A psychophysiological assessment battery

This research project was the first step in the development of a psychophysiological assessment battery. The battery consisted of eight tasks that have a history of use within the field of psychophysiology. These tasks were examined on a nonpathological, physically healthy sample. This sample was administered the assessment battery three times over the course of 16 weeks. The response systems of HR, SC, RR, TPA, and FPA were examined. Two major research questions were then examined. The first question was whether a subject would display a stable physiological profile on the assessment battery across the three administrations. The second question was whether there would be individual differences in physiological profiles on the assessment battery. These differences were examined in terms of individual response stereotypy (IRS) and stimulus response specificity (SRS). Depending on the task, from 30 to 100% of the subjects displayed stable physiological profiles across administrations. Twenty-five subjects displayed a high degree of SRS. Five subjects displayed a high degree of IRS.     

Reconfigurable task-dependent functional coupling modes cluster around a core functional architecture

Functional coupling across distributed brain regions varies across task contexts, yet there are stable features. To better understand the range and central tendencies of network configurations, coupling patterns were explored using functional MRI (fMRI) across 14 distinct continuously performed task states ranging from passive fixation to increasingly demanding classification tasks. Mean global correlation profiles across the cortex ranged from 0.69 to 0.82 between task states. Network configurations from both passive fixation and classification tasks similarly predicted task coactivation patterns estimated from meta-analysis of the literature. Thus, even across markedly different task states, central tendencies dominate the coupling configurations. Beyond these shared components, distinct task states displayed significant differences in coupling patterns in response to their varied demands. One possibility is that anatomical connectivity provides constraints that act as attractors pulling network configurations towards a limited number of robust states. Reconfigurable coupling modes emerge as significant modifications to a core functional architecture.     

Individual and sex differences in learning abilities of ravens

Behavioral and physiological characteristics of individuals within the same species have been found to be stable across time and contexts. In this study, we investigated individual differences in learning abilities and object and social manipulation to test for consistency within individuals across different tasks. Individual ravens (Corvus corax) were tested in simple color and position discrimination tasks to establish their learning abilities. We found that males were significantly better in the acquisition of the first discrimination task and the object manipulation task, but not in any of the other tasks. Furthermore, faster learners engaged less often in manipulations of conspecifics and exploration of objects to get access to food. No relationship between object and social manipulation and reversal training were found. Our results suggest that individual differences in regard to the acquisition of new tasks may be related to personalities or at least object manipulation in ravens.     

Long-Term Stability of Visual Pattern Selective Responses of Monkey Temporal Lobe Neurons

Many neurons in primate inferotemporal (IT) cortex respond selectively to complex, often meaningful, stimuli such as faces and objects. An important unanswered question is whether such response selectivity, which is thought to arise from experience-dependent plasticity, is maintained from day to day, or whether the roles of individual cells are continually reassigned based on the diet of natural vision. We addressed this question using microwire electrodes that were chronically implanted in the temporal lobe of two monkeys, often allowing us to monitor activity of individual neurons across days. We found that neurons maintained their selectivity in both response magnitude and patterns of spike timing across a large set of visual images throughout periods of stable signal isolation from the same cell that sometimes exceeded two weeks. These results indicate that stimulus-selectivity of responses in IT is stable across days and weeks of visual experience.     

Ability to Maintain Internal Arousal and Motivation Modulates Brain Responses to Emotions

Persistence (PS) is defined as the ability to generate and maintain arousal and motivation internally in the absence of immediate external reward. Low PS individuals tend to become discouraged when expectations are not rapidly fulfilled. The goal of this study was to investigate whether individual differences in PS influence the recruitment of brain regions involved in emotional processing and regulation. In a functional MRI study, 35 subjects judged the emotional intensity of displayed pictures. When processing negative pictures, low PS (vs. high PS) subjects showed higher amygdala and right orbito-frontal cortex (OFC) activity but lower left OFC activity. This dissociation in OFC activity suggests greater prefrontal cortical asymmetry for approach/avoidance motivation, suggesting an avoidance response to aversive stimuli in low PS. For positive or neutral stimuli, low PS subjects showed lower activity in the amygdala, striatum, and hippocampus. These results suggest that low PS may involve an imbalance in processing distinct emotional inputs, with greater reactivity to aversive information in regions involved in avoidance behaviour (amygdala, OFC) and dampened response to positive and neutral stimuli across circuits subserving motivated behaviour (striatum, hippocampus, amygdala). Low PS affective style was associated with depression vulnerability. These findings in non-depressed subjects point to a neural mechanism whereby some individuals are more likely to show systematic negative emotional biases, as frequently observed in depression. The assessment of these individual differences, including those that may cause vulnerability to depressive disorders, would therefore constitute a promising approach to risk assessment for depression.     

