Neurobiology of Cocaine-Induced Organic Brain Impairment: Contributions from Functional Neuroimaging

The present review is directed at imparting the current knowledge regarding functional neuroimaging as a tool for enhancing the understanding of cerebrophysiologic and neurobehavioral consequences of stimulant abuse. Stimulants like cocaine are capable of inducing clinically significant neurocognitive impairment through direct action on the brain, and indirectly through other organs that influence cerebral physiology. Neurochemical dysregulation including profound effects on the serotonergic and dopaminergic systems have substantial physiological and neurobehavioral consequences. Brain hemorrhages, transient ischemic attacks, strokes, and seizures frequently follow cocaine use. The residual cerebropathologic consequences of cocaine are seen only in significant or pronounced brain events when structural neuroimaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are employed. However, recent research with newer functional neuroimaging techniques such as single photon emission, positron emission tomography, and quantitative electroencephalography have revealed high rates of significant alteration in brain function among cocaine users, with negative structural imaging studies. These findings are often associated with impairment on neuropsychological evaluation, also in the absence of positive findings on CT and MRI. Both cerebral metabolic and hypoperfusion anomalies are seen, especially in anterior and temporal brain regions. Observed changes can persist for months, and for some patients, may represent a permanent change in brain functioning.     

Neurocognitive outcomes in pediatric HIV

Cognitive impairment has long been associated with the natural history of HIV among vertically infected children. In children, HIV may have a direct or indirect impact on the developing brain, may lead to global or highly specific consequences, and may be responsible for minor cognitive consequences or, conversely, long-term and severe disability. This differential impact is related to multiple factors that influence the individual expression of the virus in any given child. This review provides an overview of the relevant literature on neurocognitive outcomes for infants, children, and youth vertically infected with HIV, with attention to those factors impacting neurocognitive outcome within a developmental framework. Research findings in both the era preceding and following the introduction of combined therapies are reviewed, since many of the issues identified prior to state-of-the-art treatment currently available in the United States and other developed countries still apply in much of the developing world. Intervention issues and directions for future research are also discussed.     

Cognitive training programs for childhood cancer patients and survivors: A critical review and future directions

A robust literature has developed documenting neurocognitive late effects in survivors of leukemia and central nervous system (CNS) tumors, the most frequent cancer diagnoses of childhood. Patterns of late effects include deficits in attention and concentration, working memory, processing speed, and executive function, as well as other domains. As childhood cancer survivors are living longer, ameliorating deficits both in broad and specific neurocognitive domains has been increasingly recognized as an endeavor of paramount importance. Interventions to improve cognitive functioning were first applied to the field of pediatric oncology in the 1990s, based on strategies used effectively with adults who had sustained a traumatic brain injury (TBI). Compilation and modification of these techniques has led to the development of structured cognitive training programs, with the effectiveness and feasibility of such interventions currently an active area of research. Consequently, the purpose of this critical review is to: (1) review cognitive training programs intended to remediate or prevent neurocognitive deficits in pediatric cancer patients and survivors, (2) critically analyze training program strengths and weaknesses to inform practice, and (3) provide recommendations for future directions of clinical care and research.     

A Critical Review of the Clinical Effects of Therapeutic Irradiation Damage to the Brain: The Roots of Controversy

We critically examined the damaging affects of therapeutic irradiation by comparing results from cross-disciplinary studies of early- and late-delayed radiotherapy effects. Focus is attained by concentrating on clinical treatment issues (volume of brain, dose, timing of effects, age, modality types, and stereotactic treatment techniques), rather than on methodological means or problems, which is necessary to understand the mechanisms and characteristics of radiotherapy-induced behavioral dysfunction including cognition. We make observations and hypotheses about the actual risks from radiotherapy that could be informative in the treatment decision process, and which may lessen the concerns of some patients and their families about the risks they take when receiving radiation. Conditions that predispose to radiation injury are reviewed: (1) higher doses even to part of the brain versus lower doses to the whole brain, (2) combined treatment modalities, (3) malignancy itself, (4) radiation early during postnatal brain development, and (5) late-delayed effects (more than 3 years posttreatment). Current neurocognitive frameworks for understanding cognitive change over time in children and adults are summarized, along with the literature on effects of brain tumors and treatment on depression. No studies have as yet identified candidate brain regions that are more sensitive to radiotherapy. Two studies have provided early, preliminary evidence for a specific vulnerability of visual attention/memory to the early stage of late radiation damage. Furthermore, radiation effects appear severe only in a minority of patients. Risk is related to direct and indirect effects of cancer type, concurrent clinical factors, and premorbid risk factors.     

