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Random number generation, psychopathology and therapeutic change.

In two studies, 145 psychiatric inpatients were each asked to say 100 numbers in random order, using the numbers 1 through 10. Compared with normative data, patients with personality disorders and neuroses were not impaired on the random number generation (RNG) task and patients with chronic alcoholism and primary affective disorder, depression, were significantly imparied, but not as much as those with schizophrenia and organic brain syndrome. The relationship between RNG performance and psychiatric diagnosis may reflect severity of disturbed cognitive functioning. The Randomization Index was sensitive to changes in symptoms during hospitalization. The RNG task provides a brief objective measure of those components of attention, cognitive capacity, and short-term memory that are affected by severity of psychopathology.

Attention↗

Children's narratives and patterns of cardiac reactivity.

The present study examines the associations between narrative processing, narrative production, and cardiac rate and variability in children. Heart period (HP) and vagal tone (VT) were computed for fifty-eight 7-year-olds (29 males) during a resting baseline and during epochs in which the children listened to and completed a selected set of story-stems from the MacArthur Story-Stem Battery (I. Bretherton, D. Oppenheim, H. Buchsbaum, R. N. Emde, & the MacArthur Narrative Group, 1990). Significant decreases in HP and VT were observed between a resting baseline and epochs of story-stem presentation by the experimenter. In addition, HP was shorter and VT lower during children's narrative production to emotionally laden story-stems compared with narration to a neutral story-stem. Furthermore, narrative and cardiac responses to stories containing separation-reunion themes reflected increased emotional and cognitive load compared with responses to stories that did not contain such themes. Finally, children who showed VT suppression in response to emotion-laden stories produced more coherent and adaptive narratives compared to those of children who did not show VT suppression. The findings suggest interplay between the cognitive-emotional processes associated with narrative processing and production and cardiac activation patterns.

Affect↗

Gender differences in the functional neuroanatomy of emotional episodic autobiographical memory.

Autobiographical memory is based on interactions between episodic memory contents, associated emotions, and a sense of self-continuity along the time axis of one's life. The functional neuroanatomy subserving autobiographical memory is known to include prefrontal, medial and lateral temporal, as well as retrosplenial brain areas; however, whether gender differences exist in neural correlates of autobiographical memory remains to be clarified. We reanalyzed data from a previous functional magnetic resonance imaging (fMRI) experiment to investigate gender-related differences in the neural bases of autobiographical memories with differential remoteness and emotional valence. On the behavioral level, there were no significant gender differences in memory performance or emotional intensity of memories. Activations common to males and females during autobiographical memory retrieval were observed in a bilateral network of brain areas comprising medial and lateral temporal regions, including hippocampal and parahippocampal structures, posterior cingulate, as well as prefrontal cortex. In males (relative to females), all types of autobiographical memories investigated were associated with differential activation of the left parahippocampal gyrus. By contrast, right dorsolateral prefrontal cortex was activated differentially by females. In addition, the right insula was activated differentially in females during remote and negative memory retrieval. The data show gender-related differential neural activations within the network subserving autobiographical memory in both genders. We suggest that the differential activations may reflect gender-specific cognitive strategies during access to autobiographical memories that do not necessarily affect the behavioral level of memory performance and emotionality.

Adult↗

Exploring the process of inference generation in sarcasm: a review of normal and clinical studies.

This article evaluates two theoretical accounts of how sarcasm is understood; the traditional model, which asserts that listeners derive a counterfactual inference from the sarcastic comment, and relevance theory, which asserts that listeners recognize sarcasm as a scornful echo of a previous assertion. Evidence from normal speakers provides only partial support for both theories. Evidence from brain-injured populations suggests that aspects of the pragmatic process can be arrested in ways not predicted by either theory. It is concluded that sarcasm is more effortful to process than nonsarcastic comments and that inferences about the facts of the situation and the mental state of the speaker (e.g., attitudes, knowledge, and intentions) are important to comprehending sarcasm. It is questioned whether inferences about mental state are relatively more difficult for brain-injured subjects and, if so, whether this is a continuum of difficulty or reflects reliance upon different cognitive processes.

Brain Diseases↗

Opiate analgesia and its antagonism in dental event-related potentials: evidence for placebo antagonism.

