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Patients with major depression are at an increased risk for developing cardiovascular disease, respond more poorly to treatment, and exhibit worse outcomes, including increased morbidity and mortality. This article reviews the relationship between depression and heart disease, with an emphasis on epidemiology, biological substrates that likely underlie this relationship, and implications for treatment., (© 2015 New York Academy of Sciences.)

Tourette syndrome (TS) and primary complex motor stereotypies (CMS) are two relatively common, distinctly different movement disorders of childhood. Despite their frequency, the precise underlying pathophysiological mechanism(s) for tics and stereotypies remains unknown. Both are likely to involve cortical-striatal-thalamo-cortical (CSTC) pathways or their interconnecting brain regions. In recent studies, distinct, separate cortical-striatal pathways have been identified for goal-directed and habitual behavioral activity with important influences from structures, such as the hippocampus, amygdala, dorsolateral prefrontal cortex, cerebellum, ventral tegmental area, and substantia nigra pars compacta. Determining the specific site of abnormality within these circuits remains an active area of research. At the synaptic level, numerous neurotransmitters are involved in the transmission of messages through CSTC pathways, and many have been proposed as potential pathophysiological mechanisms. Which, if any, transmitter is the primary pathological factor in TS and primary CMS remains to be definitively determined., (© 2013 New York Academy of Sciences.)

Auditory imagery can represent many aspects of music, such as the starting pitches of a tune or the instrument that typically plays it. In this paper, I concentrate on more dynamic, or time-sensitive aspects of musical imagery, as demonstrated in two recently published studies. The first was a behavioral study that examined the ability to make emotional judgments about both heard and imagined music in real time. The second was a neuroimaging study on the neural correlates of anticipating an upcoming tune, after hearing a cue tune. That study found activation of several sequence-learning brain areas, some of which varied with the vividness of the anticipated musical memory. Both studies speak to the ways in which musical imagery allows us to judge temporally changing aspects of the represented musical experience. These judgments can be quite precise, despite the complexity of generating the rich internal representations of imagery., (© 2012 New York Academy of Sciences.)

Sponsored by the New York Academy of Sciences, the Warren Alpert Medical School of Brown University and the University of Massachusetts Boston, "Behavioral Epigenetics" was held on October 29-30, 2010 at the University of Massachusetts Boston Campus Center, Boston, Massachusetts. This meeting featured speakers and panel discussions exploring the emerging field of behavioral epigenetics, from basic biochemical and cellular mechanisms to the epigenetic modulation of normative development, developmental disorders, and psychopathology. This report provides an overview of the research presented by leading scientists and lively discussion about the future of investigation at the behavioral epigenetic level., (© 2011 New York Academy of Sciences.)

Experiments on humans and other animals have shown that uncertainty due to unreliable or incomplete information affects behavior. Recent studies have formalized uncertainty and asked which behaviors would minimize its effect. This formalization results in a wide range of Bayesian models that derive from assumptions about the world, and it often seems unclear how these models relate to one another. In this review, we use the concept of graphical models to analyze differences and commonalities across Bayesian approaches to the modeling of behavioral and neural data. We review behavioral and neural data associated with each type of Bayesian model and explain how these models can be related. We finish with an overview of different theories that propose possible ways in which the brain can represent uncertainty., (© 2011 New York Academy of Sciences.)

Among other things, humans talk about what they perceive and do, like "glowing,""hopping," and "squeaking." What is the relationship between our sensory-motor experiences and word meanings? Does understanding action-verbs rely on the same neural circuits as seeing and acting? The available evidence indicates that sensory-motor experience and word meanings are represented in distinct, but interacting systems. Understanding action-verbs does not rely on early modality-specific visual or motor circuits. Instead, word comprehension relies on a network of amodal brain regions in the left frontal, temporal, and parietal cortices that represent conceptual and grammatical properties of words. Interactions between word meanings and sensory-motor experiences occur in higher-order polymodal brain regions., (© 2011 New York Academy of Sciences.)

