Biomedical subjects

J C Dalrymple-Alford

Publications and source records attributed to J C Dalrymple-Alford.

17 recordsLinked to original sources

PubMed2002

Long term psychosocial outcomes after mild head injury in early childhood.

OBJECTIVES: The question of whether any adverse cognitive or psychosocial outcomes occur after mild head injury in early childhood has evoked considerable controversy. This study examined mild head injury before age 10 and potential differences in late childhood/early adolescence as a function of severity of mild injury and age at injury. METHODS: A fully prospective longitudinal design tracked a large birth cohort of children. Confirmed cases of mild head injury before age 10 were divided on the basis of outpatient medical attention (n=64-84) or inpatient observation (hospital overnight; n=26-28 ) and compared with the non-injured remainder of the cohort (reference group; n=613-807). A range of pre-injury and post-injury child and family characteristics were used to control for any potential confounds. Outcome after injury before and after age 5 was also assessed. RESULTS: After accounting for several demographic, family, and pre-injury characteristics, the inpatient but not the outpatient group displayed increased hyperactivity/inattention and conduct disorder between ages 10 to 13, as rated by both mothers and teachers. Psychosocial deficits were more prevalent in the inpatient subgroup injured before age 5. No clear effects were evident for various cognitive/academic measures, irrespective of severity of mild injury or age at injury. CONCLUSIONS: Most cases of mild head injury in young children do not produce any adverse effects, but long term problems in psychosocial function are possible in more severe cases, perhaps especially when this event occurs during the preschool years. The view that all mild head injuries in children are benign events requires revision and more objective measures are required to identify cases at risk.

Achievement↗

PubMed1999

Effects of lesions to the cerebellar vermis and hemispheres on timing and counting in rats.

The effects of lesions to the cerebellum on numerical and temporal discrimination were examined in rats using a psychophysical choice procedure. Lesions to the cerebellar hemispheres but not the cerebellar vermis produced performance deficits in a numerical discrimination task (2-8 events) and a milliseconds temporal discrimination task (0.2-0.8 s). However, temporal discriminations in the seconds range (2-8 s) were unaffected by either type of lesion. Using W. H. Meck and R. M. Church's (1983) mode-control model of timing and counting, these findings suggest that damage to the cerebellar hemispheres influences a source of constant variability (e.g., switch processes) because constant variability is a prominent source of error during both milliseconds timing and counting but is masked by other sources of variability when timing longer durations (>2 s).

Animals↗

PubMed1998

Timing ability and numerical competence in rats.

Counting and timing ability in Wistar rats was tested in 4 psychophysical choice experiments. After training naive rats with discrete sound sequences that confounded time and number, only time gained control of behavior; control by time was stronger and acquired more rapidly after training with separate time- and number-relevant signals. Two nonnumeric cues associated with periodic sequences, temporal ratio and sequence pattern, did not appear to provide the basis for numerical discrimination, as performance was unaffected by a sudden change from periodic signals to signals with unique temporal patterns. Even after highly accurate performance with number, time showed exclusive control of behavior for signals with conflicting time and number cues. This study provides an unequivocal demonstration that rats can count, but they do so according to H. Davis and J. Memmott's (1983) "last resort" hypothesis.

Animals↗

PubMed1996

Both anteromedial and anteroventral thalamic lesions impair radial-maze learning in rats.

Disruption to the anterior thalamus (AT) may be an important factor in diencephalic amnesia. Rats with small lesions of the anteromedial (AM) or anteroventral (AV) nucleus showed persistent working-memory and reference-memory deficits in a 12-arm radial maze, although they were comparable to controls during the early part of training. The only activity difference in the maze was that lesioned rats failed to run more slowly when revisiting a baited arm. For all groups, both working and reference memory were impaired after extramaze cues were removed; removal of intramaze cues further impaired performance relative to the original conditions. These findings suggest the AT makes a distinct contribution to mnemonic functions, probably as part of an integrated system involving limbic cortex and the hippocampal formation, and that AT lesions produce a general rather than a specific deficit in spatial or working memory.

Animals↗

PubMed1995

Effects of selegiline (deprenyl) on cognition in early Parkinson's disease.