The analgesic effects of the synthetic opiate fentanyl citrate (0.1 mg) on subjective pain reports (SPR) and late-wave event-related potentials (ERP) recorded during painful dental stimulation were examined in human subjects. Such waves have been shown to reflect the contribution of cognitive variables, such as expectancy and belief, to perception. In addition, the study was intended to demonstrate a dose-related narcotic antagonism with injection of naloxone (1.2 or 0.4 mg) or normal saline (double-blind) following IV fentanyl administration. Fentanyl reduced both ERP waveform amplitudes and SPR as have previously studied analgesic agents, such as nitrous oxide, acupuncture, and aspirin. Naloxone injection reversed both ERP and SPR changes, but surprisingly, a reversal of narcotic analgesia equal to that of 0.4 mg naloxone was seen with saline injection. By chance, all subjects were health-science students or professionals who were knowledgeable in opiate pharmacology, and so placebo reversal was hypothesized. Alternatively, it was hypothesized that fentanyl cleared more rapidly than predicted, thus, producing apparent reveal. In a second experiment involving similarly knowledgeable subjects with identical procedures and testing intervals, subjects received 0.1 mg fentanyl, but no reversal injection. The fentanyl effect was constant across this time period. The data, thus, support the hypothesis where the subjects were knowledgeable in opiate pharmacology, was placebo opiate antagonism.

Adult↗

EEG changes induced by carbamazepine therapy at rest and during mental processes.

The effects of carbamazepine (CBZ) on EEG background activity have been studied, at rest and during mental processes, in 18 epileptic patients suffering from focal epilepsy and starting antiepileptic treatment for the first time. The EEGs were recorded before and after CBZ therapy, at rest with eyes closed (EC), during blocking reaction (BR), fixation (FIX) and mental arithmetic (MA) tasks, and then evaluated by spectral analysis. All data underwent statistical evaluation utilizing the ANOVA and correlation coefficient. The following parameters were evaluated: mean absolute and relative power and mean frequency. The results have shown that CBZ induced a significant increase of slow activity at rest with EC, which was represented by delta potentials, and was correlated with CBZ plasma levels. In evaluating the different cortical activation patterns, a decrease of the alpha reactivity was noted during BR and FIX, while a significant increase of beta activity was observed during the performance of all tasks. The relationship between the increased beta power, possibly reflecting an increase of cognitive activity for processing information, and the lack of a significant decrease of alpha activity are discussed.

Adolescent↗

Testing the global-slowing hypothesis: are alcohol's effects on human performance process-specific or task-general?

In an interesting recent meta-analysis, Maylor and Rabbitt (1993) suggested that alcohol's effects on human performance may not be process- or stage-specific, but reflect a general, undifferentiated, cognitive slowing. According to this view, performance is globally slowed by a constant multiplicative fraction (b), such that the longer a process takes without alcohol on board (a -), the more it will be slowed by alcohol (a +). In summary: RTa+ = b b (RTa-). In this sense, the effects of alcohol are determined simply by the duration of a process or stage--not by its function or content--and attempts to map the effects of alcohol to specific cognitive operations are essentially futile. This global-slowing hypothesis entails, then, (i) that the function relating RTa+ to RTa- will be linear and increasing; (ii) that the value of b will be significantly greater than 1.0; and (iii) that all experimental factors which increase the complexity (hence, duration) of a task or stage will interact with alcohol. In this study we tested the global-slowing hypothesis directly using fixed set, varied set and concurrent sets item-recognition paradigms. All three tasks showed convincing additivity between alcohol and other key experimental factors which affect response latency (e.g., setsize, response type); there was no hint of any of the spectrum of significant interactions predicted by the global-slowing hypothesis. A meta-analysis of varied set latencies, analogous to Maylor and Rabbitt's, yielded a reasonably linear alcohol/no-alcohol function, but with a slope constant (b) less than 1.0. In all, the data provided little support for the global-slowing hypothesis.

Adolescent↗

Interregional correlations of resting cerebral glucose metabolism in old and young women.

