Cognitive Brain Research

Published by Elsevier
Print ISSN: 0926-6410
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Day-old chicks trained in a single trial passive avoidance task develop three sequentially dependent stages of discrimination memory. The second intermediate stage is made up of two phases: the initial A phase being susceptible to inhibition of oxidative metabolism in the tricarboxcylic acid (TCA) system with 2,4-dinitrophenol (DNP), and a second DNP-insensitive B phase. The studies reported in this paper found that doses of the metabolic toxins fluoroacetate (0.2 mM) and fluorocitrate (0.1 mM) previously reported to disrupt the astrocytic TCA cycle only, also disrupt the A (but not the B) phase of intermediate memory, suggesting an interaction between the astrocytic and neuronal oxidative systems may be required to meet the metabolic demands of this earlier phase. The B phase, on the other hand, was not expressed in the presence of the glycolytic inhibitor iodoacetate (1 mM), suggesting that glycolysis (known to be more efficient in astrocytes) and glycogenolysis (which may be exclusive to astrocytes) may support this second phase of intermediate memory. In this regard, the rise in forebrain noradrenaline levels previously reported to occur before the appearance of the B phase is particularly relevant. Given that noradrenaline has been shown to be capable of enhancing glycogenolysis in astrocyte-enriched cell cultures, it is conceivable that noradrenaline exerts an effect on memory by stimulating the glycolytic system in astrocytes, thereby providing energy or metabolites (e.g. pyruvate) needed to sustain the cellular processes operating during the B phase of intermediate memory.
 
Parietal cortex contains multiple representations of visual space. Single neurons in area LIP encode attended locations relative to the fovea, while some VIP neurons encode stimulus location relative to the head and some MIP neurons may encode location relative to the arm. These multiple representations are tailored to guide specific kinds of actions: eye movements, head movements and arm movements, respectively. The function of parietal cortex is to signal the location of attended objects relative to the observer. It does so in order to allow the organism to act on its environment. The many different kinds of actions that can be performed are likely to be supported by these very different kinds of spatial representations.
 
Neuropsychological investigations of substance abusers have reported impairments on tasks mediated by the frontal executive system, including functions associated with behavioral inhibition and decision making. The higher order or executive components which are involved in decision making include selective attention and short term storage of information, inhibition of response to irrelevant information, initiation of response to relevant information, self-monitoring of performance, and changing internal and external contingencies in order to "stay the course" towards the ultimate goal. Given the hypothesized role of frontal systems in decision making and the previous evidence that executive dysfunctions and structural brain changes exist in subjects who use illicit drugs, we applied fMRI and diffusion tensor imaging (DTI) techniques in a pilot investigation of heavy cannabis smokers and matched control subjects while performing a modification of the classic Stroop task. Marijuana smokers demonstrated significantly lower anterior cingulate activity in focal areas of the anterior cingulate cortex and higher midcingulate activity relative to controls, although both groups were able to perform the task within normal limits. Normal controls also demonstrated increased activity within the right dorsolateral prefrontal cortex (DLPFC) during the interference condition, while marijuana smokers demonstrated a more diffuse, bilateral pattern of DLPFC activation. Similarly, although both groups performed the task well, marijuana smokers made more errors of commission than controls during the interference condition, which were associated with different brain regions than control subjects. These findings suggest that marijuana smokers exhibit different patterns of BOLD response and error response during the Stroop interference condition compared to normal controls despite similar task performance. Furthermore, DTI measures in frontal regions, which include the genu and splenium of the corpus callosum and bilateral anterior cingulate white matter regions, showed no between group differences in fractional anisotropy (FA), a measure of directional coherence within white matter fiber tracts, but a notable increase in trace, a measure of overall isotropic diffusivity in marijuana smokers compared to controls. Overall, results from the present study indicate significant differences in the magnitude and pattern of signal intensity change within the anterior cingulate and the DLPFC during the Stroop interference subtest in chronic marijuana smokers compared to normal controls. Furthermore, although chronic marijuana smokers were able to perform the task reasonably well, the functional activation findings suggest they utilize different cortical processes from the control subjects in order to do so. Findings from this study are consistent with the notion that substance abusers demonstrate evidence of altered frontal neural function during the performance of tasks that involve inhibition and performance monitoring, which may affect the ability to make decisions.
 
Mismatch negativity (MMN) is a component of the auditory evoked event-related potentials (ERP) that assesses automatic sound change detection and is disturbed in schizophrenic patients. Animal experimental evidence has linked the generation of MMN to the N-methyl-D-aspartate (NMDA) receptor. We investigated the neuromagnetic mismatch field (MMF) in healthy volunteers before and after intravenous application of a subanesthetic dose of the NMDA receptor antagonist ketamine (0.3 mg/kg). Ketamine had a significant influence on latency and dipole moment of the MMF, whereas the N100m latency of the standard tone was not prolonged and its dipole moment remained stable. Our results suggest that ketamine interferes with aspects of preattentive information processing and is in line with the view that disturbed NMDA receptor function may mediate the deficient auditory mismatch response in patients with schizophrenia.
 
The meaning of a visual scene influences the identification of visual objects embedded in it. We investigated the nature and time course of scene effects on object identification by recording event-related brain potentials (ERPs) and response times (RTs). In three experiments, participants identified objects within a scene that were either semantically congruous (e.g., a pot in a kitchen) or incongruous (e.g., a desk in a river). As expected, RTs were faster for congruous than incongruous objects. The earliest sign of reliable scene congruity effects in the ERPs (greater positivity for congruous pictures between 300 and 500 ms) was around 300 ms. Both the morphology and time course of the N390 scene congruity effect are reminiscent of the N400 sentence congruity effect typically observed in sentence context paradigms, suggesting a functional similarity of the neural processes involved. Overall, these results support theories postulating that visual scenes do not appreciably affect object identification processes before associated semantic information is activated. We speculate that the N390 scene congruity effect reflects the action of visual scene schemata stored in the anterior temporal lobe.
 
The specific dopamine uptake inhibitor, GBR 12783 was tested on the retention performance of a one-trial passive avoidance test. For a moderate electric shock intensity, GBR 12783 (10 mg/kg), injected before acquisition session, improved retention performance. Scopolamine (0.125-0.5 mg/kg) completely blocked the promnesic effect of GBR 12783. Moreover, GBR 12783 increased hippocampal acetylcholine release in vivo. These data suggest that the promnesic effect of GBR 12783 is mediated by an increase in the septo-hippocampal cholinergic transmission.
 
We investigated the modulation of the somatosensory evoked potential (SEP) elicited by mechanical stimuli in a spatial sustained attention and a spatial trial-by-trial cueing design by means of high density electrode array EEG recordings. Subjects were instructed to detect rare tactile target stimuli at the to-be-attended hand while ignoring stimuli at the other hand. Analysis of the SEP revealed a highly complex pattern of results. The P50 component was significantly increased for attended stimuli in the sustained attention as opposed to the trial-by-trial cueing condition. However, no difference in amplitude was found for attended as opposed to unattended stimuli. High density electrode array recordings revealed a centero-frontal N140 component (N140c), which preceded the parietal N140 (N140p) by about 20 ms. The N140c exhibited an attention effect in particular in the trial-by-trial spatial cueing condition. The N140p was significantly enlarged with attention across both experimental conditions, but a closer inspection demonstrated that this was mainly due to the great attention effect in the trial-by-trial spatial cueing condition. The late positive component (190-380 ms after stimulus onset) exhibited a significant attention effect in both experimental conditions. The present experiment provides evidence that the attentional modulation of the SEP is different when tactile as opposed to electrical stimuli were used and when only somatosensory stimuli are presented with no further sensory stimulation in other modalities. Furthermore, transient as opposed to sustained spatial attention affected various components of the SEP in a different way.
 
