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PubMed2006

Traumatic brain injury produces delay-dependent memory impairment in rats.

Memory impairment following traumatic brain injury (TBI) is common in both humans and animals. A noteworthy feature of memory dysfunction in human TBI is impaired memory performance that is dependent on the delay between initial learning and recall of information. However, previous studies of TBI-induced memory impairment in animals have failed to control for the initial amount of learning between sham and injured animals. The present study demonstrates that experimental TBI in rats produces delay-dependent memory impairment, even when the initial degree of learning is controlled for. Animals were injured at a moderate level of lateral fluid percussion (LFP) injury (n = 10) or received a sham injury (n = 9), and then trained in a water T-maze version of the delayed-non-matching-to-place (DNMP) task beginning 10 days post-injury. Acquisition training consisted of 15 trials per day on post-injury days 11-15 using a minimal (7-sec) delay between the sample and choice phases of the task. Following acquisition, the delay between the sample and choice phases of the task was progressively increased to 15, 30, and 120 sec. Injured animals acquired the task at the same rate as sham animals and performed equally well at the 15-sec delay (p > 0.05). However, as the delay increased to 30 and 120 sec, the performance of the injured animals deteriorated (p < 0.05). These results indicate that LFP injury produces delay-dependent memory impairments in rats. This is therefore a valid model of an important feature of memory impairment in human TBI, and should be a useful addition to the available methods for assessing memory impairment and the effect of therapeutic interventions after TBI.

Animals↗
PubMed1994

Hyperinsulinaemia and Alzheimer's disease.

Because the aetiology of Alzheimer's disease (AD) remains unclear, and fasting hyperinsulinaemia has been incriminated in several human diseases, we examined the relationship between AD, fasting plasma insulin, glucose, body mass index and waist: hip ratio in 24 men and 24 women aged 58-90 years of whom half had probable AD. AD patients were randomly selected from the Bristol Memory Disorders Clinic, while controls were chosen from patients' spouses and the local community. Women with AD, compared with controls, have higher plasma insulin (p = 0.04), higher glucose (p = 0.04), and higher body mass index (p = 0.01). Similar differences were present in men but were not statistically significant except for body mass index (p = 0.03). We conclude that patients with AD have hyperinsulinaemia and insulin resistance, and this may be secondary to being overweight but a causal relationship cannot be excluded.

Aged↗
PubMed1977

The differential effects of meclofenoxate on memory loss in the elderly.

A double-blind study of the effects of meclofenoxate on memory performance of fit, able, elderly subjects was carried out. A number of performance measures, designed to measure various aspects of memory function were employed. These revealed that meclofenoxate appears to increase the consolidation of new information into long-term memory, but does not affect other aspects of remembering. It was also found that significantly more of the subjects receiving meclofenoxate reported an increased level of mental alertness.

Aged↗
PubMed1984

Colour anomia resulting from weakened short-term colour memory. A case study.

A patient exhibited marked colour anomia without object anomia, but was able to point to named colours. Five experiments were conducted to investigate his immediate colour memory. It was concluded that his colour anomia was the result of an impaired short-term memory deficit specific to colour. Temporary activation of specific entries in the colour lexicon enabled pointing and even naming to take place. A general model incorporating all forms of colour anomia is presented.

Anomia↗
PubMed1984

Disturbances of long-term memory in aphasic patients. A comparison of anterior and posterior lesions.

The performance of 20 aphasic patients on a verbal list-learning task was examined in relation to site of lesion, as documented by CT scan. Patients with lesions of the inferior frontal lobe and/or the basal ganglia were severely impaired in both acquisition and long-term retention of the list, while the performance of patients with posterior temporoparietal involvement was nearly normal. These results contrasted sharply with scores on short-term memory tests by the same patient groups which showed an opposite trend. The findings support a functional and neuroanatomical dissociation of short and long-term memory systems and suggest that neural connections of the inferior frontal lobe and the basal ganglia may be crucial for initiating the retrieval process.

Adult↗
PubMed1988

Temporal ordering and short-term memory deficits in Parkinson's disease.

