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PubMed2002

[Working memory impairment in early Parkinson's disease patients].

OBJECTIVE: To investigate the characteristics of working memory impairment in early Parkinson's disease (PD) patients and underlying neuropsychological and patho-physiological mechanisms. METHODS: Thirty PD cases and 30 normal controls (NCs) were tested with modified Smith's working memory software. RESULTS: The correct rate of coordinate working memory in PD cases was 71.2 +/- 11.0%, significantly lower than that in the NCs (81.9% +/- 10.8%, t =3.78, P < 0.001). The correct rate of categorical working memory was 94.8 +/- 5.7% in the PD cases, not significantly different from that in the NCs (96.6% +/- 3.8%, t =1.46, P > 0.05). CONCLUSION: There is visuo-spatial working memory impairment, mainly coordinate spatial working memory impairment, in early PD patients. The categorical spatial working memory is relatively intact in early PD. It is postulated that the different working memory subsystems apply for different neurocircuits.

Adult↗
PubMed2001

Further evidence of intact working memory in autism.

Earlier investigations have found mixed evidence of working memory impairment in autism. The present study examined working memory in a high-functioning autistic sample, relative to both a clinical control group diagnosed with Tourette Syndrome and a typically developing control group. No group differences were found across three tasks and five dependent measures of working memory. Performance was significantly correlated with both age and IQ. It is concluded that working memory is not one of the executive functions that is seriously impaired in autism. We also suggest that the format of administration of working memory tasks may be important in determining whether or not performance falls in the impaired range.

Adolescent↗
PubMed1999

Working memory impairments in children with specific arithmetic learning difficulties.

Working memory impairments in children with difficulties in arithmetic have previously been investigated using questionable selection techniques and control groups, leading to problems concluding where deficits may occur. The present study attempted to overcome these criticisms by assessing 9-year-old children with difficulties specific to arithmetic, as indicated by normal reading, and comparing them with both age-matched and ability-matched controls. A battery of 10 tasks was used to assess different aspects of working memory, including subtypes of executive function. Relative to age-matched controls, children with poor arithmetic had normal phonological working memory but were impaired on spatial working memory and some aspects of executive processing. Compared to ability-matched controls, they were impaired only on one task designed to assess executive processes for holding and manipulating information in long-term memory. These deficits in executive and spatial aspects of working memory seem likely to be important factors in poor arithmetical attainment.

Case-Control Studies↗
PubMed2006

Noradrenergic modulation of working memory and emotional memory in humans.

RATIONALE: Noradrenaline (NA) is implicated in arousal. Working memory is dependent upon prefrontal cortex, and moderate levels of NA are thought to facilitate working memory whereas higher levels during extreme stress may impair working memory and engage more posterior cortical and sub-cortical circuitry. The NA system also influences emotional memory via modulation of the amygdalae and related mediotemporal structures. NA dysfunction and abnormalities in arousal-dependent memory functions are evident in a variety of neuropsychiatric illnesses. OBJECTIVES: The authors provide a concise overview of pharmacological studies that have investigated effects of selective NA manipulations on working memory and emotional memory functions in healthy human volunteers. MATERIALS AND METHODS: Selection of relevant peer-reviewed publications was based on a PubMed search. RESULTS: Studies to date indicate that: (1) the beta-blocker propranolol impaired working and emotional memory, (2) clonidine frequently impaired working memory, and (3) reboxetine, a selective noradrenaline reuptake inhibitor, enhanced emotional memory for positive material. CONCLUSIONS: Improved understanding of coupling between NA, cortico-subcortical circuitry and human mnemonic functions will suggest novel therapeutic directions for the treatment of neuropsychiatric conditions, such as attention deficit hyperactivity disorder and post-traumatic stress disorder. Future research directions are discussed in relation to neuroimaging techniques, functional central nervous system polymorphisms and study designs.

Adrenergic Agonists↗
PubMed1999

Architecture and dynamics of the primate prefrontal cortical circuit for spatial working memory.