The Stroop and Simon tasks typify a class of interference effects in which the introduction of task-irrelevant stimulus characteristics robustly slows reaction times. Behavioral studies have not succeeded in determining whether the neural basis for the resolution of these interference effects during successful task performance is similar or different across tasks. Event-related functional magnetic resonance imaging (fMRI) studies were obtained in 10 healthy young adults during performance of the Stroop and Simon tasks. Activation during the Stroop task replicated findings from two earlier fMRI studies. These activations were remarkably similar to those observed during the Simon task, and included anterior cingulate, supplementary motor, visual association, inferior temporal, inferior parietal, inferior frontal, and dorsolateral prefrontal cortices, as well as the caudate nuclei. The time courses of activation were also similar across tasks. Resolution of interference effects in the Simon and Stroop tasks engage similar brain regions, and with a similar time course. Therefore, despite the widely differing stimulus characteristics employed by these tasks, the neural systems that subserve successful task performance are likely to be similar as well.
 
Phase synchrony during the performance of two cognitive tasks: visual perception or looking at the paintings (black), and imagination of paintings (white) for two groups: artists (upper row), and non-artist (lower). Phase synchrony values were averaged over time and all possible electrode combinations. Note the differences in the scale across different frequency bands. Difference between two tasks was most evident in gamma band for artists.
Functional and topographical differences between two groups, artists and non-artists, during the performances of visual perception and imagery of paintings were presented by means of EEG phase synchrony analysis. In artists as compared with non-artists, significantly higher phase synchrony was found in the high frequency beta and gamma bands during the perception of the paintings; in the low frequency bands (primarily delta), phase synchrony was mostly enhanced during imagery. Strong decreases in phase synchrony of alpha were found primarily in artists for both tasks. The right hemisphere was found to present higher synchrony than the left in artists, whereas hemispheric asymmetry was less significant in non-artists. In the artists, enhanced synchrony in the high frequency band is most likely due to their enhanced binding capabilities of numerous visual attributes, and enhanced synchrony in the low frequency band seems to be due to the higher involvement of long-term visual memory mostly in imagery. Thus, the analysis of phase synchrony from EEG signals yields new information about the dynamical co-operation between neuronal assemblies during the cognition of visual art.
 
In area F5 of the monkey premotor cortex there are neurons that discharge both when the monkey performs an action and when he observes a similar action made by another monkey or by the experimenter. We report here some of the properties of these 'mirror' neurons and we propose that their activity 'represents' the observed action. We posit, then, that this motor representation is at the basis of the understanding of motor events. Finally, on the basis of some recent data showing that, in man, the observation of motor actions activate the posterior part of inferior frontal gyrus, we suggest that the development of the lateral verbal communication system in man derives from a more ancient communication system based on recognition of hand and face gestures.
 
Regular sequences of sounds (i.e., non-random) can usually be described by several, equally valid rules. Rules allowing extrapolation from one sound to the next are termed local rules, those that define relations between temporally non-adjacent sounds are termed global rules. The aim of the present study was to determine whether both local and global rules can be simultaneously extracted from a sound sequence even when attention is directed away from the auditory stimuli. The pre-attentive representation of a sequence of two alternating tones (differing only in frequency) was investigated using the mismatch negativity (MMN) auditory event-related potential. Both local- and global-rule violations of tone alternation elicited the MMN component while subjects ignored the auditory stimuli. This finding suggests that (a) pre-attentive auditory processes can extract both local and global rules from sound sequences, and (b) that several regularity representations of a sound sequence are simultaneously maintained during the pre-attentive phase of auditory stimulus processing.
 
The popular recreational drug ecstasy (3,4-methylenedioxymethamphetamine=MDMA and related congeners) is neurotoxic upon central serotonergic systems in animal studies. So far, the most convincing evidence for neurotoxicity-related functional deficits in humans derives from neurocognitive studies demonstrating dose-related long-term learning and memory problems in ecstasy users. In our study we used functional magnetic resonance imaging (fMRI) and a working memory task to investigate cerebral activation in eleven heavy, but currently abstinent MDMA users and two equally sized groups of moderate users and non-users. There were no significant group differences in working memory performance and no differences in cortical activation patterns for a conservative level of significance. However, for a more liberal statistical criterion, both user groups showed stronger activations than controls in right parietal cortex. Furthermore, heavy users had a weaker blood oxygenation level-dependent (BOLD) response than moderate users and controls in frontal and temporal areas. Our results may indicate subtle altered brain functioning associated with prior MDMA use, although alternative interpretations of these group differences must be considered.
 
Prototypical stimuli and tasks used in the present study. Depiction of the encoding phases, in the top half of the figure, and the retrieval phases, in the bottom half of the figure. Besides using unique stimuli for each set, the encoding procedure was identical for item memory and source memory runs; participants were presented with abstract shapes on either the left or right side of the screen. (a) During the retrieval phase of an item memory run, shapes from the encoding phase and new shapes were presented in the center of the screen. Participants indicated whether each shape was previously presented or new. (b) During the retrieval phase of a source memory run, only shapes from the encoding phase were presented. Participants indicated the side of the screen on which each shape had been presented.  
Item memory and source memory activation results. Selected axial slices through group anatomic volume with overlay of functional activation associated with item memory, shown in yellow, and source memory, shown in red (anterior is toward the top and the left hemisphere is on the left). Within selected regions of interest, event-related activity associated with source memory, item memory, and correct rejection trials is shown in the upper part of the figure (color key to upper right). (a) The source memory vs. item memory contrast was associated with activity in the left middle frontal gyrus (LMFG, BA 9) and the item memory vs. correct rejection contrast was associated with activity in the right middle frontal gyrus (RMFG, BA 9) and the precuneous (BA 7). (b) The item memory vs. correct rejection contrast was associated with activity in the left parahippocampal gyrus (LPHG, BA 36).
In contrast to item memory, which refers to recognition or recall of previously presented information, source memory refers to memory for the context of previously presented information. The relatively few functional MRI (fMRI) source memory studies conducted to date have provided evidence that item memory and source memory are associated with differential activity in right and left prefrontal cortex, respectively. To both confirm this distinction in prefrontal cortex and to determine whether other differences in the neural substrates associated with these cognitive functions exist, an event-related fMRI study was conducted. In this study, item memory and source memory encoding phases were identical; participants viewed a series of abstract visual shapes presented on the left or right side of the screen and were instructed to remember each shape and its spatial location. During the item memory retrieval phase, shapes from the encoding phase were intermixed with new shapes and participants made an old-new judgment. During the source memory retrieval phase, all shapes were from the encoding phase and participants made a left-right judgment. An event-related analysis of item memory and source memory revealed a right and left prefrontal cortex distinction. Moreover, only item memory was associated with activity in the medial temporal lobes. These results confirm and extend previous findings that item memory and source memory are associated with distinct neural substrates.
 