The influence of selegiline (5 mg b.i.d.) on cognition of 20 levodopanaive patients with early Parkinson's disease (PD) was examined in an 8-week, randomized, placebo-controlled, double-blind trial. Clinical evaluations and cognitive tests were administered at baseline and at 8 weeks; patients with PD who received placebo were also examined 8 weeks after subsequent selegiline treatment. By comparison with non-PD controls, patients with PD were impaired on the Wisconsin card sorting task and on the advanced progressive matrices test, but not in terms of their performance on the Rivermead behavioral memory test or on the rod (spatial) orientation test. Selegiline improved scores on the mentation/mood part and the activities of daily living part of the Unified Parkinson's Disease Rating Scale, but it did not improve motor scores on this test, nor did it have clear effects on the specific neuropsychological measures that were examined.

Aged↗

PubMed1995

Behavioural consequences of frontal cortex grafts and enriched environments after sensorimotor cortex lesions.

Past studies have experienced difficulty in achieving graft survival and behavioural recovery after sensorimotor cortex lesions. In the present work, adult female rats trained preoperatively to cross a narrow beam for food reward were maintained in standard group cages or an enriched environment, commencing one week after a unilateral lesion. One month post-lesion, half of these rats received multiple suspension grafts of (E20) fetal frontal cortex, placed adjacent to the lesion cavity, and 8 days later recovery of beam-walking skills was examined for a six-week period. The grafts survived in all cases with an appropriate lesion, a notable result given the one month lesion-graft delay, but graft volume was not influenced by postoperative environment. The substantial lesion-induced deficits evident just prior to differential housing showed a marked reduction by the start of post-graft testing, but relative to intact controls a persistent deficit in foot slip errors occurred in all lesion groups. Irrespective of graft status, postoperative enrichment prevented the occurrence of severe foot slips, especially early in retraining. The frontal grafts, however, enhanced beam-walking recovery by reducing the overall frequency of foot slips on early post-grafting sessions, an effect we suggest is related to graft-derived trophic influences, but this measure was not significantly improved by postoperative enrichment.

Animals↗

PubMed1994

Behavioral effects of basal forebrain grafts after dorsal septo-hippocampal pathway lesions.

There are many reports that basal forebrain grafts ameliorate behavioral impairments produced by dorsal septo-hippocampal pathway lesions, but several studies have either found that this recovery may be unrelated to concomitant restitution of cholinergic markers, may be modest and depend on certain experimental conditions or instead that grafts may actually exacerbate lesion-induced impairments. In this study, rats received one of three lesions of the dorsal septo-hippocampal pathways or a sham lesion, at 32 days of age, and intrahippocampal basal forebrain grafts or the vehicle control 10 days later. In grafted rats with total aspirative lesion of the fimbria-fornix, there was a substantial AChE-positive hippocampal reinnervation but no improvement of the severe lesion-induced spatial learning deficits, either reference memory or working memory, whether tested at 1 or 5 months post-grafting. In rats with bilateral medial fimbria lesions, grafts were successful, normal in appearance and produced substantial hippocampal cholinergic reinnervation; relative to non-grafted counterparts, however, grafted medial fimbria rats showed an early reference memory impairment and a persistent exacerbation of a working memory deficit. Exacerbation of learning impairments was also apparent in grafted rats with partial hippocampal denervation due to lesion of the cingulate and adjacent cortex above the fimbria-fornix. Nonetheless, basal forebrain grafts normalised general activity in these lesion groups, irrespective of whether the lesion-induced change was an increase or a decrease relative to controls. Graft-derived lesion groups, irrespective of whether the lesion-induced change was an increase or a decrease relative to controls. Graft-derived AChE-positive innervation was more marked than expected in both grafted cingulate-lesioned rats and grafted sham-lesioned rats, while control grafts of fetal cortex (above the septum) produced little or no AChE-positive innervation. Size of basal forebrain grafts, originally 3 microliters at two dorsal sites per hippocampus, increased markedly from rostral to caudal dorsal hippocampus in all groups but did not differ significantly across grafted groups, even with respect to non-lesioned rats. This study adds further evidence that basal forebrain grafts, successful with respect to cholinergic reinnervation, do not always enhance cognitive functions in rat hippocampal lesion models, and confirms that these grafts may have adverse effects after partial septo-hippocampal system lesions. It is important to attend to both the potential negative and positive effects of neural grafts.