In the experimental protocol of working memory tasks using a monkey as a subject, tuned activity of the prefrontal cortical neurons that is sustained during the delay period is a neuronal substrate of the working memory. This study addresses the question as to how this tuned activity is formed and maintained in the prefrontal cortex by means of computer simulations of the dynamics of a model prefrontal cortical circuit. The model assumes that pyramidal cells receive two types of intracortical inhibition, "parallel" and "anti-parallel", in accordance with recent experimental findings. The parallel and anti-parallel refer to the relationship between the preferred directions of presynaptic interneurons and postsynaptic pyramidal cells. The following three factors are suggested to be crucial for the formation and maintenance of spatial working memory: cortical amplification of the activity due to excitatory closed-loop circuitry, suppression of excessive excitation by the parallel inhibition, and sharpening of the activity profile by the anti-parallel inhibition.

Journal Article↗
PubMed2002

Toward clinical application of neuropsychological activation probes with SPECT: a spatial working memory task.

UNLABELLED: The concept of working memory is central to theories of human cognition, because it is essential to human skills such as decision making and deductive reasoning. Although PET and functional MRI have provided robust data on the recruitment of specific pathways in working memory tasks, the experimental settings of these studies may not be transferable to a clinical situation. Hence, to develop neuropsychological SPECT activation probes that are suitable for daily clinical practice, this study reports on a neuropsychological activation task of spatial working memory under classical neuropsychological test conditions in healthy subjects. METHODS: Reaction times and accuracy were measured as behavioral parameters and functional imaging data were analyzed with statistical parametric mapping to determine significant voxel-wise changes between the perception task and the memory task. RESULTS: Subjects reacted more slowly and performed less accurately during the memory task compared with the perception task, findings that are in keeping with other neuropsychological studies. Also, the overall pattern of brain activations revealed in our experiment is consistent with the data of the literature, thereby validating our test probe. CONCLUSION: From a practical viewpoint, the close resemblance of the test conditions of the SPECT procedure with those of the investigation room and the relative simplicity of the task under study probably constitute major advantages for future clinical application of the SPECT procedure in patients with cognitive impairments.

Adult↗
PubMed1994

Evidence for spatial working memory in honeybees (Apis mellifera).

Spatial working memory (the ability to represent multiple locations in a flexible, dynamic manner) has been studied in a range of vertebrate species. The results of 3 experiments indicate that this ability also exists in at least one invertebrate (honeybees; Apis mellifera). Individual honeybees collected sugar solution from a matrix of 6 locations. They avoided revisits to locations previously depleted of solution more accurately than expected by chance. The results rule out several nonmemorial explanations for this ability, and it is therefore best explained by a spatial working memory system that allows discrimination of previously visited locations from those not yet visited. These results substantially expand the range of species in which spatial working memory has been demonstrated.

Animals↗
PubMed2003

The effect of irrelevant visual input on working memory for sign language.

We report results showing that working memory for American Sign Language (ASL) is sensitive to irrelevant signed input (and other structured visual input) in a manner similar to the effects of irrelevant auditory input on working memory for speech. Deaf signers were disrupted on serial recall of lists of ASL signs when either pseudosigns or moving shapes were presented during a retention interval. Hearing subjects asked to recall lists of printed English words did not show disruption under the same interference conditions. The results favor models that hypothesize modality-specific representations of language within working memory, as opposed to amodal representations. The results further indicate that working memory for sign language involves visual or quasi-visual representations, suggesting parallels to visuospatial working memory.

Journal Article↗
PubMed2004

False memories for compound words: role of working memory.

