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PubMed2005

fMRI hippocampal activity during a virtual radial arm maze.

Numerous studies have shown that the hippocampus is critical for spatial memory. Within nonhuman research, a task often used to assess spatial memory is the radial arm maze. Because of the spatial nature of this task, this maze is often used to assess the function of the hippocampus. Our goal was to extrapolate this task to humans and examine whether healthy undergraduates utilize their hippocampus while performing a virtual reality version of the radial arm maze task. Thirteen undergraduates performed a virtual radial arm maze during functional magnetic resonance imaging. The brain maps of activity reveal bilateral hippocampal BOLD signal changes during the performance of this task. However, paradoxically, this BOLD signal change decreases during the spatial memory component of the task. Additionally, we note frontal cortex activity reflective of working memory circuits. These data reveal that, as predicted by the rodent literature, the hippocampus is involved in performing the virtual radial arm maze in humans. Hence, this virtual reality version may be used to assess the integrity of hippocampus so as to predict risk or severity in a variety of psychiatric disorders.

Adolescent↗
PubMed2001

Spatial language and spatial representation: a cross-linguistic comparison.

We examined the relationship between spatial language and spatial memory by comparing native English, Japanese, and Korean speakers' naming of spatial locations and their spatial memory for the same set of locations. We focused on two kinds of spatial organization: axial structure of the reference object, and contact/support with respect to its surface. The results of two language (naming) tasks showed similar organization across the three language groups in terms of axial structure, but differences in organization in terms of contact/support. In contrast, the results of two memory tasks were the same across language groups for both axial structure and contact/support. Moreover, the relationship between spatial language and spatial memory in the two sets of tasks did not show a straightforward isomorphism between the two systems. We conclude that spatial language and spatial memory engage the same kinds of spatial properties, suggesting similarity in the foundations of the two systems. However, the two systems appear to be partially independent: the preservation of particular spatial properties was not mandatory across languages, nor across memory tasks, and cross-linguistic differences in spatial language did not lead to differences in the non-linguistic encoding of location. We speculate that the similarity in linguistic and non-linguistic representations of space may emerge as a functional consequence of negotiating the spatial world.

Analysis of Variance↗
PubMed2003

Spatial working memory activity of the caudate nucleus is sensitive to frame of reference.

We used event-related fMRI to test the hypothesis that the caudate nucleus is preferentially recruited by a spatial working memory task employing egocentrically defined stimuli, which are amenable to transformation into a motor code, as contrasted with allocentrically defined stimuli, which are not. Our results revealed greater delay-epoch activity in egocentric than in allocentric trials in the caudate nucleus and trends in the same direction in the putamen and the lateral premotor cortex (PMC). Response-related activity was greater for egocentric trials in the lateral PMC. We propose that the neostriatum, possibly interacting with the PMC, may contribute to the sensory-motor transformation necessary to establish a prospective motor code (e.g., the representation of a saccade or a grasp). In addition, the PMC may participate in decision-making processes, prompted by the onset of the probe stimulus, that employ this prospective motor information. This model accounts for the empirical evidence that motor distraction disrupts spatial working memory performance.

Adult↗
PubMed2006

Memory deficit in mice administered aluminum-maltolate complex.

Recently, aluminum (Al) has been identified as one of the environmental factors responsible for cause certain nerve degeneration diseases, particularly, Alzheimer's disease (AD). However, the relationship between Al and AD is controversial. We previously examined whether Al induced neurotoxin in the brain of mice when aluminum-maltolate complex (ALM) was administered daily for 120 days. Our results revealed that Al accumulated in the brain induced oxidative stress, and the nerve degeneration was detected in the brain of the ALM-treated group. On the basis of these results, we have tried to examine whether the incorporated Al affects memory in mice with regard to an indicator of spatial memory deficits depending on the chemical forms of Al, namely, as an ion (AlCl3) and in the form of a complex (ALM). We administered saline, AlCl3, and ALM at a concentration of 40 micromol Al/kg body weight to mice by daily ip injections for 60 days. We assessed spatial memory by a water maze task and determined the Al levels in the brain of the mice by the neutron activation analysis method. Spatial memory deficit as an indicator of the swimming time was related to Al accumulation in the brain of mice; the chemical form of the Al compound was important in order to exhibit the memory deficit in mice; the uptake of Al is higher in mice when it is administered in a complex form than in an ionic form.

Animals↗
PubMed1997

Comparison between the effects of ethanol and diazepam on spatial working memory in the rat.