Relationship between disruption of rhythmicity and reentrainment in surgical patients

Urine samples for assay, temperature, heart rate, and blood pressure were collected daily at 2-h intervals from 11 consenting subjects undergoing abdominal surgery, as well as 10 age-and sex-matched control subjects. Alterations in level, and timing of circadian excretion of catecholamine metabolites, adrenal cortical hormones, sodium, potassium, creatinine, and vital signs following surgery were measured. Data were examined to determine if a relationship exists between the degree of circadian alteration and the subject's return to typical circadian profiles. The data suggest that certain circadian rhythms of hospitalized subjects were altered and uncoupled from external stimuli. In addition, subjects with less disruption in some variables following surgery regained rhythmicity more quickly than more disrupted subjects. These findings suggest that health professionals should individualize patient care to promote rhythmicity. In addition, patient assessment should consider individual circadian patterns and disruption following surgery.     

Solving the brain synchrony eigenvalue problem: conservation of temporal dynamics (fMRI) over subjects doing the same task

Brain measures often show highly structured temporal dynamics that synchronize when observers are doing the same task. The standard method for analysis of brain imaging signals (e.g. fMRI) uses the GLM for each voxel indexed against a specified experimental design but does not explicitly involve temporal dynamics. Consequently, the design variables that determine the functional brain areas are those correlated with the design variation rather than the common or conserved brain areas across subjects with the same temporal dynamics given the same stimulus conditions. This raises an important theoretical question: Are temporal dynamics conserved across individuals experiencing the same stimulus task? This general question can be framed in a dynamical systems context and further be posed as an eigenvalue problem about the conservation of synchrony across all brains simultaneously. We show that solving the problem results in a non-arbitrary measure of temporal dynamics across brains that scales over any number of subjects, stabilizes with increasing sample size, and varies systematically across tasks and stimulus conditions.     

Individual Variation in Lipidomic Profiles of Healthy Subjects in Response to Omega-3 Fatty Acids

Introduction

Conflicting findings in both interventional and observational studies have resulted in a lack of consensus on the benefits of ω3 fatty acids in reducing disease risk. This may be due to individual variability in response. We used a multi-platform lipidomic approach to investigate both the consistent and inconsistent responses of individuals comprehensively to a defined ω3 intervention.

Methods

The lipidomic profile including fatty acids, lipid classes, lipoprotein distribution, and oxylipins was examined multi- and uni-variately in 12 healthy subjects pre vs. post six weeks of ω3 fatty acids (1.9 g/d eicosapentaenoic acid [EPA] and 1.5 g/d docosahexaenoic acid [DHA]).

Results

Total lipidomic and oxylipin profiles were significantly different pre vs. post treatment across all subjects (p=0.00007 and p=0.00002 respectively). There was a strong correlation between oxylipin profiles and EPA and DHA incorporated into different lipid classes (r²=0.93). However, strikingly divergent responses among individuals were also observed. Both ω3 and ω6 fatty acid metabolites displayed a large degree of variation among the subjects. For example, in half of the subjects, two arachidonic acid cyclooxygenase products, prostaglandin E₂ (PGE₂) and thromboxane B2 (TXB₂), and a lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) significantly decreased post intervention, whereas in the other half they either did not change or increased. The EPA lipoxygenase metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) varied among subjects from an 82% decrease to a 5,000% increase.

Conclusions

Our results show that certain defined responses to ω3 fatty acid intervention were consistent across all subjects. However, there was also a high degree of inter-individual variability in certain aspects of lipid metabolism. This lipidomic based phenotyping approach demonstrated that individual responsiveness to ω3 fatty acids is highly variable and measurable, and could be used as a means to assess the effectiveness of ω3 interventions in modifying disease risk and determining metabolic phenotype.     

Rhythmic expression of circadian clock genes in human leukocytes and beard hair follicle cells

Evaluating individual circadian rhythm traits is crucial for understanding the human biological clock system. The present study reports characterization of physiological and molecular parameters in 13 healthy male subjects under a constant routine condition, where interfering factors were kept to minimum. We measured hormonal secretion levels and examined temporal expression profiles of circadian clock genes in peripheral leukocytes and beard hair follicle cells. All 13 subjects had prominent daily rhythms in melatonin and cortisol secretion. Significant circadian rhythmicity was found for PER1 in 9 subjects, PER2 in 3 subjects, PER3 in all 13 subjects, and BMAL1 in 8 subjects in leukocytes. Additionally, significant circadian rhythmicity was found for PER1 in 5 of 8 subjects tested, PER2 in 2 subjects, PER3 in 6 subjects, and BMAL1 in 3 subjects in beard hair follicle cells. The phase of PER1 and PER3 rhythms in leukocytes correlated significantly with that of physiological rhythms. Our results demonstrate that leukocytes and beard hair follicle cells possess an endogenous circadian clock and suggest that PER1 and PER3 expression would be appropriate biomarkers and hair follicle cells could be a useful tissue source for the evaluation of biological clock traits in individuals.     