The relationship between behavioral and neural performance has been explored in adult animals, but rarely during the developmental period when perceptual abilities emerge. We used these naturally occurring changes in auditory perception to evaluate underlying encoding mechanisms. Performance of juvenile and adult gerbils on an amplitude modulation (AM) detection task was compared with response properties from auditory cortex of age-matched animals. When tested with an identical behavioral procedure, juveniles display poorer AM detection thresholds than adults. Two neurometric analyses indicate that the most sensitive juvenile and adult neurons have equivalent AM thresholds. However, a pooling neurometric revealed that adult cortex encodes smaller AM depths. By each measure, neural sensitivity was superior to psychometric thresholds. However, juvenile training improved adult behavioral thresholds, such that they verged on the best sensitivity of adult neurons. Thus, periods of training may allow an animal to use the encoded information already present in cortex., (© 2011 New York Academy of Sciences.)

The following review and appreciation of the pioneering work and character of Wallace I. (Wally) Welker provides a historical perspective on Welker's life-long quest for answers to fundamental questions on the relationships among brain, behavior, and evolution, and evaluates his impact upon comparative behavioral neuroscience., (© 2011 New York Academy of Sciences.)

During the 1990s and early 2000s, cognitive neuroscience investigations of human category learning focused on the primary goal of showing that humans have multiple category-learning systems and on the secondary goals of identifying key qualitative properties of each system and of roughly mapping out the neural networks that mediate each system. Many researchers now accept the strength of the evidence supporting multiple systems, and as a result, during the past few years, work has begun on the second generation of research questions-that is, on questions that begin with the assumption that humans have multiple category-learning systems. This article reviews much of this second generation of research. Topics covered include (1) How do the various systems interact? (2) Are there different neural systems for categorization and category representation? (3) How does automaticity develop in each system? and (4) Exactly how does each system learn?, (© 2010 New York Academy of Sciences.)

Explicit memory refers to the conscious retrieval of past information or experiences, whereas implicit memory refers to an unintentional or nonconscious form of retrieval. Much of the literature in cognitive psychology and cognitive neuroscience has focused on differences between explicit and implicit memory, and the traditional view is that they rely on distinct brain systems. However, the potential interplay between implicit and explicit memory is not always clear. This review draws from behavioral and functional neuroimaging evidence to evaluate three areas in which implicit and explicit memory may be interrelated. First, we discuss views of familiarity-based recognition in terms of its relationship with implicit memory. Second, we review the challenges of distinguishing between implicit memory and involuntary aware memory, at both behavioral and neural levels. Finally, we examine evidence indicating that implicit and explicit retrieval of relational information may rely on a common neural mechanism. Taken together, these areas indicate that, under certain circumstances, there may be an important and influential relationship between conscious and nonconscious expressions of memory., (© 2011 New York Academy of Sciences.)

Imprinted genes, in contrast to most mammalian genes, are monoallelically expressed in a parent-of-origin dependent manner. The idiosyncratic expression profile associated with imprinted genes arises from the differential epigenetic marking of the alleles in the paternal and maternal germlines. Although small in number, imprinted genes can profoundly influence key developmental and physiological processes, including those in the brain; work in animal models and in humans has shown that such genes can affect behavioral traits and cognition and may confer vulnerability to common mental illnesses. As a consequence of how the X chromosome is inherited, X-linked imprinting may elicit or indeed attenuate sexually dimorphic phenotypes. Thus, studying X-linked imprinting is likely to provide important general information about the evolutionary and mechanistic underpinnings of imprinting, as well as the molecular processes underlying sex-specific neurobiology and sex-biased vulnerability to psychiatric disorders.

Many kinds of body/mind practices are capable of producing remarkable behaviors and altered body states. A typology of such behaviors and states, defined as observable and intentional "extreme" alterations to the body, is presented. Epistemological and methodological issues are discussed: limitations of observational data, and role of meaning, intentionality, and consciousness. Rapprochement between Western medicine and Indo-Tibetan medicine requires rethinking biomedicine's radical grounding in physicality and reliance on "evidence-based medicine," and guarding against an ethnocentric Western intellectual hegemony motivating medical science and clinical practice to colonize and subvert non-Western traditions like Indo-Tibetan Buddhist medicine.

