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R G Morris

Publications and source records attributed to R G Morris.

At least 73 records · Page 4Linked to original sources
PubMed1999

Reversible neural inactivation reveals hippocampal participation in several memory processes.

Studies of patients and animals with brain lesions have implicated the hippocampal formation in spatial, declarative/relational and episodic types of memory. These and other types of memory consist of a series of interdependent but potentially dissociable memory processes-encoding, storage, consolidation and retrieval. To identify whether hippocampal activity contributes to these processes independently, we used a novel method of inactivating synaptic transmission using a water-soluble antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal hippocampus of rats at appropriate times during or after training in a water maze. Our findings indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial memory and for either trace consolidation or long-term storage.

Animals↗
PubMed1999

Differential spatial memory impairment after right temporal lobectomy demonstrated using temporal titration.

In this study a temporal titration method to explore the extent to which spatial memory is differentially impaired following right temporal lobectomy was employed. The spatial and non-spatial memory of 19 left and 19 right temporal lobectomy (TL) patients was compared with that of 16 normal controls. The subjects studied an array of 16 toy objects and were subsequently tested for object recall, object recognition and memory for the location of the objects. By systematically varying the retention intervals for each group, it was possible to match all three groups on object recall at sub-ceiling levels. When memory for the position of the objects was assessed at equivalent delays, the right TL group revealed disrupted spatial memory, compared with both left TL and control groups (P < 0.05). MRI was used to quantify the extent of temporal lobe resection in the two groups and a significant correlation between hippocampal removal and both recall of spatial location and object name recall in the right TL group only was shown. These data support the notion of a selective (but not exclusive) spatial memory impairment associated with right temporal lobe damage that is related to the integrity of the hippocampal functioning.

Adult↗
PubMed1999

The functional neuroanatomy of comprehension and memory: the importance of prior knowledge.

Stories are a common way in which humans convey and acquire new information. Their effectiveness and memorability require that they be understood which, in turn, depends on two factors-whether the story makes sense and the prior knowledge that the listener brings to bear. Comprehension requires the linking of related pieces of information, some provided within the story and some by the listener, in a process establishing coherence. In this study, we examined brain activations associated with story processing. During PET scanning, passages of prose were read twice to subjects during successive scans with the requirement to remember them. These were either standard stories that were readily comprehensible, or unusual stories for which the global theme was very difficult to extract without prior knowledge of the mental framework. This was manipulated by the provision of relevant, irrelevant or no visual cues shortly before the story. Ratings of comprehension provided by the subjects just after each scan confirmed that standard stories were more comprehensible than the unusual stories, as were unusual stories with a mental framework compared with those without. PET results showed activation of anterior and ventral parts of the medial parietal/posterior cingulate cortex in association with hearing unusual stories when subjects were given prior knowledge of what it might be about. Medial ventral orbitofrontal cortex and left temporal pole activations were found to be associated with more general aspects of comprehension. Medial parietal cortex (precuneus) and left prefrontal cortex were associated with story repetition. We suggest that while the temporal pole is involved in the linking of propositions to build a narrative, the anterior medial parietal/posterior cingulate cortex is concerned with linking this information with prior knowledge. All of this occurs in the context of a general memory processing/retrieval system that includes the posterior parietal (precuneus) and prefrontal cortex. Knowledge of how distinct brain regions contribute differentially to aspects of comprehension and memory has implications for understanding how these processes break down in conditions of brain injury or disease.

Acoustic Stimulation↗
PubMed1999

Some international approaches to aminoglycoside monitoring in the extended dosing interval era.

Aminoglycosides have rightly remained a cost-effective anti-microbial strategy for the treatment of gram-positive infections for some 25 years. However, in recent years there has been a review of the traditional thrice-daily administration regimen in favor of an extended dosing interval strategy that takes into account the individual patient's renal function. The general recommendations that have been provided to date have been adopted in various ways internationally. These approaches were a matter of discussion for the Clinical Pharmacokinetics Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology at its congress (Vancouver, Canada; November 1997), and will again be a workshop issue at the Cairns (Australia) congress of the Association (September 1999). The present report provides examples of how these practices have been applied at a group of centers from Canada (2 centers), The Netherlands, Egypt, and Australia. These reports demonstrate a variety of approaches and highlight the need for further research for assessing clinical outcomes from different dosing strategies.