Previous studies of remote memory function have indicated a dissociability between memory for the content and date of past events and suggested selective deficits of dating capacity in Parkinson's disease (PD). The present study examined the hypothesis that poor dating in PD is linked to a specific deficit in temporal contextual memory which also affects new learning. Patients with PD and patients with Alzheimer's disease (AD) were compared in their ability to perform tasks of content recognition and recency discrimination of words presented sequentially. Compared with AD patients, PD patients were disproportionately impaired in recency discrimination relative to content recognition. When performance was analysed as a function of retention interval, AD patients showed impairment in both tasks at all intervals. PD patients, by contrast, showed deficits in content recognition at the short stimulus-test intervals only, possibly reflecting the clinical phenomenon of bradyphrenia. These results suggest that recency discrimination deficits and impaired short-term memory processing are specific cognitive deficits in PD that may be linked to subcortical deafferentation of the frontal lobes.

Alzheimer Disease↗
PubMed1988

Ideational apraxia.

Ideational apraxia was investigated in 20 left brain-damaged patients with tests requiring the demonstration of how objects are used. On a multiple object use test the most frequent errors were those of omission, misuse and mislocation, while sequence errors were rare. Patients also failed on a single object use test, which showed a correlation of 0.85 with the multiple object use test. Neither of these tests was significantly correlated with an ideomotor apraxia test (imitation of movements). Ideational apraxia was frequently, but not exclusively, associated with damage to the left posterior temporoparietal junction. These findings support the view that ideational apraxia is an autonomous syndrome, linked to left hemisphere damage and pertaining to the area of semantic memory disorders rather than to that of defective motor control.

Apraxias↗
PubMed1990

Preserved recall versus impaired recognition. A case study.

A very pure and most unusual case of memory impairment is reported in a patient operated on for an aneurysm of the anterior communicating artery. Neuropsychological investigation performed about 8 yrs after the operation revealed a dissociation between very poor performance on recognition tests (on which the patient's performance was as poor as that in classical amnesic patients) and normal performance (estimated by the number of correct responses) in recall. This pattern has not previously been reported and is the reverse of that observed both in normal subjects and in amnesic patients. In addition, the patient was able to achieve a number of difficult learning tasks, at times normally; the relearning of one of these tasks after a delay of 1 h was perfectly normal. The recognition failure is interpreted in terms of the suggestion that memory performance results from an interaction between knowledge and subjective experience of remembering.

Brain↗
PubMed1998

Verbal short-term store-rehearsal system and the cerebellum. Evidence from a patient with a right cerebellar lesion.

We describe an 18-year-old patient who underwent surgical removal of the right cerebellar hemisphere for the presence of a neoplastic lesion. After surgery, the patient's neuropsychological examination was normal except for a transient selective verbal short-term memory (STM) impairment characterized by reduced verbal digit span and rapid forgetting of verbal material. An extensive examination of the patient's deficit was performed in order to identify which of the two components of STM (phonological short-term store and/or rehearsal system) was impaired. The functional locus of the deficit was identified at the level of the phonological output buffer, a component of the rehearsal system, as suggested by the pattern of results obtained, namely: the improvement of the digit span seen with pointing compared with the verbal response; the advantage of auditory over visual presentation of digits; and the lack of a phonological-similarity effect with visual presentation of letters. On the other hand, the functioning of the phonological store was demonstrated by the normal amplitude of the recency effect in free recall of words and by the phonological-similarity effect with auditory presentation of letters. Our finding is consistent with previous functional (PET) studies showing the involvement of the right cerebellum during tasks requiring silent recirculation of verbal information. We conclude that the cerebellum takes part in the planning of speech production at a level that does not require an overt articulation.

Brain Mapping↗
PubMed2001

Stability of the preclinical episodic memory deficit in Alzheimer's disease.

We sought to determine the course of the preclinical episodic memory deficit in Alzheimer's disease. Using data from a population-based study, we compared persons who developed Alzheimer's disease n = 15) with persons who were non-demented n = 105) 6 and 3 years prior to the diagnosis of dementia. Participants were tested on tasks assessing episodic memory free recall and recognition of words) and short-term memory digit span). The incident Alzheimer's disease cases performed more poorly than their non-demented counterparts both 3 and 6 years before diagnosis on recall and recognition. There were no group differences in either forward or backward digit span. The selective impairment of episodic memory before the diagnosis of Alzheimer's disease is consistent with the view that early changes in the hippocampal complex play an important role in the memory deficit in preclinical Alzheimer's disease. On both preclinical measurement occasions, recall and recognition made independent contributions to group classification in logistic regression analyses. However, there was no evidence for accelerated decline of episodic memory in the incident Alzheimer's disease group from 6 to 3 years before diagnosis. These results indicate that Alzheimer's disease is characterized by a long preclinical period during which episodic memory deficits are detectable. The magnitude of these deficits appears to be quite stable, at least up to 3 years before diagnosis. This may reflect the fact that those biological events that eventually result in clinically diagnosed Alzheimer's disease e.g. the appearance of amyloid plaques and neurofibrillary tangles) accumulate at a relatively slow rate.

