Emotion–Cognition Interplay in Motivating and Guiding Plans and Actions: Commentary on McClure-Tone's Socioemotional Functioning in Bipolar Disorder

McClure-Tone (2009) focused on the role of two aspects of emotion knowledge (emotion expression recognition and labeling) and on emotion regulation in bipolar disorder (BD). We encourage further research on these and on other components of emotion knowledge that probably play equally significant roles in normal and abnormal development, and perhaps particularly in BD. Despite the author finding serious gaps in the literature, it was shown that we have learned a lot about differences in neural, cognitive, and behavioral processes in children and adolescents with BD and same-age normal individuals, and that much remains unknown. We join the author in encouraging more clinical, developmental, and longitudinal research on emotion processes in BD, particularly theoretically driven studies on some neglected emotion schemas that may prove relatively distinct to the disorder.     

Nucleus accumbens and impulsivity

The multifaceted concept of impulsivity implies that different impulsivity aspects, mediated by different neural processes, influence behavior at different levels. The nucleus accumbens (NAc) is a key component of the neural processes regulating impulsivity. In this review, we discuss the findings of lesion studies in animals and functional imaging studies in humans focusing on the role of the NAc in impulsivity. Evidence supports that the extent and pattern of involvement of the NAc, and its subregions, the core and the shell, vary among different facets of impulsivity. Data from imaging studies reviewed in this article suggest the involvement of the ventral striatum/NAc in impulsive choice. Findings of animal studies indicate that lesions of the NAc core subregion facilitated impulsivity in tasks involving intertemporal choice, and promoted a risk-averse, less impulsive, tendency in tasks involving options with probability differences. Modification of neurotransmitter activity, especially of dopamine, which is proposed to underlie the changes observed in functional imaging studies, has been shown to influence afferent input pattern in the NAc and the generation of the behavioral output. Parameters of behavioral tasks reflecting response inhibition function are altered by neurochemical interventions and local electrical stimulation in both the core and the shell subregions. In toto, NAc's pattern of neuronal activity, either genetically determined or acquired, has a critical impact on the interindividual variation in the expression of impulsivity. Nevertheless, the NAc is not the only substrate responsible for impulsivity and it is not involved in each facet of impulsivity to the same extent.     

Nucleus accumbens and impulsivity

The multifaceted concept of impulsivity implies that different impulsivity aspects, mediated by different neural processes, influence behavior at different levels. The nucleus accumbens (NAc) is a key component of the neural processes regulating impulsivity. In this review, we discuss the findings of lesion studies in animals and functional imaging studies in humans focusing on the role of the NAc in impulsivity. Evidence supports that the extent and pattern of involvement of the NAc, and its subregions, the core and the shell, vary among different facets of impulsivity. Data from imaging studies reviewed in this article suggest the involvement of the ventral striatum/NAc in impulsive choice. Findings of animal studies indicate that lesions of the NAc core subregion facilitated impulsivity in tasks involving intertemporal choice, and promoted a risk-averse, less impulsive, tendency in tasks involving options with probability differences. Modification of neurotransmitter activity, especially of dopamine, which is proposed to underlie the changes observed in functional imaging studies, has been shown to influence afferent input pattern in the NAc and the generation of the behavioral output. Parameters of behavioral tasks reflecting response inhibition function are altered by neurochemical interventions and local electrical stimulation in both the core and the shell subregions. In toto, NAc's pattern of neuronal activity, either genetically determined or acquired, has a critical impact on the interindividual variation in the expression of impulsivity. Nevertheless, the NAc is not the only substrate responsible for impulsivity and it is not involved in each facet of impulsivity to the same extent.     

Affective neuroscience and psychophysiology: toward a synthesis

This article reviews the author's program of research on the neural substrates of emotion and affective style and their behavioral and peripheral biological correlates. Two core dimensions along which affect is organized are approach and withdrawal. Some of the key circuitry underlying approach and withdrawal components of emotion is reviewed with an emphasis on the role played by different sectors of the prefrontal cortex (PFC) and amygdala. Affective style refers to individual differences in valence-specific features of emotional reactivity and regulation. The different parameters of affective style can be objectively measured using specific laboratory probes. Relations between individual differences in prefrontal and amygdala function and specific components of affective style are illustrated. The final section of the article concludes with a brief discussion of plasticity in the central circuitry of emotion and the possibility that this circuitry can be shaped by training experiences that might potentially promote a more resilient, positive affective style. The implications of this body of work for a broader conception of psychophysiology and for training the next generation of psychophysiologists are considered in the conclusion.     