Aminoglycosides↗
PubMed1999

Assessment of interlaboratory performance in the provision of perhexiline therapeutic drug monitoring services in Australia.

Perhexiline is a prophylactic antianginal agent particularly useful in patients whose angina is poorly controlled or refractory to conventional drug regimens. Although perhexiline can cause serious hepatic and neurological toxicity, maintaining trough plasma concentrations between 0.15-0.60 mg/L minimizes the risk of toxicity while providing relief of angina symptoms in a majority of patients. All pathology laboratories are required to participate in interlaboratory proficiency testing (PT) programs. The authors therefore initiated a monthly PT program to assess the performance of Australian laboratories measuring perhexiline (n = 8). PT specimens included perhexiline-spiked drug-free human plasma and pooled plasma from patients administered perhexiline. The performance of 8 Australian laboratories participating in the program was examined over a 30-month period. The mean relative standard deviation of the group was 18.2%. All centers performed well with respect to accuracy, achieving mean percentage bias within +/-8% of target perhexiline concentrations. The usefulness of the PT program was highlighted by the identification of two laboratories with an unacceptable degree of variability (up to 30% of results varied more than +/-55% from the target concentration), and the identification of potential analytical problems with the use of perhexiline metabolite concentrations for determining patients' hydroxylator status. Continued and improved use of PT by pathology laboratories is essential to ensuring the safe and effective clinical use of perhexiline.

Angina Pectoris↗
PubMed1999

Evidence for cortical dysfunction in clinically non-demented patients with Parkinson's disease: a proton MR spectroscopy study.

OBJECTIVES: To investigate whether proton magnetic resonance spectroscopy (1H MRS) can detect cortical dysfunction in non-demented patients with Parkinson's disease, and to correlate changes with cognitive function on formal neuropsychological testing. METHODS: Multivoxel 1H MRS was performed in 17 patients with levodopa treated idiopathic Parkinson's disease with out clinical dementia, and 10 age match ed control subjects. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine+phosphocreatine (Cr), and Cho/Cr were obtained from right and left temporoparietal cortex and occipital cortex. Fourteen patients with Parkinson's disease underwent a full battery of neuropsychological testing including performance and verbal subtests of the WAIS-R, Boston naming test, FAS test, and California verbal learning test. RESULTS: There were significant temporoparietal cortex reductions in NAA/Cr ratios in right and left averaged spectra of the patients with Parkinson's disease (p=0.012 after Bonferroni correction) and in spectra contralateral to the worst clinically affected limbs of the patients with Parkinson's disease compared with controls (p = 0.003 after Bonferroni correction). There was a significant correlation between reduction in NAA/Cr ratios and measures of global cognitive decline, occurring independently of motor impairment (p=0.019). CONCLUSIONS: This study suggests that 1H MRS can detect temporoparietal cortical dysfunction in non-demented patients with Parkinson's disease. Further longitudinal studies are needed to investigate whether these 1H MRS changes are predictive of future cognitive impairment in the subset of patients with Parkinson's disease who go on to develop dementia, or occur as part of the normal Parkinson's disease process.

Aged↗
PubMed1999

Blocking in the spatial domain with arrays of discrete landmarks.

A characteristic feature of associative conditioning is that learning a predictive relationship between two events can block later learning about an added event. It is not yet well established whether blocking occurs in the spatial domain or the circumstances in which it does. We now report, using rats trained to search for hidden food near landmarks in an open field arena, that blocking can occur in spatial learning. The animals noticed the added landmark at the start of the blocking phase and explored it, but either failed to incorporate it into their spatial map or developed a representation in which only some landmarks actually control behavior. Additionally, performance at asymptote was controlled by the shape of the landmark array rather than the individual landmarks comprising it, indicating that blocking in the spatial domain may represent a failure to alter the encoded geometry of a learned array.

