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Study of a patient with damage to the hippocampus and surrounding neocortex reveals intact topographical knowledge of his childhood environment. New studies of spatial memory in animals are also giving insight into the process by which spatial memory becomes consolidated over time.
Previous functional studies suggest that the posterior cingulate gyrus is involved in spatial memory and its posteroventral part, in particular, is also involved in auditory memory. However, it is not clear whether the neural connections of the posteroventral part differ from those of the rest of the posterior cingulate gyrus. Here, we describe the thalamic connections of the posteroventral part of monkey area 23b (pv-area 23b), the main component of the posteroventral posterior cingulate gyrus. We compare these thalamic connections with those of the more dorsal area 23b (d-area 23b) and of adjoining retrosplenial areas 29 and 30. Thalamocortical projections to pv-area 23b originate mainly from the anterior nuclei, nucleus lateralis posterior and medial pulvinar. In contrast, projections to d-area 23b originate from the nucleus lateralis posterior, medial pulvinar, nucleus centralis latocellularis, mediodorsal nucleus and nucleus ventralis anterior and lateralis and weakly from the anterior nuclei. Projections to retrosplenial areas 29 and 30 originate from the anterior nuclei. Corticothalamic projections from pv-area 23b terminate in the anterior and laterodorsal nuclei, nucleus lateralis posterior and medial pulvinar. Projections from d-area 23b terminate in these nuclei as well as the nucleus ventralis anterior and lateralis. Projections from area 30 terminate mainly in the anterior nuclei and, to a lesser extent, in the medial pulvinar. These results show that the connections of pv-area 23b differ from those of d-area 23b or areas 29 and 30. This suggests that pv-area 23b may play distinct functional roles in memory processes, such as spatial and auditory memory.
BACKGROUND: Expressive language constitutes a major challenge to the development of individuals with Down syndrome. This paper investigates the relationships between expressive language abilities, language comprehension and the deficits in verbal short-term memory and hearing which are also associated with the syndrome. METHODS: Tests of nonverbal ability, expressive language, verbal short-term memory, visuo-spatial memory, language comprehension and hearing were administered. RESULTS: Phonological memory, measured by nonword repetition, was significantly correlated with expressive language abilities measured by MLU and sentence recall. Adjusting for word repetition skills did not reduce this correlation, suggesting that the relationship did not depend on the fact that both tests required spoken output. Hearing did not contribute significantly to expressive language scores of participants who provided an intelligible narrative. However, level of hearing loss as well as other language and memory measures did differentiate these participants from those who were unable to produce an intelligible narrative. CONCLUSION: Phonological memory was closely associated with the expressive language abilities of individuals with Down syndrome. Hearing loss appeared to be less closely related except that individuals with uncorrected mild to moderate hearing loss had difficulty with the narrative task. Further research is necessary to establish the nature of these relationships.
In neurons, the Ca(2+)/calmodulin (CaM) kinase cascade transduces Ca(2+) signaling into gene transcription. The CaM kinase cascade is known to be important for brain development as well as memory formation in adult brain, although the functions of some cascade members remain unknown. Here we have generated null and hypomorphic mutants to study the physiological role of CaM kinase kinase alpha (CaMKKalpha), which phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, the output kinases of the cascade. We show that CaMKKalpha is dispensable for brain development and long-term potentiation in adult hippocampal CA1 synapses. We find that CaMKKalpha is required for hippocampus-dependent contextual fear memory, but not spatial memory, formation. Surprisingly, CaMKKalpha is important for contextual fear memory formation in males but not in females. We show that in male mice, contextual fear conditioning induces up-regulation of hippocampal mRNA expression of brain-derived neurotrophic factor (BDNF) in a way that requires CaMKKalpha, while in female mice, contextual fear conditioning induces down-regulation of hippocampal BDNF mRNA expression that does not require CaMKKalpha. Additionally, we demonstrate sex-independent up-regulation in hippocampal nerve growth factor-inducible gene B mRNA expression that does not require CaMKKalpha. Thus, we show that CaMKKalpha has a specific complex role in memory formation in males.
OBJECTIVE: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. METHODS: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. RESULTS: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. CONCLUSIONS: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.
