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PubMed1996

Memory disorders in Alzheimer's disease and the organization of human memory.

The Squire and Zola-Morgan parallel organization model of the memory and the Tulving hierarchical model were developed mainly through the study of amnesic patients. The predictions of these two models are different, the first being more open to double dissociations and less restrictive than the second. Alzheimer's Disease is characterized by a differential impairment of the memory systems and by an interindividual variability which may take the form of dissociations between preserved and disturbed abilities in some patients. The objective of this study was to use the memory dysfunctions of patients with AD to test the validity of the two models. Analysis of the group data provided an average profile of memory disturbance consistent both with much of the data given in AD literature and with the two models. Using a multiple single-case strategy, we demonstrated several simple dissociations which are for the greater part compatible with the two models. Two of the dissociations underline the limits of the Tulving model, which otherwise accounts for a lot of results. The study supports the relevance of AD for the understanding of the cognitive architecture of the human memory.

Aged↗
PubMedDate not supplied

Memory and schizophrenia: differential link of processing speed and selective attention with two levels of encoding.

The purpose of this study was to investigate how underlying cognitive deficits such as a defect in processing speed or in selective attention contributed to different types of memory impairment observed in schizophrenia (superficial vs deep encoding). 49 schizophrenic patients and 40 normal controls were administered a verbal memory task. Superficial encoding was assessed by the ability to recall items in their serial order. Deep encoding was assessed by the ability to organise words into semantic categories. Two measures of processing speed (Digit Symbol Substitution Test and Stroop colour time) and one measure of selective attention (Stroop test) were used. Regression analyses were carried out. In the patient group, processing speed contributed to both superficial and deep encoding, and to a global verbal memory score. Selective attention only contributed to the superficial encoding processes. Thus, slowing of processing speed in schizophrenia seems to be more crucial for memory performance, since it affects memory in a pervasive way.

Adult↗
PubMedDate not supplied

Differential neuronal encoding of novelty, familiarity and recency in regions of the anterior temporal lobe.

Activity of 2072 neurones was recorded in the anterior temporal lobe--in area TE, perirhinal cortex, entorhinal cortex and hippocampus--during performance of a visual recognition task by monkeys. In area TE, perirhinal cortex and entorhinal cortex, 454 neurones (38% of the 1162 visually responsive neurones) responded differentially on the basis of the relative familiarity or recency of presentation of the stimuli; in the hippocampus only one (3%) of its 40 visually responsive neurones) did so. The differentially responsive neurones were classified into those signalling information concerning the recency (19%), familiarity (37%) or novelty (38%) of stimuli. For 98% of these neurones a decreased response signalled that stimuli had occurred previously: no large response increments were observed. The mean differential latency of each of these types of neurone was shorter (approximately 75 ms) in area TE than in the other areas. Examples of each of these types of neurone with memory spans of approximately 24 h were found in each region. The mean memory span of recency neurones was significantly longer in perirhinal cortex than area TE. For familiarity neurones a significant mean response decrement took 4-8 min to develop, indicating a slow underlying plastic change, in contrast to the rapid change seen for recency and novelty neurones. The implications of these results are discussed in relation to the neuronal basis of recognition memory.

Analysis of Variance↗
PubMed2000

Activation of 5-HT2A receptors impairs response control of rats in a five-choice serial reaction time task.