Neuropsychology of bipolar disorder: a review

BACKGROUND: Bipolar disorder (BD) may be associated with significant and persistent cognitive impairment. The aim of this study was to describe the profile of cognitive deficits in BD at different phases of the illness and determine whether it is different from that of schizophrenia and unipolar (UP) depression. METHODS: A systematic review of the computerised literature of neuropsychological studies of BD published between 1980 and 2000. RESULTS: General intellectual function: this was largely preserved in BD. Impairments when present were limited to acute episodes and to performance scores. Attention: attentional abnormalities were seen in symptomatic BD patients and persisted in remission in measures of sustained attention and inhibitory control. Memory: verbal memory was impaired even in euthymic patients while visuo-spatial memory deficits were variable depending on the tasks used. Executive function: all aspects of executive function (planning, abstract concept formation, set shifting) were impaired in symptomatic BD patients. Performance on executive function tests was sensitive to the presence of even residual symptoms but it may be normal in fully recovered patients with uncomplicated BD. Comparison to other patient groups: no major differences in cognitive profile between BD and UP depression were found. Remitted BD patients out-performed stable schizophrenics on most cognitive measures but this advantage disappeared when they were acutely symptomatic. CONCLUSIONS: Symptomatic BD patients have widespread cognitive abnormalities. Trait related deficits appear to be present in verbal memory and sustained attention. Executive function and visual memory may be also affected at least in some recovered BD patients.     

Replication of Borna disease virus in rats: age-dependent differences in tissue distribution

There are age-dependent differences in the tissue distribution of Borna disease (BD) virus in rats infected intracerebrally. While in adult rats BD virus replication is restricted to neural cells, in neonatally infected rats infectious virus or viral antigens were found in the cells of most organs. The possibility that differences in the immune status between newborn and adult animals are responsible for different tissue susceptibility could be excluded.     

Epigenetics and bipolar disorder: new opportunities and challenges

Despite significant effort, understanding of the molecular causes and mechanisms of bipolar disorder (BD) remains a major challenge. Numerous molecular genetic linkage and association studies have been conducted over the last two decades; however, the data are quite inconsistent or even controversial. This article develops an argument that molecular studies of BD would benefit significantly from adding an epigenetic (epiG) perspective. EpiG factors refer to modifications of DNA and chromatin that "orchestrate" the activity of the genome, including regulation of gene expression. EpiG mechanisms are consistent with various non-Mendelian features of BD such as the relatively high degree of discordance in monozygotic (MZ) twins, the critical age group for susceptibility to the disease, clinical differences in males and females, and fluctuation of the disease course, including interchanges of manic and depressive phases, among others. Apart from the phenomenological consistency, molecular epiG peculiarities may shed new light on the understanding of controversial molecular genetic findings. The relevance of epigenetics for the molecular studies of BD is demonstrated using the examples of genetic studies of BD on chromosome 11p and the X chromosome. A spectrum of epiG mechanisms such as genomic imprinting, tissue-specific effects, paramutagenesis, and epiG polymorphism, as well as epiG regulation of X chromosome inactivation, is introduced. All this serves the goal of demonstrating that epiG factors cannot be ignored anymore in complex phenotypes such as BD, and systematic large-scale epiG studies of BD have to be initiated.     

What do we know about aging and spatial cognition? Reviews and perspectives

In order to cope with normal cognitive aging we must understand the patterns and neurofunctional underpinnings of cognitive and behavioral changes throughout adulthood. In this review, we summarize recent advances in our understanding of age-related behavioral differences and changes in brain structure throughout the spatial domain. Although spatial cognition is critically important to everyday life, few studies have examined the relationship between this cognitive function and neural changes in the aged brain. Thus, spatial cognition is considered a key area in which the cognitive neuroscience of aging may expand in the near future. The first section of this review examines the methodologies and studies used to assess differences in spatial cognition during normal cognitive aging in animals and humans. We then relate how each domain of spatial cognition (e.g., visuospatial perception, mental imagery, memory and navigation) is affected by the aging process, and discuss possible links with changes in neural mechanisms. Lastly, we address putative links among the age-related deterioration patterns of the various spatial domains and make suggestions for future research.     