Performance-based and parent ratings of attention in children treated for a brain tumor: The significance of radiation therapy and tumor location on outcome

Children are at increased risk for cognitive difficulties following the diagnosis and treatment of a brain tumor. Radiation therapy (RT) and tumor location are commonly-cited predictors of neurocognitive functioning. Disruptions to foundational neurocognitive processes such as attention, working memory, and processing speed underlie declines on measures of general intellectual functioning. While several studies have examined visual sustained attention in pediatric brain tumor patients, auditory sustained attention has yet to be examined. This study employs a longitudinal design to examine performance-based and parent ratings of attention in children undergoing surgical resection of a brain tumor (n = 29) and treated with (n = 11) or without (n = 18) RT at 6.79 months post-surgery (baseline) and then again at 30.56 months post-surgery (follow-up). The measures include an auditory continuous performance test (CPT) and parent ratings of attention and hyperactivity on a behavior rating scale. Ultimately, children treated with and without RT performed similarly on performance-based and parent ratings of attention. However, the performance on the auditory CPT differed according to tumor location, with children with infratentorial tumors committing more inattention and inhibitory control errors compared to children with supratentorial tumors. Parent ratings did not differ according to tumor location, and parent ratings and auditory sustained attention performance are not significantly correlated. The findings are interpreted in the context of neurocognitive and brain development.     

Computerized Neurocognitive Testing in the Management of Sport-Related Concussion: An Update

Since the late nineties, computerized neurocognitive testing has become a central component of sport-related concussion (SRC) management at all levels of sport. In 2005, a review of the available evidence on the psychometric properties of four computerized neuropsychological test batteries concluded that the tests did not possess the necessary criteria to warrant clinical application. Since the publication of that review, several more computerized neurocognitive tests have entered the market place. The purpose of this review is to summarize the body of published studies on psychometric properties and clinical utility of computerized neurocognitive tests available for use in the assessment of SRC. A review of the literature from 2005 to 2013 was conducted to gather evidence of test-retest reliability and clinical validity of these instruments. Reviewed articles included both prospective and retrospective studies of primarily sport-based adult and pediatric samples. Summaries are provided regarding the available evidence of reliability and validity for the most commonly used computerized neurocognitive tests in sports settings.     

Neurobiology of prenatal cocaine exposure effect on developing monoamine systems

Cocaine and crack belong to a broad category of agents that act primarily as central nervous system stimulants at the level of the monoaminergic neurotransmitter system (dopamine, norepinephrine, and serotonin). These neurotransmitters are involved in the regulation of a number of basic psychological functions including attention and arousal and play a crucial role in the defining of brain structure and neuronal formation. This paper outlines what is currently known about the direct effects of cocaine on the mature and developing central nervous system. Three general points are reviewed: (1) Cocaine has differing effects on structural and functional brain development throughout gestation (e.g., there is not a single, all or none effect); (2) No one area of the brain is singularly affected. Areas related by the monoaminergic system are differentially influenced and affecting one area may result in a functional change in another; and (3) Because substantial brain growth, synaptic formation, and remodeling occur in the first months after birth, ongoing postnatal exposure to cocaine also carries risk for direct effects on brain function. Understanding the developmental neurobiological effects of cocaine provides data to guide studies in infants and young children of how prenatal cocaine exposure may contribute to specific, biologically based areas of neurological vulnerability that will be expressed behaviorally and developmentally in the first 3 to 5 years of life.     

Timed performance weaknesses on computerized tasks in pediatric brain tumor survivors: A comparison with sibling controls

With more children surviving a brain tumor, insight into the late effects of the disease and treatment is of high importance. This study focused on profiling the neurocognitive functions that might be affected after treatment for a pediatric brain tumor, using a broad battery of computerized tests. Predictors that may influence neurocognitive functioning were also investigated. A total of 82 pediatric brain tumor survivors (PBTSs) aged 8–18 years (M = 13.85, SD = 3.15, 49% males) with parent-reported neurocognitive complaints were compared to a control group of 43 siblings (age M = 14.27, SD = 2.44, 40% males) using linear mixed models. Neurocognitive performance was assessed using measures of attention, processing speed, memory, executive functioning, visuomotor integration (VMI), and intelligence. Tumor type, treatment, tumor location, hydrocephalus, gender, age at diagnosis, and time since diagnosis were entered into regression analyzes as predictors for neurocognitive functioning. The PBTSs showed slower processing speeds and lower intelligence (range effect sizes .71–.82, p < .001), as well as deficits in executive attention, short-term memory, executive functioning, and VMI (range effect sizes .40–.57, p < .05). Older age at assessment was associated with better neurocognitive functioning (B = .450, p < .001) and younger age at diagnosis was associated with lower intelligence (B = .328, p < .05). Medical risk factors, e.g., hydrocephalus, did not show an association with neurocognitive functioning. Late effects in PBTSs include a broad range of neurocognitive deficits. The results suggest that even PBTSs that were traditionally viewed as low risk for neurocognitive problems (e.g., surgery only, no hydrocephalus) may suffer from decreased neurocognitive functioning.     