Acetylcholinesterase↗

PubMed1994

Forgetting in rats following medial septum or mammillary body damage.

This study examined the effects of medial septal (MS) and mammillary body (MB) radio-frequency lesions in an automated delayed-matching-to-sample (DMTS) procedure using lever-position stimuli and rats. Memory performance pre- and postsurgery was assessed with a negative exponential decay function fitted to bias-free measures of recognition. Part 1 showed that MS, but not MB or sham-control surgery, impaired DMTS performance. This impairment in the MS group was best characterized as an increase in the rate of forgetting. Part 2 examined the interaction between MS and MB lesion effects and proactive interference arising from responses made on the previous DMTS trial. The results indicated that proactive interference effects were similar for all groups. These results provide further support for the critical role of the MS region in memory function but indicate that damage to this brain region does not disrupt memory function through a heightened sensitivity to proactive interference.

Animals↗

PubMed1994

A central executive deficit in patients with Parkinson's disease.

Eight patients with Parkinson's disease and eight matched controls were tested for concurrent task performance to examine whether Parkinson's disease produces deficits in the coordinating and integrating function of the central executive component of Baddeley's working memory model. Consistent with this prediction, the patients showed a significant decline in performance on a random pursuit tracking task while recalling digit span forward sequences, whereas the controls showed no such change. Performance on the component pursuit and digit span tasks, which did not differ between groups, was equated across subjects by varying the size of a target square and by using individual subjects' digit spans. The patient group also produced poorer word fluency scores and reported higher levels of depression, but there was no significant impairment on the Wisconsin card sort test. There was no association between dual task performance and any psychometric measure, target size, or disease related variables. Baddeley's working memory model is advantageous in providing a rich conceptual basis to explore and characterise cognitive abilities in patients with Parkinson's disease.

Aged↗

PubMed1993

List item memory in rats: effects of delay and delay task.

The Serial Position Effect (SPE) was studied in rats using 2 manipulations analogous to those that have been shown to decrease the recency effect but leave the primacy effect intact in human Ss. In Part 1, delays (5 s to 60 s) were imposed between exposure to a sequence of arms presented in a 12-arm radial maze and a subsequent test phase. In Part 2, the effect of free access to food in a short (10-s) delay was examined. The results from Parts 1 and 2 showed that the primacy and recency effects were differentially sensitive to the delay and events within it. In particular the recency effect was found to be more sensitive to disruption from these sources. The present demonstration of a reduction in recency with procedures analogous to those used with humans extends the evidence, suggesting that the SPE obtained in rats and humans is a similar phenomenon.

Animals↗

PubMed1992

Production of a serial position effect in rats using a 12-arm radial maze.

The effects of item position (the serial position effect: SPE) on the recognition of a list of arms presented in an 8-arm radial maze have not been shown to be robust across studies which differ in numbers of subjects, amount of training and task difficulty. The present study examined whether more robust SPEs could be obtained in rats with a 12-arm radial maze using a matching-to-sample serial probe recognition (SPR) procedure. In Part 1, 23 rats received extensive training on recognition of list of arms from a 5-arm list and, in Part 2, 20 rats received training with a 7-arm list. Both Parts 1 and 2 showed that a reliable and persistent SPE emerged due to superior recognition of items at the first and last serial positions compared with the middle positions. However, the SPE was more pronounced with the 7-arm than 5-arm list. It is argued that adequate task difficulty along with sufficient subject and trial numbers is necessary to produce a clear SPE. In Part 3, an alternative means of assessing accuracy derived from signal-detection theory is examined, and the procedural requirements for its use are identified. Although this measure did not alter the conclusions reached using percent correct, it is proposed that the bias-free measure, log d, is superior to traditional indices of memory performance which may obscure the presence of, or changes in, the SPE. The procedures used here provide a valuable means to produce clear, reliable and persistent SPEs. Such procedures are essential if researchers are to be confident about the effects of lesions or drugs upon list memory in their attempts to explore the neurological bases of memory and model human neurological disorders.