Specificity of cognitive deficits in bipolar disorder versus schizophrenia. A systematic review

BACKGROUND: More and more epidemiological, genetic and neuroimaging studies show similarities between bipolar disorder (BD) and schizophrenia (SZ). Cognitive functions are known to be highly impaired in SZ and are increasingly studied in BD. When both populations are compared, the conclusions appear to be contradictory. The purpose of this review is to help define the profile of cognitive deficits in BD and in SZ. METHODS: A systematic review of the literature of neuropsychological studies comparing BD and SZ was made, beginning in January 1990 and ending in January 2005. Thirty-eight studies met the required quality criteria and were included in this review. RESULTS: Bipolar patients exhibit extensive cognitive abnormalities with a pattern of deficits that is not unique to this disease. However, when compared to schizophrenic patients, bipolar patients demonstrate a lesser degree of deficits, particularly concerning premorbid and current intelligence quotient and perhaps attention, verbal memory and executive functions. When looking into effect sizes, there seem to be different profiles even in studies finding no significant differences. CONCLUSIONS: The neuropsychological differences reported between both groups could be due to the presence of psychotic features, to environmental factors (stressful events, duration of the disease and number of hospitalisations) and could also be related to differences during the neurodevelopmental phase. Further studies should confirm whether these results are truly related to different neurobiological backgrounds.     

Evolutionary insights into the regulation of courtship behavior in male amphibians and reptiles

Comparative studies of species differences and similarities in the regulation of courtship behavior afford an understanding of evolutionary pressures and constraints shaping reproductive processes and the relative contributions of hormonal, genetic, and ecological factors. Here, we review species differences and similarities in the control of courtship and copulatory behaviors in male amphibians and reptiles, focusing on the role of sex steroid hormones, the neurohormone arginine vasotocin (AVT), and catecholamines. We discuss species differences in the sensory modalities used during courtship and in the neural correlates of these differences, as well as the value of particular model systems for neural evolution studies with regard to reproductive processes. For example, in some genera of amphibians (e.g., Ambystoma) and reptiles (e.g., Cnemidophorus), interspecific hybridizations occur, making it possible to compare the ancestral with the descendant species, and these systems provide a window into the process of behavioral and neural evolution as well as the effect of genome size. Though our understanding of the hormonal and neural correlates of mating behavior in a variety of amphibian and reptilian species has advanced substantially, more studies that manipulate hormone or neurotransmitter systems are required to assess the functions of these systems.     

Emotion regulation in children and adolescents: boundaries between normalcy and bipolar disorder

Much controversy has surrounded the diagnosis of bipolar disorder (BD) in children and adolescents. However, recent work from an affective neuroscience perspective has advanced what is known about the boundaries of emotion regulation in BD compared to typically developing youth. In this article, we first briefly review the clinical issues that have contributed to this diagnostic controversy. Second, we discuss our phenotyping system, which can be used to guide neurobiological research designed to address these controversial issues. Third, we review what is known about the fundamentals of emotion regulation in human and nonhuman primate models. Fourth, we present recent data demonstrating how children and adolescents with BD differ from those without psychopathology on measures of emotion regulation. Taken as a whole, this work implicates a neural circuit encompassing the prefrontal cortex, amygdala, and striatum in the pathophysiology of pediatric BD.     

In pursuit of neural risk factors for weight gain in humans

Obesity is a multifactorial disease associated with an increased risk of type 2 diabetes, coronary artery disease, cancer, and consequently, with a reduced length of life. Metabolic phenotypes of reduced energy expenditure have been associated with weight gain, but their contribution has been estimated to be relatively small. On the other hand, excessive food intake is likely to be the major determinant of positive energy balances and it is underlied by both non-conscious (homeostatic) and conscious (perceptual, emotional, and cognitive) phenomena processed in the brain. Functional neuroimaging is a promising tool to investigate these neural substrates in humans, because it provides a measurement of state-dependent brain regional activity, bridging the gap between neural events and behavioral responses. Using this technology, a few studies have provided the first evidence of functional differences between obese and lean individuals in the brain's response to energy intake and investigated the presence of neural risk factors of weight gain.     