In autism, physiological indices of selective attention have been shown to be abnormal even in situations where behaviour is intact. This divergence between behaviour and physiology suggests the action of some compensatory process of attention, one which may hold clues to the aetiology of autism's characteristic cognitive phenotype. Six subjects with autism spectrum disorders and six normal control subjects were studied with functional magnetic resonance imaging while performing a bilateral visual spatial attention task. In normal subjects, the task evoked activation in a network of cortical regions including the superior parietal lobe (P<0.001), left middle temporal gyrus (P=0.002), left inferior (P<0.001) and middle (P<0.02) frontal gyri, and medial frontal gyrus (P<0.02). Autistic subjects, in contrast, showed activation in the bilateral ventral occipital cortex (P<0.03) and striate cortex (P<0.05). Within the task condition, a region-of-interest comparison of attend-left versus attend-right conditions indicated that modulation of activation in the autistic brain as a function of the lateral focus of spatial attention was abnormally decreased in the left ventral occipital cortex (P<0.03), abnormally increased in the left intraparietal sulcus (P<0.01), and abnormally variable in the superior parietal lobe (P<0.03). These results are discussed in terms of a model of autism in which a pervasive defect of neural and synaptic development produces over-connected neural systems prone to noise and crosstalk, resulting in hyper-arousal and reduced selectivity. These low-level attentional traits may be the developmental basis for higher-order cognitive styles such as weak central coherence.
 
The aim of this study was to explore whether there are networks of regions where maturation of white matter and changes in brain activity show similar developmental trends during childhood. In a previous study, we showed that during childhood, grey matter activity increases in frontal and parietal regions. We hypothesized that this would be mediated by maturation of white matter. Twenty-three healthy children aged 8-18 years were investigated. Brain activity was measured using the blood oxygen level-dependent (BOLD) contrast with functional magnetic resonance imaging (fMRI) during performance of a working memory (WM) task. White matter microstructure was investigated using diffusion tensor imaging (DTI). Based on the DTI data, we calculated fractional anisotropy (FA), an indicator of myelination and axon thickness. Prior to scanning, WM score was evaluated. WM score correlated independently with FA values and BOLD response in several regions. FA values and BOLD response were extracted for each subject from the peak voxels of these regions. The FA values were used as covariates in an additional BOLD analysis to find brain regions where FA values and BOLD response correlated. Conversely, the BOLD response values were used as covariates in an additional FA analysis. In several cortical and sub-cortical regions, there were positive correlations between maturation of white matter and increased brain activity. Specifically, and consistent with our hypothesis, we found that FA values in fronto-parietal white matter correlated with BOLD response in closely located grey matter in the superior frontal sulcus and inferior parietal lobe, areas that could form a functional network underlying working memory function.
 
These experiments were designed to investigate the role of the noradrenergic system in promoting investigation of novelty in rats. Behavior was monitored in a hole board equipped with photoelectric cells strategically placed so that locomotor activity, rearing and investigation of each of the holes could be quantified independently. Specially designed computer software permitted recording of the sequence and cumulative duration of the visits to specific holes throughout the session. Dose-response curves of the sedative effect of the alpha 2 adrenergic receptor agonist clonidine were established, a sedative effect being defined as a decrease in overall horizontal displacements, rearings and hole visits. After a one week interval, the rats were rerun in the holeboard, with novel objects placed in four of the nine holes. Previous experiments had shown that rats spend significantly more time investigating holes containing objects than empty holes in this apparatus and this was replicated here. Doses of clonidine which were below threshold for inducing any sedative effect (10 micrograms/kg) totally eliminated preference for holes with objects while having no effect on total time investigating the holes. A subsequent experiment showed that the beta receptor antagonist propranolol (10 mg/kg) produced a similar effect. These results suggest that the noradrenergic system is implicated in stimulus seeking behavior and the post-synaptic beta receptors are involved in mediating the behavior.
 
NC-1900, an arginine-vasopressin derivative, has been reported to enhance memory for avoidance behavior. Specifically, NC-1900 ameliorated cycloheximide-induced learning impairments in a passive avoidance test in rats. In the present study, we investigated that effects of NC-1900 on place learning in rats with selective lesions in the CA1 subfield of the hippocampal formation produced by transient forebrain ischemia. NC-1900 was administered daily (1 microg/kg, p.o.) 1 h before the place learning task. A rat was required to alternate between 2 small circular areas located diametrically opposite each other on the circumference of an open field in order to obtain intracranial electrical stimulation reward (the spatial navigation task). Rats with hippocampal lesions showed severe place learning impairments both in task performance (indicated by number of rewards obtained per a session) and in navigation performance (forming efficient trails) over the 30-day test period. Treatment with NC-1900 ameliorated deficits in the place learning exhibited by rats with the same hippocampal lesions, such that their performance reached normal levels. There were no significant differences in the ischemic hippocampal lesions, spontaneous locomotor activity, and stimulation current intensity between the treated and untreated rats. The results demonstrated that NC-1900 reduced place learning impairments produced by hippocampal lesions.
 
Rodents are the animals most commonly employed to model human cognitive functions, but serious problems arise from the non-selective use of behavioral paradigms that measure different processes in rodents than those found in humans. To avoid problems stemming from the use of different paradigms on humans and mice, a new experimental paradigm for mice was developed to study the cognitive functions involved in delayed response tasks. The experiments were conducted in an olfactory tubing maze using three successive delayed response tasks: an alternation task, a non-alternation task, and a reversal task. Mice had to discover the rule by themselves by choosing one of two identical odor cues presented simultaneously at the left and right sides of a testing chamber. The success criterion was set at 10, 8, 6, or 4 consecutive correct responses, with a maximum of 80 trials per task, as used in primates. In the delayed alternation task with the criterion of 10 or 8 consecutive successful trials, the rule was discovered but required many more than 80 trials for most of the mice. With a criterion of 6 or 4, the mice were successful but twice as many trials were necessary to reach the criterion of 6 as opposed to 4. In the delayed non-alternation and reversal tasks, more than 80 trials were needed to figure out the new rule with the criterion of 10 or 8. All mice were successful with the criterion of 6 or 4. The results indicated that no matter what criterion was used, mice were able to discover the two rules on the three consecutive delayed response tasks, but they did so with more or less ease. This novel paradigm for mice should be useful in experiments on pharmacological treatments or for testing transgenic or gene-targeting mice to gain insight into the brain structures involved in this type of task.
 
Rhesus monkeys (6) were trained on a test battery including cognitive tests adapted from a human neuropsychological assessment battery (CANTAB; CeNeS, Cambridge, UK) as well as a bimanual motor skill task. The complete battery included tests of memory (delayed non-match to sample, DNMS; self-ordered spatial search, SOSS), reaction time (RT), motivation (progressive ratio; PR) and fine motor coordination (bimanual). The animals were trained to asymptotic performance in all tasks and then were administered two of the four CANTAB tasks on alternate weekdays (PR/SWM; DNMS/RT) with the bimanual task being administered on each weekday. The effect of acute administration of scopolamine (3-24 microg/kg, i.m.) on performance was then determined. Although performance on DNMS was impaired there was no interaction of drug treatment with retention interval, suggesting that scopolamine does not increase the rate of forgetting in this task. Scopolamine administration produced a decrement in SOSS performance that was dependent on task difficulty as well as dose. Scopolamine also impaired motor responses, resulting in increased time required to complete the bimanual motor task and increased movement time in the RT task. Performance in the PR task was decreased in a dose-dependent fashion by scopolamine. The results suggest that scopolamine interferes with memory storage and motor responses but not memory retention/retrieval or vigilance. The findings demonstrate that the test battery is useful for distinguishing the effects of neuropharmacological manipulation on various aspects of cognitive performance in monkeys.
 