The phenomenon of synesthesia has occupied the thoughts of philosophers and artists for decades. With the advent modern behavioral and brain imaging techniques, scientific research on synesthesia has also moved into the mainstream of thought. Here I provide a cognitive neuroscience perspective on the condition, with a particular emphasis on grapheme-color synesthesia, the most common variant, in which individuals report vivid and consistent experiences of color in association with numerals, letters, and words. Behavioral studies have revealed several fundamental properties of induced synesthetic colors. First, although they seem to arise automatically, without the need for voluntary control, they are strongly modulated by selective attention. Second, they attain salience relatively early in visual processing, and so can influence perceptual judgments and guide focal attention in cluttered, achromatic displays. Third, brain activity during synesthetic color experiences arises from within the ventral temporal lobe, including color-selective area V4. It has been speculated that grapheme-color synesthesia arises from disinhibited feedback or abnormal cross-wiring between brain regions involved in extracting visual form and color.

We studied the behavior and neuroendocrine regulation under social disruption stress of C57BL/6J mice in which mitochondria were substituted by mitochondria from AKR/J or FVB/N strains. C57BL/6J-mt(FVB/N) mice were significantly more anxious in the elevated plus-maze test than C57BL/6J-mt(AKR/J) and C57BL/6J mice at base line. In addition, they showed a reduced corticosterone response and an activation of serotonergic and dopaminergic neurotransmitter systems after repeated challenge, i.e., social defeat and elevated plus-maze test. Our findings suggest that mitochondrial variations could affect anxiety-like behavior as well as corticosterone and neurotransmitter response to psychological stress.

Neuroimmunomodulation describes the field focused on understanding the mechanisms by which the central nervous system interacts with the immune system, potentially leading to changes in animal behavior. Nonetheless, not many articles dealing with neuroimmunomodulation employ behavior as an analytical endpoint. Even fewer papers deal with social status as a possible modifier of neuroimmune phenomena. In the described sets of experiments, we tackle both, using a paradigm of social dominance and subordination. We first review data on the effects of different ranks within a stable hierarchical relationship. Submissive mice in this condition display more anxiety-like behaviors, have decreased innate immunity, and show a decreased resistance to implantation and development of melanoma metastases in their lungs. This suggests that even in a stable, social, hierarchical rank, submissive animals may be subjected to higher levels of stress, with putative biological relevance to host susceptibility to disease. Second, we review data on how dominant and submissive mice respond differentially to lipopolysaccharide (LPS), employing a motivational perspective to sickness behavior. Dominant animals display decreased number and frequency in several aspects of behavior, particularly agonistic social interaction, that is, directed toward the submissive cage mate. This was not observed in submissive mice that maintained the required behavior expected by its dominant mate. Expression of sickness behavior relies on motivational reorganization of priorities, which are different along different social ranks, leading to diverse outcomes. We suggest that in vitro assessment of neuroimmune phenomena can only be understood based on the behavioral context in which they occur.

A classical view of the neuroendocrine-immune network assumes bidirectional interactions where pro-inflammatory cytokines influence hypothalamic-pituitary-adrenal (HPA) axis-derived hormones that subsequently affect cytokines in a permanently servo-controlled circle. Nevertheless, this picture has been continuously evolving over the last years as a result of the discovery of redundant expression and extended functions of many of the molecules implicated. Thus, cytokines are not only expressed in cells of the immune system but also in the central nervous system, and many hormones present at hypothalamic-pituitary level are also functionally expressed in the brain as well as in other peripheral organs, including immune cells. Because of this intermingled network of molecules redundantly expressed, the elucidation of the unique roles of HPA axis-related molecules at every level of complexity is one of the major challenges in the field. Genetic engineering in the mouse offers the most convincing method for dissecting in vivo the specific roles of distinct molecules acting in complex networks. Thus, various immunological, behavioral, and signal transduction studies performed with different HPA axis-related mutant mouse lines to delineate the roles of beta-endorphin, the type 1 receptor of corticotropin-releasing hormone (CRHR1), and its ligand CRH will be discussed here.

Anorexia nervosa (AN) is a psychiatric condition characterized by deliberate reduction of body weight. Some patients with AN exhibit overactivity that can worsen their state of malnutrition. Employing an evolutionary psychiatry line of inquiry, we propose that rigidity of thinking and overactivity are behavioral phenotypic changes in AN patients that are normal to tree-dwelling mammals, such as monkeys. Such behavior can lead to good functioning as ballet dancers and athletes but lead to certain disadvantages in other areas of modern life. The overactivity in AN, though under conscious control may be neurobehavioral and driven subconsciously by disordered cerebral neuropsychopharmacology.

