Neuropsychological Functioning and Antiretroviral Treatment in HIV/AIDS: A Review

This article presents a review of studies that have investigated the neuropsychological effects of antiretroviral treatment (ART) for HIV-1 infection. It provides a brief overview of the era of monotherapy, dual-therapy, and an extended overview of the current era of combination antiretroviral therapy (CART). This review highlights that while CART has had a dramatic effect on the incidence and the severity of HIV-associated neurocognitive disorders (HAND), HAND, in its mild form, still remains prevalent. New causes of this sustained prevalence are poor CNS penetration of some antiretroviral agents, drug resistance, poor adherence, potential neurotoxicity, co-morbidities such as the long-term CART side effects in relation to cardio-vascular disease, and chronic HIV brain infection that may facilitate the expression of new forms of neurodegenerative processes. The review emphasizes the need to address methodological limitations of published studies and the need for large and representative cross-disciplinary longitudinal investigations across the HIV illness span.     

HIV-related neurocognitive impairment--a review

Neurocognitive impairments following central nervous system opportunistic infections and HIV-associated dementia (HAD) were common clinical features of HIV infection prior to anti-retroviral therapy. As HIV infection has evolved from an invariably fatal disease with a poor prognosis to a condition requiring long-term management, HIV-related neurocognitive disorders have been the subject of increasing research. This review will examine the recent changes in the understanding of the HIV-associated neurocognitive disorders (HAND) including the changing epidemiology, risk factors associated with its development, methods for screening for the disorders and evolving treatment options.     

Cognitive Neurorehabilitation of HIV-associated Neurocognitive Disorders: A Qualitative Review and Call to Action

Despite significant advances in the virologic management of HIV infection over the last two decades, effective treatments for HIV-associated neurocognitive disorders (HAND) remain elusive. While pharmacological interventions have yielded some success in improving neurocognitive outcomes in HIV, there is a dearth of rigorous studies examining the efficacy of cognitive rehabilitation for remediating HIV-associated neurocognitive impairment. This qualitative review summarizes and critiques the emerging literature on cognitive and behavioral treatments for HAND, which provides many reasons for optimism, but also has major limitations that underscore the scope of the work that lies ahead. Considering the notable real-world consequences of HAND, the development, validation, and clinical deployment of cognitive neurorehabilitation interventions tailored to the needs of persons living with HIV infection is a priority for clinical neuroAIDS investigators. In describing potential future directions for this endeavor, particular attention was paid to the application of cognitive neuropsychological principles in developing theory-driven approaches to managing HAND, improving everyday functioning, and enhancing HIV health outcomes.     

Heterogeneity of Neuropsychological Impairment in HIV Infection: Contributions from Mild Cognitive Impairment

Despite longstanding acknowledgement of the heterogeneity of HIV-associated neurocognitive disorders (HAND), existing HAND diagnostic methods classify according to the degree of impairment, without regard to the pattern of neuropsychological strengths and weaknesses. Research in mild cognitive impairment (MCI) has demonstrated that classifying individuals into subtypes by both their level and pattern of impairment, using either conventional or statistical methods, has etiologic and prognostic utility. Methods for characterizing the heterogeneity of MCI provide a framework that can be applied to other disorders and may be useful in clarifying some of the current challenges in the study of HAND. A small number of studies have applied these methods to examine the heterogeneity of neurocognitive function among individuals with HIV. Most have supported the existence of multiple subtypes of neurocognitive impairment, with some evidence for distinct clinicodemographic features of these subtypes, but a number of gaps exist. Following a review of diagnostic methods and challenges in the study of HAND, we summarize the literature regarding conventional and empirical subtypes of MCI and HAND and identify directions for future research regarding neurocognitive heterogeneity in HIV infection.     

Health-Related Decision-Making in HIV Disease

Individuals living with HIV show moderate decision-making deficits, though no prior studies have evaluated the ability to make optimal health-related decisions across the HIV healthcare continuum. Forty-three HIV+ individuals with HIV-associated neurocognitive disorders (HAND+), 50 HIV+ individuals without HAND (HAND?), and 42 HIV? participants were administered two measures of health-related decision-making as part of a comprehensive neuropsychological battery: (1) The Decisional Conflict Scale (DCS), and (2) The Modified UCSD Brief Assessment for Capacity to Consent (UBACC-T). Multiple regression analyses revealed that HAND was an independent predictor of both the DCS and the UBACC-T, such that the HAND+ sample evidenced significantly poorer scores relative to comparison groups. Within the HIV+ sample, poorer health-related decision-making was associated with worse performance on tests of episodic memory, risky decision-making, and health literacy. Findings indicate that individuals with HAND evidence moderate deficits in effectively comprehending and evaluating various health-related choices.     

