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PubMed2001

Thiamin treatment and working memory function of alcohol-dependent people: preliminary findings.

BACKGROUND: Wernicke-Korsakoff syndrome (WKS) is most often seen in people who are alcohol dependent. Treatment with thiamin may rapidly resolve acute symptoms. However, much evidence suggests that identification of WKS on clinical examination is relatively insensitive when compared with diagnosis at postmortem. No study has investigated the therapeutic effect of thiamin in a sample of alcohol-dependent people without the clinical triad of acute WKS. METHODS: We conducted a randomized, double-blind, multidose study of thiamin treatment in 107 subjects who were detoxifying from alcohol. Five groups of subjects were assessed with the Mini-Mental State Examination and were examined for the presence of neurological signs. Subjects were given different doses of intramuscular thiamin for two consecutive days. The posttreatment performance of these groups then was examined on a test of working memory derived from comparative neuropsychology, namely, the delayed alternation task. This test has been established as sensitive to the neuropathology of WKS. RESULTS: Pretreatment measures of mental status and neurological signs were equivalent across groups. Groups were equated with respect to the background variables of age, education, typical daily alcohol consumption, and years of drinking. On the posttreatment measure, a superior performance was found in the group that received the highest dose of thiamin, compared with the other four treatment groups. CONCLUSIONS: A therapeutic relationship between dose and working memory performance was indicated. These results have important implications for the management and prevention of WKS, but further investigations are needed to substantiate the nature of the therapeutic relationship.

Adult↗
PubMed2005

Striatal and forebrain nuclei volumes: contribution to motor function and working memory deficits in alcoholism.

BACKGROUND: Striatal structures are involved in dopaminergic alcohol reward mechanisms and aspects of motor control. Basal forebrain structures hold cholinergic mechanisms influencing memory formation, vulnerable to chronic alcoholism; however, alcoholism's effect on volumes of these structures has seldom been considered with in vivo measurement. METHODS: We measured bilateral volumes of caudate nucleus, putamen, nucleus accumbens, and medial septal/diagonal band (MS/DB) in 25 men with alcohol dependence and 51 age-matched control men. Six alcoholic subjects had been drinking recently, and 19 had been sober. RESULTS: Volumes of caudate and putamen were smaller in the alcoholics than in the control subjects, regardless of length of sobriety. Recent drinkers showed greater deficits in nucleus accumbens than sober alcoholics. Putamen volume was positively correlated with grip strength; MS/DB volume was positively correlated with verbal working memory independently of the negative association between age-standardized MS/DB and age in alcoholics. CONCLUSIONS: Caudate and putamen volume deficits occur and endure in chronic alcoholism. Nucleus accumbens might be especially sensitive to recent alcohol exposure. Striatal volumes should be considered in functional imaging studies of alcohol craving that target striatal brain regions. The age-alcohol interaction for MS/DB volumes is consistent with a cholinergic mechanism for the working memory impairment observed in the alcoholics.

Adult↗
PubMed1997

Effects of acute daily administration of diazepam on spatial learning and working memory.

This study evaluated the acute or daily effects of diazepam (DZP) on the acquisition and performance of rats in an 8-arm radial maze. Male Wistar rats (200-250 g) were divided into three groups: saline-saline (SS), saline-DZP (SD) and DZP-DZP (DD). The SS group always received intraperitoneal (i.p.) saline (SAL) in daily or acute treatments. The SD group received SAL (i.p.) daily during the task acquisition (30 days), DZP (2.5 mg/kg, i.p.) 45 min before the acute 5 s and 1 h delay tests, and it also received DZP (10 mg/kg, i.p.) for 70 days. The DD group received DZP (10 mg/kg, i.p.) daily during 30 days in the task acquisition, DZP (2.5 mg/kg, i.p.) 45 min before the acute 5 s and 1 h delay tests and further received DZP (10 mg/kg, i.p.) for an additional 70 days. Our results showed that as compared to control (SS group), 8-10 h prior administration of a single daily dose of DZP (10 mg/kg) did not alter the learning and the performance of short- (5 s delay) and long-term (1 h delay) working memory. However, the acute administration of DZP (2.5 mg/kg) impaired the performance of the short delay task (5 s delay) in animals previously exposed (DD group) or not (SD group) to daily DZP treatment. Therefore, the acute administration of an anxiolytic dose of DZP (2.5 mg/kg) produced a significant impairment of short-term working memory, even in animals exposed to daily DZP treatment for a long time.

