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PubMed1993

The psychopathology, neuropsychology, and neurobiology of associative and working memory in schizophrenia.

A large number of psycholinguistic findings on how human beings store lexical information suggest the existence of associative memory, which may be characterized by a large capacity and a long duration. Its anatomical basis supposedly is, at least in part, the frontal lobes, and some of its functional characteristics have been tentatively linked to dopamine release. Working memory has a limited capacity, lasts only for seconds and is relevant for goal-directed behavior. Its anatomical basis in the frontal cortex is established and strong evidence suggests the involvement of dopaminergic pathways. Experimental evidence using several lexical decision tasks and a delayed response task is provided to demonstrate that some characteristic features of schizophrenic thinking--in particular the rapid shift of associations, the indirect relationship of associations, the overly abstract or overly concrete use of concepts, the lack of context-sensitivity and of general integrative function and intellectual capacity--can be explained in terms of an activation or disinhibition of associative memory, and of a dysfunctional working memory. The findings serve as an example of schizophrenia research in a cognitive neuroscience framework.

Adult↗

PubMed2005

Long-lasting capture of tactile attention by body shadows.

Four experiments addressed the role of cast shadows of the body in orienting tactile spatial attention to the body itself. We used a modified spatial-cueing paradigm to examine whether viewing of the cast shadow of a hand can elicit spatial shifts of tactile attention to that very same hand. Participants performed a speeded tactile-discrimination task (thumb versus index finger, regardless of touched hand), while viewing the shadow of either the touched or untouched hand cast in front of them by a lateral light-source. The hand casting the shadow changed either between blocks (expt 1) or unpredictably within each block (expts 2-4). In experiments 1 and 2 tactile targets were preceded by central non-informative visual cues delivered near the shadow of the index finger and thumb. Despite the fact that cast shadows were always task-irrelevant and non-predictive of which hand was stimulated, tactile discrimination was consistently faster at the hand casting the shadow than at the other hand. This effect was not modulated by the duration of cue-target asynchrony, nor did it depend on whether the visual cue was present or not (expt 3). In addition, it was still reliable when vision of the hands was precluded, whereas it became inconsistent when the cast shadow of the hand was replaced by the cast shadow of an object (expt 4). Our results suggest that body shadows can induce a long-lasting capture of tactile attention for stimuli at the body itself.

Adult↗

PubMed1993

"Probing" the nature of the CNV.

A widespread depolarization in the dendritic trees of cortical pyramidal neurons generates surface-negative potentials. In turn, such potentials may indicate facilitatory processes, while positive-going waves may result from a lowering in cortical excitability. Accordingly, we may expect the processing of "probe" stimuli presented during surface-positive waves, i.e., during phases of lesser excitability, to be inhibited and probes presented during surface-negative waves to be facilitated. This hypothesis was tested by presenting acoustic probe stimuli at various points in time during a forewarned reaction time task. The warning stimulus (WS) elicited a late positive complex followed by a negative slow potential shift (CNV). In 75% of the total of 120 trials a probe could be presented 1.5 sec prior to the WS interval, 0.5, 1, 1.5 or 2 sec after the onset of the 3 sec visual WS, and 3 sec following the imperative signal (WS offset, requiring a fast button press response), while 25% of the trials were without any probe. Only one probe occurred during a trial. The EEG was recorded along the midsagittal line; responses to the probes were evaluated by reaction time (RT) and probe-evoked potentials. RT to probes presented late in the anticipatory interval were speeded up and probe-evoked potentials were enhanced during this interval, in parallel to the development of the slow potential and the CNV in particular. Results suggest that probe stimuli presented during the development of the CNV were processed more intensely, thereby supporting the hypothesis that slow cortical potentials indicate the timing of excitability in cortical neuronal networks.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1991

On the functionality of the visually deprived occipital cortex in early blind persons.

In early blind mammals, the deprived visual cortex undergoes anatomical and functional alterations. Its functional role was investigated in the early human blind by using patterns of cortical activation as measured by scalp-recorded event-related slow negative DC potential shifts. The blind showed higher occipital negativity than did sighted persons both during a tactile reading task and a non-reading tactile control task. Results point to a possible role for the blind's visual cortex in tactile processes.

Adult↗

PubMed2006

Ecological validity in neuropsychological assessment: a case for greater consideration in research with neurologically intact populations.