Cognitive Neuropsychology of HIV-Associated Neurocognitive Disorders

Advances in the treatment of the human immunodeficiency virus (HIV) have dramatically improved survival rates over the past 10 years, but HIV-associated neurocognitive disorders (HAND) remain highly prevalent and continue to represent a significant public health problem. This review provides an update on the nature, extent, and diagnosis of HAND. Particular emphasis is placed on critically evaluating research within the realm of cognitive neuropsychology that aims to elucidate the component processes of HAND across the domains of executive functions, motor skills, speeded information processing, episodic memory, attention/working memory, language, and visuoperception. In addition to clarifying the cognitive mechanisms of HAND (e.g., impaired cognitive control), the cognitive neuropsychology approach may enhance the ecological validity of neuroAIDS research and inform the development of much needed novel, targeted cognitive and behavioral therapies. The research described was supported by MH73419 and MH62512 from the National Institutes of Health. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government.     

Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology

Effects on the immune system caused by changes in behavioral state or brain activity are mediated, at least in part, through neuroendocrine-immune pathways. Life stress and depression may be associated with altered blood levels of central nervous system-released neuropeptides, including substance P (SP). SP acts as a neuroregulator or neurotransmitter in the conduction of nociceptive stimuli, and is a modulator of neuroimmunoregulation. This review summarizes current knowledge regarding the role of the neuropeptide, SP, in psychoneuroimmunology, in particular as it relates to human immunodeficiency virus infection and acquired immunodeficiency disease syndrome. The association between depression, anxiety, and stress in HIV-disease progression suggests that neurobiologic and neurophysiologic factors play a role in modulating HIV infection and responses to antiretroviral therapy. Individuals with HIV or AIDS may experience stressful life circumstances that can result in increased symptoms of anxiety, stress, and/or depression. Furthermore, psychological and psychiatric symptoms, which occur in individuals with HIV and AIDS, may be related to the progression of AIDS disease. This review presents evidence from the literature, as well as findings from basic investigations conducted in the authors' laboratories, demonstrating that SP may play an important role in HIV pathophysiology. SP can impact the susceptibility of immune cells to HIV infection and modulate immune cell functions in ways that may affect the course of HIV in infected individuals. Moreover, modulation of SP activity and SP receptor is being explored for its potential as a novel therapeutic approach to the treatment of some psychological and psychiatric disorders and to the design of new anti-HIV therapy.     

The Biology of Morality

Abstract. The morality of human beings, defined here as our ability to determine whether our actions are right or wrong, depends not just on following rules but also on understanding the impact of our actions on another person. How we understand the impact of our actions on another person depends on our state of consciousness, which is mediated by our brain and nervous system. We describe how we understand our morality to flow naturally from the biological state we are living in and how we see our biology and our morality as mutually interactive. A change in one changes the other. Another way of saying this is that changing either our morality or our biology changes both—changes who we are and what we do.     

Estrogen and Neural Plasticity

Converging clinical evidence suggests that postmenopausal estrogen therapy in women is associated with improved cognition and a reduced incidence of Alzheimer's disease. In experimental work, investigators have found estrogen to promote changes in synaptic plasticity within the nervous system. In this article, we review both the clinical and the experimental literature, and consider mechanisms of action of estrogen on neurons and synaptic plasticity, and how they might protect against the cognitive impairments of old age.     

Neuroprogressive disease of post-infectious origin: a review of a resurging subacute sclerosing panencephalitis (SSPE)

Subacute sclerosing panencephalitis (SSPE) is a progressive, essentially untreatable, disease of the nervous system. When first described in the 20th Century, it was characterized more for its neuropathological features than for its pathophysiology or cause. It was not until the 1960s that a clear relationship to the measles virus was established. It is now thought that this uncommon infectious encephalopathy is caused by a "slow," altered or persistent form of the wild measles virus which has harbored in the nervous system for years. Then a "breakout" occurs and the more lytic and virulent organisms produce the progressive and spreading inflammatory and destructive lesions which are confined to the nervous system. Epidemiological study of the disease confirms its relationship to measles. In the years since the development of national measles immunization programs, there has been a dramatic decline in the incidence of measles exanthem and until recently a corresponding decline in the incidence of SSPE. In recent years there has been a mild to moderate increase in cases of SSPE as reported to the USA/International SSPE Registry. As yet, there has not been a totally effective treatment. The purpose of this paper is to give an overall review on SSPE and its relationship to measles. This review will include a prospectus of its history, considerations as to its etiology, correlation of clinicopathological features, and thoughts on the past and present epidemiology and treatment.     