The present experiments investigated the effects of agents acting at serotonin (5-HT)-2 receptors on the performance of rats in a choice serial reaction time (5-CSRT) task in order to examine the role of 5-HT2 receptors in the modulation of attention and response control. The results indicate that DOI, [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride; 0.05, 0.1 and 0.2 mg/kg, subcutaneously], a 5-HT(2A/2C) agonist, slightly impaired the choice accuracy of the well performing rats and markedly increased their premature responding. DOI (0.05 and 0.1 mg/kg) had no effect on the latency to collect earned food pellets or to respond correctly, indicating that these lower doses of DOI did not reduce motivation for the food reward in this task. The selective effect of a low dose of DOI (0.1 mg/kg) on premature responding was completely blocked by ketanserin (0.2 mg/kg), a 5-HT2A antagonist, and ritanserin (0.3 mg/kg), a 5-HT(2A/2C) antagonist, but only partially blocked by a high dose of SER082 (1.0 mg/kg), a 5-HT2C antagonist. In contrast to DOI, mCPP, [1-(3-phenyl)piperazine; 0.05 and 0.15 mg/kg], a 5-HT2C agonist, had no effect on choice accuracy or premature responding, but it reduced behavioral activity and/or arousal as indicated by the decreased number of trials completed and increased the probability of omissions. SER082 (1.0 mg/kg) blocked the effects of mCPP on performance. These data suggest that the overactivation of 5-HT2A receptors impairs response control in a 5-CSRT task, whereas the overactivation of 5-HT2C receptors can affect behavioral activity and/or arousal state of the animals for this food rewarded task.

Adrenergic alpha-Antagonists↗
PubMed2000

Is the organisation of goal-directed action modality specific? A common temporal structure.

With the help of kinematic analysis, the temporal organization of the complex daily activity 'drinking from a bottle with a glass' was described in detail. The analysis focused on the sequential action structure, the prehensile acts, and the bimanual coordination as well as on the effect of different instruction modalities on these parameters to explore the underlying representation for this complex action. Movements of the two arms were recorded in three-dimensional space with the help of an optoelectronic device in 12 normal subjects under four conditions: (1) action pantomime after verbal instruction; (2) action imitation after observation of the action performed by the experimenter without the objects; (3) action pantomime while seeing, but not touching the objects; and finally (4) action execution with objects. Despite high execution variability, the temporal structure of the action could be precisely described by the relative duration and peak velocity of action segments, by the MGA-object size-correlation, and by linear regression analysis between the onsets of functionally related action segments. A similar structure of the action as characterized by these kinematic parameters was retained across different instruction modalities. Only when the action was executed with the objects, the interval between the movement onsets of either hand and the peak velocity of the manipulative acts were reduced, while no change was observed across the other three instruction modalities. This stability of the temporal structure suggests the existence of a level in the representation of an action where all the modalities converge.

Attention↗
PubMed2000

ERP effects of listening to speech compared to reading: the P600/SPS to syntactic violations in spoken sentences and rapid serial visual presentation.

In this study, event-related brain potential effects of speech processing are obtained and compared to similar effects in sentence reading. In two experiments sentences were presented that contained three different types of grammatical violations. In one experiment sentences were presented word by word at a rate of four words per second. The grammatical violations elicited a Syntactic Positive Shift (P600/SPS), 500 ms after the onset of the word that rendered the sentence ungrammatical. The P600/SPS consisted of two phases, an early phase with a relatively equal anterior-posterior distribution and a later phase with a strong posterior distribution. We interpret the first phase as an indication of structural integration complexity, and the second phase as an indication of failing parsing operations and/or an attempt at reanalysis. In the second experiment the same syntactic violations were presented in sentences spoken at a normal rate and with normal intonation. These violations elicited a P600/SPS with the same onset as was observed for the reading of these sentences. In addition two of the three violations showed a preceding frontal negativity, most clearly over the left hemisphere.

Adult↗
PubMed2002

On the role of the SMA in the discrete sequence production task: a TMS study. Transcranial Magnetic Stimulation.

Participants practiced two discrete six-key sequences for a total of 420 trials. The 1 x 6 sequence had a unique order of key presses while the 2 x 3 sequence involved repetition of a three-key segment. Both sequences showed a long interkey interval halfway the sequence indicating hierarchical sequence control in that not only the 2 x 3 but also the 1 x 6 sequence was executed as two successive motor chunks. Besides, the second part of both sequences was executed faster than the first part. This supports the earlier notion of a motor processor executing the elements of familiar motor chunks and a cognitive processor triggering either these motor chunks or individual sequence elements. Low-frequency, off-line transcranial magnetic stimulation (TMS) of the supplementary motor area (SMA) counteracted normal improvement with practice of key presses at all sequence positions. Together, these results are in line with the notion that with moderate practice, the SMA executes short sequence fragments that are concatenated by other brain structures.