The present study compared the effects of ethanol and diazepam on a task that allows for the assessment of both spatial working memory and the acquisition of spatial information within each day. During the first trial of each day, subjects were shown the spatial location of a food reward on a six-arm radial-arm maze. During nine subsequent free-choice trials, subjects were reinforced for returning to that same spatial location. The location of the food reward varied across days. Thus, choosing correctly on any given trial required subjects to remember where food had been received during the previous trials of that day. The effects of ethanol and diazepam on working memory were assessed by analyzing the overall number of errors committed during the nine free-choice trials of each day. The effects of ethanol and diazepam on within-day acquisition were assessed by comparing the number of errors committed during the first three trials of each day to the number of errors committed during the last three trials of each day. Ethanol and diazepam both produced dose-dependent increases in working memory errors, and both did so without impairing within-day acquisition. The results of the present study provide further evidence of the similarities between the effects of ethanol and benzodiazepine receptor agonists on learning and memory, and are consistent with the hypothesis that ethanol's potentiation of GABA at GABAA receptors contributes to the learning and memory impairments produced by ethanol.

Adaptation, Psychological↗
PubMed2004

Spatial working memory deficits in children at ages 3-4 who were low birth weight, preterm infants.

The aim of this study was to investigate attention and perceptual and spatial working memory abilities in preterm, low birth weight preschool children without evident brain disorders as determined by normal cerebral ultrasound findings and normal motor development. The authors evaluated 19 preterm and 19 typically developing children who were matched for IQ and chronological age. Results indicated that children born prematurely without major neurological deficits and with a normal cognitive level may have specific difficulty in sustained attention, visuospatial processing, and spatial working memory when evaluated at ages 3-4. This finding is relevant for understanding the qualitative aspects of cognitive development in preterm children and the neurobiological substrate underlying this development.

Attention↗
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↗
PubMed1995

Time course of increased vulnerability of cholinergic neurotransmission following traumatic brain injury in the rat.

We have previously shown that spatial memory changes following experimental traumatic brain injury (TBI) include long-term changes that are (1) 'overt': detected by routine behavioral assessments, or (2) 'covert': undetected in the absence of a secondary pharmacological challenge, such as by the cholinergic antagonist, scopolamine. Our objective in this study was to extend this finding by characterizing the time course of recovery of overt and covert spatial memory performance following two magnitudes of experimental TBI. The Morris water maze was used to assess cognitive performance. Rats received either moderate magnitude (6 m/s, 1.77 mm deformation) or low magnitude (6 m/s, 1 mm deformation) impacts through a lateral craniectomy under isoflurane anesthesia. Sham rats underwent identical surgical procedures but were not injured. To avoid motor deficits, water maze testing started two weeks post-injury. Rats were given four trials per day for seven consecutive days. For each trial, latency to find a hidden platform was timed. On the sixth, rats were injected (i.p.) with scopolamine (1 mg/kg) 15 min prior to maze testing. The next day, rats were retested. This testing regimen was repeated, beginning 4, 6, and 10 weeks post-TBI. Results showed that, while the low-magnitude injury produced no overt spatial memory deficits, the moderate-magnitude group exhibited overt deficits during the first test regimen. Also, while both injury magnitudes produced an enhanced sensitivity to spatial memory impairment by scopolamine at two weeks post-TBI, this covert deficit persisted only in the severe group at 4, 6, and 10 weeks post-TBI. Qualitative light microscopy showed that both injury groups had graded cortical necrosis. However, underlying subcortical structures such as the hippocampus appeared intact, with no overt cellular or parenchymal damage to the neuropil. These data suggest three distinct stages of functional recovery: (1) the initial period when overt deficits are present, (2) a period following recovery from overt deficits within which covert deficits can be reinstated by a pharmacological challenge, and (3) a period following recovery from both overt and covert deficits. Covert deficits can persist long after the recovery of overt deficits and, like other neurological deficits, the rate of recovery is dependent on the magnitude of TBI. Finally, spatial memory deficits can occur in the absence of light microscopic evidence of cell death in the hippocampus.

Acetylcholine↗
PubMed1999

Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children.

BACKGROUND: Executive function deficits have been reported repeatedly in children with Attention Deficit Hyperactivity Disorder (ADHD). Stimulant medication has been shown to be effective in improving cognitive performance on most executive function tasks, but neuropsychological tests of executive function in this population have yielded inconsistent results. Methodological limitations may explain these inconsistencies. This study aimed to measure executive function in medicated and non-medicated children with ADHD by using a computerized battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), which is sensitive to executive function deficits in older patients with frontostriatal neurological impairments. METHODS: Executive function was assessed in 30 children with ADHD: 15 were stimulant medication naive and 15 were treated with stimulant medication. These two groups were compared to 15 age, sex and IQ matched controls. RESULTS: The unmedicated children with ADHD displayed specific cognitive impairments on executive function tasks of spatial short-term memory, spatial working memory, set-shifting ability and planning ability. Impairments were also seen on spatial recognition memory and delayed matching to sample, while pattern recognition memory remained intact. The medicated children with ADHD were not impaired on any of the above executive function tasks except for deficits in spatial recognition memory. CONCLUSIONS: ADHD is associated with deficits in executive function. Stimulant medication is associated with better executive function performance. Prospective follow-up studies are required to examine these effects.