Subjects studied pairs of compound words; pair members were presented simultaneously (one above the other) for 2 sec or sequentially (one immediately following the other) for 1 sec each, and 6-sec interstimulus intervals separated the end of presentation of one pair and the start of that of another. A subsequent recognition test included within-pair and between-pair conjunction foils (recombinations of stimulus parts from the same study pair and from separate pairs, respectively). Previous experiments using faces as stimuli have demonstrated that when faces are presented simultaneously there are many more false alarms to within-pair than to between-pair conjunction items, and when faces are presented sequentially there is an equal number of false alarms in those two conditions. However, Experiment 1 showed that for compound word stimuli there were equally high false alarm rates toboth types of foils in both study conditions relative to completely new test items. Experiment 2 showed that when rehearsal of compound words was prevented, the pattern of conjunction errors was very similar to the one typically obtained for faces. In Experiment 3, subjects falsely recalled conjunctions of within-pair compound words but not conjunctions of between-pair words in the simultaneous-study condition; no conjunctions were recalled in the sequential-study condition. The results support the idea that working memory processing is necessary for binding stimulus parts together in episodic memory.

Humans↗
PubMed2003

The neural basis of individual differences in working memory capacity: an fMRI study.

Using fMRI, neural substrates of verbal working memory were investigated with respect to differences in working memory capacity. Listening-span test (LST), Listen, and Remember conditions were performed. Two subjects groups were selected: those who had large working memory capacities, labeled high-span subjects (HSS) according to the working memory span test, and those who had small working memory capacities, labeled low-span subjects (LSS). Significant activation was found mainly in three regions in comparison with resting control: left prefrontal cortex (PFC), anterior cingulate cortex (ACC) and temporal language area. For both groups, fMRI signal intensity increased in PFC during the LST condition compared to the Listen condition. A group difference was found in the ACC region; specifically, a significant increase in signal intensity was observed in ACC only for the HSS group and not for the LSS group. Behavioral data also showed that the performance was better in HSS than in LSS. These results indicate that the attention controlling system, supported by ACC, is more effective in HSS compared to that of LSS.

Adult↗
PubMed1997

Performance of patients with schizophrenia on a pen and paper visuospatial working memory task with short delay.

Human and nonhuman primate data suggest that visuospatial working memory is mediated by a neural network that includes the prefrontal cortex. Simple working memory tasks are less complex than standard neuropsychological tests of frontal dysfunction. As such, they are less vulnerable to general performance factors such as amotivation and uncooperativeness in schizophrenic patients. These tasks thus hold promise as potential measures of frontal dysfunction in schizophrenia. However, the specific parameters of visuospatial working memory deficit in schizophrenia have not been established. This study assessed working memory functions in 18 schizophrenic patients and 28 controls using a pen-and-paper analogue of a monkey prefrontal cortex activation task. Schizophrenic patients and controls performed similarly on a sensory-guided task that did not require working memory functions, yet schizophrenic patients performed significantly worse than controls on tasks that required subjects to retain visuospatial information for delay periods of 10 and 20 s. These data suggest that the working memory deficits in patients with schizophrenia begin to appear less than 10 s following encoding of visuospatial information and that these working memory deficits can be assessed with easily administered pen-and-paper tasks.

Adult↗
PubMed2005

Phase locking of single neuron activity to theta oscillations during working memory in monkey extrastriate visual cortex.

Working memory has been linked to elevated single neuron discharge in monkeys and to oscillatory changes in the human EEG, but the relation between these effects has remained largely unexplored. We addressed this question by measuring local field potentials and single unit activity simultaneously from multiple electrodes placed in extrastriate visual cortex while monkeys were performing a working memory task. We describe a significant enhancement in theta band energy during the delay period. Theta oscillations had a systematic effect on single neuron activity, with neurons emitting more action potentials near their preferred angle of each theta cycle. Sample-selective delay activity was enhanced if only action potentials emitted near the preferred theta angle were considered. Our results suggest that extrastriate visual cortex is involved in short-term maintenance of information and that theta oscillations provide a mechanism for structuring the recurrent interaction between neurons in different brain regions that underlie working memory.

Action Potentials↗
PubMed2001

The case for sensorimotor coding in working memory.