Drug addiction is a compulsive behavioral abnormality. In spite of pharmacologic and psychosocial treatments to reduce or eliminate drug taking, addiction tends to persist over time. Preclinical and human observations have converged on the hypothesis that addiction represents the pathologic deterioration of neural processes that normally serve affective and cognitive functioning. The major elements of persistent compulsive drug use are hypothesized to be molecular and cellular mechanisms that underlie enduring changes in a number of forebrain circuits (involving the ventral striatum and prefrontal cortex) that receive input from midbrain dopamine neurons and are involved in affective and cognitive mechanisms, respectively. Here we review progress in identifying crucial elements useful in understanding the pathophysiology of the disease and its pharmacologic treatment. Pharmacologic targeting of K-opiate receptors, with their discrete distribution within the dopaminergic system(s), and thus different actions on dopaminoceptive areas, may provide beneficial effects at the affective and cognitive level.

Bipolar disorder can be understood as a disorder of behavioral regulation. Manic and depressed individuals are impaired in the titration of appetitive arousal, possibly at the level of neuronal plasticity. An experiment in which fixed 5% CO2 stimulates respiration and blocks satiety tests the regulation of appetitive arousal. In preliminary analysis of data from 35 individuals (24 with bipolar disorder) individuals with bipolar disorder were more likely to fail to find a stable state of respiratory adjustment to CO2. If confirmed, the unstable respiratory response to CO2 may prove useful as a bipolar-disorder endophenotype.

Multiple neuronal systems contribute to the promotion and maintenance of the wake state, which is characterized by cortical activation and behavioral arousal. Using predominantly glutamate as a neurotransmitter, neurons within the reticular formation of the brainstem give rise to either ascending projections into the forebrain or descending projections into the spinal cord to promote through relays fast cortical activity or motor activity with postural muscle tone. Using acetylcholine, cholinergic neurons in the brainstem project to forebrain relays and others in the basal forebrain to the cortex, by which they stimulate fast gamma activity during waking and during rapid eye movement or paradoxical sleep (PS). Other neuromodulatory systems, such as noradrenergic locus coeruleus neurons, give rise to highly diffuse projections through brain and spinal cord and simultaneously stimulate cortical activation and behavioral arousal. Although such neuromodulatory systems were thought to be redundant, a recently discovered peptide called orexin (Orx) or hypocretin, contained in diffusely projecting neurons of the hypothalamus, was found to be essential for the maintenance of waking with muscle tone, since in its absence narcolepsy with cataplexy occurred. Orx neurons discharge during active waking and cease firing during sleep. Since cholinergic neurons discharge during waking and PS, they would stimulate cortical activation in association with muscle tone when orexinergic neurons are also active but would stimulate cortical activation with muscle atonia when orexinergic neurons are silent, as in natural PS, or absent, as in pathological narcolepsy with cataplexy.

A concept of generalized arousal of the CNS is presented and given an operational definition that leads to quantitative physical measures. Because this primitive arousal function underlies all motivated behavioral responses, cognitive functions, and emotional expression, disorders of generalized arousal can be associated with a large number of problems in medicine and public health, including vegetative states, attentional disorders, depression, occupational hazards, and problems with sleep and anesthesia. Some of its known mechanisms are briefly reviewed, at the levels of neuroanatomy, neurophysiology, and functional genomics. Generalized arousal contributes to the excitement and the activation of behaviors during specific arousal states. Data are summarized for four genomic/neurochemical systems through which changes in generalized arousal could affect sexual arousal, two of which heighten, and the other two of which reduce arousal.

