Neuropsychological assessment methodology revisited: metatheoretical reflections.

Theory building in neuropsychology, similar to other disciplines, rests on metatheoretical assumptions of philosophical origin. Such assumptions regarding the relation of psychological and physiological variables influence research methodologies as well as assessment strategies in fields of application. Here, we revisit the classic procedure of Double Dissociation (DD) to illustrate the connection of metatheory and methodology. In a seemingly unbridgeable opposition, the classical neuropsychological procedure of DD can be understood as either presupposing localizationism and a modular view of the brain, or as a special case of the generalized neuro-lens model for neuropsychological assessment. In the latter case, it is more easily compatible with a perspective that emphasizes the systemic-network, rather than the modular, nature of the brain, which as part of the organism, proportionately mediates the situatedness of the human being in the world. This perspective not only makes it possible to structure ecological validation processes and give them a metatheoretical foundation, but also to interlace it with the phenomenological insight that the laboratory as one context of empirical research may be analyzed in terms of situated experience. We conclude with showing that both the localizationist and the system science approach can agree on a view of the brain as a dynamical network, and that metatheory may thus offer important new perspectives of reconciliation.

Trust your gut: vagal nerve stimulation in humans improves reinforcement learning.

Whereas the effect of vagal nerve stimulation on emotional states is well established, its effect on cognitive functions is still unclear. Recent rodent studies show that vagal activation enhances reinforcement learning and neuronal dopamine release. The influence of vagal nerve stimulation on reinforcement learning in humans is still unknown. Here, we studied the effect of transcutaneous vagal nerve stimulation on reinforcement learning in eight long-standing seizure-free epilepsy patients, using a well-established forced-choice reward-based paradigm in a cross-sectional, within-subject study design. We investigated vagal nerve stimulation effects on overall accuracy using non-parametric cluster-based permutation tests. Furthermore, we modelled sub-components of the decision process using drift-diffusion modelling. We found higher accuracies in the vagal nerve stimulation condition compared to sham stimulation. Modelling suggests a stimulation-dependent increase in reward sensitivity and shift of accuracy-speed trade-offs towards maximizing rewards. Moreover, vagal nerve stimulation was associated with increased non-decision times suggesting enhanced sensory or attentional processes. No differences of starting bias were detected for both conditions. Accuracies in the extinction phase were higher in later trials of the vagal nerve stimulation condition, suggesting a perseverative effect compared to sham. Together, our results provide first evidence of causal vagal influence on human reinforcement learning and might have clinical implications for the usage of vagal stimulation in learning deficiency.

Social context effects on error-related brain activity are dependent on interpersonal and achievement-related traits.

Brain correlates of performance monitoring, such as the Error-Related Negativity (ERN), are considerably influenced by situational factors. For instance, errors committed during social interaction typically elicit enhanced ERNs. While individual differences in ERN magnitude have been implicated in a wide variety of psychopathologies, it remains unclear how individual dispositions may interact with situational incentives to influence performance monitoring. Here, we analysed how interpersonal (Affiliation) and achievement-related (Agency) traits moderated the effects of interpersonal competition and interpersonal cooperation on the ERN. For this purpose, electroencephalography was collected from 78 participants while they performed a Flanker Task either in a competitive or in a cooperative social context (i.e., between-subjects design). We found that competition predicted enhanced error-related activity patterns compared to cooperation. Furthermore, participants who scored high in Affiliation elicited enhanced error-related activity. Conversely, high Agency scores were associated with reduced error-related activity, but this was only observed in the competitive context. These results indicate that the brain's response to error commission is not only sensitive to social incentives. Rather, the activity of the evaluative system that produces error signals appears to be crucially determined by the personal relevance of the incentives present in the context in which performance is evaluated.

Mood-congruent memory in daily life: evidence from interactive ambulatory monitoring.