The medial frontal cortex, especially the anterior cingulate cortex (ACC), is involved in action monitoring. We studied the role of moderate amounts of caffeine in action monitoring as expressed by the error-related negativity (ERN), an event-related brain component that reflects ACC activity. In a double-blind, placebo-controlled, within-subjects experiment, two caffeine doses (3 and 5 mg/kg body weight) and a placebo were administered to habitual coffee drinkers. Compared with placebo, both caffeine doses enlarged the ERN. Amplitudes of the P2 and P3 components were not affected by caffeine. Thus, the enlarged ERN after caffeine reflects a specific effect on action monitoring. We conclude that consumption of a few cups of coffee strengthens central information processing, specifically the monitoring of ongoing cognitive processes for signs of erroneous outcomes. Brain areas related to action monitoring such as the ACC presumably mediate these caffeine effects.
 
To clarify the dynamical processing aspect of biological motion (BM) perception from a developmental point of view, we measured event-related potentials (ERPs) in 8-month-old infants during the perception of BM or a scrambled motion (SM; randomization of BM's spatial structure). We found that activation of the right hemisphere in 8-month-old infants was similar to that of adults, suggesting that the neural substrates for processing BM perception begin to mature at around 8 months of age.
 
Recent neuroscience research is beginning to discover the brain regions involved in decision-making under uncertainty, but little is known about whether or how these regions functionally interact with each other. Here, we used event-related functional magnetic resonance imaging to examine both changes in overall activity and changes in functional connectivity during risk-taking. Results showed that choosing high-risk over low-risk decisions was associated with increased activity in both anterior cingulate and orbitofrontal cortices. Connectivity analyses revealed that largely distinct, but somewhat overlapping, cortical and subcortical regions exhibited significant functional connectivity with anterior cingulate and orbitofrontal cortices. Additionally, connectivity with the anterior cingulate in some regions, including the orbitofrontal cortex and nucleus accumbens, was modulated by the decision participants chose. These findings (1) elucidate large networks of brain regions that are functionally connected with both anterior cingulate and orbitofrontal cortices during decision-making and (2) demonstrate that the roles of orbitofrontal and anterior cingulate cortices can be functionally differentiated by examining patterns of connectivity.
 
Most decisions must be made without advance knowledge of their consequences. Economists and psychologists have devoted much attention to modeling decisions made under conditions of risk in which options can be characterized by a known probability distribution over possible outcomes. The descriptive shortcomings of classical economic models motivated the development of prospect theory (D. Kahneman, A. Tversky, Prospect theory: An analysis of decision under risk. Econometrica, 4 (1979) 263-291; A. Tversky, D. Kahneman, Advances in prospect theory: Cumulative representation of uncertainty. Journal of Risk and Uncertainty, 5 (4) (1992) 297-323) the most successful behavioral model of decision under risk. In the prospect theory, subjective value is modeled by a value function that is concave for gains, convex for losses, and steeper for losses than for gains; the impact of probabilities are characterized by a weighting function that overweights low probabilities and underweights moderate to high probabilities. We outline the possible neural bases of the components of prospect theory, surveying evidence from human imaging, lesion, and neuropharmacology studies as well as animal neurophysiology studies. These results provide preliminary suggestions concerning the neural bases of prospect theory that include a broad set of brain regions and neuromodulatory systems. These data suggest that focused studies of decision making in the context of quantitative models may provide substantial leverage towards a fuller understanding of the cognitive neuroscience of decision making.
 
Performance in cognitive tasks which require the subject to wait and/or to process a large amount of information can be disrupted by an increase in impulsive-like behaviour. Accordingly, a decrease in impulsive-like behaviour can improve performance in such tasks. Conversely, impulsive-like behaviour may improve performance in cognitive tasks where simple and fast responses and/or only little information processing is required. Thus, impulsivity constitutes a confounding factor in studies of cognitive function. Impulsive-like behaviour may be modified by serotonergic (5-HT) activity, with underactivity in 5-HT neurotransmission increasing impulsivity and vice versa. Drug- or lesion-induced alteration in 5-HT neurotransmission may, therefore, constitute suitable tools to investigate the role of impulsivity in animal tests of cognitive function. Benzodiazepines also increase impulsive-like behaviour, possibly by decreasing 5-HT neurotransmission. Hence, the effects of modulation of 5-HT systems and of the benzodiazepine-binding site on performance in animals tests of cognitive function will be discussed. It is predicted that the effects of manipulations of serotonergic activity or of benzodiazepine administration depend upon the nature of the response required, and that these effects may be mediated through changes in impulse control.
 
The search for a better understanding of cognitive decline in man has lead to the use of increasingly complex procedures in animal research. The analysis of the data generated in such experiments has been greatly facilitated by the wider use of computer assisted techniques. These techniques can only be as good as the hypotheses they are used to test. Signal detection theory (SDT) provides a rational framework within which to work. The procedures are derived from human cognitive neuropsychology and are already used to some extent in primate but to a lesser degree in rodent research. The use of SDT offers two main advantages: first, a testable hypothesis as to the manner in which competing processes arrive at choice between various courses of action; second, the statistical procedures offer clear advantages over more traditional approaches by reducing the chances of misinterpretation. Though relatively easy to apply some care must be exercised in the protocol design and the choice of SDT indices if the full value of the approach is to be achieved. If experimental designs can be developed to include the appropriate use of SDT analysis; both the power of such protocols, and their value in the understanding of cognitive function, will provide a major step forward for animal-based research.
 
Schematic diagram of the subject viewing the flickering LED display. The four bars on each side show the four possible color configu- rations for each bar. A light circle represents a red LED and a dark circle a green LED. The standard flicker Ž all five LEDs red . was present most of the time, with color changes Ž either Target or non-Target configura- tions . occurring at randomized intervals of 576, 720 and 884 ms. Gray oval is the fixation point. Dots on schematic head show approximate electrode locations. 
Slice of the MNI probability mask. The grey scale encodes probability of grey matter. Black corresponds to p s 0, white to p s 1. The grid points used for evaluation of the current in this slice are superimposed upon the probability mask. 
Steady-state visual evoked potentials (SSVEPs) were recorded from the scalp of subjects who attended to a flickering LED display in one visual field while ignoring a similar display (flickering at a different frequency) in the opposite visual field. The flicker frequencies were 20.8 Hz in the left-field display and 27.8 Hz in the right-field display. The SSVEP to the flicker in either field was enhanced in amplitude when attention was directed to its location. The scalp distribution of this SSVEP enhancement was narrowly focused over the posterior scalp contralateral to the visual field of stimulation. A source analysis using Variable Resolution Electromagnetic Tomography (VARETA) indicated that the source current densities for the SSVEP attention effect had a focal origin in the contralateral parieto-occipital cortex.
 