Neural recruitment during failed motor inhibition differentiates youths with bipolar disorder and severe mood dysregulation

Controversy exists about whether non-episodic irritability (operationalized as severe mood dysregulation, SMD) should be considered a developmental presentation of pediatric bipolar disorder (BD). While assessments of brain function may address this controversy, only one fMRI study has compared BD versus SMD. We compared neural activation in BD, SMD, and controls during a motor inhibition task, since motor disinhibition is an important clinical feature in both BD and SMD. During failed inhibition, BD youths exhibited less activation in the right anterior cingulate cortex (ACC) and right nucleus accumbens relative to both SMD and healthy youths. Exploratory analyses indicate that, in BD youths, reduced activation in the right ACC may be independent of comorbid ADHD. These findings highlight neural distinctions between the phenotypically related BD and SMD populations.     

Anterior cingulate volume in pediatric bipolar disorder and autism

BACKGROUND: An increasing number of studies indicate the anterior cingulate gyrus (ACG) may play a role in the attention deficits associated with pediatric bipolar disorder (BD). Age, medications, and intelligence quotient (IQ) may affect ACG volume; few studies have controlled for these effects. METHODS: We recruited 16 children with BD and 24 children with autism spectrum disorder (ASD); 15 children with no psychiatric diagnosis (NP) were also included. All participants were evaluated with the K-SADS and a DSM-IV Autism/Asperger's Checklist; the ADI-R was also administered to ASD participants shortly after the study began. The participants completed a brain MRI scan on a 1.5Tesla Signa GE scanner. We segmented the ACG and compared left and right ACG volumes between groups. The influence of medications on the ACG volume was assessed while controlling for the effects of age and IQ. RESULTS: The left ACG volume was significantly smaller in the BD group compared to the NP (p=0.004) and ASD (p=0.006) groups. No significant differences were found in the right ACG volume. These differences do not appear to be attributable to medication use or IQ. CONCLUSIONS: Pediatric BD patients have a smaller left ACG volume compared to NP children and children diagnosed with ASD. This replication and extension of previous studies suggest that the ACG volume abnormality may be a biomarker for BD.     

Bilateral deficit and symmetry in finger force production during two-hand multifinger tasks

A comprehensive study of patterns of finger forces during one-hand and two-hand multifinger maximal force production trials was performed with particular emphasis on differences between tasks involving symmetrical and asymmetrical finger groups (symmetrical and asymmetrical tasks). Twelve healthy right-handed subjects performed maximal voluntary force production tasks with different finger combinations. Force deficit (FD) for a finger group within a hand was defined as a drop in peak force in a multifinger task as compared to the sum of individual finger peak forces in single-finger tasks. FD showed a dependence on both the number of fingers within the hand and the number of fingers in the other hand. An additional drop in peak finger forces was seen in two-hand tests (bilateral deficit, BD). BD summed over two hands was independent of the number of fingers involved in the two-hand tasks, but dependent on the distribution of fingers between the two hands. BD for a hand was larger for tasks involving fewer fingers within the hand and more fingers in the other hand. It was higher for asymmetrical tasks than for symmetrical tasks. The difference between asymmetrical and symmetrical tasks was due to the different behavior of asymmetrically involved fingers. FD was larger for asymmetrical master (explicitly involved) fingers, while forces produced involuntarily by asymmetrical slave (explicitly non-involved) fingers were larger. These differences brought down the total moment produced by both hands in the frontal plane. FD and BD are phenomena of different origin whose effects sum up. The observations have led to further development of a previously proposed double-representation, mirror-image (DoReMi) hypothesis and refinement of the neural network underlying the two-hand finger interaction.     

Genetic and neurocognitive foundations of emotion abnormalities in bipolar disorder

Introduction. Bipolar Disorder (BD) is a serious mood disorder, the aetiology of which is still unclear. The disorder is characterised by extreme mood variability in which patients fluctuate between markedly euphoric, irritable, and elevated states to periods of severe depression. The current research literature shows that BD patients demonstrate compromised neurocognitive ability in addition to these mood symptoms. Viable candidate genes implicated in neurocognitive and socioemotional processes may explain the development of these core emotion abnormalities. Additionally, links between faulty neurocognition and impaired socioemotional ability complement genetic explanations of BD pathogenesis. This review examines associations between cognition indexing prefrontal neural regions and socioemotional impairments including emotion processing and regulation. A review of the effect of COMT and TPH2 on these functions is also explored.