Evidence from the psychological laboratory indicates that emotional states tend to facilitate the encoding and retrieval of stimuli of the same emotional valence. To explore mood-congruent memory and the role of arousal in daily life, we applied a new interactive ambulatory technique. Psychophysiological arousal as indexed by non-metabolic heart rate, self-reported emotions and situational information were assessed during 24-h recordings in 70 healthy participants. The emotional state was used to trigger word list presentations on a minicomputer. Our results show that psychophysiological arousal at the time of encoding enhanced the recall of negative words in negative emotional conditions, whereas low psychophysiological arousal facilitated recall of positive words. In positive contexts, mood congruency was more prominent when arousal was low. These results demonstrate how automated experimentation with an ambulatory technique may help to assess emotional memory in real-world contexts, thus providing new methods for diverse fields of application.

Emotional learning during dissociative states in borderline personality disorder.

BACKGROUND: Neurobiological findings and clinical data suggest that dissociative experience inhibits conditioning processes, but experimental studies are lacking. The aim of our study was to determine whether high states of dissociative experience would specifically alter emotional learning, but not declarative knowledge. METHODS: We used an aversive differential delay conditioning procedure in 33 unmedicated patients with borderline personality disorder (BPD) and 35 healthy controls. RESULTS: Patients with BPD who had high state dissociative experiences (BPD D+) showed diminished acquisition of differential aversive delay conditioning with respect to emotional learning compared with those who did not experience dissociative symptoms (BPD D-) and healthy controls (skin conductance response; interaction dissociation x quadratic time x type, p = 0.009). Specifically, the control group and the BPD D- subgroup showed an increase in valence and arousal to the conditioned stimulus (CS+) during the conditioning procedure (all p < 0.012) and demonstrated differential skin conductance responses in the acquisition and extinction phases. In contrast, the BPD D+ subgroup showed no increase in valence and arousal to CS+ or differential response regarding skin conductance. We examined general psychopathology, trauma history, perceptual differences and posttraumatic stress disorder as confounding factors, but we found no evidence of bias. LIMITATIONS: Subdividing the BPD group reduced power. In addition, because our sample included only women, the generalizability of our results is constrained. Furthermore, we performed no separate analysis of the influence of different aspects of dissociation on the learning process. CONCLUSION: Emotional, amygdala-based learning processes seem to be inhibited during state dissociative experience. State dissociative experience may alter acquisition and extinction processes and should be closely monitored in exposure-based psychotherapy.

Separating deceptive and orienting components in a Concealed Information Test.

The Concealed Information Test (CIT) requires the examinee to deceptively deny recognition of known stimuli and to truthfully deny recognition of unknown stimuli. Because deception and orienting are typically coupled, it is unclear how exactly these sub-processes affect the physiological responses measured in the CIT. The present study aimed at separating the effects of deception from those of orienting. In a mock-crime study, using a modified CIT, thirty-six of seventy-two subjects answered truthfully ('truth group'), whereas the other thirty-six concealed their knowledge ('lie group'). Answering was delayed for 4 s after item presentation. Electrodermal activity (EDA), respiration (RLL), and phasic heart rate (HR) were recorded. A decomposition of EDA responses revealed two response components; the response in the first interval was expected to indicate orienting, stimulus evaluation, and answer preparation, whereas the response in the second interval was assumed to reflect answer-related processes. Inconclusively, both EDA components differentiated between 'probe' and 'irrelevant' items in both groups. Phasic HR and RLL differed between item classes only in the 'lie' group, thus reflecting answer-related processes, possibly deception, rather than merely orienting responses. The findings further support the notion that psychophysiological measures elicited by a modified CIT may reflect different mental processes involved in orienting and deception.

An interfering Go/No-go task does not affect accuracy in a Concealed Information Test.