The focus of the discipline of neuropsychology is shifting towards a greater emphasis on understanding the relationship between assessment results and performance of everyday tasks (ecological validity). To date, the literature has highlighted the importance of this concept in the assessment of patients with brain injury or disease (e.g. in rehabilitation and forensic settings). This paper presents the argument that there is another important area in which the ecological validity of neuropsychological assessments should be considered: in clinical outcomes studies using neurologically intact participants. For example, determining the extent to which a medical procedure or intervention affects performance of everyday cognitive tasks can provide useful information that can potentially guide decision-making regarding treatment options. It is argued that tests designed with ecological validity in mind (the verisimilitude approach), as opposed to traditional tests, may be most effective at predicting everyday functioning. Explanations are proposed as to why researchers may be reluctant to use tests with verisimilitude in favor of more traditional measures.

Brain Injuries↗

PubMed2004

How 'generalized' is the 'slowed processing' in SLI? The case of visuospatial attentional orienting.

The study was designed to assess the speed and efficiency of visuospatial attentional orienting and the speed of visual processing and motor response in school-age children diagnosed with specific language impairment (SLI). Fifteen participants with SLI (7-15 years old) and their gender- and age-matched normally developing peers performed two formats of a simple visual discrimination task, one requiring the use of attentional orienting for accurate performance, and the other not requiring shifts of attention. The SLI group was characterized by (a) slower visual processing, and (b) slower motor response, but (c) similar attentional orienting speed, relative to the control group. The results are discussed in relation to the 'generalized slowing hypothesis' in SLI and the neural underpinning of visuospatial attentional orienting and SLI.

Adolescent↗

PubMed2004

The influence of NMDA receptors in the dorsomedial striatum on response reversal learning.

In mammals, the dorsomedial striatum is one brain area shown to be critical for the flexible shifting of response patterns. At present, the neurochemical mechanisms that underlie learning during a shift in response patterns are unknown. The present study examined the effects of NMDA competitive antagonist, DL-2-amino-5-phosphonopentanoic acid (AP-5), injected into the dorsomedial striatum on the acquisition and reversal of a response discrimination. Male Long-Evans rats were tested across two consecutive days in a modified cross-maze. Rats received an infusion of either saline or AP-5 (5 or 25 nmol) 5 min prior to each test session. In the acquisition phase rats learned to turn in one direction (right or left) to receive a cereal reinforcement. In the reversal learning phase rats learned to turn in the opposite direction as in the acquisition phase. In both phases, criterion was achieved when a rat made 10 consecutive correct trials. Infusions of AP-5 did not impair acquisition, but impaired reversal learning of a response discrimination in a dose-dependent fashion. The reversal learning deficit induced by AP-5 resulted from reversions back to the originally learned response pattern following the initial shift. These results suggest that activation of NMDA receptors in the dorsomedial striatum are critical for the flexible shifting of response patterns by enhancing the reliable execution of a new response pattern under changing task contingencies.

2-Amino-5-phosphonovalerate↗

PubMed2006

Effects of antiepileptic drugs on learning as assessed by a repeated acquisition of response sequences task in rats.

Patients with epilepsy can have impaired cognitive abilities. Antiepileptic drugs (AEDs) may contribute to the cognitive deficits observed in patients with epilepsy, and have been shown to induce cognitive impairments in healthy individuals. However, there are few systematic data on the effects of AEDs on specific cognitive domains. We have previously demonstrated that a number of AEDs can impair working memory and attention. The purpose of the present study was to evaluate the effects of AEDs on learning as measured by a repeated acquisition of response sequences task in nonepileptic rats. The GABA-related AEDs phenobarbital and chlordiazepoxide significantly disrupted performance by shifting the learning curve to the right and increasing errors, whereas tiagabine and valproate did not. The sodium channel blockers carbamazepine and phenytoin suppressed responding at higher doses, whereas lamotrigine shifted the learning curve to the right and increased errors, and topiramate was without significant effect. Levetiracetam also shifted the learning curve to the right and increased errors. The disruptions produced by triazolam, chlordiazepoxide, lamotrigine, and levetiracetam were qualitatively similar to the effects of the muscarinic cholinergic receptor antagonist scopolamine. The present results indicate that AEDs can impair learning, but there are differences among AEDs in the magnitude of the disruption in nonepileptic rats, with drugs that enhance GABA receptor function and some that block sodium channels producing the most consistent impairment of learning.