Animals↗
PubMed2005

Tourette's syndrome: performance on tests of behavioural inhibition, working memory and gambling.

BACKGROUND: Tourette's syndrome (TS) is a neurodevelopmental disorder associated with fronto-striatal dysfunction. There is debate as to the extent to which TS is associated with cognitive impairment. Some authors argue that any impairments seen are attributable to comorbid psychiatric symptomatology, whilst others have suggested that uncomplicated TS is associated with mild deficits limited primarily to inhibitory processes. The present study was designed to examine this issue using carefully screened participants with TS and experimental measures thought to involve different areas of the frontal lobes. METHODS: Adolescents with TS who were screened for comorbid psychiatric disorder were compared with a healthy control group on a set of executive measures. Two tasks involving behavioural inhibition were used: a Sentence Completion task in which sentences had to be completed first with straightforward and then with nonsensical endings, and a Flanker task in which a central stimulus was surrounded by either compatible or incompatible flankers. Working memory was assessed using an N-back task, and reward learning was assessed using a Gambling task. Both accuracy and reaction times were measured for each task. RESULTS: The TS group differed significantly from the control group on both the Sentence Completion task and on the Flanker task. On the Sentence Completion task, they were slower to make both sensible and nonsensical completions, and they had higher error scores on the nonsensical completions. On the Flanker task, the TS participants were less accurate than the control group, since they were poorer on the incompatible but not the compatible trials. A similar interaction with trial type was found for speed, where the TS participants were slowed more by the incompatible versus compatible trials, although overall their performance tended to be faster than the controls. The TS group did not differ significantly from the control group on measures of working memory or reward learning. CONCLUSIONS: The findings provide further evidence that uncomplicated TS is not associated with widespread executive impairments. However, it was not clear that any differences between the groups could be attributed solely to selective inhibitory impairment.

Adolescent↗
PubMed1991

Quisqualate lesions of rat NBM: selective effects on working memory in a double Y-maze.

Some authors have reported that quisqualic acid lesions of the nucleus basalis magnocellularis (NBM), although producing large cortical cholinergic losses, have little effect on memory. The purpose of the present study was to investigate the effects of quisqualic acid lesions of the NBM on working and reference memory in a double Y-maze. Each trial started with placement into one of the two end arms of the first Y-maze, and the correct response was to go down the stem (reference memory). Access was then given to the second Y-maze, the correct response being conditional upon the side of the first Y-maze from which that trial had begun (working memory). Rats were trained to an 88% correct criterion and were then given either bilateral quisqualic acid (60 nM, 0.5 microliters) or sham lesions (0.9% saline, 0.5 microliters) of the NBM. One week postsurgery, rats were tested on the double Y-maze task with delays of 0, 5 or 30 seconds being introduced prior to both the working and reference memory choice. NBM lesions produced a 63.2 +/- 6.2% decrease of cortical choline acetyltransferase (ChAT) compared to unoperated controls. Delays affected only the working memory of the sham group. Rats with lesions showed a significant impairment of working memory at all delays, but no change in reference memory. Results indicate that quisqualic acid lesions of the NBM that produce significant reductions in cortical ChAT selectively impair working memory.

Animals↗
PubMed1998

P3, positive slow wave and working memory load: a study on the functional correlates of slow wave activity.