Aged↗
PubMed2001

Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease.

To examine functional interactions between prefrontal and medial temporal brain areas during face memory, blood flow was measured in patients with Alzheimer's disease and healthy controls using PET. We hypothesized that controls would show correlated activity between frontal and posterior brain areas, including the medial temporal cortex, whereas patients would not, although frontal activity per se might be spared or even increased compared with controls. We used a delayed match to sample paradigm with delays from 1 to 16 s. There was no change in recognition accuracy with increasing delay in controls, whereas patients showed impaired recognition over all delays that worsened as delay increased. Controls showed increased activity in the bilateral prefrontal and parietal cortex with increasing delay, whereas the patients had increased activity in the right prefrontal, anterior cingulate and left amygdala. Increased activity in the right prefrontal cortex was associated with better memory performance in both groups and activity in the left amygdala was correlated with better performance in the patients. Based on these task and behavioural effects, we examined functional connectivity of the right prefrontal cortex and left amygdala in both groups by determining those areas whose activity was correlated with activity in these regions. In controls, activity in the right prefrontal cortex was positively correlated with blood flow in the left prefrontal cortex, bilateral extrastriate and parietal areas and the right hippocampus. In patients, activity in the right prefrontal cortex was correlated mainly with other prefrontal regions. Areas where activity was correlated with the left amygdala in patients included the bilateral posterior parahippocampal gyri, a number of left prefrontal regions, anterior and posterior cingulate, thalamus, and insula. Controls had a relatively restricted set of regions where activity correlated with the left amygdala, mainly temporal and occipital areas. These results support the idea of a functional disconnection between the prefrontal cortex and the hippocampus in Alzheimer's disease and suggest that memory breakdown in early Alzheimer's disease is related to a reduction in the integrated activity within a distributed network that includes these two areas. The unexpected finding of increased involvement of the amygdala suggests that the patients may have processed the emotional content of the faces to a greater degree than did the controls. Furthermore, the positive association between amygdala activity and memory performance in the patients suggests a possible compensatory role for an emotion-related network of regions.

Aged↗
PubMed2003

Neuroanatomical correlates of episodic encoding and retrieval in young and elderly subjects.

Lesion studies have shown convincingly that the medial temporal lobes (MTL) and frontal lobes are critical to episodic memory. Ageing generally has been found to have a generally negative effect on episodic memory performance, which might relate to neurofunctional changes in the frontal and medial temporal brain regions. In the present study, we used functional MRI (fMRI) to investigate separately the contributions of encoding and retrieval to the age-related decline in memory. To this end, we compared brain activity patterns obtained during incidental encoding (pleasant/unpleasant judgements about nouns) and subsequent retrieval (recognition) in three groups: a group of young subjects, a group of elderly subjects showing reduced memory performance (ELD-RED), and a group of elderly subjects who still performed in the normal range (ELD-NORM). This allowed us to differentiate between age-related changes in brain activity that affect memory function and those that do not have an apparent effect on memory function, because they are found in both elderly groups. Contrary to previous imaging studies on this topic, we used (self-paced) event-related fMRI to control for differences in performance level across groups by including correct responses only. Comparing the encoding of successfully remembered items with baseline (press left/press right), the young subjects showed a significant increase in brain activation in the left anterior MTL compared with the ELD-RED but not the ELD-NORM subjects. Comparing correctly rejected items (retrieval attempt) with baseline, the ELD-RED group showed much increased overall activity throughout the brain compared with the other groups. However, when correctly recognized items (retrieval attempt + success) were compared directly with correctly rejected items (retrieval attempt), these differences were greatly reduced, revealing common activity in the left parietal, retrosplenial and left anterior prefrontal regions. Therefore, we conclude that the reduced performance in the ELD-RED group is likely to be due to MTL dysfunction during encoding. The differences observed during retrieval attempts may reflect strategic differences. The lack of differences observed in relation to retrieval success suggests that ageing does not affect the processes that support the actual recovery of information.

Adult↗
PubMed2005

Functional recovery of children and adolescents after cerebellar tumour resection.