Although the effects of static allocations of visual spatial attention have been investigated using event-related potentials, most studies of shifts in visual spatial attention have been limited to behavioural measures. This study applied electroencephalographic measures to shifts in visual spatial attention in an effort to elucidate the time courses of such shifts. Using a custom-developed steady-state evoked potential analysis system, we analysed amplitude changes in EEG responses to rapid, periodic visual stimulation during a behavioural task that required rapid, repetitive shifts in visual spatial attention. Both stimulus-evoked oscillations (that is, those signals whose phases matched the phase of the steady-state stimulus) and ongoing, background (non-phase-locked) oscillations were measured. This analysis revealed a transient increase in phase-locked amplitude, in the interval 0-300-ms post-stimulus, contralateral to the visual hemifield in which an attended target appeared. The magnitude of this increase varied with the length of the interval since the previous shift. In addition, by about 600-ms post-stimulus, phase-locked amplitude increased in the hemisphere contralateral to the newly-attended visual hemifield and decreased in the ipsilateral hemisphere. In the case of long inter-target intervals, phase-locked amplitude increased in the right hemisphere regardless of the laterality of the target. Non-phase-locked amplitude exhibited a complementary pattern of modulation: it decreased contralaterally to the newly-attended visual hemifield and increased ipsilaterally. These components may be electrophysiological concomitants of both transient and long-lasting alterations in neural function that implement shifts in visual spatial attention. In particular, we suggest that they may reflect orienting to a target stimulus, and reorienting to a cued location.
 
A typical scene contains many different objects that compete for neural representation due to the limited processing capacity of the visual system. At the neural level, competition among multiple stimuli is evidenced by the mutual suppression of their visually evoked responses and occurs most strongly at the level of the receptive field. The competition among multiple objects can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention. Functional brain imaging studies reveal that biasing signals due to selective attention can modulate neural activity in visual cortex not only in the presence but also in the absence of visual stimulation. Although the competition among stimuli for representation is ultimately resolved within visual cortex, the source of top-down biasing signals likely derives from a distributed network of areas in frontal and parietal cortex. Competition suggests that once attentional resources are depleted, no further processing is possible. Yet, existing data suggest that emotional stimuli activate brain regions "automatically," largely immune from attentional control. We tested the alternative possibility, namely, that the neural processing of stimuli with emotional content is not automatic and instead requires some degree of attention. Our results revealed that, contrary to the prevailing view, all brain regions responding differentially to emotional faces, including the amygdala, did so only when sufficient attentional resources were available to process the faces. Thus, similar to the processing of other stimulus categories, the processing of facial expression is under top-down control.
 
Acetylcholine (ACh) efflux in the frontoparietal cortex was studied with in vivo microdialysis while rats performed in an operant task designed to assess sustained attention. Transferring animals from the baseline environment into the operant chambers elicited a robust increase in cortical ACh efflux that persisted throughout the 18-min pre-task period. Subsequent performance in the 36-min sustained attention task was associated with further significant increases in frontoparietal ACh efflux, while the termination of the task resulted in a delayed decline in ACh levels. Upon the 12-min presentation of a visual distracter (flashing houselight, 0.5 Hz) during task performance, animals initially developed a significant response bias to the left lever in the first 6-min distracter block, reflecting a reduction of attentional effort. Under continued conditions of increased attentional demand, performance recovered during the second 6-min distracter block. This return to attentional processing was accompanied by an increase in cortical ACh efflux, suggesting that the augmentation of attentional demand produced by the distracter elicited further increases in ACh release. The enhancement of cortical ACh efflux observed prior to task performance implies the presence of complex relationships between cortical ACh release and anticipatory and/or contextual factors related to operant performance and attentional processing. This finding, along with the further increases in cortical ACh efflux associated with task performance, extends hypotheses regarding the crucial role of cortical cholinergic transmission for attentional functions. Furthermore, the effects of the distracter stimulus provide evidence for a direct relationship between attentional effort and cortical ACh release.
 
In order to account for the memory span [G.A. Miller, The magical number seven, plus minus two: some limits on our capacity for processing information, Psychol. Rev. 63 (1956) 81-97.], the magical number seven, plus minus two, and high-speed scanning in human memory ¿S. Sternberg, High speed scanning in human memory, Science 153 (1966) 652-654., Lisman and collaborators [O. Jensen, J.E. Lisman, An oscillatory short-term memory buffer model can account for data on the Sternberg task, J. Neurosci. 18 (1998) 10688-10699; J.E. Lisman, M.A.P. Idiart, Storage of 7+/-2 short-term memories in oscillatory subcycles, Science 267 (1995), 1512-1515.] proposed an oscillatory short-term memory buffer model. In this neurophysiological model: "a single brain network can separately maintain up to seven memories by a multiplexing mechanism that uses theta and gamma brain oscillations for clocking. A memory is represented by groups of neurons that fire in the same gamma cycle" ¿O. Jensen, J.E. Lisman, An oscillatory short-term memory buffer model can account for data on the Sternberg task, J. Neurosci. 18 (1998) 10688-10699, p. 10688. To test this model, we tried to modify the memory scanning time by shifting the gamma oscillation frequency. To this aim, we replicated the visual short-term memory scanning task ¿S. Sternberg, High speed scanning in human memory, Science 153 (1966) 652-654., and we simultaneously used the protocol that Treisman ¿M. Treisman, A. Faulkner, P.L.N. Naish, D. Brogan, The internal clock: evidence for a temporal oscillator underlying time perception with some estimates of its characteristics frequency, Perception 19 (1990) 705-743. designed to drive, slowing down or speeding up, a temporal oscillator acting in the gamma range ¿J.G.R. Jefferys, R.D. Traub, M.A. Whittington, Neuronal networks for induced "40 Hz rhythms, Trends Neurosci. 19 (1996) 202-208; W. MacKay, Synchronized neuronal oscillations and their role in motor processes, Trends Cog. Sci. 1 (1997) 176-183; M. Treisman, N. Cook, P.L.N. Naish, J.K. MacCrone, The internal clock: electroencephalographic evidence for oscillatory processes underlying time perception, Q. J. Exp. Psychol. 47A (1994) 241-289.. In this protocol, an auditory periodic stimulus (click train) was delivered at various frequencies during the task. The reaction time (RT), the slope, and the intercept of the linear function associating RT to memorized list length showed systematic modulations according to the stimulation frequency. The predicted driving effects due to the click trains were obtained, consisting of localised modulations of performance on the stimulation frequency band. We argue that memory scanning is indeed paced by a temporal oscillator, thus providing behavioral arguments for the serial oscillatory model of Lisman.
 
We studied the effects of CGP 35348, a centrally active blocker of GABAB receptors, on scopolamine-induced amnesia for a passive avoidance response in the mouse. Both pre-training or post-training intraperitoneal administration of the GABAB antagonist (75, 150 and 300 mg/kg i.p.) significantly reduces the amnesic effect of scopolamine (1.0 mg/kg i.p.). Our results are in agreement with previous observations indicating a role for the GABAB receptors in the modulation of memory function, and suggest a possible role of GABAB receptor antagonists as nootropic drugs.
 