The subject mice were thymectomized 4 weeks after birth. Ten months after the thymectomy, learning behaviors in passive and active avoidance performances and a spatial memory task, the contents of brain monoamines and brain choline acetyltransferase (ChAT) activity, as well as the immune response were evaluated. DX-9386, a traditional Chinese medicinal prescription consisting of ginseng, polygala, acorus and hoelen, was prepared in CE-2 mouse food (1%, w/w) and given to the thymectomized mice after the operation until all the experiments were finished. DX-9386 treatment significantly ameliorated the learning and memory ability impaired by thymectomy in passive avoidance performances and in a spatial memory task, and the mice tended to improve in the active avoidance performance of a lever press test. However, DX-9386 treatment did not improve the thymectomy-reduced immune response. The contents of hypothalamic norepinephrine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and hypothalamic ChAT activity were significantly increased in thymectomized mice, and DX-9386 restored them to the control levels. These results suggested that DX-9386 mainly affected the cognitive process of the central nervous system to ameliorate the learning and memory deficit induced by thymectomy.
Rhesus monkeys were exposed to low, chronic levels of lead acetate either pre- or postnatally. Considerable neural and behavioral evidence indicates that the hippocampus is preferentially affected by low-level lead exposure. Hippocampal dysfunction is known to result in disruption of spatial memory. The monkeys in these experiments were tested as juveniles on a spatial memory test, the Hamilton Search Task. The monkeys exposed prenatally to lead did not show a deficit, while those exposed postnatally showed a significant deficit on the Hamilton Search Task. The deficit was not apparent until the monkeys were required to meet the most strict criterion, suggesting that the impairment may be due to the memory rather than the learning components of the task. The fact that the deficit was seen more than 3 years after the end of lead exposure indicates that the lead-induced cognitive effect is quite long-lasting and perhaps permanent.
Food-storing birds, black-capped chickadees (Poecile atricapilla), and nonstoring birds, dark-eyed juncos (Junco hyemalis), matched color or location on a touch screen. Both species showed a divided attention effect for color but not for location (Experiment 1). Chickadees performed better on location than on color with retention intervals up to 40 s, but juncos did not (Experiment 2). Increasing sample-distractor distance improved performance similarly in both species. Multidimensional scaling revealed that both use a Euclidean metric of spatial similarity (Experiment 3). When choosing between the location and color of a remembered item, food storers choose location more than do nonstorers. These results explain this effect by differences in memory for location relative to color, not division of attention or spatial discrimination ability.
Previous studies indicated that intensity level may be a determining factor in the beneficial or detrimental effects of exercise on spatial memory, as chronic low-intensity level exercise appears to enhance learning and memory which stressful situations may impair. This study examines the effects of different intensity levels of acute exercise (treadmill running) on spatial memory in rats. Using the Morris water maze, spatial learning was measured in animals exposed to treadmill running at low- (20-22 m/min for 25 min daily) and high-intensity (25 m/min for 25 min daily) levels of exercise. A stress control using an electric foot shock was used to examine if the high-intensity exercise was sufficient to serve as a stressor. Stress level was estimated by examining tail flick latencies as a measure of stress-induced analgesia. The results indicate that high-intensity exercise at a level that may not induce an analgesic state is sufficient to impair early acquisition of spatial learning. However, with additional trials, all animals are capable of learning the task. Acute exposure to the electric foot shock impaired learning in the Morris water maze. Surprisingly, across all studies, there was a significantly higher analgesic state post-swim as compared to pre-swim. The results indicate that irrespective of stress level prior to water maze testing, swimming in the Morris water maze repeatedly for short durations of time is enough to induce an analgesic state.