Children show gradual and protracted improvement in an array of behaviors involved in the conscious control of thought and emotion. Behavioral research has shown that these abilities, collectively referred to as executive functions (EF), can be dissociated into separable processes, such as inhibition and working memory. Furthermore, noninvasive neuroimaging shows that these component processes often rely on separable neural circuits involving areas of the frontal cortex and nuclei of the basal ganglia. As additional noninvasive methodologies become available, it is increasingly possible to continue to dissect and dissociate components of EF and also test predictions made by a number of theoretical neuroanatomical models. One method of late is genetics, which is noninvasive and readily used in concert with neuroimaging. The biological data obtained with neuroimaging and genetics is particularly able to inform neuroanatomical models that link specific brain systems with higher more abstract process models derived from purely behavioral work. As much progress in this area continues to occur, we seek to evaluate the age dependency and manner in which certain aspects of EF and certain anatomical circuits show changes and interactions as children develop. Some examples are taken from research on children with the developmental disability attention deficit hyperactivity disorder. A review of selected developmental research shows that current cognitive and neuroanatomical models of EF offer a great many system- and synaptic-level hypotheses that can be tested using imaging and imaging genetics in longitudinal and cross-sectional study designs. Here, we focus on age-related changes in inhibition and working memory.

The lives of plants, animals, and human beings are all regulated by circadian clocks. In mammals, 24-hour rhythms of physiology and behavior are directed by a master clock in the suprachiasmatic nucleus (SCN) of the brain hypothalamus, which in turn entrains "slave" oscillators of similar molecular composition in most cells of the body. These peripheral clocks are interesting not only because they control many aspects of circadian physiology, but also because they are model systems through which we understand how the SCN regulates complex behavior. To this end, peripheral oscillators have been exploited both biochemically to understand the proteins that make up biological clocks, and genetically to decipher the ways in which individual differences in human chronotype might arise.

In the history of science, technical advances often precede periods of rapid accumulation of knowledge. Within the past three decades, discoveries that enabled the noninvasive measurement of the psychobiology of stress (in saliva) have added new dimensions to the study of health and human development. This widespread enthusiasm has led to somewhat of a renaissance in behavioral science. At the cutting edge, the focus is on testing innovative theoretical models of individual differences in behavior as a function of multilevel biosocial processes in the context of everyday life. Several new studies have generated renewed interest in salivary alpha-amylase (sAA) as a surrogate marker of the autonomic/sympathetic nervous system component of the psychobiology of stress. This article reviews sAA's properties and functions; presents illustrative findings relating sAA to stress and the physiology of stress, behavior, cognitive function, and health; and provides practical information regarding specimen collection and assay. The overarching intent is to accelerate the learning curve such that investigators avoid potential pitfalls associated with integrating this unique salivary analyte into the next generation of biobehavioral research.

The ultimate goal of this report is to learn how to manipulate the level of memory T cells for more effective treatment of such neurological diseases as multiple sclerosis (MS), where certain T cell subsets recognize self-antigens as opposed to pathogen antigens, and Alzheimer's disease (AD). Brain lesions (electrolitically, by kainic acid, with AlCl, and with 6-OHDA); stimulations (electrical, magnetic, or pharmacological); or restoration of some neurological functions (thermoregulatory and behavioral) by fetal graft allotransplantations in bilaterally lesioned anterior hypothalamic area (AHA-immune regulation) and nucleus basalis magnocellularis (NBM-experimental AD) in our studies were designed to reproduce immune and cognitive deficits induced by lesions of these brain structures. To localize memory traces in the immune system and in the brain we used ethanol and drugs such as kainic acid and 6-OHDA, which have been used very effectively to produce temporary lesions in the brain. Rats showed no learning and memory ability as well as inhibition of immune reactions.

Structural hippocampus and prefrontal cortex changes occur in patients with posttraumatic stress disorder (PTSD) that appears correlated with cognitive dysfunction. In these brain regions, serotonin (5HT) plays a prominent role in symptom presentation and treatment of PTSD. However, 5HT is both anxiogenic and anxiolytic, and while 5HT reuptake inhibitors are effective in treatment, the role of 5HT in the development of PTSD remains uncertain. Using a model of repeated trauma in rats, we observed significant spatial memory impairment together with significantly increased 5HT(1A) receptor density (B(max)), decreased 5HT(1A) receptor affinity (K(d)), and significantly increased 5HT(2A) receptor affinity on day 7 poststress. The serotonergic agent fluoxetine (FLX; 10 mg/kg/d ip) administered 1 week before stress and continuing throughout the stress procedure, but not the 5HT depleter p-chloro-phenylalanine (PCPA; 300/100/50 mg/kg/d ip), prevented stress-induced cognitive dysfunction. PCPA, however, reversed stress-induced hippocampal 5HT(1A) receptor affinity changes, with FLX narrowly missing significance. Neither drug reversed stress effects on 5HT(2A) receptor affinity. Thus, 5HT plays an important part in the cognitive-behavioral changes evoked by repeated trauma. That raised 5HT activity may mediate hippocampal 5HT(1A) receptor changes evoked by stress suggests a bidirectional role for 5HT in the development of PTSD.

