Nonspatial Working Memory Research Articles

Effect of Nigella sativa and wheat germ oils on scopolamine-induced memory impairment in rats

AimTo investigate the possible memory enhancing effects of Nigella sativa oil (NSO) and wheat germ oil (WGO) on scopolamine-induced amnesic rats. MethodsMale Wistar rats received either saline or scopolamine (16mg/kg, i.p.). The other three groups were pretreated with NSO (1ml/kg, p.o.), WGO (170mg/kg, p.o.) or donepezil used as a reference drug (10mg/kg, p.o.) for 14days before scopolamine injection. Cognitive and biochemical measurements were then assessed. Principal resultsNSO and WGO treated rats significantly reversed scopolamine-induced deficit of spatial and non-spatial working memory impairment in the T maze alternation task and object recognition test, respectively. Administration of NSO prior to scopolamine showed a significant decrease in malondialdehyde (MDA) and increase in Glutathione (GSH) brain contents to be similar to that observed in donepezil group. It did not alter cholinesterase activity and showed a significant decrease in brain tumor necrosis factor-alpha (TNF-α) content to be similar to donepezil-treated rats.Scopolamine-demented rats pretreated with WGO did not change MDA brain content significantly as compared to scopolamine and donepezil groups. WGO-treated rats showed a significant increase in GSH to a level similar to that observed in the donepezil group, it showed a significant decrease in cholinesterase activity as compared to scopolamine group and significantly elevated brain TNF-α content when compared to donepezil group. ConclusionsMemory enhancing effect of NSO in the present study might be due to its antioxidant and anti-inflammatory activities, while that of WGO might be via its antioxidant and anticholinesterase activities.

Object Working Memory Performance Depends on Microstructure of the Frontal-Occipital Fasciculus

Re-entrant circuits involving communication between the frontal cortex and other brain areas have been hypothesized to be necessary for maintaining the sustained patterns of neural activity that represent information in working memory, but evidence has so far been indirect. If working memory maintenance indeed depends on such temporally precise and robust long-distance communication, then performance on a delayed recognition task should be highly dependent on the microstructural integrity of white-matter tracts connecting sensory areas with prefrontal cortex. This study explored the effect of variations in white-matter microstructure on working memory performance in two separate groups of participants: patients with multiple sclerosis and age- and sex-matched healthy adults. Functional magnetic resonance imaging was performed to reveal cortical regions involved in spatial and object working memory, which, in turn, were used to define specific frontal to extrastriate white-matter tracts of interest via diffusion tensor tractography. After factoring out variance due to age and the microstructure of a control tract (the corticospinal tract), the number of errors produced in the object working memory task was specifically related to the microstructure of the inferior frontal-occipital fasciculus. This result held for both groups, independently, providing a within-study replication with two different types of white-matter structural variability: multiple sclerosis-related damage and normal variation. The results demonstrate the importance of interactions between specific regions of the prefrontal cortex and sensory cortices for a nonspatial working memory task that preferentially activates those regions.

Spatial working memory load affects counting but not subitizing in enumeration

The present study investigated whether subitizing reflects capacity limitations associated with two types of working memory tasks. Under a dual-task situation, participants performed an enumeration task in conjunction with either a spatial (Experiment 1) or a nonspatial visual (Experiment 2) working memory task. Experiment 1 showed that spatial working memory load affected the slope of a counting function but did not affect subitizing performance or subitizing range. Experiment 2 showed that nonspatial visual working memory load affected neither enumeration efficiency nor subitizing range. Furthermore, in both spatial and nonspatial memory tasks, neither subitizing efficiency nor subitizing range was affected by amount of imposed memory load. In all the experiments, working memory load failed to influence slope, subitizing range, or overall reaction time. These findings suggest that subitizing is performed without either spatial or nonspatial working memory. A possible mechanism of subitizing with independent capacity of working memory is discussed.

Sigma-1 receptor stimulation by dehydroepiandeosterone (DHEA) ameliorates the cognitive deficits via CaMKII, PKC and ERK activities in olfactory bulbectomized mice

Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD).OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively.OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M1 receptor expression without affecting muscarinic M3 receptor expression or AChE activity.These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD.