Adult↗
PubMed2002

Sustained attention deficit in bipolar disorder is not a working memory impairment in disguise.

Euthymic patients with bipolar disorder have been reported to show persistent deficits in sustained attention. However, the sustained attention task which was used also placed demands on working memory. Bipolar disorder patients in the euthymic state were therefore compared with healthy controls on two measures of sustained attention with and without a working memory component. Signal detection methodology was applied to the results. Euthymic patients with bipolar disorder were particularly impaired at detecting targets in the sustained attention task without a working memory component. This deficit was still apparent in a sub-group of patients who were not currently receiving lithium medication. By contrast, performance in the sustained attention task involving working memory task was not significantly different in the two groups. Sustained attention deficits apparent during the euthymic period of bipolar disorder cannot be explained in terms of working memory impairment and represents a reduced inherent capacity rather than a change in response bias. Deficits in sustaining attention may help explain the difficulties in psychological and occupational functioning in bipolar disorder patients during remission.

Adult↗
PubMed2003

Coordination of fingertip forces during precision grasping in multiple system atrophy.

While the pathology and autonomic nervous system components of multiple system atrophy (MSA) have been well described, little is known about the associated motor dysfunction. One prominent feature of MSA is parkinsonism, although ataxias and pyramidal tract signs are frequently present. To investigate the nature of motor deficits in MSA, a natural grip-lift movement requiring a precision grasp was used to examine force coordination. Subjects were asked to grasp an instrumented object using the fingertips of the thumb and index finger and lift it 10 cm above the table surface. Subjects with MSA demonstrated a prolonged duration between object contact and initiation of the lifting drive that increased with the weight of the object. During this period these subjects produced large grasping forces generating a significant portion of the eventual grip force employed to hold the object. In contrast, control subjects generated grip and load forces in parallel after establishing contact with the object. Therefore, subjects with MSA showed a disrupted performance on both the sequential (grasp, then lift) and simultaneous (grip and load force development) portions of this task. Only after initiation of the vertical lifting drive did subjects with MSA generate forces in a similar manner to control subjects. These findings demonstrate that subjects with MSA exhibit a disrupted coordination of grasp and could suggest a general deficit in motor control resulting from multi-focal neural degeneration.

Adaptation, Physiological↗
PubMed1999

The dependence of span and delayed-response performance on prefrontal cortex.

Theoretical and empirical research on the cognitive functions of the prefrontal cortex have established that this region mediates what have been called 'executive' processes that can influence working and long-term memory. Despite the accumulation of such empirical evidence, the dependence of purely mnemonic portions of memory tasks on PFC remains unresolved. To address this issue, we performed an analysis of reports of performance on tests of working memory of patients with lesions of the dorsolateral prefrontal cortex, focusing on published reports in the literature of simple span and delayed-response tasks. We found that none of the eleven studies of forward verbal and spatial span in patients with prefrontal cortical lesions that we reviewed (reflecting the performance of 166 individual patients) demonstrated a statistically significant deficit relative to normal controls. In contrast, our review of the delayed-response literature indicated that there are conditions under which PFC lesions disrupt delayed-response performance. Based on the results of our review of the literature, we present testable hypotheses about the working memory functions of the PFC.

Attention↗
PubMed2000

The role of speech production in auditory-verbal short-term memory: evidence from progressive fluent aphasia.

We report investigations of auditory-verbal short-term memory (AVSTM) in a patient with progressive fluent anomic aphasia. Despite having apparently normal AVSTM as measured by digital span, FM was significantly impaired in immediate serial recall of short sequences of familiar words, and even in reproducing a single word after a filled delay of just a few seconds. In both tasks, unlike normal subjects, she produced numerous phonological errors, often consisting of phonological segments from the intended target word concatenated with segments from other words in the stimulus sequence. Her success in these tasks was modulated (i) consistently by word frequency (high > low), (ii) inconsistently by word imageability (high > low), and (iii) most dramatically by 'nameability': that is, FM was much more likely to reproduce a word correctly in AVSTM if it was a word that she could also produce successfully in picture-naming tasks. On the basis of these and additional experiments designed to exclude other interpretations, we conclude that AVSTM may be crucially supported by activation of the lexical phonological representations responsible for production of content words in speech.