Proteomic analysis of individual variation in normal livers of human beings using difference gel electrophoresis

Normal Chinese Liver Proteome Expression Profile is one of the major parts of Human Liver Proteome Project. Before starting the studies, it is necessary to examine the interindividual variation of normal liver proteome and evaluate the minimal size of samples for proteomic analysis. In this study, normal liver samples from ten individual volunteers were collected and the proteome profiles of these samples were analyzed using 2-D difference gel electrophoresis (DIGE) combined with MALDI-TOF/TOF MS. The individual liver tissue lysates were labeled with Cy3 and Cy5 while the pooled sample was labeled with Cy2 as an internal standard, which minimized gel-to-gel variation. After analysis by the DeCyder software, up to 2056 protein spots were detected on the master gel. The CV of standardized abundance was calculated for the protein spots that were matched across all ten gels. The CV values of these protein spots ranged from 6.4 to 108.5% and the median CV was approximately 19%, which demonstrated that the protein expression of normal liver among different individuals was relatively stable. The eight proteins with CV values over 50% were identified which would be a caveat when considering these proteins as potential disease-related markers. Moreover, the one-way ANOVA feature showed a correlation between sample size and individual variations. The results showed that when the sample size exceeded 7, the individual variations were not significant to the whole pool. Our results are an important basis for liver protein expression profiles and comparative proteomics of liver disease.     

Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer

Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer.     

NONPHOSPHORUS LIPIDS IN PERIPHYTON REFLECT AVAILABLE NUTRIENTS IN THE FLORIDA EVERGLADES,USA1

Algal and plant production of nonphosphorus lipids in place of phospholipids is a physiological response to low phosphorus (P) availability. This response has been shown in culture and in marine plankton studies, but examples from freshwater algae remain minimal. Herein, we analyzed the nutrient contents and lipid composition of periphyton communities across the Florida Everglades ecosystem. We hypothesized that in phosphate‐poor areas, periphyton in high‐ and low‐sulfate waters would vary the proportion of sulfolipids (SLs) and betaine lipids (BLs), respectively. In phosphate‐enriched areas, periphyton would produce more phospholipids (PLs). We observed that at low‐P sites, PLs were a minor lipid component. In cyanobacteria‐dominated periphyton where sulfate was abundant, BLs were only slightly more abundant than SLs. However, in the low‐P, low‐sulfate area, periphyton were comprised to a greater degree green algae and diatoms, and BLs represented the majority of the total lipids. Even in a P‐rich area, PLs were a small component of periphyton lipid profiles. Despite the phosphorus limitations of the Everglades, periphyton can develop tremendous biomass. Our results suggest a physiological response by periphyton to oligotrophic conditions whereby periphyton increase abundances of nonphosphorus lipids and have reduced proportions of PLs.     

Characterization of the psychological, physiological and EEG profile of acute betel quid intoxication in naïve subjects

Betel quid use and abuse is wide spread in Asia but the physiological basis of intoxication and addiction are unknown. In subjects na?ve to the habit of betel quid intoxication, the psychological and physiological profile of intoxication has never been reported. We compared the effect of chewing gum or chewing betel quid, and subsequent betel quid intoxication, on psychological assessment, prospective time interval estimation, numerical and character digit span, computerized 2 choice tests and mental tasks such as reading and mathematics with concurrent monitoring of ECG, EEG and face temperature in healthy, non-sleep deprived, male subjects na?ve to the habit of chewing betel quid. Betel quid intoxication, dose dependently induced tachycardia (max 30 bpm) and elevated face temperature (0.7°C) (P<0.001) above the effects observed in response to chewing gum (max 12 bpm and 0.3°C) in 12 subjects. Gross behavioral indices of working memory such as numerical or character digit span in 8 subjects, or simple visual-motor performance such as reaction speed or accuracy in a two choice scenario in 8 subjects were not affected by betel quid intoxication. Betel quid intoxication strongly influenced the psychological aspects of perception such as slowing of the prospective perception of passage of a 1 minute time interval in 8 subjects (P<0.05) and perceived increased arousal (P<0.01) and perceived decreased ability to think (P<0.05) in 31 subjects. The EEG spectral profile recorded from mental states associated with open and closed eyes, and mental tasks such as reading and eyes closed mental arithmetic were significantly modified (P<0.05) relative to chewing gum by betel quid intoxication in 10 subjects. The prevalence of betel quid consumption across a range of social and work settings warrants greater investigation of this widespread but largely under researched drug.     