Spatial working memory load affects counting but not subitizing in enumeration

The present study investigated whether subitizing reflects capacity limitations associated with two types of working memory tasks. Under a dual-task situation, participants performed an enumeration task in conjunction with either a spatial (Experiment 1) or a nonspatial visual (Experiment 2) working memory task. Experiment 1 showed that spatial working memory load affected the slope of a counting function but did not affect subitizing performance or subitizing range. Experiment 2 showed that nonspatial visual working memory load affected neither enumeration efficiency nor subitizing range. Furthermore, in both spatial and nonspatial memory tasks, neither subitizing efficiency nor subitizing range was affected by amount of imposed memory load. In all the experiments, working memory load failed to influence slope, subitizing range, or overall reaction time. These findings suggest that subitizing is performed without either spatial or nonspatial working memory. A possible mechanism of subitizing with independent capacity of working memory is discussed.

Spatial and Nonspatial Working Memory and Visual Search

It has been indicated that visual search is interfered with in spatial working memory (WM), although not in nonspatial WM. In this study, the effects on visual search of individual differences in spatial and nonspatial WM were examined. Two visual search conditions were used: a conjunction search condition comprising two features (color and shape) and a disjunction condition comprising only one feature (color or shape). 96 participants (42 men, 54 women, M age = 20.9 yr., SD = 3.5) participated in this study. The participants were divided into high and low WM groups based on their spatial and nonspatial WM test scores. As a result, statistically significant group differences in the conjunction search rate were observed in spatial WM but not in nonspatial WM. These results suggest there is a relationship between visual search and the individual spatial WM ability, but this does not hold for nonspatial WM.

Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice

Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD). OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively. OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M₁ receptor expression without affecting muscarinic M₃ receptor expression or AChE activity. These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD.

Changes in cognitive functions of students in the transitional period from elementary school to junior high school

Background: When students proceed to junior high school from elementary school, rapid changes in the environment occur, which may cause various behavioral and emotional problems. However, the changes in cognitive functions during this transitional period have rarely been studied. Methods: In 158 elementary school students from 4th- to 6th-grades and 159 junior high school students from 7th- to 9th-grades, we assessed various cognitive functions, including motor processing, spatial construction ability, semantic fluency, immediate memory, delayed memory, spatial and non-spatial working memory, and selective, alternative, and divided attention. Results: Our findings showed that performance on spatial and non-spatial working memory, alternative attention, divided attention, and semantic fluency tasks improved from elementary to junior high school. In particular, performance on alternative and divided attention tasks improved during the transitional period from elementary to junior high school. Conclusion: Our finding suggests that development of alternative and divided attention is of crucial importance in the transitional period from elementary to junior high school.

Effects of spatial and non-spatial working memory on location- and object-based attention

Effects of spatial and non-spatial working memory on location- and object-based attention

Nicotinamide prevents the long-term effects of perinatal asphyxia on apoptosis, non-spatial working memory and anxiety in rats

There is no established treatment for the long-term effects produced by perinatal asphyxia. Thus, we investigated the neuroprotection provided by nicotinamide against the effects elicited by perinatal asphyxia on hippocampus and behaviour observed at 30-90 days of age. Asphyxia was induced by immersing foetuses-containing uterine horns, removed from ready-to-deliver rats into a water bath at 37 degrees C for 20 min. Caesarean-delivered siblings were used as controls. Saline or nicotinamide (0.8 mmol/kg, i.p.) was administered to control and asphyxia-exposed animals 24, 48, and 72 h after birth. The animals were examined for morphological changes in hippocampus, focusing on delayed cell death and mossy fibre sprouting, and behaviour, focusing on cognitive behaviour and anxiety. At the age of 30-45 days, asphyxia-exposed rats displayed (1) increased apoptosis, assessed in whole hippocampus by nuclear Hoechst staining, and (2) increased mossy fibre sprouting, restricted to the stratum oriens of dorsal hippocampus, assessed by Timm's staining. Rats from the same cohorts displayed (3) deficits in non-spatial working memory, assessed by a novel object recognition task, and (4) increased anxiety, assessed by an elevated plus-maze test when examined at the age of 90 days. Nicotinamide prevented the effects elicited by perinatal asphyxia on apoptosis, working memory, and anxiety.