Anomia↗
PubMed1999

Parallel and serial search in two teenagers with lesions of the mesial parietal cortex.

Visual-spatial attention was examined in two 14-year-olds who had undergone occipital-parietal craniotomies for removal of mesial parietal tumors, one in the right and one in the left hemisphere. Neither patient showed clinically significant visual neglect. They were administered two visual search tasks from Treisman and Souther [43] that make significantly different demands on visual spatial attention. In feature-present (parallel) search, they searched for the presence of a feature. In feature-absent (serial) search, they searched for its absence. Search rate was estimated from the slope of the function relating display size to response time. Both patients had flat slopes in feature-present search to target-present (TP) displays, indicating that they could conduct parallel search at the same rate as controls. Although the patient with the right-hemisphere lesion also had a flat slope to target-absent (TA) displays, the patient with the left-hemisphere lesion had a steep slope (30 ms/item) in this condition. In feature-absent search, the patients had equally slow search rates compared to controls, suggesting that the mesial parietal cortex is part of the network that mediates serial shifts of attention. Results support the distinction between detection of the target in parallel vs serial search and suggest that processes involved in TP and TA trials in parallel search are also dissociable.

Adolescent↗
PubMed1997

Dexmedetomidine reduces response tendency, but not accuracy of rats in attention and short-term memory tasks.

The present study investigated the role of alpha 2-adrenergic mechanisms in the performance of motor responses, attention and short-term memory in rats. A low dose (3.0 micrograms/kg, s.c.) of dexmedetomidine, an alpha 2-adrenoceptor agonist, reduced response tendency in an attentional task and a working memory task, but it did not affect the choice accuracy of rats. Atipamezole (300 micrograms/kg), an alpha 2-adrenoceptor antagonist, increased anticipatory responding. Although atipamezole did not affect the number of omissions, it reversed the effects of dexmedetomidine on that parameter. We also investigated the effects of dexmedetomidine in rats with partial destruction of noradrenergic nerves induced by the neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride). On its own, DSP-4 treatment did not affect choice accuracy or behavioural activity of rats in the attentional task. The effects of dexmedetomidine (0.3-3.0 micrograms/kg) on anticipatory responses did not differ between controls and DSP-4 group. Furthermore, the effect on omissions was not consistently diminished in DSP-4 treated rats. These results suggest that the activation of postsynaptic alpha 2-adrenoreceptors may be responsible for dexmedetomidine-induced reduction of response tendency while attention and short-term memory are not markedly affected.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2004

Semantic short-term memory and its role in sentence processing: a replication.

Previous studies have shown that an aphasic patient (AB) with a semantic short-term memory deficit (STM) had difficulties comprehending and producing sentences with structures that demanded the simultaneous retention of several individual word meanings (Martin & Freedman, 2001a, 2001b; Martin & Romani, 1994; Martin, Shelton, & Yaffee, 1994). The present study provides a replication of these findings with an additional case (ML) who shows a striking dissociation between preserved semantic knowledge and disrupted semantic STM. ML performed poorly on comprehension tasks for sentences that required the retention of single word meanings across several intervening words. In contrast, he did not show an effect of intervening words on processing grammatical relations. ML had difficulty producing adjective-noun phrases, though able to produce the individual nouns and adjectives. These findings support the contention that there is a semantic retention capacity, involved in both comprehension and production, that is separate from semantic knowledge representations.

Aged↗
PubMed2002

The phonological similarity effect in short-term memory serial recall in schizophrenia.