OBJECTIVE: To review the main findings on the glutathione role in cognitive function and synaptic plasticity processes, as well as, its involvement in neurotrophic and neurodegenerative events in rodents. DEVELOPMENT: The tripeptide glutathione and its related enzymes participate in the maintenance of oxidant homeostasis in aerobic cells. Oxidative damage to neuronal components underlies the molecular basis of neurodegeneration and brain aging. Several biomolecules with redox dependent activity are involved in the neuronal plasticity events that have a role in learning and memory functions. The maintenance of normal glutathione level is important for acquisition, but not consolidation, of spatial memory. Glutathione unavailability induces failures in hippocampal synaptic plasticity mechanisms, which are possibly related to a spatial memory deficit. On the other hand, several studies have suggested that the beneficial effects of neurotrophic treatments are mediated by the modulation of antioxidant defense mechanisms. In fact, nerve growth factor treatment to cognitively impaired rats stimulates glutathione reductase and can prevent the increases in glutathione peroxidase activity, pointing these enzymes as possible intracellular targets of neurotrophin actions on oxidant homeostasis. CONCLUSION: There is a closed link between glutathione metabolism and oxidant homeostasis, which is expressed in learning and synaptic plasticity deficits in conditions of low glutathione content, as well as, in neurodegeneration induced glutathione metabolism changes that can be prevented by neurotrophic treatment
OBJECTIVE: To determine the contribution of conversion of testosterone (T) to estradiol on cognitive processing in a population of healthy older men who received T supplementation. METHODS: Sixty healthy, community-dwelling volunteers aged 50 to 90 years completed a randomized, double-blind, placebo-controlled study. Participants were randomized to receive weekly IM injections of 100 mg T enanthate plus daily oral placebo pill (T group, n = 20), 100 mg testosterone enanthate plus 1 mg daily of anastrozole, an aromatase inhibitor (oral pill), to block the conversion of T to estradiol (AT group, n = 19), or saline injection and placebo pill (placebo group, n = 21) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3 and week 6 of treatment, and after 6 weeks of washout. RESULTS: Circulating total T was increased from baseline an average of 238% in the T and AT treatment groups. Estradiol increased an average of 81% in the T group and decreased 50% in the AT group during treatment. Significant improvements in spatial memory were evident in the AT and T treatment groups. However, only the group with elevated estradiol levels (T group) demonstrated significant verbal memory improvement. CONCLUSION: In healthy older men, improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol, whereas improvement in spatial memory occurs in the absence of increases in estradiol.
RATIONALE: Tyrosine depletion has been shown to reduce dopamine over activity in animal and human investigations. However, the effects on basal dopamine function have not been explored. Such information could establish tyrosine depletion as an effective probe of dopamine function in healthy volunteers and would also have relevance for future therapeutic applications of this manipulation. OBJECTIVE: The present study investigated the effect of acute tyrosine depletion on dopamine function in healthy volunteers using a combination of neuroendocrine, neuropsychological and subjective measures. METHODS: On one occasion, volunteers received an amino acid drink selectively lacking tyrosine and phenylalanine (TYR-free), whilst on the other they received a balanced (BAL) amino acid drink. Plasma prolactin, amino acid levels and subjective state were monitored over 6 h following the two drinks, and volunteers also completed a battery of tests from the CANTAB, including measures of spatial memory previously found to be sensitive to changes in dopamine function. RESULTS: Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, indicative of decreased dopamine neurotransmission within the hypothalamus. Following the TYR-free drink, volunteers were impaired at spatial recognition memory and spatial working memory. Volunteers also tended to report that they felt less good following the TYR-free than the BAL mixture. CONCLUSION: Tyrosine depletion in healthy volunteers affected baseline dopamine function on the different measures employed in this study. Tyrosine depletion would thereby seem valuable as a probe of dopamine function in human volunteers. Ratings of depression and other aspects of cognitive function were unaffected, suggesting that this manipulation may be free of significant side effects when used as a treatment for conditions characterised by dopamine over activity, such as acute mania and schizophrenia.
There is a growing body of evidence showing that the formation of associative memories is associated with an increase in phosphorylated cAMP response element-binding protein (pCREB) levels. We recently reported increased pCREB levels in the rat hippocampus after an exploration to a novel environment. In the present work, we studied whether this increment in CREB activation is associated with the formation of memory of habituation to a novel environment or with the detection of novelty. Rats were submitted to consecutive open field sessions at 3-h intervals. Measurement of the hippocampal pCREB level, carried out 1 h after each training session, showed that (1) it did not increase when rats explored a familiar environment; (2) it did not increase after a reexposure that improves the memory of habituation; (3) it increased after a brief novel exploration unable to form memory of habituation; and (4) it increased in amnesic rats for spatial habituation. Taken as a whole, our results suggest that the elevated pCREB level after a single open field exploration is not associated with the memory formation of habituation. It is indeed associated with the detection of a novel environment.