Probabilistic models in human sensorimotor control

Sensory and motor uncertainty form a fundamental constraint on human sensorimotor control. Bayesian decision theory (BDT) has emerged as a unifying framework to understand how the central nervous system performs optimal estimation and control in the face of such uncertainty. BDT has two components: Bayesian statistics and decision theory. Here we review Bayesian statistics and show how it applies to estimating the state of the world and our own body. Recent results suggest that when learning novel tasks we are able to learn the statistical properties of both the world and our own sensory apparatus so as to perform estimation using Bayesian statistics. We review studies which suggest that humans can combine multiple sources of information to form maximum likelihood estimates, can incorporate prior beliefs about possible states of the world so as to generate maximum a posteriori estimates and can use Kalman filter-based processes to estimate time-varying states. Finally, we review Bayesian decision theory in motor control and how the central nervous system processes errors to determine loss functions and select optimal actions. We review results that suggest we plan movements based on statistics of our actions that result from signal-dependent noise on our motor outputs. Taken together these studies provide a statistical framework for how the motor system performs in the presence of uncertainty.     

浅谈神经干细胞在临床应用中的伦理问题

神经干细胞在治疗中枢神经系统退形性病变中发挥重要作用,但在其移植治疗中也面临着一些问题,例如伦理问题及技术问题。如何合理地引导人们正确地认识这项研究,消除对神经干细胞移植治疗的种种误解,使全社会都能客观理性地面对这一新兴医疗技术,看到这一技术的巨大应用前景是我们要继续努力的目标。     

Biology of elderly suicide.

Most studies of suicide in younger patients have demonstrated significant alterations in the serotonin system. Although a high percentage of completed suicides occur in late-life, to date very few studies of the biology of suicide have focused on this age group. This chapter describes age-related changes in the central nervous system pertinent to the biology of suicide, then reviews post-mortem biological studies of the brains of suicides and suicide attempters. As suicide attempts in the elderly are characterized by the use of violent means, biologic studies of impulsive violence are discussed. Finally we describe data on the effect of degenerative diseases on the serotonin system and the possible link to increased suicidal behavior in affected patients. This review underscores the need for further study of the biology of suicide in the geriatric age group.     

Identity in bipolar disorder: Self-worth and achievement

This article considers self and self-concept in bipolar disorder. Bipolar disorder, defined on the basis of manic symptoms, is a highly debilitating psychopathology. It is heavily grounded in biology but symptom course is still very responsive to psychological and social forces in the lives of persons who have the disorder. This review assumes an overall view of the self that is typical of personality psychology: self as traits, self as goals and aspirations, and ongoing efforts to attain those goals. In this review, we will discuss two different facets of self and identity in bipolar disorder. First, we review a body of goal pursuit literature suggesting that persons with bipolar disorder endorse heightened ambitions for attaining goals and recognition from others. Second, we will review multiple findings which suggest that among persons with bipolar disorder, self-worth depends on measurable success in an extreme way. We will consider how the intersection of these two themes may lead to unique identity challenges for people with bipolar disorder, drawing from self-report, behavioral, and neuroscience findings to critically examine this viewpoint.     

The New Biology and its Impact in Biomedical Strategies Against HIV/AIDS

Abstract. The sequencing of the human genome and the initiation of the structural genomics projects have ushered in a new age of biology that involves multi‐lab, high‐cost projects with broad task‐oriented goals rather than the more conventional hypothesis‐driven approach of the past. The new biology has led to the development of new sets of tools for the scientist to use in the quest to solve mysteries of human disease, biomolecular structure‐function relationships, and other burning biological questions. Nevertheless, the impact of the new biology on the field of AIDS investigation has been minimal, predominantly because many of the tools in the HIV field of study were developed before the full advance of the new biology was felt in the biomedical community. Many of the high‐cost megaprojects that involve large technological advances and are marketed as projects of promise to the biomedical community are not likely to significantly impact the field of HIV/AIDS research and cannot serve as a substitute for direct funding to the HIV/AIDS scientists working for vaccine development, an understanding of mechanisms of disease causation, and new tools for therapeutic intervention.     