Epidemiological evidence suggests that an adverse fetal environment permanently programs physiology, leading to increased risks of cardiovascular, metabolic, and neuroendocrine disorders in adulthood. Prenatal glucocorticoid excess or stress might link fetal maturation and adult pathophysiology. In a variety of animal models, prenatal glucocorticoid exposure or inhibition of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the fetoplacental "barrier" to maternal glucocorticoids, reduces birth weight and causes permanent hypertension, hyperglycemia, and increased hypothalamic-pituitary-adrenal axis (HPA) activity and behavior resembling anxiety. In humans, 11beta-HSD2 gene mutations cause low birth weight and reduced placental 11beta-HSD2 activity associated with intrauterine growth retardation. Low birth weight babies have higher plasma cortisol levels throughout adult life, indicating HPA programming. The molecular mechanisms may reflect permanent changes in the expression of specific transcription factors; key is the glucocorticoid receptor itself. Differential programming of the glucocorticoid receptor in different tissues reflects effects upon one or more of the multiple tissue-specific alternate first exons/promoters of the glucocorticoid receptor gene. Overall, the data suggest that either pharmacological or physiological exposure to excess glucocorticoids prenatally programs pathologies in adult life.

This paper summarizes the goals of this section and considers current knowledge about the association between hormonal changes that occur over pubertal development and the changes in behavior and brain function over the adolescent period. It reviews the cascade of neural and hormonal changes that occur with puberty; discusses mechanisms by which these changes can affect higher-order brain processes; reviews the current limited state of knowledge about links between puberty and changes in affect regulation in the adolescent period; identifies hurdles that have made progress in our understanding of these relationships difficult; and suggests areas for future investigation that will allow us to obtain a much more comprehensive understanding of these interrelationships. This overview of the physiological processes occurring at puberty indicates that puberty (1) encompasses changes in a number of neural systems; (2) results in altered secretion of a number of hormones; (3) involves hormones that are secreted in a pulsatile manner so that collection of a single blood sample does not clearly delineate hormone profiles; and (4) shows considerable individual variation in the rate of progression and in hormone secretion during progression. The important role that gonadal steroid hormones play throughout development and adulthood in regulating plastic changes in neuronal structure and function is noted, highlighting the need for further studies to determine the extent to which the dramatic increases in circulating steroid hormones at puberty modulate brain circuits that underlie changes in social behaviors, risk-taking behaviors, and cognitive function at adolescence.

Adolescence is a period in life marked by change, encompassing physiological changes associated with pubertal development, changes in social status and the social stresses that an individual faces, and changes in behavioral affect regulation. The interactions between activity in the reproductive axis, the neural systems that regulate stress, hormones produced in response to stress, and neural systems governing behavioral affect regulation are complex and multifaceted. Although our understanding of these interactions remains rudimentary, we do know that stress can suppress activity of the reproductive axis, that reproductive hormones can modulate the activity of neural systems that govern the body's responses to stress, that both reproductive function and stress responsiveness can be altered in depressed individuals, and that the function of some of the key neural systems regulating behavioral affect (i.e., serotonergic, noradrenergic, dopaminergic systems) are modulated by both gonadal steroid hormones and adrenal steroid hormones. This summary reviews the central interactions discussed in this session on the interrelationships between hormones, behavior, and affect during adolescence and identifies key topics that require further investigation in order to understand the role that pubertal changes in reproductive function, interacting with increased exposure to life stresses, play in modulating behavioral affect regulation during the adolescent period.