Here, the perception of auditory spatial information as indexed by behavioral measures is linked to brain dynamics as reflected by the N1m response recorded with whole-head magnetoencephalography (MEG). Broadband noise stimuli with realistic spatial cues corresponding to eight direction angles in the horizontal plane were constructed via custom-made, individualized binaural recordings (BAR) and generic head-related transfer functions (HRTF). For comparison purposes, stimuli with impoverished acoustical cues were created via interaural time and level differences (ITDs and ILDs) and their combinations. MEG recordings in ten subjects revealed that the amplitude and the latency of the N1m exhibits directional tuning to sound location, with the amplitude of the right-hemispheric N1m being particularly sensitive to the amount of spatial cues in the stimuli. The BAR, HRTF, and combined ITD + ILD stimuli resulted both in a larger dynamic range and in a more systematic distribution of the N1m amplitude across stimulus angle than did the ITD or ILD stimuli alone. Further, the right-hemispheric source loci of the N1m responses for the BAR and HRTF stimuli were anterior to those for the ITD and ILD stimuli. In behavioral tests, we measured the ability of the subjects to localize BAR and HRTF stimuli in terms of azimuthal error and front-back confusions. We found that behavioral performance correlated positively with the amplitude of the N1m. Thus, the activity taking place already in the auditory cortex predicts behavioral sound detection of spatial stimuli, and the amount of spatial cues embedded in the signal are reflected in the activity of this brain area.
 
Na+,K(+)-ATPase density in human cerebral cortex was for the first time studied by vanadate facilitated [3H]ouabain binding to intact samples. Fresh human cerebral cortical biopsies were obtained as a result of diagnostic frontal lobe biopsy from patients with normal pressure hydrocephalus (NPH) syndrome and associated dementia. For control measurements post-mortem samples were obtained from patients without clinically observed dementia. [3H]ouabain binding kinetics were evaluated: when incubating samples in 1 microM [3H]ouabain binding equilibrium was obtained after 6 h of incubation, non-specific uptake and retention amounted to only 2.3% of total uptake and retention of [3H]ouabain and release of specifically bound [3H]ouabain during washout in the cold occurred only slowly (T1/2 = 37 h). Evaluation of receptor affinity for ouabain was in agreement with a heterogeneous population of [3H]ouabain binding sites. [3H]Ouabain binding was significantly reduced after frozen storage of samples before measurements. Post-mortem degradation of cerebral [3H]ouabain binding sites occurred only slowly (T1/2 = 75 h). No significant variation in [3H]ouabain binding site density was observed between the cerebral lobes with occipital, parietal and temporal values (means +/- S.E.M., n = 5) amounting to 10281 +/- 649, 11267 +/- 1011 and 9263 +/- 615 pmol/g wet wt., respectively. [3H]Ouabain binding measured in frontal cortical samples gave values of (means +/- S.E.M., n = 5) 4274 +/- 1020 and 11397 +/- 976 pmol/g wet wt. delta % = 62; P < 0.05) in patients with dementia and controls, respectively. Human cerebral cortical capacity for active K+ uptake was around 37- and 16-fold greater than in skeletal muscular and myocardial tissue, respectively.
 
A three-stimulus oddball paradigm (target, standard, nontarget) was employed in which subjects responded to an infrequent target, when its discrimination from the frequent standard was difficult. In separate auditory and visual modality conditions, the stimulus characteristics of an infrequent nontarget were manipulated such that its perceptual distinctiveness from the target was varied systematically. For both the low and high distinctiveness conditions, target stimulus P300 amplitude was larger than the nontarget only at the parietal electrode. In contrast, nontarget P3a amplitude was larger and earlier than the target P300 over the frontal/central electrode sites. The distinctiveness manipulation between the target and nontarget produced larger P3a component profiles for the auditory compared to visual stimuli. The results support previous findings that target/standard stimulus context determines P3a generation for both auditory and visual stimulus modalities and suggest that the distinctiveness of the eliciting stimulus contributes to P3a amplitude. Theoretical implications are discussed.
 
In this functional magnetic resonance imaging (fMRI) study, we investigated the influence of two task (lexical decision, LDT; phonological decision, PDT) on activation in Broca's region (left Brodmann's areas [BA] 44 and 45) during the processing of visually presented words and pseudowords. Reaction times were longer for pseudowords than words in LDT but did not differ in PDT. By combining the fMRI data with cytoarchitectonic anatomical probability maps, we demonstrated that the left BA 44 and BA 45 were stronger activated for pseudowords than for words. Separate analyses for LDT and PDT revealed that the left BA 44 was activated in both tasks, whereas left BA 45 was only involved in LDT. The results are interpreted within a dual-route model of reading with the left BA 44 supporting grapheme-to-phoneme conversion and the left BA 45 being related to explicit lexical search.
 
In order to study neural systems which are involved in motor timing we used whole-brain functional resonance imaging while subjects performed a paced finger-tapping task (PFT) with their right index finger. During one condition, subjects were imaged while tapping in synchrony with tones separated by a constant interval (auditory synchronisation, AS), followed by tapping without the pacing stimulus (auditory continuation, AC). In another condition, subjects were imaged while tapping in synchrony with a visual stimulus presented at the same frequency as the tones (visual synchronisation, VS) followed by a tapping sequence without visual pacing (visual continuation, VC). The following main results were obtained: (1) tapping in the context of visual pacing was generally more variable than tapping in the context of auditory stimuli; (2) during all conditions, a fronto-parietal network was active including the dorsal lateral premotor cortex (dPMC), M1, S1, inferior parietal lobule (LPi), supplementary motor cortex (SMA), the right cerebellar hemisphere, and the paravermial region; (3) stronger activation in the bilateral ventral premotor cortex (vPMC), the left LPi, the SMA, the right inferior cerebellum, and the left thalamus during both auditory conditions (AS and AC) compared to the visual conditions (VS and VC); (4) stronger activation in the right superior cerebellum, the vermis, and the right LPi during the visual conditions (VS and VC); (5) similar activations for the AS and AC conditions; but (6) marked differences between the VS and VC conditions especially in the dorsal premotor cortex (dPMC) and LPi areas; and (7) finally, there were no activations in the auditory and visual cortices when the pacing stimuli were absent. These findings were taken as evidence for a general difference between the motor control modes operative during the auditory and visual conditions. Paced finger tapping in the context of auditory pacing stimuli relies more on brain structures subserving internal motor control while paced finger-tapping in the context of visual pacing stimuli relies on brain structures relying on the subserving processing or imagination of visual pacing stimuli.
 
Administration of (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-588), a cognitive enhancer, like the acetylcholine esterase inhibitors physostigmine and tacrine, stimulated phosphorylation of extracellular signal-regulated kinases (ERK) in the mouse hippocampus. The effect of T-588 on ERK phosphorylation was persistent from 2 to 6 h after injection. Immunohistochemical study showed that T-588 stimulated neuronal ERK phosphorylation in rat hippocampal CA1 pyramidal subfield. These findings suggest that systemic T-588 stimulates the ERK kinase pathway in the hippocampal neurons.
 