Neurocognitive Effects of Methamphetamine: A Critical Review and Meta-analysis

This review provides a critical analysis of the central nervous system effects of acute and chronic methamphetamine (MA) use, which is linked to numerous adverse psychosocial, neuropsychiatric, and medical problems. A meta-analysis of the neuropsychological effects of MA abuse/dependence revealed broadly medium effect sizes, showing deficits in episodic memory, executive functions, information processing speed, motor skills, language, and visuoconstructional abilities. The neuropsychological deficits associated with MA abuse/dependence are interpreted with regard to their possible neural mechanisms, most notably MA-associated frontostriatal neurotoxicity. In addition, potential explanatory factors are considered, including demographics (e.g., gender), MA use characteristics (e.g., duration of abstinence), and the influence of common psychiatric (e.g., other substance-related disorders) and neuromedical (e.g., HIV infection) comorbidities. Finally, these findings are discussed with respect to their potential contribution to the clinical management of persons with MA abuse/dependence.     

Functional Consequences of HIV-Associated Neuropsychological Impairment

This review focuses on the “real world” implications of infection with HIV/AIDS from a neuropsychological perspective. Relevant literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment, driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical, cognitive, psychosocial, and psychiatric issues on whether someone with HIV/AIDS will be able to return to work, adhere to a complicated medication regimen, or safely drive a vehicle will be discussed. Methodological issues that arise in the context of measuring medication adherence or driving capacity are also explored. Finally, the impact of HIV/AIDS on mood state, fatigue, and interpersonal relationships are addressed, with particular emphasis on how these variables interact with cognition and independent functioning. The purpose of this review is to integrate neuropsychological findings with their real world correlates of functional behavior in the HIV/AIDS population.     

The Parieto-Frontal Integration Theory (P-FIT) of intelligence: converging neuroimaging evidence

"Is there a biology of intelligence which is characteristic of the normal human nervous system?" Here we review 37 modern neuroimaging studies in an attempt to address this question posed by Halstead (1947) as he and other icons of the last century endeavored to understand how brain and behavior are linked through the expression of intelligence and reason. Reviewing studies from functional (i.e., functional magnetic resonance imaging, positron emission tomography) and structural (i.e., magnetic resonance spectroscopy, diffusion tensor imaging, voxel-based morphometry) neuroimaging paradigms, we report a striking consensus suggesting that variations in a distributed network predict individual differences found on intelligence and reasoning tasks. We describe this network as the Parieto-Frontal Integration Theory (P-FIT). The P-FIT model includes, by Brodmann areas (BAs): the dorsolateral prefrontal cortex (BAs 6, 9, 10, 45, 46, 47), the inferior (BAs 39, 40) and superior (BA 7) parietal lobule, the anterior cingulate (BA 32), and regions within the temporal (BAs 21, 37) and occipital (BAs 18, 19) lobes. White matter regions (i.e., arcuate fasciculus) are also implicated. The P-FIT is examined in light of findings from human lesion studies, including missile wounds, frontal lobotomy/leukotomy, temporal lobectomy, and lesions resulting in damage to the language network (e.g., aphasia), as well as findings from imaging research identifying brain regions under significant genetic control. Overall, we conclude that modern neuroimaging techniques are beginning to articulate a biology of intelligence. We propose that the P-FIT provides a parsimonious account for many of the empirical observations, to date, which relate individual differences in intelligence test scores to variations in brain structure and function. Moreover, the model provides a framework for testing new hypotheses in future experimental designs.     

Psychosocial risk factors, natural immunity, and cancer progression: Implications for intervention

One of the more important and emerging fields in which psychologists collaborate with other disciplines is psychoimmunology. Centuries of clinical anecdote and decades of psychosomatic hypotheses have gained credibility in the eyes of the medical establishment—and many patients—by the systematic investigation of mechanisms potentially explaining how events intrapsychic and interpersonal could affect physical disease processes. The central nervous system is connected with the immune system by both neuronal and endocrinological pathways. The immune system has been found to mediate the organism’s response to aberrations of its own normal functions, as well as to invading organisms from without. AIDS, arthritis, asthma, lupus, and herpes are some of the illnesses in which research is demonstrating important relationships among psychosocial and immunological factors and disease course. In this article, we first discuss the immunological apparatus in order to provide a base for subsequent discussions of the effects of stress on immune function. Then we discuss malignant diseases and current evidence that disease course is related to both psychosocial stressors and immune function. We next discuss a model of these interactions, and finally we talk about interventions incorporating psychosocial factors aimed at influencing immune status and, thus, disease course.