Parietal positivities of the 'slow wave' type are known to emerge after the P300 whenever target detection leads to a complex subsidiary task. Although the functional correlates of these 'positive slow waves' (PSW) are not known, it has been suggested that they may index (a) the selection or decision processes, (b) the preparation of the response or (c) the evaluation of its correctness. We investigated whether PSW could be dissociated from each of these putative steps of information processing by means of a paradigm devoid of motor components and needing very long reaction times. In our protocol, target stimuli acted as the triggering signal to perform silently one of 4 different tasks, namely (a) simple updating of a target count; (b) counting backward in threes; (c) simultaneous updating of two items (day of the week and ordinal of the month) and (d) updating of 3 items (the two above plus the month of the year). Reaction times to the same stimuli were obtained in 5 subjects during separate sessions. The different tasks did not modify the latencies of N2 or P3b components, but attenuated the amplitude of P3 as a mirror image of the subjective difficulty scores. A conspicuous parietal PSW appeared in conditions where two or 3 items had to be updated. This PSW developed 1-2 s earlier than the reaction times to the same experiments and could be therefore dissociated from the selection and decision processes. PSW latency was correlated with the number of items to be updated, but not with subjective difficulty. In the present paradigm PSW appeared to index the retrieval of information from working memory; however, in more general terms our results suggest that PSW is a non-specific activity that signals the completion of any synchronized operation immediately following target detection. Our data suggest a functional link between P3 and PSW, also supported by the similarity of their respective scalp topographies. The present paradigm proved to be easy to implement and suitable to study the 'executive' functions governing attentional and working-memory control during the performance of multiple tasks.

Adult↗
PubMed1995

Contrasting effects of clonidine and diazepam on tests of working memory and planning.

The alpha 2 adrenoceptor has recently been implicated in working memory (WM), a function dependent on the integrity of the prefrontal cortex. Using a double-blind, placebo-controlled design, the present investigation examines the effects of two doses (1.5 micrograms/kg and 2.5 micrograms/kg) of the mixed alpha 1/alpha 2 adrenoceptor agonist clonidine (CLO) on performance of various computerised tests of WM and planning in healthy, young volunteers. These are compared to the effects produced by two doses (5 mg and 10 mg) of diazepam (DZP) on largely the same set of neuropsychological tests in a comparable set of subjects. Administration of CLO resulted in impulsivity of responding in a planning task, as well as differential dose-dependent effects on two analogous tests of spatial and visual WM. The nature of these effects were suggestive of mnemonic, rather than executive, dysfunction. Conversely, DZP produced specific deficits on tests of spatial WM and planning very similar to those seen following lesions to the frontal lobes. Therefore, these two sedative drugs produce doubly dissociable, dose-dependent effects on different aspects of cognitive function.

Adult↗
PubMed2003

Cortical capacity constraints for visual working memory: dissociation of fMRI load effects in a fronto-parietal network.

Working memory (WM) capacity limitations and their neurophysiological correlates are of special relevance for the understanding of higher cognitive functions. Evidence from behavioral studies suggests that restricted attentional resources contribute to these capacity limitations. In an event-related functional magnetic resonance imaging (fMRI) study, we probed the capacity of the human visual WM system for up to four complex nonnatural objects using a delayed discrimination task. A number of prefrontal and parietal areas bilaterally showed increased blood oxygen level-dependent activity, relative to baseline, throughout the task when more than one object had to be held in memory. Monotonic increases in response to memory load were observed bilaterally in the dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (pre-SMA). Conversely, activity in the frontal eye fields (FEFs) and in areas along the intraparietal sulcus (IPS) peaked when subjects had to maintain only two or three objects and decreased in the highest load condition. This dissociation of memory load effects on cortical activity suggests that the cognitive operations subserved by the IPS and FEF, which are most likely related to attention, fail to support visual WM when the capacity limit is approached. The correlation of brain activity with performance implies that only the operations performed by the DLPFC and pre-SMA, which support an integrated representation of visual information, helped subjects to maintain a reasonable level of performance in the highest load condition. These results indicate that at least two distinct cortical subsystems are recruited for visual WM, and that their interplay changes when the capacity limit is reached.