Neurocognitive outcomes following pediatric brain injury: A developmental approach

Developmental neuropsychologists postulate that “immaturity” of the cerebral cortex should no longer be perceived as a protective factor. They argue that injury to the young brain may affect new learning by disrupting the skills in the midst of being acquired and skills that are yet to be developed. Cognitive deficits or weaknesses that are not detectable in the acute phase following a traumatic brain injury (TBI) may emerge over development as more complex skills are needed, thereby creating a developmental lag between children who sustained a pediatric TBI and typical age peers. This literature review was conducted to evaluate the developmental perspective on neurocognitive recovery/development following a TBI. Overall, the described findings support a developmental view and suggest that predictions of prognosis should be based on the child's remaining ability to learn.     

Administration and Environment Considerations in Computer-Based Sports-Concussion Assessment

Computer-based testing has become a vital tool for the assessment of sport-related concussion (SRC). An increasing number of papers have been published on this topic, focusing on subjects such as the purpose and validity of baseline testing, the performance of special populations on computer-based tests, the psychometric properties of different computerized neurocognitive tools, and considerations for valid and reliable administration of these tools. The current paper describes several considerations regarding computerized test design, input and output devices, and testing environment that should be described explicitly when administering computer-based cognitive testing, regardless of whether the assessment is used for clinical or research purposes. The paper also reviews the conclusions of recent literature (2007–2013) using computer-based testing for the assessment of SRC, with special attention to the methods used in these studies. We also present an appendix checklist for clinicians and researchers that may be helpful in ensuring proper attention to factors that could influence the reliability and validity of computer-based cognitive testing. We believe that explicit attention to these technological factors may lead to the development of standards for the development and implementation of computer-based tests. Such standards have the potential to enhance the accuracy and utility of computer-based tests in SRC.     

Neuropsychological Consequences of Opiate Use

Approximately 3.7 million individuals have used heroin and other opiate substances in their lifetime. Despite increasing knowledge of the effects of heroin, it remains the most abused opiate and use among adults has recently increased. The empirical literature examining the neurocognitive effects of acute and chronic opioid use remains limited; however, findings to date suggest that the use of opiates has both acute and long-term effects on cognitive performance. Neuropsychological data indicate deficits in attention, concentration, recall, visuospatial skills and psychomotor speed with both acute and chronic opioid use. The long-term effects of opiate use appear to have the greatest impact on executive functions, including the ability to shift cognitive set and inhibit inappropriate response tendencies. Factors that contribute to addiction and recovery are also discussed, as it is difficult to disentangle the effects of opiate use on cognitive performance from other factors that may affect neurobehavioral measures.     

Working memory and attention in pediatric brain tumor patients treated with and without radiation therapy

Children are at risk for cognitive difficulties following the diagnosis and treatment of a brain tumor. Longitudinal studies have consistently demonstrated declines on measures of intellectual functioning, and recently it has been proposed that specific neurocognitive processes underlie these changes, including working memory, processing speed, and attention. However, a fine-grained examination of the affected neurocognitive processes is required to inform intervention efforts. Radiation therapy (RT) impacts white matter integrity, likely affecting those cognitive processes supported by distributed neural networks. This study examined working memory and attention in children during the early delayed stages of recovery following surgical resection and RT. The participants included 27 children diagnosed with pediatric brain tumor, treated with (n = 12) or without (n = 15) RT, who completed experimental and standardized measures of working memory and attention (n-back and digit span tasks). Children treated with radiation performed less well than those who did not receive radiation on the n-back measure, though performance at the 0-back level was considerably poorer than would be expected for both groups, perhaps suggesting difficulties with more basic processes such as vigilance. Along these lines, marginal differences were noted on digit span forward. The findings are discussed with respect to models of attention and working memory, and the interplay between the two.     

Predictors of therapeutic response to treatments for depression: a review of electrophysiologic and dichotic listening studies

There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment outcome remain to be determined in future studies.     