Adolescent↗
PubMedDate not supplied

A re-examination of the role of basal forebrain cholinergic neurons in spatial working memory.

The basal forebrain cholinergic system, which innervates widespread cortical and limbic structures, has traditionally been considered important for learning and memory. The use of an immunotoxin, 192 IgG-saporin, has brought this functional designation into question; selective immunolesions of basal forebrain cholinergic neurons have failed to reproduce a number of behavioral deficits that were observed with less selective lesion methods. Recent reports, however, have indicated that a mild impairment is observed in rats on a spatial working memory task after 192 IgG-saporin lesions of the rostral groups of cholinergic neurons located in the medial septal area (MSA). Those studies used a lesion protocol in which a single large volume injection of the immunotoxin was made into the MSA. In the current study, multiple small injections were made at the locations of cholinergic neurons in the MSA, producing a cholinergic depletion comparable to that reported in the earlier studies where deficits were observed. In the current study, however, rats with cholinergic lesions had no impairment in the spatial working memory task, even when delays ranging from 60 s to 8 h were imposed within a trial. The current report indicates that selective removal of cholinergic neurons in the basal forebrain may not be sufficient to produce a deficit in spatial working memory.

Animals↗
PubMed2002

Eye movement abnormality suggestive of a spatial working memory deficit is present in parents of autistic probands.

Autistic probands exhibit impaired spatial accuracy and impaired response suppression errors during a delayed oculomotor response task. Family members of autistic probands, and thus the possible familial nature of these deficits, have not been assessed. Eleven parents of autistic probands and 17 adults from unaffected families, ages 25-50 years, completed oculomotor delayed-response tasks. Parents of autistic probands demonstrated poorer spatial accuracy than the comparison group (p = .002), with no significant differences between groups on percentage of premature saccades or latency of remembered saccades. Spatial working memory deficits, as measured by the delayed oculomotor response task, appear to be familial in families with an autistic proband. These deficits deserve further evaluation as a potential endophenotypic marker for genetic risk for autism.

Adult↗
PubMed2006

Spatial working memory and inhibition of return.

Recently we showed that maintaining a location in spatial working memory affects saccadic eye movement trajectories, in that the eyes deviate away from the remembered location (Theeuwes, Olivers, and Chizk, 2005). Such saccade deviations are assumed to be the result of inhibitory processes within the oculomotor system. The present study investigated whether this inhibition is related to the phenomenon of inhibition of return (IOR), the relatively slow selection of previously attended locations as compared with new locations. The results show that the size of IOR to a location was not affected by whether or not the location was kept in working memory, but the size of the saccade trajectory deviation was affected. We conclude that inhibiting working memory-related eye movement activity is not the same as inhibiting a previously attended location in space.

Humans↗
PubMed1996

Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover in the prefrontal cortex and cognitive impairment on the delayed alternation task. The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390. These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.

Analysis of Variance↗
PubMed2005

Evaluation of spatial working memory function in children and adults with fetal alcohol spectrum disorders: a functional magnetic resonance imaging study.

Magnetic resonance imaging (MRI) and functional MRI studies involving n-back spatial working memory (WM) tasks were conducted in adults and children with Fetal Alcohol Spectrum Disorders (FASD), and in age- and sex-matched controls. FMRI experiments demonstrated consistent activations in regions of the brain associated with working memory. Children with FASD displayed greater inferior-middle frontal lobe activity, while greater superior frontal and parietal lobe activity was observed in controls. Control children also showed an overall increase in frontal lobe activity with increasing task difficulty, while children with FASD showed decreased activity. FASD adults demonstrated less functional brain activity overall, but greater inferior-middle frontal lobe activity during the simpler tasks, relative to controls. Control adults demonstrated greater inferior frontal activity with increasing task difficulty, while this pattern was not consistently observed in FASD adults. All four groups showed increasing activity with increases in task difficulty in the parietal and frontal regions at more superior slice levels. The results suggest impairment in spatial working memory in those with FASD that does not improve with age, and that fMRI may be useful in evaluation of brain function in these individuals.

Adult↗
PubMed1998

Networks of domain-specific and general regions involved in episodic memory for spatial location and object identity.