Animals↗
PubMed1999

Methods for diagnosis and treatment of stimulus-correlated motion in generic brain activation studies using fMRI.

Movement-related effects in realigned fMRI timeseries can be corrected by regression on linear functions of estimated positional displacements of an individual subject's head during image acquisition. However, this entails biased (under)estimation of the experimental effect whenever subject motion is not independent of the experimental input function. Methods for diagnosing such stimulus-correlated motion (SCM) are illustrated by application to fMRI data acquired from 5 schizophrenics and 5 normal controls during periodic performance of a verbal fluency task. The schizophrenic group data were more severely affected by SCM than the control group data. Analysis of covariance (ANCOVA) was used, with a voxelwise measure of SCM as a covariate, to estimate between-group differences in power of periodic signal change while controlling for variability in SCM across groups. Failure to control for SCM in this way substantially exaggerated the number of voxels, apparently demonstrating a between-group difference in task response.

Adult↗
PubMed1998

Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.

Specific patterns of neuronal firing induce changes in synaptic strength that may contribute to learning and memory. If the postsynaptic NMDA (N-methyl-D-aspartate) receptors are blocked, long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission and the learning of spatial information are prevented. The NMDA receptor can bind a protein known as postsynaptic density-95 (PSD-95), which may regulate the localization of and/or signalling by the receptor. In mutant mice lacking PSD-95, the frequency function of NMDA-dependent LTP and LTD is shifted to produce strikingly enhanced LTP at different frequencies of synaptic stimulation. In keeping with neural-network models that incorporate bidirectional learning rules, this frequency shift is accompanied by severely impaired spatial learning. Synaptic NMDA-receptor currents, subunit expression, localization and synaptic morphology are all unaffected in the mutant mice. PSD-95 thus appears to be important in coupling the NMDA receptor to pathways that control bidirectional synaptic plasticity and learning.

Animals↗
PubMed1998

Impaired spatial learning after saturation of long-term potentiation.

If information is stored as activity-driven increases in synaptic weights in the hippocampal formation, saturation of hippocampal long-term potentiation (LTP) should impair learning. Here, rats in which one hippocampus had been lesioned were implanted with a multielectrode stimulating array across and into the angular bundle afferent to the other hippocampus. Repeated cross-bundle tetanization caused cumulative potentiation. Residual synaptic plasticity was assessed by tetanizing a naïve test electrode in the center of the bundle. Spatial learning was disrupted in animals with no residual LTP (<10 percent) but not in animals that were capable of further potentiation. Thus, saturation of hippocampal LTP impairs spatial learning.

Animals↗
PubMed1998

Serine proteases in rodent hippocampus.

Brain serine proteases are implicated in developmental processes, synaptic plasticity, and in disorders including Alzheimer's disease. The spectrum of the major enzymes expressed in brain has not been established previously. We now present a systematic study of the serine proteases expressed in adult rat and mouse hippocampus. Using a combination of techniques including polymerase chain reaction amplification and Northern blotting we show that tissue-type plasminogen activator (t-PA) is the major species represented. Unexpectedly, the next most abundant species were RNK-Met-1, a lymphocyte protease not reported previously in brain, and two new family members, BSP1 (brain serine protease 1) and BSP2. We report full-length sequences of the two new proteases; homologies indicate that these are of tryptic specificity. Although BSP2 is expressed in several brain regions, BSP1 expression is strikingly restricted to hippocampus. Other enzymes represented, but at lower levels, included elastase IV, proteinase 3, complement C2, chymotrypsin B, chymotrypsin-like protein, and Hageman factor. Although thrombin and urokinase-type plasminogen activator were not detected in the primary screen, low level expression was confirmed using specific polymerase chain reaction primers. In contrast, and despite robust expression of t-PA, the usual t-PA substrate plasminogen was not expressed at detectable levels.