This study examined whether lesions to the cerebellum obtained in early childhood are better compensated than lesions in middle childhood or adolescence. Since cerebellar lesions might affect motor as well a cognitive performance, posture, upper limb and working memory function were assessed in 22 patients after resection of a cerebellar tumour (age at surgery 1-17 years, minimum 3 years post-surgery). Working memory was only impaired in those patients who had received chemo- or radiation therapy. Postural sway was enhanced in 64% of the patients during dynamic posturography conditions, which relied heavily on vestibular input for equilibrium control. Upper limb function was generally less impaired, but 54% of the patients revealed prolonged deceleration times in an arm pointing task, which probably does not reflect a genuine cerebellar deficit but rather the patients' adopted strategy to avoid overshooting. Age at surgery, time since surgery or lesion volume were poor predictors of motor or cognitive recovery. Brain imaging analysis revealed that lesions of all eight patients with abnormal posture who did not receive chemo- and/or radiation therapy included the fastigial and interposed nuclei (NF and NI). In patients with normal posture, NI and NF were spared. In 11 out of 12 patients with abnormal deceleration time, the region with the highest overlap included the NI and NF and dorsomedial portions of the dentate nuclei in 10 out of 12 patients. We conclude that cerebellar damage inflicted at a young age is not necessarily better compensated. The lesion site is critical for motor recovery, and lesions affecting the deep cerebellar nuclei are not fully compensated at any developmental age in humans.

Adolescent↗
PubMed2006

Functions of the left superior frontal gyrus in humans: a lesion study.

The superior frontal gyrus (SFG) is thought to contribute to higher cognitive functions and particularly to working memory (WM), although the nature of its involvement remains a matter of debate. To resolve this issue, methodological tools such as lesion studies are needed to complement the functional imaging approach. We have conducted the first lesion study to investigate the role of the SFG in WM and address the following questions: do lesions of the SFG impair WM and, if so, what is the nature of the WM impairment? To answer these questions, we compared the performance of eight patients with a left prefrontal lesion restricted to the SFG with that of a group of 11 healthy control subjects and two groups of patients with focal brain lesions [prefrontal lesions sparing the SFG (n = 5) and right parietal lesions (n = 4)] in a series of WM tasks. The WM tasks (derived from the classical n-back paradigm) allowed us to study the impact of the SFG lesions on domain (verbal, spatial, face) and complexity (1-, 2- and 3-back) processing within WM. As expected, patients with a left SFG lesion exhibited a WM deficit when compared with all control groups, and the impairment increased with the complexity of the tasks. This complexity effect was significantly more marked for the spatial domain. Voxel-to-voxel mapping of each subject's performance showed that the lateral and posterior portion of the SFG (mostly Brodmann area 8, rostral to the frontal eye field) was the subregion that contributed the most to the WM impairment. These data led us to conclude that (i) the lateral and posterior portion of the left SFG is a key component of the neural network of WM; (ii) the participation of this region in WM is triggered by the highest level of executive processing; (iii) the left SFG is also involved in spatially oriented processing. Our findings support a hybrid model of the anatomical and functional organization of the lateral SFG for WM, according to which this region is involved in higher levels of WM processing (monitoring and manipulation) but remains oriented towards spatial cognition, although the domain specificity is not exclusive and is overridden by an increase in executive demand, regardless of the domain being processed. From a clinical perspective, this study provides new information on the impact of left SFG lesions on cognition that will be of use to neurologists and neurosurgeons.

Adult↗
PubMed2006

Centella asiatica (L.) leaf extract treatment during the growth spurt period enhances hippocampal CA3 neuronal dendritic arborization in rats.

Centella asiatica (CeA) is a creeping plant growing in damp places in India and other Asian countries. The leaves of CeA are used for memory enhancement in the Ayurvedic system of medicine, an alternative system of medicine in India. In this study, we have investigated the effect during the rat growth spurt period of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal CA3 neurons, one of the regions of the brain concerned with learning and memory. Neonatal rat pups (7 days old) were fed with 2, 4 or 6 ml kg(-1) body weight of fresh leaf extract of CeA for 2, 4 or 6 weeks. After the treatment period the rats were killed, their brains were removed and the hippocampal neurons were impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were traced using a camera lucida, and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with data for age-matched control rats. The results showed a significant increase in the dendritic length (intersections) and dendritic branching points along the length of both apical and basal dendrites in rats treated with 4 and 6 ml kg(-1) body weight per day of CeA for longer periods of time (i.e. 4 and 6 weeks). We conclude that the constituents/active principles present in CeA fresh leaf extract have a neuronal dendritic growth stimulating property; hence, the extract can be used for enhancing neuronal dendrites in stress and neurodegenerative and memory disorders.

Journal Article↗