The highly influential Baddeley and Hitch model of working memory (Baddeley & Hitch, 1974; see also Baddeley, 1986) posited analogical forms of representation that can be broadly characterized as sensorimotor, both for verbal and for visuospatial material. However, difficulties with the model of verbal working memory in particular have led investigators to develop alternative models that avoid appealing either to sensory coding or to motoric coding, or to both. This paper examines the evidence for sensorimotor coding in working memory, including evidence from neuropsychology and from sign language research, as well as from standard working memory paradigms, and concludes that only a sensorimotor model can accommodate the broad range of effects that characterize verbal working memory. In addition, several findings that have been considered to speak against sensorimotor involvement are reexamined and are argued to be in fact compatible with sensorimotor coding. These conclusions have broad implications, in that they support the emerging theoretical viewpoint of embodied cognition.

Attention↗
PubMed2006

Effects of treatment with the atypical neuroleptic quetiapine on working memory function: a functional MRI follow-up investigation.

BACKGROUND: Working memory as a part of higher-order executive functions is defined by the parallel storage and processing of information. Recent functional fMRI studies have revealed a functional, interregional disintegration of a neuronal network connecting cortical, subcortical and cerebellar regions in schizophrenic patients (SZ). Cognitive impairment in working memory is a core psychopathological correlate of schizophrenic symptoms. Atypical neuroleptics such as quetiapine have shown good efficacy in treating positive and negative symptoms. The presented study evaluated the impact of a neuroleptic steady state treatment with quetiapine on the altered working memory activation patterns in schizophrenia. METHODS: Patients were examined by fMRI at baseline and after 12 weeks of steady state treatment with quetiapine. Matched healthy controls (HC) underwent baseline examination. In the scanner, stimuli were presented in a 2-back and 0-back condition of a working memory (wm) paradigm, whereby a degraded and a non-degraded version were used each time. Additionally, behavioural responses (reaction time to target stimuli and error ratio) were measured. RESULTS: At baseline, healthy controls revealed increased activity in the frontal lobe, especially in regions of the prefrontal cortex. Compared to HC, SZ showed hypoactivation in the right dorsolateral prefrontal cortex (DLPFC) and the ventrolateral prefrontal cortex (VLPFC) bilaterally for the 2-back condition. In the 2-back degraded condition there was a hypoactivation in both, the right DLPFC and the VLPFC. Additionally, patients showed bilaterally decreased activation in the basalganglia in the 2-back and in the right caudatus in the 2-back degraded condition compared to healthy controls. After treatment with quetiapine, patients activations patterns were increased. The pre-post comparison of the 2-back condition revealed a significant increase of activation in the left VLPFC at a significance level of 0.001 (uncorrected). The 2-back degraded condition led to a significant activation pattern in the lingual gyrus and the right precuneus. In both wm conditions, at baseline there were no differences in reaction time but only a worse performance in SZ. After treatment, behavioural measurement of responses, including reaction time and performance, showed slight improvements in SZ, although these did not reach statistical significance. CONCLUSIONS: The neuronal networks underlying working memory are clearly altered in schizophrenia. After 12 weeks of treatment with quetiapine monotherapy, patients showed significant clinical improvement and revealed increased BOLD activity in the VLPFC during a working memory task, although there was no improvement of cognitive performance.

Adult↗
PubMed1999

Glutamatergic and dopaminergic afferents to the prefrontal cortex regulate spatial working memory in rats.

The integrity of the prefrontal cortex is critical for the expression of working memory. The prefrontal cortex is innervated by dopaminergic afferents from the ventral tegmental area and glutamatergic afferents from the mediodorsal thalamus. To determine the role of dopaminergic and glutamatergic afferents in the regulation of working memory, rats were trained to perform a spatial delayed alternation task in a T-maze. The microinjection of the ionotropic glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione or 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid into the prefrontal cortex impaired working memory. Consistent with a role for glutamate receptor activation, microinjecting the GABA(B) agonist baclofen into the mediodorsal thalamus produced a dose-dependent disruption of working memory. In contrast, inhibition of the mesocortical dopamine projection was without effect on working memory. The blockade of D1 and/or D2 dopamine receptors with SCH-23390 and sulpiride was without effect on working memory. Likewise, the microinjection of baclofen into the ventral tegmental area did not impair working memory. However, stimulating mu-opioid receptors in the ventral tegmental area with [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin produced a dose-dependent impairment of working memory that was reversed by blocking D1 dopamine receptors with SCH-23390 in the prefrontal cortex. These data demonstrate that increased dopamine tone or reduced glutamate tone in the prefrontal cortex disrupts working memory in a spatial delayed alternation task.