Adult↗
PubMed2005

rTMS evidence of different delay and decision processes in a fronto-parietal neuronal network activated during spatial working memory.

The existence of a specific and widely distributed network for spatial working memory (WM) in humans, involving the posterior parietal cortex and the prefrontal cortex, is supported by a number of neuroimaging studies. We used a repetitive transcranial magnetic stimulation (rTMS) approach to investigate the temporal dynamics and the reciprocal interactions of the different areas of the parieto-frontal network in normal subjects performing a spatial WM task, with the aim to compare neural activity of the different areas in the delay and decision phases of the task. Trains of rTMS at 25 Hz were delivered over the posterior parietal cortex (PPC), the premotor cortex (SFG) and the dorsolateral prefrontal cortex (DLPFC) of the right hemisphere alternatively during the two phases. We found a pattern of interference of TMS during the delay phase for both parietal and DLPFC sites of stimulation, with no effect observed for the SFG site. When rTMS trains were applied during the decision phase, an interference was observed selectively for DLPFC. The present study shows the existence of a parallel processing in the parieto-frontal network of spatial WM during the delay phase. Furthermore, it provides new evidence of the critical role of the DLPFC during both the delay and the decision phases. We suggest that in DLPFC, two different networks coexist: A local neural network subserving the decisional processes and a second neural population functionally interconnected with the PPC and activated when a certain spatial information has to be kept in memory, available to use.

Adult↗
PubMed2005

Working memory can guide pop-out search.

Top-down feedback from working memory (WM) can exert an early and involuntary influence on visual selection for targets that are relatively difficult to discriminate [Soto, D., Heinke, D., Humphreys, G. W., & Blanco, M. J. (2005) Journal of Experimental Psychology: Human Perception and Performance, 31, 248]. Here, we demonstrate similar effects even on search for a pop-out target. At the beginning of each trial, participants memorized a prime that could contain either the search target or a distracter in the subsequent search array. Targets and distractors were easily discriminable. Despite this, the prime in WM affected responses latencies and the direction of the first saccade. Top-down search, guided by the contents of WM, can modulate selection even when salient bottom-up cues are present.

Adolescent↗
PubMed2003

Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia.

BACKGROUND: Schizophrenic patients show deficits in working memory (WM) and inhibition of prepotent responses. We examined brain activity while subjects performed tasks that placed demands on WM and overriding prepotent response tendencies, testing predictions that both processes engage overlapping prefrontal cortical (PFC) regions and that schizophrenic patients show reduced PFC activity and performance deficits reflecting both processes. METHODS: Functional magnetic resonance imaging data were acquired while 16 schizophrenic and 15 healthy subjects performed the N-Back task that varied WM load and a version of the AX-CPT that required overriding a prepotent response tendency. RESULTS: Both tasks engaged overlapping cortical networks (e.g., bilateral dorsolateral PFC, Broca's area, parietal cortex). Increased WM load monotonically increased activity; preparation to override a prepotent response produced greater and more enduring activity. Group differences on each task emerged in a right dorsolateral PFC region: schizophrenic subjects showed lesser magnitude increases under conditions of high WM and prepotent response override demands, with concomitant performance impairments. CONCLUSIONS: Schizophrenic patients exhibit PFC-mediated deficits in WM and preparation to override prepotent responses. Findings are consistent with the operation of a single underlying PFC-mediated cognitive control mechanism and with physiologic dysfunction of the dorsolateral PFC in schizophrenic patients reflecting impairments in this mechanism.

Adult↗
PubMed2000

A "theory of relativity" for cognitive elasticity of time and modality dimensions supporting constant working memory capacity: involvement of harmonics among ultradian clocks?