Long-lasting alterations in the efficacy of glutamatergic synapses, such as long-term potentiation (LTP) and long-term depression (LTD), are prominent models for mechanisms of information storage in the brain. It has been suggested that exposure to drugs of abuse produces synaptic plasticity at glutamatergic synapses that shares many features with LTP and LTD, and that these synaptic changes may play roles in addiction. We have examined the involvement of particular neurotransmitters in synaptic plasticity at glutamatergic synapses within the striatum, a brain region with prominent roles in initiation and sequencing of actions, as well as habit formation. Our studies indicate that multiple neurotransmitters interact to produce striatal synaptic plasticity, and that the relative strength and patterning of the afferent inputs that release the various neurotransmitters determines whether LTP or LTD is activated. Drugs of abuse interact with glutamatergic synaptic plasticity in multiple ways, including alterations in dopamine release and more direct effects on glutamate release and glutamate receptors. We hypothesize that these effects contribute to addiction by facilitating the formation of new, drug-centered habits, and by disruption of more adaptive behaviors.

It is customary to acquire behavior ratings of children with ADHD from parents and teachers, but comparable informants are typically not available for adults. Self-rating is substituted. The present study presents self-ratings of ADHD and control adults on a 43-item scale. The groups differed significantly on all but 4 descriptors, and 3 sufficed to account for more than 50% of the variance, reflecting distractibility, impulsivity and lack of control of behavior, respectively. Discriminant analysis revealed 83% and 90% correct classification of ADHD and controls, respectively. The results support the usefulness of self-rating in adults with ADHD and corroborate the resemblance and continuity between childhood and adult ADHD.

Musical imagery refers to the experience of "replaying" music by imagining it inside the head. Whereas visual imagery has been extensively studied, few people have investigated imagery in the auditory domain. This article reviews a program of research that has tried to characterize auditory imagery for music using both behavioral and cognitive neuroscientific tools. I begin by describing some of my behavioral studies of the mental analogues of musical tempo, pitch, and temporal extent. I then describe four studies using three techniques that examine the correspondence of brain involvement in actually perceiving vs. imagining familiar music. These involve one lesion study with epilepsy surgery patients, two positron emission tomography (PET) studies, and one study using transcranial magnetic stimulation (TMS). The studies converge on the importance of the right temporal neocortex and other right-hemisphere structures in the processing of both perceived and imagined nonverbal music. Perceiving and imagining songs that have words also involve structures in the left hemisphere. The supplementary motor area (SMA) is activated during musical imagery; it may mediate rehearsal that involves motor programs, such as imagined humming. Future studies are suggested that would involve imagery of sounds that cannot be produced by the vocal tract to clarify the role of the SMA in auditory imagery.

This chapter is a slightly modified version of Chapter 1 of my book, Investigations. I discuss "autonomous agents," the origin of life, autocatalytic sets of polymers, work cycles, puzzles-about evolutionary theory, and the birth of a general biology dealing with biospheres anywhere in the universe.

The Human Genome Project and the tools of modern molecular biology bring enormous promise for the understanding of human biology. Juxtaposed, however, is a conceptual stagnation reflected in the continued nature/nurture debate. More sophisticated models reflecting the inevitable interdependence of gene and environment are essential if we are to realize the potential offered by today's technological advances.

In this paper, some of the features of models of planning emerging from the area of artificial intelligence (AI) are explored. The goal of this exposition is to explain how researchers are getting machines to attack problems that appear to be similar to those handled in the human prefrontal cortex. In particular, I tried to explain some of the features of AI models that might help explain how planned behavior can occur, with an eye toward examining the specific information-processing constraints necessary for computational models of planning. I described how some AI researchers are converging on a model in which (1) a memory of complex planning information is used in guiding long-term behavior, (2) hierarchically ordered schemata are used to represent this information, (3) activation spreading-like effects occur both in the choice of the memory schemata to use and in monitoring the processing during the execution of those schemata, (4) schemata processing is activated and/or affected by environmental stimuli, and (5) multiple schemata with differing temporal extent are active in parallel. A specific AI planning model, developed in conjunction with Dr. Lee Spector of Hampshire College, was also presented; it was shown how it uses the features above to give rise to interesting planning behaviors for robotic systems.