Analysis of Variance↗

PubMed2003

Effects of prismatic adaptation on judgements of spatial extent in peripersonal and extrapersonal space.

Recent research has shown that visuomotor adaptation to a lateral displacement of the visual field induces significant perceptual aftereffects in normal observers, and in right hemisphere patients with spatial neglect [Neuroreport 11 (2000) 1899; Nature 395 (1998) 166]. These findings suggest that adaptive realignment following prism exposure induces a bias in visual space perception, even in tasks that require no visually guided motor response. Given recent neurophysiological and behavioural data suggesting independent visual representations for peripersonal and extrapersonal space, here we asked whether adaptive aftereffects extend beyond participants' immediate reaching space to stimuli presented beyond arms' reach (i.e. in extrapersonal space). Thirty-two participants underwent adaptive realignment to 10 degrees left- or right-displacing wedge-prisms. Before and after adaptation participants performed a visual landmark task that required estimation of the midpoint of horizontal line stimuli. There was a significant rightward shift in visual midpoint judgements following adaptation to left-deviating prisms, which was evident in both peripersonal and extrapersonal space. Paradoxically, a significant rightward shift also occurred following adaptation to right-deviating prisms, but only in extrapersonal space. We suggest that the pattern of adaptive aftereffects observed reflects the different reference frames used by participants to perform spatial judgements in peripersonal and extrapersonal space. We also propose that an underlying hemispheric asymmetry in the processing of spatial errors during adaptation may contribute to the direction of aftereffects in both normal observers, and in patients with unilateral lesions.

Adaptation, Physiological↗

PubMed2000

Economic challenges in breast imaging. A survivor's guide to success.

Most breast imaging centers today operate under financial strain. Among strategies designed to improve their bottom line, more efficient use of the radiologist's time is the most fundamental strategy and the one most likely to succeed in all breast imaging centers. Tasks performed by the radiologist that are not directly related to interpretation and consultation should be shifted to other personnel. Other strategies that may help some breast imaging centers include accepting only self-paying patients, renegotiating the hospital contract, performing more interventional procedures, and extending the hours of operation. Measures that can improve the economic efficiency of screening mammography include batch interpretation of mammograms; paperwork reduction; brief automated reports; limiting requests for previous films from other facilities to only potentially necessary cases; dedicated screening mammography examination rooms; reduction in recall rates; and, in certain circumstances, extension of breast center hours. Measures that can improve the economic efficiency of diagnostic mammography performance and interpretation include dedicated diagnostic mammography examination rooms, automated film rotators, improved scheduling, and efficient work-flow patterns for examination performance. Measures that can improve the economic efficiency of both screening and diagnostic mammography include improved triage of screening and diagnostic patients, reminder telephone calls to confirm mammography appointments, greater use of medical assistants to help the radiologists and technologists, and streamlined film library procedures and operations. Measures that can improve the economic efficiency of breast interventional procedures include preprocedure work-up, establishment of scheduling protocols, and greater involvement of technologists and medical assistants in assisting the radiologist who performs the interventional procedures. All of these methods are intended to create a breast imaging center that is cost efficient while maintaining a patient-friendly atmosphere and diagnostic accuracy.

Allied Health Personnel↗

PubMed2001

Age related signal decrease in functional magnetic resonance imaging during motor stimulation in humans.

Right handed healthy volunteers underwent functional magnetic resonance imaging (fMRI) examinations on a 1.5 Tesla MRI-scanner (Gyroscan ACS NT; Philips, Best, NL). Blood oxygen level dependent (BOLD) images were obtained using a three dimensional multi-shot echo planar imaging sequence employing a shifted echo technique (Principles of echo shifting with a train of observations). Finger tapping of the right hand was used as a task for motor stimulation. A total of 86 subjects was included into statistical analysis. Absolute and relative signal differences and cluster sizes of activation for the left motor cortex were obtained. In addition, Z-score, pooled Z-score and cross correlation activation maps were calculated and matched with high resolution anatomic images. A significant decrease with age could be detected for absolute and relative signal intensity differences for the whole group and for the male subgroup. Correlation analysis for the female subgroup also bore negative albeit non-significant correlation coefficients. An age-related decline of BOLD-contrast can be assumed to explain signal decrease. This age-related effect should be considered in clinical fMRI applications.

Adult↗

PubMed2001

Neural activities during Wisconsin Card Sorting Test--MEG observation.