1. The capacity of working memory (WM) for about 7+/-2 ("the magical number") serially organized simple verbal items may represent a fundamental constant of cognition. Indeed, there is the same capacity for sense of familiarity of a number of recently encountered places, observed in radial maze performance both of lab rats and of humans. 2. Moreover, both species show a peculiar capacity for retaining WM of place over delays. The literature also describes paradoxes of extended time duration in certain human verbal recall tasks. Certain bird species have comparable capacity for delayed recall of about 4 to 8 food caches in a laboratory room. 3. In addition to these paradoxes of the time dimension with WM (still sometimes called "short-term" memory) there are another set of paradoxes of dimensionality for human judgment of magnitudes, noted by Miller in his classic 1956 paper on "the magical number." We are able to reliably refer magnitudes to a rating scale of up to about seven divisions. Remarkably, that finding is largely independent of perceptual modality or even of the extent of a linear interval selected within any given modality. 4. These paradoxes suggest that "the magical number 7+/2" depends on fundamental properties of mammalian brains. 5. This paper theorizes that WM numerosity is conserved as a fundamental constant, by means of elasticity of cognitive dimensionality, including the temporal pace of arrival of significant items of cognitive information. 6. A conjectural neural code for WM item-capacity is proposed here, which extends the hypothetical principle of binding-by-synchrony. The hypothesis is that several coactive frequencies of brain electrical rhythms each mark a WM item. 7. If, indeed, WM does involve a brain wave frequency code (perhaps within the gamma frequency range that has often been suggested with the binding hypothesis) mathematical considerations suggest additional relevance of harmonic relationships. That is, if copresent sinusoids bear harmony-like ratios and are confined within a single octave, then they have fast temporal properties, while avoiding spurious difference rhythms. Therefore, if the present hypothesis is valid, it implies a natural limit on parallel processing of separate items in organismic brains. 8. Similar logic of periodic signals may hold for slower ultradian rhythms, including hypothetical ones that contribute to time-tagging and fresh sense of familiarity of a day's event memories. Similar logic may also hold for spatial periodic functions across brain tissue that, hypothetically, represent cognitive information. Thus, harmonic transitions among temporal and spatial periodic functions are a possible vehicle for the cognitive dimensional elasticity that conserves WM capacity. 9. Supporting roles are proposed of (a) basal ganglia, as a high-capacity cache for traces of recent experience temporarily suspended from active task-relevant processing and (b) of hippocampus as a phase and interval comparator for oscillating signals, whose spatiotemporal dynamics are topologically equivalent to a toroidal grid.

Animals↗
PubMed1999

Regional brain activity during tasks devoted to the central executive of working memory.

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.

Adult↗
PubMed1995

Individual differences in spatial working memory in relation to schizotypy.

With a delayed-response task, spatial working memory function was assessed in normal students who were selected for schizotypy. The Wisconsin Card Sorting Test was also administered. Twenty-eight undergraduate students who scored high on the Perceptual Aberration Scale (PerAb) and 23 who scored low on this scale participated in this study. High PerAb students performed less accurately compared with the low PerAb controls on the delayed-response task, and they were more than twice as likely as low PerAb students to be impaired. The groups did not differ in the number of perseverative errors or number of categories achieved on the Wisconsin Card Sorting Test, but, as predicted, high PerAb students were less able to maintain set than were the low PerAb students. Neuropsychological implications of these data are discussed.

Adolescent↗
PubMed1999

An examination of verbal working memory capacity in children with specific language impairment.

This study investigated verbal working memory capacity in children with specific language impairment (SLI). The task employed in this study was the Competing Language Processing Task (CLPT) developed by Gaulin and Campbell (1994). A total of 40 school-age children participated in this investigation, including 20 with SLI and 20 normal language (NL) age-matched controls. Results indicated that the SLI and NL groups performed similarly in terms of true/false comprehension items, but that the children with SLI evidenced significantly poorer word recall than the NL controls, even when differences in nonverbal cognitive scores were statistically controlled. Distinct patterns of word-recall errors were observed for the SLI and NL groups, as well as different patterns of associations between CLPT word recall and performance on nonverbal cognitive and language measures. The findings are interpreted within the framework of a limited-capacity model of language processing.