Overlapping functional anatomy for working memory and visual search

Recent behavioural findings using dual-task paradigms demonstrate the importance of both spatial and non-spatial working memory processes in inefficient visual search (Anderson et al. in Exp Psychol 55:301–312, 2008). Here, using functional magnetic resonance imaging (fMRI), we sought to determine whether brain areas recruited during visual search are also involved in working memory. Using visually matched spatial and non-spatial working memory tasks, we confirmed previous behavioural findings that show significant dual-task interference effects occur when inefficient visual search is performed concurrently with either working memory task. Furthermore, we find considerable overlap in the cortical network activated by inefficient search and both working memory tasks. Our findings suggest that the interference effects observed behaviourally may have arisen from competition for cortical processes subserved by these overlapping regions. Drawing on previous findings (Anderson et al. in Exp Brain Res 180:289–302, 2007), we propose that the most likely anatomical locus for these interference effects is the inferior and middle frontal cortex of the right hemisphere. These areas are associated with attentional selection from memory as well as manipulation of information in memory, and we propose that the visual search and working memory tasks used here compete for common processing resources underlying these mechanisms.

Effects of chronic manganese exposure on working memory in non-human primates

Human exposure to manganese (Mn) has been associated with a variety of cognitive deficits including learning and memory deficits. However, results from epidemiological studies have been inconsistent in describing the nature of such cognitive deficits. The present study was conducted to evaluate the effects of chronic Mn exposure on memory functioning in non-human primates and to correlate behavioral outcome with brain Mn levels in an attempt to explain outcome variability seen in prior studies. Cynomolgus macaque monkeys were trained to perform memory-related tasks (spatial working memory, non-spatial working memory, reference memory) and exposed to manganese sulfate (15–20 mg/kg/week) over an exposure period lasting 227.5 ± 17.3 days. Blood manganese levels were in the upper range of levels reported for human environmental, medical or occupational exposures. By the end of the manganese exposure period, animals developed mild deficits in spatial working memory, more significant deficits in non-spatial working memory and no deficits in reference memory. Linear regression analyses showed that for most brain regions sampled, there was a significant inverse relationship between working memory task performance and brain Mn concentration. These results suggest that chronic exposure to levels of manganese achieved in this study may have detrimental effects on working memory and that Mn levels achieved in several brain regions are inversely related to working memory performance.

Location- and Object-Based Inhibition of Return are Affected by Different Kinds of Working Memory

Castel, Pratt, and Craik (2003) have shown that inhibition of return (IOR, the delayed response to a recently cued item) is disrupted by a secondary task that involves spatial working memory (WM), and they suggest that IOR is mediated by spatial WM. However, they did not specify what kind of IOR was involved. We used a dual-task paradigm to examine whether the two kinds of IOR (location- and object-based IOR) are affected by two kinds of secondary task that involve spatial and nonspatial WM, respectively. The results show that location-based IOR was disrupted by a spatial secondary task while the object-based IOR was disrupted by a nonspatial secondary task. The present study further elaborates the conclusion of Castel et al. (2003) by differentiating the effect of the two kinds of WM (spatial vs. nonspatial) on the two kinds of IOR (location based vs. object based).

Transient and selective overexpression of D 2 receptors in the striatum causes persistent deficits in conditional associative learning

Cognitive deficits in schizophrenia are thought to derive from a hypofunction of the prefrontal cortex (PFC), but the origin of the hypofunction is unclear. To explore the nature of this deficit, we genetically modified mice to model the increase in striatal dopamine D(2) receptors (D(2)Rs) observed in patients with schizophrenia. Previously, we reported deficits in spatial working memory tasks in these mice, congruent with the working memory deficits observed in schizophrenia. However, patients with schizophrenia suffer from deficits in many executive functions, including associative learning, planning, problem solving, and nonspatial working memory. We therefore developed operant tasks to assay two executive functions, conditional associative learning (CAL) and nonspatial working memory. Striatal D(2)R-overexpressing mice show a deficit in CAL because of perseverative behavior, caused by interference from the previous trial. D(2)R up-regulation during development was sufficient to cause this deficit, because switching off the transgene in adulthood did not rescue the phenotype. We validated prefrontal dependency of CAL by using neurotoxic lesions. Lesions of the medial PFC including the anterior cingulate, infralimbic, and prelimbic cortices impair CAL because of increased interference from previously rewarded trials, exactly as observed in D(2)R transgenic mice. In contrast, lesions restricted to the infralimbic and prelimbic cortices have no effect on CAL but impair performance in the nonspatial working memory task. These assays not only give us insight into how excess striatal D(2)Rs affect cognition but also provide tools for studying cognitive endophenotypes in mice.