Following the idea that response inhibition processes play a central role in concealing information, the present study investigated the influence of a Go/No-go task as an interfering mental activity, performed parallel to the Concealed Information Test (CIT), on the detectability of concealed information. 40 undergraduate students participated in a mock-crime experiment and simultaneously performed a CIT and a Go/No-go task. Electrodermal activity (EDA), respiration line length (RLL), heart rate (HR) and finger pulse waveform length (FPWL) were registered. Reaction times were recorded as behavioral measures in the Go/No-go task as well as in the CIT. As a within-subject control condition, the CIT was also applied without an additional task. The parallel task did not influence the mean differences of the physiological measures of the mock-crime-related probe and the irrelevant items. This finding might possibly be due to the fact that the applied parallel task induced a tonic rather than a phasic mental activity, which did not influence differential responding to CIT items. No physiological evidence for an interaction between the parallel task and sub-processes of deception (e.g. inhibition) was found. Subjects' performance in the Go/No-go parallel task did not contribute to the detection of concealed information. Generalizability needs further investigations of different variations of the parallel task.

Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine.

BACKGROUND: Dosage of T(4) in central hypothyroidism is primarily guided by the free serum T(4) level (fT4). However, the optimum fT4 range is ill defined, and subtle hypothyroidism might be missed using this approach. OBJECTIVES: Our aim was to investigate the effects of a body weight (bw)-adapted T(4) treatment, alone or in combination with T(3), on metabolism, well-being, and cognitive function in comparison to a regimen leading to normal fT4. DESIGN: This was a placebo-controlled trial (double-blind, crossover). PATIENTS: A total of 29 patients (age 52 +/- 2 yr; females/males, 8/21) with hypopituitarism, including TSH deficiency, participated in the study. INTERVENTIONS: Three regimens were compared (5 wk each): "EMPIRICAL-T4," empirical T(4) dosage (1 +/- 0.05 microg/kg bw) leading to normal fT4; BW-ADAPTED-T4 (1.6 microg/kg bw T(4)); and "BW-ADAPTED-T3T4," bw-adapted combination of T(3) and T(4) (ratio of 1:10). RESULTS: BW-ADAPTED-T4 administration increased mean fT4 concentrations to the upper limit of the normal range (peak levels). Compared with EMPIRICAL-T4, BW-ADAPTED-T4 treatment resulted in a lower body mass index (BMI) (29.0 +/- 0.7 vs. 29.5 +/- 0.7 kg/m(2); P < 0.03), lower total cholesterol (198 +/- 9 vs. 226 +/- 7 mg/dl; P < 0.01), and lower low-density lipoprotein (LDL) cholesterol (116 +/- 5 vs. 135 +/- 7 mg/dl; P < 0.01). BW-ADAPTED-T3T4 treatment was associated with additional beneficial effects on ankle reflex time and working memory but resulted in supraphysiological free serum T(3) (fT(3)) levels. LIMITATIONS: Long-term side effects may have been missed. CONCLUSIONS: Using a dose of 1.6 microg/kg bw improved markers commonly associated with central hypothyroidism. This suggests that T(4) dosage based on bw and aiming at fT4 in the upper reference range is superior to titration of T(4) aiming at middle normal fT4 concentrations in those patients.

Imaging emotional brain functions: conceptual and methodological issues.

This article reviews the psychophysiological and brain imaging literature on emotional brain function from a methodological point of view. The difficulties in defining, operationalising and measuring emotional activation and, in particular, aversive learning will be considered. Emotion is a response of the organism during an episode of major significance and involves physiological activation, motivational, perceptual, evaluative and learning processes, motor expression, action tendencies and monitoring/subjective feelings. Despite the advances in assessing the physiological correlates of emotional perception and learning processes, a critical appraisal shows that functional neuroimaging approaches encounter methodological difficulties regarding measurement precision (e.g., response scaling and reproducibility) and validity (e.g., response specificity, generalisation to other paradigms, subjects or settings). Since emotional processes are not only the result of localised but also of widely distributed activation, a more representative model of assessment is needed that systematically relates the hierarchy of high- and low-level emotion constructs with the corresponding patterns of activity and functional connectivity of the brain.

Intra-subject variability in attention-deficit hyperactivity disorder.