Lists of phonologically similar items are more often recalled in the wrong order than phonologically dissimilar items. At recall, patients with schizophrenia were neither especially susceptible to confusing phonologically similar items nor to making disproportionate movement (i.e. order) errors with phonologically similar lists of items. We conclude that patients with schizophrenia employ recall strategies for phonologically similar items in short-term memory that are equivalent to those of healthy controls.

Adult↗
PubMed2000

Effect of subtype selective nicotinic compounds on attention as assessed by the five-choice serial reaction time task.

Nicotine can improve attentional functioning in humans, and a number of studies have recently demonstrated that under specific task conditions, nicotine can also improve attention in the rat. Neuronal nicotinic receptors comprise combinations of alpha(2-9) and beta(2-4) subunits, arranged to form a pentameric receptor, with the principal CNS subtypes currently believed to be alpha(4)beta(2) and a homomeric alpha(7) receptor. In the present studies, we attempted to delineate the particular nicotinic receptor subtype(s) contributing to the effects of nicotine on attention by assessing various nicotinic ligands on performance in the five-choice serial reaction time task (5-CSRTT). In rats performing below criterion (<80% correct, >20% omissions to a 1-s visual stimulus), subchronic dosing with nicotine (0.2 mg/kg sc) and the alpha(4)beta(2) agonist SIB 1765F (5 mg/kg sc) increased correct responding and decreased response latencies across the treatment week; whereas the alpha(7) agonist AR-R 17779 (20 mg/kg sc) was without effect. In subjects meeting the criterion, the competitive high affinity (including alpha(4)beta(2)) nicotine receptor antagonist DHbetaE (1-10 mg/kg sc) and the alpha(7) antagonist methyllycaconitine (MLA: 5-10 mg/kg i.p.) did not disrupt performance, whereas at the highest dose, the non-competitive antagonist mecamylamine (0.3-3 mg/kg sc) decreased accuracy and increased response latencies. These changes bore some similarities to those of pre-feeding and the non-competitive NMDA antagonist dizocilpine (0.03-0.06 mg/kg sc), suggesting that mecamylamine-induced performance disruption may relate to non-nicotinic receptor effects. In subjects chronically treated with nicotine, acute nicotine challenge (0.4 mg/kg sc) significantly increased accuracy whilst having no effect on any other performance measures. Finally, in these same nicotine pre-treated rats, the decrease in latency and increase in premature responses induced by nicotine (0.2 mg/kg sc) to a target stimulus of 150 ms was fully antagonised by DHbetaE (3 mg/kg sc) but not MLA (5 mg/kg i.p.). These results suggest that alpha(7) receptors do not play a role in any of the behavioural effects of nicotine observed in the 5-CSRTT, whereas a high affinity site, perhaps alpha(4)beta(2), is more likely involved.

Animals↗
PubMed2001

Effects of dorsal and ventral striatal lesions on delayed matching trained with retractable levers.

Recent evidence has suggested that thalamic amnesia results from damage to the intralaminar nuclei, an important source of input to striatum. To test the hypothesis that intralaminar damage disrupts functions mediated by striatum, we studied the effects of striatal lesions on a delayed matching task known to be affected by intralaminar lesions. Rats were trained to perform the task and given one of five treatments: sham surgery or a lesion of medial or lateral caudate/putamen, nucleus accumbens, or ventral striatum. Rats with ventral striatal lesions were impaired compared to all other groups. Rats with medial caudate/putamen or nucleus accumbens lesions were impaired compared to controls. The effects of ventral striatal lesions were sufficient to account for impairments in the accuracy and latency of delayed matching responses observed in previous studies of intralaminar and medial frontal cortical lesions. The ventral striatal lesions involved portions of ventral pallidum and thus it seems likely that they affected functions mediated by the nucleus accumbens as well as striatal areas of the tubercle. Serial reversal learning trained in the same apparatus with the same reinforcer was unaffected by all of the lesions. These results are discussed in terms of the roles of midline thalamic nuclei and of thalamo-cortico-striatal circuits in delayed conditional discrimination tasks.

Animals↗