Neurons in the parietal cortex represent spatial memory of visual stimuli in an eye-centered coordinate frame. To preserve spatial stability across eye movements, spatial memory must be updated during each eye movement. Because eye movement signals in the parietal cortex are known to be modulated by eye position in the orbit, estimates of eye displacement on the basis of these signals could also be influenced by eye position. The present study examined the possible effect of eye position on the accuracy of memory-guided saccades in monkeys following saccades or smooth pursuit during the memory period. The results showed that eye position has a modest effect on saccade localization, suggesting that eye position signal plays a modulatory role in updating visuospatial working memory.
Two groups of Clark's nutcrackers (Nucifraga columbiana) were trained to use either a stay or shift response strategy in a radial maze analogue. Each trial had a preretention stage, a retention interval, and a postretention test. In Experiment 1, acquisition with a 5-min retention interval was studied. Response strategy did not affect the rate at which the task was learned. Performance following longer retention intervals was tested in Experiments 2-4. Changes in retention intervals were presented in trial blocks of increasing duration in Experiment 2 and were randomly presented between trials in Experiment 3. Experiment 4 extended the retention interval to 24 hr. No difference in performance was found between the 2 groups in any of these experiments. These results suggest a flexible relationship between spatial memory and response requirement in food-hoarding birds for at least 1 spatial memory task.
The present study investigated the effect of different doses of estradiol treatment on performance in the non-spatial delayed alternation T-maze a task in which performance is mediated by the integrity of the prefrontal cortex (PFC). Ovariectomized (OVX) female rats were injected with estradiol benzoate (0.3 microg/0.1 ml sesame oil (EB0.3), 5 microg/0.1 ml sesame oil (EB5) or 10 microg/0.1 ml sesame oil (EB 10)) or vehicle (sesame oil, 0.1 ml). Approximately 2 h after each injection, animals were trained daily on the T-maze with an initial delay of 10 s (short delay). Following a month with no treatment animals were re-trained at a 40 s delay (long delay). Days to reach criterion (one error per day for three consecutive days), mean total errors, errors across days, change in performance across training (short subtracted from long delay), and latency to reach goal arm, were scored. At the short delay, there was a weak effect for the low dose of estradiol (EB0.3 low-to-medium physiological) to significantly decrease the number of working memory errors compared to controls. However at the longer delay the higher doses of estradiol EB5 (high physiological) and to a lesser extent EB10 (suupraphysiological) significantly increased the number of working memory errors compared to controls. These data demonstrate the differential effect of estradiol during short and long delays on prefrontal cortex dependent working memory. High levels of estradiol impair PFC-dependent working memory at longer delays, while low level estradiol weakly facilitates PFC-dependent working memory at a shorter delay. These data suggest that estradiol's facilitatory effects on working memory may not be mediated through the PFC, while estradiols inhibitory effects on working memory may be mediated at least in part through the PFC.
Little is known about the way people learn technological skills. This investigation was carried out to see how 100 brain injured, 50 controls and two amnesic patients performed on a task requiring them to learn a six-step programme for an electronic memory aid. Performance was correlated with other measures of memory to determine whether the technological skill was similar to a procedural learning task, a spatial memory task, a visual task, a verbal task or an amalgam of these. All controls but only 59 percent of the patients learned the task within three trials. The two amnesic patients also failed to learn the new skill. There was a high correlation between overall performance on a standardized test of everyday memory (the Rivermead Behavioural Memory Test) but little evidence that the technological skill was similar to a procedural learning task; nor was it specifically related to visual, verbal or spatial memory. It is concluded that a combination of skills is required to learn the technological task. Implications for the concept of procedural learning are discussed.
Previous research has shown that pigeons can remember which of four spatially distinct responses was last reinforced, for at least 72 h. The present study sought to replicate this finding using rats. Rats were tested in an operant chamber containing four spatially distinct levers. In each session one lever was randomly selected to provide reinforcement for 15 min. This reinforced period was preceded by a non-reinforced period that was 30s long, on average. During the non-reinforced period the amount the rat pressed on the previously reinforced lever was compared to responding on the other three levers, and was taken as a measure of memory. Sessions were separated either by 17 min, 24 or 72 h. Unlike pigeons, rats responded at chance levels following each of these retention intervals. This finding adds to previous research suggesting differences in cognitive processes in rats and pigeons.