Experimental stimuli: (A) human naturalistic, (B) robotic naturalistic, (C) human schematic, (D) robotic schematic. Within each panel, the top image is the warning stimulus, and the two images below are the opened (left) and closed (right) imperative stimuli. 
Visual angle, luminance and surface area values for each posture in each stimulus format
Mean RT on compatible (open bars) and incompatible (shaded bars) trials for the human naturalistic, human schematic, robotic naturalistic and robotic schematic stimuli. Images on the horizontal axis exemplify stimulus type and style using the open stimulus. Vertical bars indicate the standard error of the mean. 
Mean RT on incompatible trials minus mean RT on compatible trials for human (open bars) and robotic (shaded bars) for five segments of the RT distribution. Vertical bars indicate the standard error of the mean. 
Mean RT on compatible (open bars) and incompatible (shaded bars) trials for human stimuli and robotic stimuli on days 1 and 2 of testing. Vertical bars indicate the standard error of the mean. 
Recent behavioural and neuroimaging studies have found that observation of human movement, but not of robotic movement, gives rise to visuomotor priming. This implies that the 'mirror neuron' or 'action observation-execution matching' system in the premotor and parietal cortices is entirely unresponsive to robotic movement. The present study investigated this hypothesis using an 'automatic imitation' stimulus-response compatibility procedure. Participants were required to perform a prespecified movement (e.g. opening their hand) on presentation of a human or robotic hand in the terminal posture of a compatible movement (opened) or an incompatible movement (closed). Both the human and the robotic stimuli elicited automatic imitation; the prespecified action was initiated faster when it was cued by the compatible movement stimulus than when it was cued by the incompatible movement stimulus. However, even when the human and robotic stimuli were of comparable size, colour and brightness, the human hand had a stronger effect on performance. These results suggest that effector shape is sufficient to allow the action observation-matching system to distinguish human from robotic movement. They also indicate, as one would expect if this system develops through learning, that to varying degrees both human and robotic action can be 'simulated' by the premotor and parietal cortices.
 
Alcohol consumption has been shown to increase the number of errors in tasks that require a high degree of cognitive control, such as a go/no-go task. The alcohol-related decline in performance may be related to difficulties in maintaining attention on the task at hand and/or deficits in inhibiting a prepotent response. To test these two accounts, we investigated the effects of alcohol on stimulus- and response-locked evoked potentials recorded during a go/no-go task that involved the withholding of key presses to rare targets. All participants performed the task prior to drinking and were then assigned randomly to either a control, low-dose, or moderate-dose treatment. Both doses of alcohol increased the number of errors relative to alcohol-free performance. Success in withholding a prepotent response was associated with an early-enhanced stimulus-locked negativity at inferior parietal sites, which was delayed when participants failed to inhibit the motor command. Moreover, low and moderate doses of alcohol reduced N170 and P3 amplitudes during go, no-go, and error trials. In comparison with the correct responses, errors generated large response-locked negative (Ne) and positive (Pe) waves at central sites. Both doses of alcohol reduced the Ne amplitude whereas the Pe amplitude decreased only after moderate doses of alcohol. These results are consistent with the interpretation that behavioral disinhibition following alcohol consumption involved alcohol-induced deficits in maintaining and allocating attention thereby affecting the processing of incoming stimuli and the recognition that an errant response has been made.
 
Altered frontal lobe activity and executive control associated with working memory (WM) dysfunction are recognized as core deficits in schizophrenia. These impairments have been discussed as being associated with deficits in self-regulated action monitoring and anticipatory action plan generation. To study electrophysiological correlates of executive control -- specifically action monitoring and action rule switching -- under varying WM load, we used a paradigm derived from classic N-back (WM) tasks and requiring monitoring of simple actions. We focused on event-related changes in post-stimulus theta oscillatory activity during varying cognitive and WM demand in healthy controls and schizophrenia patients. The results show significant WM load and rule-switching-related increases of post-stimulus theta amplitude at fronto-central locations in controls. In patients with schizophrenia, there was no such modulation, but -- apart from an increased early theta at left temporal locations -- generally reduced late theta responses in all tasks and at all locations. Furthermore, the patients with schizophrenia showed significant differences in their error patterns, which imply differences in automation and anticipation of actions between controls and patients. These findings suggest that theta oscillations are involved in mediating frontal lobe activity and functions related to enhanced executive control. We conclude that the patients with schizophrenia showed deficits in acquiring a mental task set which appear to be associated with impairments in action monitoring and task-specific regulation of executive control.
 
Our earlier findings of a cerebellar activation during motor imagery (Brain Res., 535 (1990) 313-317) were made with a technique with low regional resolution. Therefore we could not elucidate the distribution of the cerebellar activation. In the present study the cerebellar regional cerebral blood flow (rCBF) changes during motor imagery (MI) was measured with a single photon emission computed tomography (SPECT) rCBF method (99mTc-HMPAO) with higher regional resolution during (1) silent counting, and (2) MI (which included silent counting) in 17 normal subjects. Comparing the SPECT results from the two tasks revealed the regional activations during MI. We confirmed that the most pronounced regional activations during MI were found in the cerebellum, especially in its infero-lateral parts on both sides.
 
In schizophrenia, aberrant brain activity has been reported both during stimulus processing and at rest. Evoked response amplitude is a function of both the number and synchronization of neurons firing in relation to a stimulus. It is at present unclear whether schizophrenia patients have normal synchronization of neural activity in relation to stimulus processing, and whether the amount and time course of synchronization is related to their evoked response amplitudes. EEG brain dynamics in response to visual steady-state stimulation were assessed in 12 schizophrenia and 12 healthy subjects at three stimulation durations (2, 4, and 6 s). Group differences in the visual evoked potential, the visual steady-state response, and the local coherence of the visual steady-state response were evaluated over time. Schizophrenia patients had smaller and delayed event-related potentials. Moreover, they had a slower buildup of steady-state amplitude following stimulation onset and a prolonged decrease after stimulation offset. Groups did not differ during mid-segments of steady-state stimulation. Increase in coherence to stimulation onset did not differ between-groups, but coherence decay of the visual steady-state response following stimulus offset was delayed in schizophrenia patients. The initial response to visual stimulation among schizophrenia subjects, therefore, may be reduced in amplitude due to weak signal strength, not poor coordination between distant cortical regions. The prolonged recovery function of schizophrenia patients' visual system may indicate abnormal nonlinearity in neural response. These findings have implications understanding the nature of evoked response differences between schizophrenia and normal groups especially in repetitive stimulus paradigms.
 
The Tower of London (ToL) is a well-known test of planning ability, and commonly used for the purpose of neuropsychological assessment and cognitive research. Its widespread application has led to numerous versions differing in a number of respects. The present study addressed the question whether differences in instruction, cueing, and learning processes systematically influence ToL performance across five difficulty levels (three to seven moves). A total of 81 normal adults were examined in a mixed design with the between-subject factor instruction (online versus mental preplanning) and the within-subject factors cueing (cue versus non-cue test version) and learning processes (first block and second block). We also assessed general intelligence for further analyses of differences between instruction groups. In general, there was a significant main effect across the difficulty levels indicating that the rate of incorrect solutions increased with problem difficulty. The participants who were instructed to make full mental plans before beginning to execute movements (preplanning) solved significantly more problems than people who started immediately with task-related movements (online). As for the cueing conditions, participants with the minimum number of moves predetermined (cue) could solve more trials than people who were only instructed to solve the problems in as few moves as possible (non-cue). Participants generally increased performance in the second part of the test session. However, an interaction of presentation order of the cueing condition with learning indicated that people who started the tasks with the non-cue version showed significantly better performance in the following cue condition, while participants who started with the cue condition stayed at the same performance level for both versions. These findings suggest that instruction, cueing conditions, and learning processes are important determinants of ToL performance, and they stress the necessity of standardized application in research and clinical practice.
 