A correlational analysis of normalized (regional to whole-brain) regional cerebral metabolic rates for glucose obtained in the 'resting' state (eyes covered, ears plugged) using [18F]fluorodeoxyglucose, demonstrated differences between old and young women in patterns of functional associations. Fifteen healthy young (age less than 40 years) and 17 healthy old women (age greater than 64 years) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest. The old women had fewer and less positive correlations between pairs of metabolic ratios in the frontal and parietal cortices. The results suggest an age-related reduction in frontal and parietal functional interactions in the 'resting' state that is consistent with a prior correlation analysis using a low resolution ECAT II scanner on young and old men. Reduced functional interactions may reflect age-related cognitive changes.

Adult↗

Characteristics of the Edinburgh Post Natal Depression Scale in The Netherlands.

The Edinburgh Post Natal Depression Scale (EPDS), a 10-item self-rating depression scale, was translated into Dutch and compared in 293 postpartum women with other self-rating scales commonly in use in The Netherlands. In addition the structure of EPDS was analyzed by various factor analyses to reveal some of its dimensional aspects. The Dutch version of EPDS was found to be a self-rating scale with good psychometric characteristics which measures what it claims to measure: the strength of depressive symptoms. With LISREL a 2-factor model could be distinguished which contained subscales reflecting depressive symptoms and cognitive anxiety.

Adult↗

Evoked potential topography in major depression. I. Comparisons with nonpatients and schizophrenics.

This study compared evoked potential (EP) topography in major depression (MD), schizophrenia and nonpatient controls. EPs to four kinds of stimuli were recorded from 15 locations. Patients were 69 MDs and 52 schizophrenics, currently unmedicated. EP waveforms of 195 controls were subjected to principal component factor analysis (PCA). The structures of 32 factors so extracted have been shown to encompass the data space of disparate groups; they were used to compute factor scores for all subjects. Age- and gender-matched groups were compared. Factor scores were normalized across leads (Z-transform) to distinguish between topographic and mean level differences. Topographic differences (P < 0.05) between MD and controls were demonstrated for scores of 8 factors, with 2 others at P = 0.053. Unlike those for schizophrenia/control comparisons, these topographic differences did not converge regionally in MD. EP findings were not related to duration of withdrawal from drugs. There were few differences between bipolar and unipolar patients. Topographies of 5 factors differed between MDs and schizophrenics; these involved all modalities and reflected long latency, cognition-related events, such as P300. These topographic differences were antero-posterior (AP); values were greater posteriorly in MDs and anteriorly in schizophrenics. Deviant AP gradients appear specific to MD; gradients were similar in schizophrenics and controls.

Adolescent↗

Wave form variations in auditory event-related potentials evoked by a memory-scanning task and their relationship with tests of intellectual function.

The inter-subject wave form variability of auditory event-related potentials (ERPs) evoked by digit probe identification in a memory-scanning task (Sternberg paradigm) and the effects of reaction time (RT) and task difficulty were studied in 26 healthy subjects. The response wave forms were compared with the performance of psychological tests of intelligence and memory. ERPs to 1-digit sets consisted of a sequence of waves identified as P100, N170, P250, N290, P400, P560 and N640. The major inter-subject difference in the response wave form was either the presence or absence of the late parietal positive wave P560. This wave occurred significantly more often in responses associated with larger memory sets and slow RT, suggesting that its presence reflects subjective difficulty in performing a task. With increasing set size, the P400 showed variable effects in different subjects, ranging from relative preservation of amplitude, through attenuation, to replacement or overlap by a broad surface-negative wave. This predominantly 'negative-going' effect of increasing task difficulty on the P400 was significantly correlated with scores of psychological tests; the greater the amplitude difference between the responses to easy and more difficult tasks, the better the scores, suggesting that these wave form changes reflect a more effective cognitive processing mechanism.

Acoustic Stimulation↗

Laser-evoked potentials: exogenous and endogenous components.