A role for spatial and nonspatial working memory processes in visual search.

Searching a cluttered visual scene for a specific item of interest can take several seconds to perform if the target item is difficult to discriminate from surrounding items. Whether working memory processes are utilized to guide the path of attentional selection during such searches remains under debate. Previous studies have found evidence to support a role for spatial working memory in inefficient search, but the role of nonspatial working memory remains unclear. Here, we directly compared the role of spatial and nonspatial working memory for both an efficient and inefficient search task. In Experiment 1, we used a dual-task paradigm to investigate the effect of performing visual search within the retention interval of a spatial working memory task. Importantly, by incorporating two working memory loads (low and high) we were able to make comparisons between dual-task conditions, rather than between dual-task and single-task conditions. This design allows any interference effects observed to be attributed to changes in memory load, rather than to nonspecific effects related to "dual-task" performance. We found that the efficiency of the inefficient search task declined as spatial memory load increased, but that the efficient search task remained efficient. These results suggest that spatial memory plays an important role in inefficient but not efficient search. In Experiment 2, participants performed the same visual search tasks within the retention interval of visually matched spatial and verbal working memory tasks. Critically, we found comparable dual-task interference between inefficient search and both the spatial and nonspatial working memory tasks, indicating that inefficient search recruits working memory processes common to both domains.

Advancing the spontaneous hypertensive rat model of attention deficit/hyperactivity disorder.

To advance the spontaneous hypertensive rat (SHR) model of attention deficit/hyperactivity disorder (ADHD), experiments examined the SHR in tasks recognized to assess functioning of the prefrontal cortex or dorsal striatal. Tasks included odor-delayed win-shift (nonspatial working and reference memory), win-stay (habit learning), and attentional set-shifting (attention and behavioral flexibility). In Experiment 1, the SHR strain was compared with Wistar-Kyoto (WKY) and Wistar-Kyoto Hypertensive (WKHT) strains on the first 2 tasks. In Experiment 2, oral methylphenidate (1.5 mg/kg) and vehicle (water) were evaluated on all 3 tasks in SHR and WKY strains. Results demonstrated that the SHR made significantly more errors in the odor-delayed win-shift, win-stay, and attentional set-shifting tasks compared with the WKY. Similar performances in the WKY and WKHT indicated that deficits observed in the SHR were not related solely to hypertension. Treating the SHR with methylphenidate eliminated strain differences in all 3 tasks. These findings provide evidence that the SHR is a valid model for studying ADHD-associated neurocognitive deficits. Moreover, the current behavioral approach is appropriate to assess novel medications developed to target ADHD-associated neurocognitive deficits.

Neurochemical and neurobehavioral effects of ganstigmine (CHF2819), a novel acetylcholinesterase inhibitor, in rat prefrontal cortex: An in vivo study

Ganstigmine (CHF2819) is a novel, orally active acetylcholinesterase inhibitor that induces a stimulation of brain cholinergic transmission. In vivo studies show that, in rat prefrontal cortex, extracellular acetylcholine (ACh) concentrations are significantly increased either after local (1 and 10 μM) or oral (1.5 and 3 mg/kg) administration. Moreover, repeated oral treatment (six consecutive days; 3 mg/kg) with ganstigmine significantly increases basal extracellular concentrations of ACh in rat prefrontal cortex. Then, acute ganstigmine administration induces a significant increase in extracellular ACh concentrations (actual values) with respect to the last sample in ganstigmine-treated rats. Concentrations of serotonin (5-HT) and noradrenaline (NA) are not affected by any oral dose of ganstigmine (1.5 and 3 mg/kg) used. Moreover, levels of dopamine (DA) and metabolites are not modified either. Basal extracellular concentrations of 5-HT, NA, DA and metabolites are not affected by repeated (six consecutive days) ganstigmine treatment (3 mg/kg). Furthermore, there is no effect of the challenge dose of ganstigmine (3 mg/kg) on 5-HT, NA, DA and metabolites levels. Finally, ganstigmine reverses the scopolamine-induced deficits of habituation and non-spatial working memory in rats. Taken together, these findings suggest that ganstigmine appears to be a suitable candidate for the treatment of the cholinergic deficit in patients with Alzheimer's disease.

Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats’ memory

Crocus sativus L. is a plant cultivated in various parts of the world. Its involvement in learning and memory processes has been proposed. Crocins are water-soluble carotenoids and are among the active components of C. sativus L. The present study was designed to investigate in the rat the effects of crocins on recognition and spatial memory. For this aim, the object recognition task which evaluates non-spatial working memory and a novel version of the radial water maze which assesses spatial reference and spatial working memory were chosen. In a first study, crocins (15 and 30 mg/kg) counteracted delay-dependent recognition memory deficits in the normal rat, suggesting that these carotenoids modulate storage and/or retrieval of information. In a subsequent study, treatment with crocins (30 mg/kg and to a lesser extent also 15 mg/kg) attenuated scopolamine (0.2 mg/kg)-induced performance deficits in the radial water maze test. The present results support and extend the enhancing effects of crocins on memory and, then, to our knowledge, for the first time, demonstrate its implication in the mechanisms underlying recognition and spatial memory.

Domain‐related differentiation of working memory in the Japanese macaque (Macaca fuscata) frontal cortex: a positron emission tomography study

The lateral prefrontal cortex (LPFC) is important for working memory (WM) task performance. Neuropsychological and neurophysiological studies in monkeys suggest that the lateral prefrontal cortex is functionally segregated based on the working memory domain (spatial vs. non-spatial). However, this is not supported by most human neuroimaging studies, and the discrepancy might be due to differences in methods and/or species (monkey neuropsychology/physiology vs. human neuroimaging). We used positron emission topography to examine the functional segregation of the lateral prefrontal cortex of Japanese macaques (Macaca fuscata) that showed near 100% accuracy on spatial and non-spatial working memory tasks. Compared with activity during the non-working memory control tasks, the dorsolateral prefrontal cortex (DLPFC) was more active during the non-spatial, but not during the spatial, working memory task, although a muscimol microinjection into the dorsolateral prefrontal cortex significantly impaired the performance of both working memory tasks. A direct comparison of the brain activity between the two working memory tasks revealed no differences within the lateral prefrontal cortex, whereas the premotor area was more active during the spatial working memory task. Comparing the delay-specific activity, which did not include task-associated stimulus/response-related activity, revealed more spatial working memory-related activity in the posterior parietal and premotor areas, and more non-spatial working memory-related activity in the dorsolateral prefrontal cortex and hippocampus. These results suggest that working memory in the monkey brain is segregated based on domain, not within the lateral prefrontal cortex but rather between the posterior parietal-premotor areas and the dorsolateral prefrontal-hippocampus areas.

The neural correlates of non-spatial working memory in velocardiofacial syndrome (22q11.2 deletion syndrome)

Velocardiofacial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a neurogenetic disorder that is associated with both learning disabilities and a consistent neuropsychological phenotype, including deficits in executive function, visuospatial perception, and working memory. Anatomic imaging studies have identified significant volumetric reductions in the parietal lobe of individuals with VCFS, but several studies have reported that the frontal lobe is relatively preserved. We used functional magnetic resonance imaging to investigate the neural correlates of non-spatial working memory in 17 youths with VCFS, 10 of their unaffected siblings, and 10 community controls (with the same proportion of learning disabilities as the VCFS youths). Task performance of siblings tended to be more accurate than children with VCFS, who did not differ from community controls. All three-study groups recruited parietal regions that were equivalent in location and magnitude. Whereas the sibling group also recruited the dorsolateral prefrontal cortex (DLPFC), Broca's area, and anterior cingulate, DLPFC activation was absent in the whole brain analyses of children with VCFS and controls. Moreover, the magnitude of frontal activation in VCFS participants was restricted relative to both siblings and controls. These findings suggest that VCFS participants exhibit frontal hypoactivation that is not attributable to performance. In addition, VCFS children and controls (many with idiopathic learning disabilities) appear to rely on phonological rehearsal to hold information on line instead of the DLPFC. Despite previous anatomic MRI reports of preserved frontal lobe volumes in VCFS therefore, these fMRI findings suggest that the frontal component of the distributed network subserving executive function and working memory may be disrupted in youth with this disorder.