20 of the studies controlled for age as a confounding variable, although in several studies the possibility for residual confounding by age remained. 16 studies controlled for intellectual ability before exposure; all of them used educational level for this purpose. Of the five studies that used direct or surrogate measures of cumulative exposure to or absorption of lead, two were thought to be of low usefulness because of inadequate duration of exposure. The three remaining studies found stronger associations of neurobehavioural performance with recent exposure measures than with those of cumulative exposure. CONCLUSION: The current scientific literature provides inadequate evidence to conclude whether or not cumulative exposure to or absorption of lead adversely affects performance in neurobehavioural tests in adults. The current evidence is flawed because of inadequate estimation of cumulative exposure to or absorption of lead and inadequate control for age and intellectual ability before exposure.

Age Factors↗

PubMed1994

Neurologic health outcomes and Agent Orange: Institute of Medicine report.

The National Academy of Sciences' Institute of Medicine conducted an independent scientific investigation to evaluate the strength of evidence for human health effects among veterans exposed to herbicides used in Vietnam and to suggest future research recommendations. Neurologic domains where multiple studies had been performed in military, occupational, or environmental situations were (1) cognitive and neuropsychiatric effects, (2) motor/coordination dysfunction and other central nervous system disorders, and (3) peripheral neuropathy. In all categories, no strong evidence established an association between herbicides used in Vietnam and clinical neurologic disorders. Methodologic weaknesses, long durations between exposure and assessments, and poor exposure measures limited many studies. The committee concluded that the available evidence was insufficient to determine an association between neurologic disorders and exposure to herbicides used in Vietnam. Neurotoxicologic studies available did not suggest strong biological plausibility for neurologic alterations related to herbicide exposure. Furthermore, given the large uncertainties in the epidemiologic studies reviewed and inadequate control for important confounders, the committee could not quantify a degree of risk for neurologic disorders from herbicide exposure likely to be experienced by Vietnam veterans. Although not part of the neurologic report, the risk of brain tumors was considered in the cancer analysis, and the committee concluded that there is limited/suggestive evidence of no association between exposure to herbicides and brain tumors.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1993

Decrements in neurobehavioral performance associated with mixed exposure to organic and inorganic lead.

In 1990, 222 current employees of a chemical facility in the eastern United States that manufactured tetraethyl lead were administered a neurobehavioral test battery, tests of olfactory function and peripheral vibration threshold, and questionnaires that assessed neuropsychiatric symptoms. A cumulative variable of exposure to inorganic and organic lead was derived from 12 years of personal industrial hygiene sampling data and an occupational history interview that assessed work in each of 29 exposure zones in the lead area. The range of assigned exposure intensities in these 29 zones was 4-119 micrograms/m3 for organic lead and 1-56 micrograms/m3 for inorganic lead. Cumulative lead exposure and exposure duration were defined as categorical variables (four groups) in multiple linear regression models. The adjusted mean differences in neurobehavioral test scores were estimated by comparing the average scores of the moderate, high, and highest exposure groups with the low exposure (reference) group. After adjustment for premorbid intellectual ability, age, race, and alcohol consumption, neurobehavioral test scores were poorer as measures of both cumulative lead exposure and exposure duration increased; many of the associations evidenced dose-response relations. Associations were observed in most cognitive and functional domains tested, but were most common in two domains: manual dexterity and verbal memory/learning. On the affected neuropsychologic measures, the groups with the highest exposure averaged scores 5-22% lower than those of the reference groups. Overall, the data revealed generally consistent and coherent associations between two measures of lead exposure and poorer neurobehavioral test performance.

Adult↗