Child↗
PubMed2004

Visuo-spatial working memory span: a sensitive measure of cognitive deficits in children with ADHD.

Working memory (WM) has been hypothesised to be impaired in attention-deficit/hyperactivity disorder (ADHD). However, there are few studies reported on tests measuring visuo-spatial WM (VSWM) in ADHD. Some of these studies used paradigms including episodic memory, others only used low memory loads. In the present study we used a VSWM test that has not been used previously in ADHD research. The sensitivity of the VSWM test and a choice reaction time (CRT) test was evaluated in a pilot study by comparing them to two commonly used tests in ADHD-research; the Continuous Performance Test (CPT) and a Go/no-go test, in children with and without ADHD. The groups differed significantly in performance on the VSWM test (P < .01) and CRT (P < .05) but not on the CPT (P > .1) or on the Go/no-go test (P > .1). The results from the VSWM and CRT tests were replicated in a larger sample of participants (80 boys; 27 boys with ADHD and 53 controls, mean age 11.4 years). The difference between the groups was significant for both the VSWM test (P < .01) and the CRT test (P < .01). The effect size (ES) of the VSWM test was 1.34. There was a significant age-by-group interaction on the VSWM test, with larger group differences for the older children (P < .01). Our results show that the VSWM test is a sensitive measure of cognitive deficits in ADHD and it supports the hypothesis that deficits in VSWM is a major component of ADHD.

Adolescent↗
PubMed2002

Segregation of areas related to visual working memory in the prefrontal cortex revealed by rTMS.

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. Storage and processing functions might be segregated in ventral and dorsal areas of the prefrontal cortex, respectively. If so, storage functions might be spared, irrespective of informational domain, following damage or dysfunction in dorsolateral areas. Alternatively, WM and prefrontal function in general might be segregated according to informational domains (e.g. spatial versus object-based information). In the present study we used repetitive transcranial magnetic stimulation (rTMS) to directly test these competing hypotheses. We applied rTMS to transiently and selectively disrupt the function of the dorsomedial, dorsolateral or ventral prefrontal cortex in normal human volunteers performing either a spatial or a face-recognition delayed-response task. Performance in the spatial task was impaired by rTMS of the dorsomedial prefrontal cortex. Performance in the face-recognition (non-spatial) task was impaired by rTMS of the ventral prefrontal cortex. Transient disruption of the dorsolateral prefrontal cortex affected performance in both tasks. These findings provide evidence of domain-specific segregation of WM functions in widely separated areas of prefrontal cortex.

Adult↗
PubMed2004

Specific cerebral networks for maintenance and response organization within working memory as evidenced by the 'double delay/double response' paradigm.

Most of the working memory (WM) tasks used in functional imaging studies are based on the principle of the delayed response in which both the storage and the response organization are present during the delay period. It is therefore difficult to isolate activation specific to the storage function from that specific to the organization of the response. To determine the specific neural networks associated with these two WM operations, we performed a functional MRI study in healthy subjects using a new paradigm, 'the double delay/double response' tasks. This paradigm isolates maintenance from response organization by dividing the delay into two separate parts, the first being dedicated to memory, while the second includes response organization. Activation within the dorsolateral prefrontal cortex (DLPFC) followed a relative hemispheric dissociation: activation related to maintenance was predominant in the right DLPFC but was only detected when the load exceeded three items. Activation related to response organization was predominant in the left DLPFC, regardless of whether this response was based on information held in WM ('memory guided') or was independent of WM ('visually-guided'). These results suggest that activation of the DLPFC, should be interpreted in terms of executive processing for both maintenance and response organization.

Adult↗