赌博障碍的认知功能缺陷及神经基础

赌博障碍是指持续且反复的赌博行为,给个人、家庭和社会都带来了严重后果,近年来受到越来越多研究者的关注。本研究总结了赌博障碍的认知功能缺陷及其神经基础,主要集中在如下四个方面：①认知扭曲、②奖赏和惩罚敏感性、③注意偏向和④决策。未来研究应多从认知神经科学角度深入探究赌博障碍的发生机制和发展过程,关注大脑结构变化及功能网络改变,并将其整合到一个统一的神经生物机制框架中,找到更加有效的干预和治疗手段。     

赌博障碍的认知功能缺陷及神经基础

赌博障碍是指持续且反复的赌博行为,给个人、家庭和社会都带来了严重后果,近年来受到越来越多研究者的关注。本研究总结了赌博障碍的认知功能缺陷及其神经基础,主要集中在如下四个方面：①认知扭曲、②奖赏和惩罚敏感性、③注意偏向和④决策。未来研究应多从认知神经科学角度深入探究赌博障碍的发生机制和发展过程,关注大脑结构变化及功能网络改变,并将其整合到一个统一的神经生物机制框架中,找到更加有效的干预和治疗手段。     

EEG Biofeedback for Addictive Disorders—The State of the Art in 2004

This paper reviews studies of brainwave biofeedback as a therapeutic technique for substance use disorder. This modality is attractive as a medication free, neurophysiologic, and self actualizing treatment for a substance based, brain impaired and self-defeating disorder. Three approaches are described and the literature for each reviewed. Alpha–theta occipital feedback was originally employed to facilitate autosuggestion in hypnagogic states to augment standard therapy approaches in substance abuse treatment programs and appears most suited for chronic treatment resistant alcoholics. Beta augmentation feedback in conjunction with alpha/theta feedback has been employed in mixed substance abuse and stimulant abuse with good results. Individualized brainwave biofeedback based on correcting EEG abnormalities, or based on addressing comorbid conditions is a third approach that has been described, and may be most appropriate where confounding comorbid conditions are present. Although effectiveness in certain hard to treat populations (conventional treatment resistant alcoholics, crack cocaine addicts, cognitively impaired substance abusers) is promising, better-designed controlled studies are needed.     

Bayesian Diagnostics of Hidden Markov Structural Equation Models with Missing Data

Cocaine is a type of drug that functions to increase the availability of the neurotransmitter dopamine in the brain. However, cocaine dependence or abuse is highly related to an increased risk of psychiatric disorders and deficits in cognitive performance, attention, and decision-making abilities. Given the chronic and persistent features of drug addiction, the progression of abstaining from cocaine often evolves across several states, such as addiction to, moderate dependence on, and swearing off cocaine. Hidden Markov models (HMMs) are well suited to the characterization of longitudinal data in terms of a set of unobservable states, and have increasingly been used to uncover the dynamic heterogeneity in progressive diseases or activities. However, the existence of outliers or influential points may misidentify the hidden states and distort the associated inference. In this study, we develop a Bayesian local influence procedure for HMMs with latent variables in the presence of missing data. The proposed model enables us to investigate the dynamic heterogeneity of multivariate longitudinal data, reveal how the interrelationships among latent variables change from one state to another, and simultaneously conduct statistical diagnosis for the given data, model assumptions, and prior inputs. We apply the proposed procedure to analyze a dataset collected by the UCLA center for advancing longitudinal drug abuse research. Several outliers or influential points that seriously influence estimation results are identified and removed. The proposed procedure also discovers the effects of treatment and individuals’ psychological problems on cocaine use behavior and delineates their dynamic changes across the cocaine-addiction states.     

The Long-Term Neurocognitive Consequences of Prenatal Alcohol Exposure: A 14-Year Study

Prenatal alcohol exposure, at doses not generally associated with maternal alcohol problems, produces a broad array of neurocognitive deficits in offspring even in the absence of effects on growth and morphology. This report presents a summary of neurobehavioral, growth, and morphology findings from long-term follow-up of a birth cohort of 500 from apopulation-based study that has revealed attention, memory, and information processing deficits from birth through 14 years. Also observed (from school age through 14 years) have been problems with antisocial and delinquent behaviors, and classroom learning and behaviors; some of these problems may be secondary to earlier neurocognitive disabilities. Continuing research in behavioral and neurobehavioral teratology provides important opportunities for the neurosciences and for improved health of future generations.     

The role of neuropsychology in UK pediatric HIV care: Relevance to clinical practice and research

There has been a dramatic improvement in the survival of children with perinatally-acquired HIV (PHIV) following the introduction of effective treatment in 1990s. The care for children living with PHIV is now focused on more accurately understanding the effects of both HIV and HIV treatment on the developing body and brain. An evaluation of current HIV neuroimaging, and neurocognitive research, when combined with clinical experience in the area of HIV, could help to inform United Kingdom (UK) PHIV service provision. This paper argues that an understanding from a neuropsychological perspective will help these young people to optimize their health, quality of life, and future functioning. The aim of the paper is to bring together research and clinical understanding of HIV and its treatment effects on the developing brain, together with an understanding of other potential neurological risk factors. It is argued here that there is a need for targeted neuropsychology assessment and preventative interventions, supported by clinical and preliminary research on the neurocognitive effects of HIV and its treatments.