The aim of this study was to distinguish the exogenous component (related to the physical properties of the stimulus) and the endogenous component (reflecting event-related cognitive processing) of the laser-evoked potential (LEP). Short painful radiant heat pulses generated by a CO2-laser were applied to the dorsum of the right and left foot. LEPs were recorded with 5 scalp electrodes in the midline versus linked earlobes in 26 healthy subjects. In order to identify the exogenous component, the LEP was recorded during a standardised distraction task (reading a short story). To identify the endogenous component P3 for the LEP, a 2-stimulus oddball paradigm was used (20% probability of targets). When the task of the oddball paradigm consisted of pressing a button, a movement-related long-latency negativity (N 1200) was recorded in frontal leads that was absent in a counting task. The LEP of targets, frequent non-targets and during distraction was dominated by a single large positivity. The amplitude of this positivity was task-dependent and increased the more attention the subject payed to the laser stimuli (distraction < neutral < non-target < target). The laser-evoked positivity during distraction had a peak latency of about 400 msec (P400) and a maximum amplitude at the vertex, which was independent of inter-stimulus interval. The P3 following laser stimulation had a significantly later peak at about 570 msec (P570) and a different scalp topography with a parietal maximum. Its amplitude decreased when the interstimulus interval was reduced from 10 to 6 sec. Under neutral instructions, the LEP positivity consisted of a superposition of both the exogenous P 400 and the endogenous P570.

Adult↗

Molecular mechanisms of the specialization of human synapses in the neocortex.

Synapses of the neocortex specialized during human evolution to develop over extended timescales, process vast amounts of information and increase connectivity, which is thought to underlie our advanced social and cognitive abilities. These features reflect species-specific regulations of neuron and synapse cell biology. However, despite growing understanding of the human genome and the brain transcriptome at the single-cell level, linking human-specific genetic changes to the specialization of human synapses has remained experimentally challenging. In this review, we describe recent progress in characterizing divergent morphofunctional and developmental properties of human synapses, and we discuss new insights into the underlying molecular mechanisms. We also highlight intersections between evolutionary innovations and disorder-related dysfunctions at the synapse.

Humans↗

Verbal memory performance of patients with a first depressive episode and patients with unipolar and bipolar recurrent depression.

Depression is usually associated with episodic memory impairment. The main clinical features of depression associated with that memory impairment are not clearly defined. The main goal of that study was to assess the role of the diagnostic subtypes and the number of depressive episodes on the memory performance of acute unipolar (UP) and bipolar (BP) depressed patients.Twenty-three patients with a first major depressive episode (FE), 28 patients meeting DSM-IV criteria for UP recurrent depression (UR) and 18 BP patients with recurrent depression were compared with 88 healthy subjects on a verbal episodic memory task. Patients suffering from a first depressive episode did not show verbal memory impairment as compared to normal controls. Unlike FE patients, UR and BP patients exhibited verbal memory deficits with impaired free recall and normal cued recall and recognition. The memory deficits of the UR and BP patients was present in the first free recall trial. Depressed patients improved their memory performance across the three trials of the task at the same rate than normal controls. Our results suggest that the number of depressive episodes has a negative influence on verbal memory performance of acute depressed patients. The effects of the repetition of the depressive episodes are not modulated by the subtypes of depression and may reflect sensitization to the cognitive impact of depression associated with increasing prefrontal dysfunction.

Adult↗

Single-trial discrimination of truthful from deceptive responses during a game of financial risk using alpha-band MEG signals.

We studied whether magnetoencephalography (MEG) could detect deceptive responses on a single-subject, trial-by-trial basis. To elicit spontaneous, ecologically valid deception, we developed a paradigm in which subjects in a simulated customs setting were presented with a series of pictures of items which might be in their baggage, and for each item, they decided whether to "declare" (tell the truth) or "smuggle" (lie). Telling the truth involved a small but certain monetary penalty, whereas lying involved both greater monetary risk and greater potential reward. Most subjects showed decreased signal power in the 8-12 Hz (alpha) range during deceptive responses as compared to truthful responses. In a cross-validation analysis, we were able to use alpha power to classify truthful and deceptive responses on a trial-by-trial basis, with significantly greater predictive accuracy than that achieved using simultaneously recorded skin conductance signals. Average predictive accuracy for spontaneous deception was greater than 78%, and for some subjects, predictive accuracy exceeded 90%. Our results raise the possibility that alpha power modulation during deception may reflect risk management and/or cognitive control.

Adult↗

Dissociation of neural responses and skin conductance reactions during fear conditioning with and without awareness of stimulus contingencies.