The present study recorded activities of magnetoencephalography (MEG) to the presentation of cards, and to the presentation of feedback signals in 12 normal subjects while they performed the Wisconsin Card Sorting Test (WCST), to observe temporal and spatial processing during the task. The MEG responses were compared between two different conditions in the presentation both of cards and of feedback signals: the cards proceeded by the first wrong [W1st(C)] and by the 4th correct feedback signals [C4th(C)]; and the feedback of the first wrong [W1st(FB)] and the 4th correct signals [C4th(FB)]. A multi-dipole model, brain electric source analysis (BESA), was used to explore the dipole sources responsible for the MEG activities. We found that MEG activity differences between the W1st(C) and the C4th(C) condition occurred in the period of 190-220 ms (M190 and M200), and 300-440 ms (M300 and M370) mainly at the supramarginal gyrus, the dorsolateral prefrontal, and the middle and inferior frontal gyrus. MEG differences between the W1st(FB) and the C4th(FB) condition occurred 460-640 ms (M460) after the presentation of the feedback signals, with the activation of the dorsolateral prefrontal cortex and the middle frontal cortex. No significant location differences were found between the frontal responses (M370) of the W1st(C) and M460 of the W1st(FB). Our results proved that the WCST task activates a broad frontal area and the parieto-frontal network across time streaming. Both shifting attention to the wrong feedback and enhanced visual working memory to the sorting shifting condition of the card presentation occur in the same areas at different time points.

Adult↗

PubMed2006

Event-related fMRI of word classification and successful word recognition in subjects at genetically enhanced risk of schizophrenia.

BACKGROUND: Verbal declarative memory is a core deficit in schizophrenia patients, seen to a lesser extent in unaffected biological relatives. Neuroimaging studies suggest volumetric differences and aberrant function in prefrontal and temporal regions in schizophrenia patients compared to controls. These deficits are also reflected in the small number of similar investigations in unaffected biological relatives. However, it is unclear the extent to which dysfunction is genetically mediated or a feature of the established illness. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation in 68 biological relatives of schizophrenia patients (of whom 27 experienced transient or isolated psychotic symptoms) and 21 controls during verbal classification and recognition. RESULTS: During word classification, the high-risk group showed a greater response relative to controls in the right inferior frontal gyrus. During correct recognition (relative to correct rejection), the high-risk group showed significantly greater response relative to controls in the right cerebellum. When the high-risk group was split into those with (HR+) and without (HR-) psychotic symptoms, the increased response in the right inferior frontal gyrus was only seen when the HR+ were compared to controls. The greater cerebellar response was seen when both HR groups were compared to controls. CONCLUSIONS: Activation increases in the right inferior frontal gyrus and cerebellum in high-risk subjects compared to controls during a relatively low-load memory task are likely to represent compensation for genetically mediated abnormalities. This is consistent with a leftward shift of the inverted 'U' load-response model of cognitive function in schizophrenia.

Adolescent↗

PubMed1993

Selective attention and temporal-order judgment.

A procedure originally introduced by Sternberg and coworkers was used to examine the effect of selective attention on temporal-order judgment. Two-response and three-response paradigms were employed. As in Sternberg et al's work, a shift of psychometric functions for the two-response paradigm was found that suggested shorter latency for the stimulus to which attention was directed. However, no shift was noted for the three-response paradigm. This discrepancy can be explained by the assumption that the shift obtained for the two-response paradigm results from an artifact caused by a specific task. The artifact occurs because the instruction to attend to a particular stimulus induces a response bias when the subject is forced to guess in situations where he/she cannot recognize the temporal order of stimuli. The artifact disappears with the three-response paradigm where the subject has the additional option to respond "simultaneous".

Artifacts↗

PubMed1997

Perinatal choline supplementation increases the threshold for chunking in spatial memory.

Chunking and perinatal choline supplementation each provide rats with alternative memory processing advantages. Evidence from radial-arm maze performance of adult (2- to 5-month-old) rats indicates that chunking of multiple food types (sunflower seeds, Noyes pellets and rice puffs) emerges for stable, differentiable baiting patterns as a function of the memory load (6, 12, 18 or 24 maze arms). The number of maze arms appeared to determine both the level of task difficulty at which rats began to implement a chunking strategy as well as when they were unable to successfully implement such a strategy due to the excess memorial demands of the task. In comparison to control rats, rats treated perinatally with choline supplementation displayed a horizontal rightward shift of the response function that related level of clustering of like-food types to the number of maze arms. These results indicate a higher threshold for implementing a chunking strategy in rats treated perinatally with choline supplementation, possibly due to a choline-induced increase in memory capacity.