Animals↗
PubMed2006

Working memory training decreases hippocampal neurogenesis.

The relationship between adult hippocampal neurogenesis and cognition appears more complex than suggested by early reports. We aimed to determine if the duration and task demands of spatial memory training differentially affect hippocampal neurogenesis. Adult male rats were trained in the Morris water maze in a reference memory task for 4 days, or alternatively working memory for either 4 or 14 days. Four days of maze training did not impact neurogenesis regardless of whether reference or working memory paradigms were used. Interestingly, 2 weeks of working memory training using a hidden platform resulted in fewer newborn hippocampal neurons compared with controls that received either cue training or no maze exposure. Stress is a well-established negative regulator of hippocampal neurogenesis. We found that maze training in general, and a working memory task in particular, increased levels of circulating corticosterone after 4 days of training. Our study indicates that working memory training over a prolonged period of time reduces neurogenesis, and this reduction may partially be mediated by increased stress.

Analysis of Variance↗
PubMed2005

Working memory, psychiatric symptoms, and academic performance at school.

Previous studies of the relationship among working memory function, academic performance, and behavior in children have focused mainly on clinical populations. In the present study, the associations of the performance in audio- and visuospatial working memory tasks to teacher reported academic achievement and psychiatric symptoms were evaluated in a sample of fifty-five 6-13-year-old school children. Working memory function was measured by visual and auditory n-back tasks. Information on incorrect responses, reaction times, and multiple and missed responses were collected during the tasks. The children's academic performance and behavioral and emotional status were evaluated by the Teacher Report Form. The results showed that good spatial working memory performance was associated with academic success at school. Children with low working memory performance, especially audiospatial memory, were reported to have more academic and attentional/behavioral difficulties at school than children with good working memory performance. An increased number of multiple and missed responses in the auditory and visual tasks was associated with teacher reported attentional/behavioral problems and in visual tasks with teacher reported anxiety/depressive symptoms. The results suggest that working memory deficits may underlie some learning difficulties and behavioral problems related to impulsivity, difficulties in concentration, and hyperactivity. On the other hand, it is possible that anxiety/depressive symptoms affect working memory function, as well as the ability to concentrate, leading to a lower level of academic performance at school.

Adolescent↗
PubMed2002

Spatial working memory deficits in schizophrenia patients and their first degree relatives from Palau, Micronesia.

Spatial working memory deficits associated with dorsolateral prefrontal dysfunction have been found in Caucasian samples of schizophrenia patients and their first-degree relatives. This study evaluated spatial working memory function in affected and unaffected members of multiplex schizophrenia families from the Republic of Palau to determine whether the spatial working memory deficits associated with schizophrenia extend to this non-Caucasian population. Palau is an isolated island nation in Micronesia with an elevated prevalence of schizophrenia and an aggregation of cases in large multigenerational families. Our objective was to evaluate the potential for spatial working memory function to serve as one of multiple endophenotypes in a genetic linkage study of these Palauan schizophrenia families. A spatial delayed response task requiring resistance to distraction and a sensorimotor control task were used to assess spatial working memory in 32 schizophrenia patients, 28 of their healthy first-degree relatives, and 19 normal control subjects. Schizophrenia patients and their relatives were significantly less accurate than normal control subjects on the spatial delayed response task but not on the sensorimotor control task. On both tasks, patients and relatives were slower to respond than the normal controls. There were no age or gender effects on accuracy, and working memory performance in schizophrenia patients was not significantly correlated with medication dosage. In summary, spatial working memory deficits that have been found in Caucasian schizophrenia patients and relatives were confirmed in this isolated Pacific Island family sample. These results suggest that spatial working memory deficits may be a potentially useful addition to the endophenotypic characterization of family members to be used in a comprehensive genome wide linkage analysis of these Palauan families.

Adult↗