This study investigates the effect of awareness of stimulus contingencies on BOLD responses within the amygdala, the orbitofrontal, and the occipital cortex, and on differential skin conductance responses (SCRs) during fear conditioning. Of two geometric figures, the paired conditioned stimulus (CS+) predicted an electrical stimulus (unconditioned stimulus = UCS), whereas the unpaired conditioned stimulus (CS-) was not followed by the UCS. Awareness of stimulus contingencies was manipulated experimentally, creating an aware and an unaware group: a distracter figure and a working memory task were introduced to conceal the stimulus contingencies of the conditioning paradigm, hence preventing contingency detection in the unaware group. The aware group was informed beforehand about the relation between CS+, CS-, and UCS. Differential SCRs were only obtained in the aware but not in the unaware group. Conversely, we observed enhanced responses of the amygdala, the orbitofrontal, and the occipital cortex to the CS+ in the unaware group only. Thus, we found a dissociation of SCR differentiation and the activation of a neural fear network depending on the presence or absence of awareness. These results support a model of fear conditioning that distinguishes between a more cognitive level of learning, reflected in contingency awareness and differential SCRs, and the awareness independent activation of a fear network.

Adult↗

Feedback about previous action improves executive functioning in schizophrenia: An analysis of maze solving behaviour.

Disturbances of executive functions (EF) in schizophrenia have received special attention during the past years, but there is still an ongoing debate whether impairment in EF tasks can be linked to deficits of EF themselves or if they rather reflect impairment of other cognitive functions such as working memory processes that are additionally required for task solving. In the present study, we analyzed whether impairments in the maintenance of previous processing assumed to be related to working memory contribute to the impairments in EF tasks seen in schizophrenia. Twenty-five schizophrenic patients treated with atypical antipsychotic agents and 25 healthy controls matched according to age, sex, and education were instructed to solve novel two-dimensional maze tasks by steering a pen through a system of paths. Low demands on maintaining previous actions by giving feedback on preceding movements (visualising the trace of the pen) were contrasted with high demands, i.e. without such a trace of past processing. Without feedback of previous action, task solution was less successful and the control of motor action was deficient in schizophrenic patients. With feedback, both domains of behaviour improved to the level of healthy controls at the costs of higher time demands. The behaviour of healthy controls was not influenced by the experimental manipulation. Lower demands on the maintenance of previous action seem to enable schizophrenic patients to perform executive functions successfully. But data suggest that task solving of schizophrenic patients is characterized by alterations in the coordination of executive functions with other cognitive processes.

Adult↗

Lead-induced attenuation in the aggregation of acetylcholine receptors during the neuromuscular junction formation.

Lead (Pb2+) toxicity is more common in children and is associated with cognitive deficits, which may reflect lead-induced changes in central synaptic development and function. Aside from neurotoxicity, lead exposure may also impact mature neuromuscular junction (NMJ) and cause muscle weakness. NMJ is known as a peripheral cholinergic synapse and its signaling cascades responsible for development are similar to those for the central synapses. However, the effect of lead exposure on the formation of NMJ in mammals is unclear. In the present study, a NG108-15/C2C12 coculture model was used to measure the acetylcholine receptor (AChR) aggregates formed on the myotubes which was an early hallmark for the NMJ formation. AChR aggregates were identified by alpha-bungarotoxin under fluorescent microscope. Single dose of lead acetate with final concentrations at 10(-3), 10(-1), or 10 microM was applied to dishes at the beginning of coculturing. Following 3-day exposure, although NG108-15 cells could extend long neurites to nearby myotubes, obvious dose-dependent attenuation in AChR aggregation was shown. The averaged area of an AChR aggregate, the averaged number of AChR aggregates per myotube, and the total area of AChR aggregates per myotube were all significantly decreased. In addition, the distribution percentages of various sizes of AChR aggregates showed that almost half of the AChR aggregates were formed with a size of 2-5 microm2 regardless of lead exposure. After treating 10 microM of lead acetate, significantly more AChR aggregates ranged from 2 to 20 microm2 were formed and significantly less AChR aggregates larger than 20 microm2 were formed. These results indicated that lead exposure reduced the extent of AChR aggregation concerning both the size and number of AChR aggregates and large AChR aggregates could hardly be formed after acute high-level lead exposure. No significant change was found in the total amount of AChRs on the myotubes after lead exposure, which indicated that the attenuation of AChR aggregation was not caused by reducing the synthesis of AChRs but by remaining dispersed pattern of AChRs on the myotubes. These data suggest that lead exposure exerts detrimental effects on the formation of NMJ.

Animals↗