Positron emission tomography (PET) was used to investigate human episodic memory for spatial location and object identity. We measured regional cerebral bloodflow (rCBF) while subjects engaged in perceptual matching of the location or the identity of line drawings of objects. Perceptual matching also involved incidental encoding of the presented information. Subsequently, rCBF was measured when subjects retrieved the location or the identity of these objects from memory. Using the multivariate partial least squares image analysis, we identified three patterns of activity across the brain that allowed us to distinguish structures that are differentially involved in processing spatial location and object identity from structures that are differentially involved in encoding and retrieval but operate across both domains. Domain-specificity was evident by increased rCBF during the processing of spatial location in the right middle occipital gyrus, supramarginal gyrus, and superior temporal sulcus, and by increased rCBF during the processing of object identity in portions of bilateral lingual and fusiform gyri. There was a nearly complete overlap between domain-specific dorsal and ventral extrastriate cortex activations during perceptual matching and memory retrieval. Evidence of domain-specificity was also found in the prefrontal cortex and the left hippocampus, but the effect interacted with encoding and retrieval. Domain-general structures included bilateral superior temporal cortex regions, which were preferentially activated during encoding, and portions of bilateral middle and inferior frontal gyri, which were preferentially activated during retrieval. Together, our data suggest that encoding and retrieval in episodic memory depend on the interplay between domain-specific structures, most of which are involved in memory as well as perception, and domain-general structures, some of which operate more at encoding and others more at retrieval.

Adult↗
PubMed2006

Exogenous cortisol shifts a motivated bias from fear to anger in spatial working memory for facial expressions.

Studies assessing processing of facial expressions have established that cortisol levels, emotional traits, and affective disorders predict selective responding to these motivationally relevant stimuli in expression specific manners. For instance, increased attentional processing of fearful faces (attentional bias for fearful faces) is associated with fear and anxiety and diminishes after administration of the anxiolytic hormone testosterone. Conversely, attentional bias for angry faces has been associated with higher levels of approach motivation (e.g. anger) and testosterone, but lower levels of cortisol. This negative relation between cortisol levels and bias for angry faces was also seen in a test of biased working memory performance. However, previous research suggests that exogenous glucocorticoids acutely decrease fearful and inhibited behavior and increase aggressiveness. Hypothesizing from these findings, the present study tested this spatial working memory for faces of various emotional expressions (neutral, happy, fearful, and angry) after double-blind, placebo-controlled administration of 40 mg cortisol in 18 healthy young men. It was predicted that cortisol would acutely attenuate memory bias for fearful expressions while increasing memory bias for angry expressions, in effect creating a shift in biased motivated memory from fear to anger. Results largely confirmed the hypotheses. This is the first causal evidence that cortisol differentially regulates spatial working memory for different facial expressions. Possible biological mechanisms are discussed.

Adolescent↗
PubMed1997

Effects of methylphenidate on spatial working memory and planning in healthy young adults.

Previous studies of the effects of the psychomotor stimulant, methylphenidate, have concentrated on vigilance and reaction time tasks. In this study, the effects of methylphenidate on more complex aspects of cognition were studied using tasks from the CANTAB battery and related tests which have been shown to be sensitive to frontal lobe dysfunction. Twenty-eight young healthy men participated in a counterbalanced, double-blind, placebo-controlled study of the effects of methylphenidate. Cognitive assessment included tests of spatial working memory, planning, verbal fluency, attentional set-shifting and sustained attention. Methylphenidate had significant effects on performance of the tests of spatial working memory and planning but not on the attentional and fluency tests. When the drug was taken on the first test session, performance on the spatial tests was enhanced by the drug compared to placebo. However, when the drug was taken second, performance accuracy was impaired whereas response latencies were decreased. These results are consistent with a hypothesis that methylphenidate influences performance in two conflicting ways; enhancing executive aspects of spatial function on novel tasks but impairing previously established performance. This pattern of effects is discussed within the framework of dual, interacting arousal mechanisms.

Adult↗
PubMedDate not supplied

Parallel working memory for spatial location and food-related object cues in foraging pigeons: binocular and lateralized monocular performance.

During foraging, animals can increase their success by both remembering feeding sites and remembering food-related object cues. Because earlier studies have tested either the site or object memory in isolation, the aim of the present study was to evaluate how efficiently birds can utilize both memories simultaneously. Furthermore, the idea was tested that lateralization might be the principle of brain organization that allows for efficient parallel processing. Pigeons learned to search for food in a complex maze with 16 baited sites. To obtain the maximum reward they had to perform two tasks in parallel, a spatial working memory task and an object-specific working memory task. Birds performed well on this dual task but, compared with spatial working memory alone, they were impaired during the first choices of a trial (Experiment 1). When the left and the right brain hemispheres were tested separately by means of monocular occlusion (Experiment 2), object discrimination was better when birds used their right eye/left hemisphere. This was most pronounced during the first choices of a trial. On the spatial component of the task, performance on binocular trials was better than on monocular trials, but monocularly both hemispheres performed at the same level. Results show that on this dual task, discrimination of food-related object cues predominantly involved the left brain hemisphere whereas both hemispheres contributed equally to spatial performance.

Animal Feed↗