Methods. Major computer databases including PsycINFO, Google Scholar, and Medline were consulted in order to conduct a comprehensive review of the genetic and cognitive literature in BD.

Results. This review determines that COMT and TPH2 genetic variants contribute susceptibility to abnormal prefrontal neurocognitive function which oversees the processing and regulation of emotion. This provides for greater understanding of some of the emotional and cognitive symptoms in BD.

Conclusions. Current findings in this direction show promise, although the literature is still in its infancy and further empirical research is required to investigate these links explicitly.     

Neurophysiology of perceptual and motor aspects of interception

The interception of moving targets is a complex activity that involves a dynamic interplay of several perceptual and motor processes and therefore involves a rich interaction among several brain areas. Although the behavioral aspects of interception have been studied for the past three decades, it is only during the past decade that neural studies have been focused on this problem. In addition to the interception itself, several neural studies have explored, within that context, the underlying mechanisms concerning perceptual aspects of moving stimuli, such as optic flow and apparent motion. In this review, we discuss the wealth of knowledge that has accumulated on this topic with an emphasis on the results of neural studies in behaving monkeys.     

Temperature modulation (hypothermic and hyperthermic conditions) and its influence on histological and behavioral outcomes following cerebral ischemia

Core temperature (T(C)) is a critical determinant of the severity of neural damage that results from focal or global ischemia. Former studies indicated that especially intra-ischemic but also post ischemic mild hypothermia significantly decreased necrotic neural damage of a focal or global insult, as assessed between 3-7 days post-insult. More recent work shows that prolonged post-ischemic hypothermia reduces neural damage and inhibits associated behavioral deficits for up to one year after the insult (i.e. true neuroprotection with behavioral preservation). Alternatively, increases in core temperature via external heating or with pyrogens resulting from bacterial infections, at the time of the global ischemia insult worsen the neural damage of ischemic animals from those of respective normothermic controls given the same insult. This is paralleled in the clinical setting whereby approximately 50% of ischemic patients develop fevers within 2 days of the insult and have worsened neurological outcomes than non-febrile patients. The review discusses the possible mechanisms of neuroprotection of hypothermic therapy from cerebral ischemia as well as mechanisms involved in the exacerbation of neural damage of hypoxic ischemia under hyperthermic conditions. Questions are raised as to whether the medical community has sufficient evidence to begin appropriate hypothermic therapy of acute stroke patients. The importance of accurate monitoring core temperatures of all suspected stroke patients is emphasized, noting the differences in temperature that can occur with age, sex, medication or lifestyle so that appropriate temperature treatment could be implemented, if required.     

Mutational specificity: Assessment of 1,3-butadiene mutagenicity in the bone marrow of B6C3F1 lacl transgenic mice (Big Blue®): A review of mutational spectrum and LACL mutant frequency after a 5-day 625 PPM 1,3-butadiene exposure

1,3-Butadiene (BD) is a carcinogen that is bioactivated to at least two genotoxic metabolites. In the present article, we review briefly our previous studies on the in vivo, mutagenicity and mutational spectra of BD in bone morrow and extend these studies to examine the effect of exposure time (5-day vs. 4-week exposure to 625 ppm BD used in previous studies) on the lacl mutant frequency in the bone marrow. Inhalation exposure to BD at 625 ppm and 1,250 ppm was mutagenic in vivo inducing an increase in the transgene mutant and mutation frequency in the bone marrow. Analysis of the mutational spectrum in BD-exposed and air control mice demonstrated that BD exposure induced an increased frequency of mutations at A:T base pairs. There was no difference in the lacl mutant frequency determined in the bone marrow between a short-term exposure to BD (5 days) and a longer-term exposure (4 weeks). These data taken together demonstrate that inhalation exposure to BD induces in vivo somatic cell mutation. © 1996 Wiley-Liss, Inc.