Impairment in Task-Specific Modulation of Muscle Coordination Correlates with the Severity of Hand Impairment following Stroke

Significant functional impairment of the hand is commonly observed in stroke survivors. Our previous studies suggested that the inability to modulate muscle coordination patterns according to task requirements may be substantial after stroke, but these limitations have not been examined directly. In this study, we aimed to characterize post-stroke impairment in the ability to modulate muscle coordination patterns across tasks and its correlation with hand impairment. Fourteen stroke survivors, divided into a group with severe hand impairment (8 subjects) and a group with moderate hand impairment (6 subjects) according to their clinical functionality score, participated in the experiment. Another four neurologically intact subjects participated in the experiment to serve as a point of comparison. Activation patterns of nine hand and wrist muscles were recorded using surface electromyography while the subjects performed six isometric tasks. Patterns of covariation in muscle activations across tasks, i.e., muscle modules, were extracted from the muscle activation data. Our results showed that the degree of reduction in the inter-task separation of the multi-muscle activation patterns was indicative of the clinical functionality score of the subjects (mean value = 26.2 for severely impaired subjects, 38.1 for moderately impaired subjects). The values for moderately impaired subjects were much closer to those of the impaired subjects (mean value = 46.1). The number of muscle modules extracted from the muscle activation patterns of a subject across six tasks, which represents the degree of motor complexity, was found to be correlated with the clinical functionality score (R = 0.68). Greater impairment was also associated with a change in the muscle module patterns themselves, with greater muscle coactivation. A substantial reduction in the degrees-of-freedom of the multi-muscle coordination post-stroke was apparent, and the extent of the reduction, assessed by the stated metrics, was strongly associated with the level of clinical impairment.     

A controlled short-term exposure study to investigate the odor differences among three different formulations of gasoline

Control subjects (CON) and self-reported methyl tertiary butyl ether (MTBE)-sensitive subjects (SRS) were evaluated to distinguish between the following gasoline blends: gasoline versus gasoline + MTBE (15% MTBE v/v); and gasoline versus gasoline + MTBE + reodorant. The study also investigated the ability of a reodorant to conceal the odor of MTBE in a gasoline mixture. In each of two separate sessions, seven men (four CON, three SRS) and seven women (four CON, three SRS) were asked, in a forced-choice format, to sniff 28 randomized bottle pairs to determine if the odors in each pair were the same or different. Chi-square analyses revealed that, with the exception of one male CON, subjects were unable to distinguish between gasoline and gasoline with MTBE or gasoline with MTBE and the reodorant. Thus, a reodorant is of limited value as an additive which alters the ability of an individual to detect MTBE in a blended gasoline. The results suggest that at the level used in the experiment, no mask would be required to blind a participant from the odor of MTBE if that level is used in a controlled human health effects study of the additive.     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.     

Novel environmental enrichment may provide a tool for rapid assessment of animal personality: a case study with giant pandas (Ailuropoda melanoleuca)

Historically, the assessment of nonhuman animal personality has included a variety of methods--from direct behavioral observations in a variety of test situations to assessments provided by animal caretakers or trainers. Careful observation of how animals in zoos interact with novel enrichment may provide reliable insight into their personality. This study sought to describe a process for evaluating whether different methods of assessing personality result in similar conclusions. The study exposed 4 giant pandas at the Smithsonian National Zoological Park and Zoo Atlanta to 10 novel enrichment items and recorded their behavior. Keepers also rated each panda on 23 behavioral characteristics on a survey. The study obtained individual behavior profiles for each panda. Significant differences across individuals in both the novel enrichment trials and keeper surveys formed the basis for the profiles. These methods also provided some insight into differences between the sexes that--based on the natural history of giant pandas--are qualitatively similar to what would be expected. The study found some consistency between assessment methods. However, there is a need for further study to validate these measures in a larger sample of giant pandas.     

High proportion of smaller ranged hummingbird species coincides with ecological specialization across the Americas

Ecological communities that experience stable climate conditions have been speculated to preserve more specialized interspecific associations and have higher proportions of smaller ranged species (SRS). Thus, areas with disproportionally large numbers of SRS are expected to coincide geographically with a high degree of community-level ecological specialization, but this suggestion remains poorly supported with empirical evidence. Here, we analysed data for hummingbird resource specialization, range size, contemporary climate, and Late Quaternary climate stability for 46 hummingbird–plant mutualistic networks distributed across the Americas, representing 130 hummingbird species (ca 40% of all hummingbird species). We demonstrate a positive relationship between the proportion of SRS of hummingbirds and community-level specialization, i.e. the division of the floral niche among coexisting hummingbird species. This relationship remained strong even when accounting for climate, furthermore, the effect of SRS on specialization was far stronger than the effect of specialization on SRS, suggesting that climate largely influences specialization through species'' range-size dynamics. Irrespective of the exact mechanism involved, our results indicate that communities consisting of higher proportions of SRS may be vulnerable to disturbance not only because of their small geographical ranges, but also because of their high degree of specialization.     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.