Amino Acid Sequence↗
PubMed1998

Contingent versus incidental context processing during conditioning: dissociation after excitotoxic hippocampal plus dentate gyrus lesions.

This experiment explored whether excitotoxic hippocampus plus dentate gyrus (HPC/DG) lesions in rats would dissociate the differential processing of contextual cues during the performance of learned associations when (1) their processing during training is incidental to successful learning or (2) the solution of a discrimination problem is contingent on their processing. A series of training stages were conducted, beginning with appetitive conditioning to two stimuli (X and Y), each of which was trained in one of two different contexts (operant chambers A and B) (i.e., AX+, BY+). Conditioning was indexed as appetitive responding. The animals were then trained on a biconditional contextual discrimination with these same stimuli (AX+, AY-; BY+, BX-). The next stage involved conditioning trials to two new stimuli (W and Z), one in each context, while the animals were actively discriminating contexts A and B by continuing to perform the original biconditional discrimination (AX+, AY-, AW+; BY+, BX-, BZ+). Finally, they were trained on a second biconditional discrimination involving these new stimuli (AX+, AY-, AW+, AZ-; BY+, BX-, BZ+, BW-). The incidental use of context cues was examined by looking at the rate of conditioned responding to cues X, Y, W, and Z in their original training contexts or a different context; HPC/DG lesioned rats differed from controls in being unaffected by a change of context. The contingent use of context cues was examined by looking at performance of each of the two biconditional tasks; HPC/DG lesioned rats reached levels of conditional performance indistinguishable from those of controls. These findings point to two distinct ways in which contextual information is processed in the brain, revealing a dissociation between incidental and contingent processing of contextual cues after HPC/DG lesions.

Acoustic Stimulation↗
PubMed1998

Gene-trapping to identify and analyze genes expressed in the mouse hippocampus.

Mice harboring random gene-trap insertions of a lacZ (beta-galactosidase)-neomycin resistance fusion cassette (beta-geo) were analyzed for expression in the hippocampus. In 4 of 15 lines reporter gene activity was observed in the hippocampal formation. In the obn line, enzyme activity was detected in the CA1-3 hippocampal subfields, in hpk expression was restricted to CA1, but in both lines reporter activity was also present in other brain regions. In the third line, kin, reporter activity was robustly expressed throughout the stratum pyrimidale of CA1-3, with only low-level expression elsewhere. The final line (glnC) displayed ubiquitous expression of the reporter and was not analyzed further. Fusion transcripts for the first three lines were characterized; all encode polypeptides with features of membrane-associated signalling proteins. The obn fusion identified a human cDNA (B2-1) encoding a pleckstrin homology (PH) domain, while hpk sequences matched the Epstein-Barr Virus (EBV) inducible G-protein coupled receptor, EBI-1. kin identified an alternative form of the abl-related nonreceptor tyrosine kinase c-arg. Electrophysiological studies on mice homozygous for the insertions revealed normal synaptic transmission, paired pulse facilitation and paired-pulse depression at Schaffer collateral-commissural CA1 synapses, and normal long-term potentiation (LTP) in obn and kin. hpk mice displayed an increase in hippocampal CA1 long-term potentiation (LTP), suggesting a role for this receptor in synaptic plasticity.

Amino Acid Sequence↗
PubMed1998

Recognition memory and memory for order in script-based stories following frontal lobe excisions.

Memory for stories was investigated in 25 patients with frontal lobe excisions and 25 control subjects. The subjects were presented with three different story types that either conformed to a well-known script, contained the same elements as a script but in a randomised order, or described a novel event. Subjects were asked to perform a test of recognition memory and memory for order on words presented in each story. The frontal lobe patients were unimpaired on the recognition memory test for salient words taken from each story. However, an impairment was observed in the frontal patients when they were asked to order the words taken from the novel story only. This deficit was no longer seen when the subjects were required to order sentences describing the key events in the story. These findings help to elucidate the role of the frontal lobes in memory for order information.

Adult↗