Animals↗

PubMed1998

Neuropsychological evidence of the functional integration of visual, auditory and proprioceptive spatial maps.

We infer the functional integration of the visual, auditory and proprioceptive spatial maps from the behaviour of a patient (G.A.) with left visual neglect, i.e. a derangement of visual space representation. G.A. was required to point manually to left, centre or right acoustic stimuli, under visual control or blindfolded, with the responding hand (left or right) located either on the left, centre or right space. G.A.'s manual pointing responses to left auditory stimuli were strongly influenced by the visual spatial information and by the proprioceptive spatial information related to the position of the responding effector. In the visual control condition, when the patient performed the task with the left effector located on the left, pointing responses to left auditory stimuli were shifted towards the right intact visual space. In contrast, when the visual spatial information was rendered less salient, i.e. in the blindfolded condition, and the effector was again located on the left, manual pointing responses were confined to the previously ignored left space. These findings are consistent with the view that the acoustic representation is modulated by the impaired visual representation and by the proprioceptive spatial map related to the position of the responding effector.

Acoustic Stimulation↗

PubMed1996

Detection of frequency changes in transposed sequences of tones.

The ability to detect frequency changes in transposed sequences of tones was examined in a series of seven experiments. Listeners were asked to judge which of two transposed (i.e., frequency-shifted) comparison patterns preserved the sequence of relative frequencies presented in a preceding standard pattern. The task was performed with five-tone and two-tone patterns under conditions of high and minimal pattern uncertainty. Regardless of pattern length or level of uncertainty, frequency discrimination thresholds for a change in the relative frequency of a single tone were considerably higher when patterns were transposed than when they were not. There was a tendency for performance to worsen with increasing degrees of transposition (primarily under high uncertainty) but most of the detrimental effects of transposition occurred within the first two semitones of transposition. Minimal uncertainty testing resulted in large improvements with five-tone patterns (as much as one order of magnitude), but there was no effect of level of uncertainty on performance with two-tone patterns. Thresholds for changes in two-tone patterns were similar to (although slightly higher than) those for five-tone patterns under minimal-uncertainty testing. This pattern of results reveals that the effects of stimulus complexity (sequence length) and pattern familiarity (level of uncertainty) on relative-frequency discrimination are quite similar to the effects of these variables on absolute-frequency discrimination.

Auditory Perception↗

PubMed2001

KT3.2 and KT3.3, two novel human two-pore K(+) channels closely related to TASK-1.

We report the cloning of human KT3.2 and KT3.3 new members of the two-pore K(+) channel (KT) family. Based on amino acid sequence and phylogenetic analysis, KT3.2, KT3.3, and TASK-1 constitute a subfamily within the KT channel mammalian family. When Xenopus oocytes were injected with KT3.2 cRNA, the resting membrane potential was brought close to the potassium equilibrium potential. At low extracellular K(+) concentrations, two-electrode voltage-clamp recordings revealed the expression of predominantly outward currents. With high extracellular K(+) (98 mM), the current-voltage relationship exhibited weak outward rectification. Measurement of reversal potentials at different [K(+)](o) revealed a slope of 48 mV per 10-fold change in K(+) concentration as expected for a K(+)-selective channel. Unlike TASK-1, which is highly sensitive to changes of pH in the physiological range, KT3.2 currents were relatively insensitive to changes in intracellular or extracellular pH within this range due to a shift in the pH dependency of KT3.2 of 1 pH unit in the acidic direction. On the other hand, the phorbol ester phorbol 12-myristate 13-acetate (PMA), which does not affect TASK-1, produces strong inhibition of KT3.2 currents. Human KT3.2 mRNA expression was most prevalent in the cerebellum. In rat, KT3.2 is exclusively expressed in the brain, but it has a wide distribution within this organ. High levels of expression were found in the cerebellum, medulla, and thalamic nuclei. The hippocampus has a nonhomogeneous distribution, expressing at highest levels in the lateral posterior and inferior portions. Medium expression levels were found in neocortex. The KT3.2 gene is located at chromosome 8q24 1-3, and the KT3.3 gene maps to chromosome 20q13.1.

4-Aminopyridine↗