BACKGROUND: This study is based on a comprehensive survey of the neuropsychological attention-deficit hyperactivity disorder (ADHD) literature and presents the first psychometric analyses of different parameters of intra-subject variability (ISV) in patients with ADHD compared to healthy controls, using the Continuous Performance Test, a Go-NoGo task, a Stop Signal Task, as well as N-back tasks. METHODS: Data of 57 patients with ADHD and 53 age- and gender-matched controls were available for statistical analysis. Different parameters were used to describe central tendency (arithmetic mean, median), dispersion (standard deviation, coefficient of variation, consecutive variance), and shape (skewness, excess) of reaction time distributions, as well as errors (commissions and omissions). RESULTS: Group comparisons revealed by far the strongest effect sizes for measures of dispersion, followed by measures of central tendency, and by commission errors. Statistical control of ISV reduced group differences in the other measures substantially. One (patients) or two (controls) principal components explained up to 67% of the inter-individual differences in intra-individual variability. CONCLUSIONS: Results suggest that, across a variety of neuropsychological tests, measures of ISV contribute best to group discrimination, with limited incremental validity of measures of central tendency and errors. Furthermore, increased ISV might be a unitary construct in ADHD.

Functional neuroimaging of emotional learning and autonomic reactions.

This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.

Effects of expectation and caffeine on arousal, well-being, and reaction time.

The objective of this study is to determine the impact of expectation associated with placebo and caffeine ingestion. We used a three-armed, randomized, double-blind design. Two three-armed experiments varying instruction (true, false, control) investigated the role of expectations of changes in arousal (blood pressure, heart rate), subjective well-being, and reaction time (RT). In Experiment 1 (N = 45), decaffeinated coffee was administered, and expectations were produced in one group by making them believe they had ingested caffeinated coffee. In Experiment 2 (N = 45), caffeinated orange juice was given in both experimental groups, but only one was informed about the true content. In Experiment 1, a significant effect for subjective alertness was found in the placebo treatment compared to the control group. However, for RT and well-being no significant effects were found. In Experiment 2, no significant expectancy effects were found. Caffeine produced large effects for blood pressure in both treatments compared to the control group, but the effects were larger for the false information group. For subjective well-being (alertness, calmness), considerable but nonsignificant changes were found for correctly informed participants, indicating possible additivity of pharmacologic effect and expectations. The results tentatively indicate that placebo and expectancy effects primarily show through introspection.

Neuropsychological effects of chronic low-dose exposure to polychlorinated biphenyls (PCBs): a cross-sectional study.

BACKGROUND: Exposure to indoor air of private or public buildings contaminated with polychlorinated biphenyls (PCBs) has raised health concerns in long-term users. This exploratory neuropsychological group study investigated the potential adverse effects of chronic low-dose exposure to specific air-borne low chlorinated PCBs on well-being and behavioral measures in adult humans. METHODS: Thirty employees exposed to indoor air contaminated with PCBs from elastic sealants in a school building were compared to 30 non-exposed controls matched for education and age, controlling for gender (age range 37-61 years). PCB exposure was verified by external exposure data and biological monitoring (PCB 28, 101, 138, 153, 180). Subjective complaints, learning and memory, executive function, and visual-spatial function was assessed by standardized neuropsychological testing. Since exposure status depended on the use of contaminated rooms, an objectively exposed subgroup (N = 16; PCB 28 = 0.20 microg/l; weighted exposure duration 17.9 +/- 7 years) was identified and compared with 16 paired controls. RESULTS: Blood analyses indicated a moderate exposure effect size (d) relative to expected background exposure for total PCB (4.45 +/- 2.44 microg/l; d = 0.4). A significant exposure effect was found for the low chlorinated PCBs 28 (0.28 +/- 0.25 microg/l; d = 1.5) and 101 (0.07 +/- 0.09 microg/l; d = 0.7). Although no neuropsychological effects exceeded the adjusted significance level, estimation statistics showed elevated effect sizes for several variables. The objectively exposed subgroup showed a trend towards increased subjective attentional and emotional complaints (tiredness and slowing of practical activities, emotional state) as well as attenuated attentional performance (response shifting and alertness in a cued reaction task). CONCLUSION: Chronic inhalation of low chlorinated PCBs that involved elevated blood levels was associated with a subtle attenuation of emotional well-being and attentional function. Extended research is needed to replicate the potential long-term low PCB effects in a larger sample.