Frontal-subcortical circuits provide a comprehensive framework for understanding the anatomy, biochemistry, and pharmacology of behavior. The three principal behaviorally relevant circuits originate in the dorsolateral prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex, respectively. Circuit-specific marker behaviors associated with each circuit are executive dysfunction (dorsolateral prefrontal-subcortical circuit), disinhibition and OCD (orbitofrontal-subcortical circuit), and apathy (medial frontal-subcortical circuit). Environmental dependency is common to all prefrontal-subcortical syndromes and may reflect disruption of working memory. Depression, mania, and psychosis are mediated by structures involved in prefrontal-subcortical circuits and are circuit-related but not circuit-specific behaviors. The actions of PCP, LSD, serotonergic antidepressants, anxiolytics, sedative-hypnotics, antipsychotic agents, and ethanol may all be partially or primarily mediated through transmitter systems and receptor effects expressed through frontal-subcortical circuits.

The principle of evaluative bivalence asserts that behavioral processes often organize along the evaluative dimension, due to a fundamental pattern of bivalent neurobehavioral organization extending throughout the neuraxis. This principle offers a powerful approach to the explication of complex behavioral relationships and the integration of diverse literatures. It also offers a guiding conceptual framework for the study of neurobehavioral relationships which holds the promise of integrating rather than diversifying the study of neural mechanisms for disparate behavioral phenomena.

Comparison of the results of the studies of cognitive development and normal aging suggests a large degree of commonality in both behavioral and ERP effects across a wide age range. Whether measured in young children, adolescents, young, middle-aged or elderly adults, the size of the ERP repetition effect did not differ among the various age groups. This was true whether memory was tested directly during continuous recognition or indirectly during variants of semantic categorization tasks. Similarly, in the studies of adult aging, the degree of RT facilitation during the semantic task did not differ with age and, in both the studies of cognitive development and aging, the degree of RT prolongation during the explicit tasks did not appear to differ as a function of age. Moreover, in the studies of adult aging, the effects of three versus two exposures of a word assessed in the PM session (TABLE 1), modulated RT similarly in all three age groups. These data argue for continuity of information processing across a very wide age range during both direct and indirect memory tasks, when retention is assessed during the recognition (for explicit testing) and repetition (for implicit testing) phases of the task. Since ERP and RT modulation do not appear to differ with age during the retrieval phases of these experiments, how can the performance differential seen in young children and older adults be explained? Some evidence comes from the ERP data recorded during the study phases of our explicit tasks. During continuous recognition, both young children and elderly adults did not show the typical subsequent "memory effect." In the case of the children, the subsequently unrecognized ERP was larger than the subsequently recognized ERP, whereas for the older adults, there was no difference between these two ERPs. Moreover, during these same tasks, the young children did show the "crossover" (new greater than old) pattern for slow wave activity, whereas the older adults did not. Since these ERP findings were obtained during the acquisition phase (i.e., to new items that had to be encoded for subsequent retrieval), the data argue for encoding difficulties as one means of explaining the performance differences seen at the two ends of the age spectrum. However, since the older adults displayed a different new/old pattern for slow wave activity, the two age groups may differ qualitatively in the strategies employed to encode items for subsequent retrieval.(ABSTRACT TRUNCATED AT 400 WORDS)

In summary, what we have tried to do in this paper is to present our view of the ways in which the ERP field has become more complex in recent years. It is not an overstatement to say that, in a certain sense, we know less now than we thought we knew five to ten years ago. New advances have brought with them new problems. But they also point, though not yet with complete clarity, to directions for new solutions. Possibly, as we make further progress toward the definition of various generators for different components, our problems may be simplified. But even this prediction cannot be made with certainty. It should be noted that we have tended in this chapter to emphasize the problems. There has also been a positive side to the recent developments. Because we are more aware of the overlap problem, we now work with methods that attempt to deal with it. We now know, for example, that P3b and SW can relate quite differently to behavioral variables. Decision time, which we had thought occurred at P3 latency, can now be assumed on the basis of recent findings to occur earlier, at the N2 component. The separation of the formerly unitary CNV into several components makes it more possible to develop unique functional roles for each of the components. A similar development has occurred with the separation of the poststimulus negativities into several components. Our constructs for various components are still on the fuzzy side, but the field has better tools at its disposal for making them more precise. Finally, the multiplicity of components, which appears overwhelming initially, provides us with more degrees of freedom in attempting to relate electrophysiological activity to behavior. A number of investigators have commented that the complexity of factors that enter into behavior could not be reflected in the relatively few ERP components we were dealing with. Now that more components are coming to be distinguished, the likelihood increases that we may be able to obtain ERP correlates of more of the dimensions involved in behavior.