Cognitive abilities related to learning ability and intelligence involve 8 levels of fundamental processes. Any and all of such cognitive abilities reduce to these 8 levels or to combinations of them. The 8 levels are hierarchical because lower levels, generally, are prerequisites for higher levels. An animal's general cognitive ability is determined by how many of the fundamental processes it can use. Although the processes are hierarchical, an animal will use all processes available to it in serial or in parallel as the situation requires. A perusal of contemporary journals' contents will show that behavioral neuroscientists, including behavioral pharmacologists, rarely study cognitive abilities that require the use of processes at the highest 4 levels. Yet, all vertebrates may be capable of using level-5 processes, and several avian and mammalian species have been shown to use level-6 processes. The use of level-7 processes has been shown in non-human primates and likely can be shown in non-primate species, too. The present article provides an overview of the basic cognitive processes as well as types of tasks that might be used to investigate the neural correlates or substrates of higher cognitive processes in animals. Unless and until better measures of cognitive ability are used, a vast potential for research will be unrealized.
 
Although under some conditions the attention-related late positive event-related potential (ERP) response (LPC) is apparently normal in autism during visual processing, the LPC elicited by visuospatial processing may be compromised. Results from this study provide evidence for abnormalities in autism in two components of the LPC generated during spatial processing. The early frontal distribution of the LPC which may reflect attention orienting was delayed or missing in autistic subjects during conditions in which attention was to peripheral visual fields. The later parietal distribution of the LPC which may be associated with context updating was smaller in amplitude in autistic subjects regardless of attention location. Both abnormalities suggest disruption of function in spatial attention networks in autism. Evidence that the cerebellar abnormalities in autism may underlie these deficits comes from: (1) similar results in ERP responses and spatial attention deficits in patients with cerebellar lesions; (2) brain-behavior correlations in normally functioning individuals associating the size of the posterior cerebellar vermis and the latency of the frontal LPC; and (3) a previously reported complementary correlation between the size of the posterior vermal lobules and spatial orienting speed. Although the scalp-recorded LPC is thought to be cortically generated, it may be modulated by subcortical neural activity. The cerebellum may serve as a modulating influence by affecting the task-related antecedent attentional process. The electrophysiological abnormalities reported here index spatial attention deficits in autism that may reflect cerebellar influence on both frontal and parietal spatial attention function.
 
Stimulus-locked grand average waveforms (filtered 2 – 12 Hz) from electrodes Fz, Fcz and Cz evoked by xxx , xxy and xyz trials in the slot-machine task. Left panel: loss condition, right panel: gain condition. 
Current source density (CSD) maps at the time of the component peaks associated with averted gains and averted losses in the slot-machine task, incorrect feedback in the time estimation task and incorrect reactions in the flanker task. CSDs in left panel are based on raw ERPs, CSDs in right panel are based on difference waves. 
The feedback-related negativity (FRN) is an event-related brain potential component that is elicited by feedback stimuli indicating unfavorable outcomes. Until recently, the FRN has been studied primarily using experimental paradigms in which outcomes appeared to be contingent upon the participants' behavior. The present study further addressed the question whether an FRN can be elicited by outcomes that are not contingent on any preceding choice or action. Participants took part in a simple slot-machine task in which they experienced monetary gains and losses in the absence of responses. In addition, they performed a time estimation task often used to study the FRN and a flanker task known to elicit the error-related negativity. Outcomes in the slot-machine task elicited an FRN-like mediofrontal negativity whose amplitude correlated with the amplitude of the FRN associated with negative feedback in the time estimation task. However, the mediofrontal negativity was observed both for (unfavorable) outcomes that averted a gain and for (favorable) outcomes that averted a loss of money. The results are discussed in the framework of current conceptions of the FRN and related electrophysiological components.
 
Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.
 
This paper addresses the issue of mind-brain correspondence, using a novel way to reduce brain electric field data in the frequency domain to estimates of intracerebral model source locations, and applying this method to brain electric data collected during the 2-s epochs immediately before the randomly solicited reports of spontaneous, conscious, covert experiences from 12 normal volunteers. The mentation reports were classified into visual imagery and abstract thought. The mean locations of the EEG model sources associated with abstract thoughts were generally more anterior and deeper than those of visual imagery, particularly significant for the delta/theta band; the finding was common across subjects. Thus, different brain functional states involving different geometries of activated neural populations exist during conscious, spontaneous, task-free mentations of the visual imagery type and of the abstract thought type.
 
We examined the neural correlates of semantic ambiguity by measuring changes in MEG recordings during a visual lexical decision task in which the properties of ambiguous words were manipulated. Words that are ambiguous between unrelated meanings (like bark, which can refer to a tree or to a dog) were accessed more slowly than words that have no unrelated meanings (such as cage). In addition, words that have many related senses (e.g., belt, which can be an article of clothing or, closely related in sense, a fan belt used in machinery) were accessed faster than words that have few related senses (e.g., ant). The findings are inconsistent with accounts that posit that both kinds of ambiguity involve separate lexical entries, but instead offer both behavioral and neurophysiological support for separate entry accounts only for homonymy, and a single-entry model of polysemy. The findings also provide neural correlates for a behavioral study of lexical ambiguity that demonstrated that the frequently reported ambiguity advantage in lexical decision tasks is not due to the presence of many unrelated meanings but to the presence of many related senses.
 
We investigated whether the mental representation of numbers is abstract amodal or modality-dependent. Subjects verified simple additions. In an event-related potential (ERP) experiment, subjects added an Arabic digit (S2) to a preceding number (S1) offsetting 3 s before S2. S1 was either a visually shown Arabic digit, a written number word or an acoustically presented number word. In a behavioral experiment, we measured the speed of addition using a modified paradigm. In the ERPs to S2, the amplitude of the parietal N1, the fronto-central P2, and the late positivity between 320 and 460 ms were more positive and RTs were faster when S1 was a heard number word than when S1 was a written number word. ERP amplitudes and reaction times took intermediate positions between the other two conditions when S1 was an Arabic digit. Between the Arabic and heard number conditions, this so-called numeral modality effect (NME) was present at electrodes Pz, P4, P3 and Cz when number size was small, whereas it was significant over electrode C4 and P4 when number size was large. Our results suggest that numbers presented in different surface-formats have differential access to number representations. Conclusions for models of number processing are drawn and the possible role of parietal number representations is discussed. We replicated the N270 ERP component and elicited the ERP numerical distance effect in response to incongruent arithmetical results.
 
Top-cited authors
Giacomo Rizzolatti
  • Università di Parma
Vittorio Gallese
  • Università di Parma
Luciano Fadiga
  • University of Ferrara
Leonardo Fogassi
  • Università di Parma
Mark D'Esposito
  • University of California, Berkeley