Animals↗

PubMed1988

Behavioral deficits after intrahippocampal fetal septal grafts in rats with selective fimbria-fornix lesions.

Fetal septal transplants have been shown to promote behavioral recovery in young adult rats with aspiration fimbria-fornix lesions, rats with septal lesions and in intact aged rats. The present study examined the behavioral impact of intrahippocampal septal cell suspension transplants (T) in young female rats that had received, 10 days earlier, either medial fimbria lesions (Group FI.T), dorsal (subcallosal) fornix lesions (Group FO.T) or these two lesions together (Group FIFO.T). Relative to rats with lesions only (groups FI, FO and FIFO), grafted rats, irrespective of lesion locus, displayed unexpected impairments in (i) a serial alternation learning task, 5 weeks and 6 months after transplantation, and (ii) in a radial maze, 7 months after transplantation. In the first alternation test, Group FIFO showed impaired performance relative to Groups FI, FO and the sham-operated controls (Group S). In the second alternation test, Groups FO.T and FO showed impaired performance relative to Groups FI.T and FI, and only the performance of Group FI did not differ from that of Group S. In the radial maze, Groups FI, FO and FIFO all showed impaired performance relative to Group S. By contrast, there were no deleterious effects of lesions or of grafts in the acquisition and retention of a step-through passive avoidance task, 10 weeks after transplantation. Our findings on the effects of selective fimbria-fornix lesions did not confirm the report that rats with FI lesions but not those with FO lesions are unable to learn a serial alternation task, nor the report that FO lesions impair passive avoidance retention. Acetylcholinesterase (AChE) histochemistry revealed that grafts were present but graft-derived innervation of the host hippocampus varied from extensive to almost non-existent in all transplant groups. AChE-positivity in the dorsal hippocampus (DH) was not related to behavioral performance. However, the grafts often grew to a considerable size within the host brain and in many rats, especially those in Group FI.T, produced moderate to extreme damage of the host DH. There was a significant positive correlation between errors in the radial maze and graft-induced DH damage but no relationship between errors and graft size. The results indicate that, after partial lesions of the fimbria-fornix, intrahippocampal septal grafts survive well but are likely to damage recipient structures and result in behavioral impairments.

Acetylcholinesterase↗

PubMed1988

Housing conditions modulate the effects of intracerebral grafts in rats with brain lesions.

The aim of this study was to examine whether the behavioural effects of intracerebral grafts in rats with brain lesions can be modulated by postoperative housing conditions. Sixty-six young adult female rats were used. Twenty-two rats were sham-operated (S) and 44 rats sustained a complete aspirative lesion (L) of the fimbria-fornix and overlying tissue. The cavity was used in half the rats as the implantation site for solid fetal septal transplants (LT). Two days later, half the rats of each group were housed in an 'enriched' condition (S.EC, L.EC and LT.EC); the other half remained in standard condition (S.SC, L.SC and LT.SC). Two and 10 months later, the rats were tested in a Hebb-Williams maze. Two months after surgery, there was a highly significant lesion effect, no graft effect and no environmental effect except in S rats, S.EC rats making fewer initial errors than S.SC rats. Ten months after surgery, L rats still made more errors than S rats and S.EC rats made fewer initial errors than S.SC rats; however, the lesion-induced deficits were significantly attenuated in LT.EC rats, but not in LT.SC rats. These data show that both the enriched environment and the implant were unable alone to promote behavioural recovery but, applied together, they reduced the lesion-induced deficits. Dorsal hippocampus acetylcholinesterase (AChE)-staining intensity was reduced by the lesions, but this reduction was partially compensated for by the grafts; however, environmental conditions did not affect AChE-staining significantly. This latter observation suggests that the graft-derived partial cholinergic reinnervation of the hippocampus probably does not underly the behavioural improvement observed only in LT.EC rats.

Acetylcholinesterase↗

PubMed1988

Effects of physostigmine and d-amphetamine on the behavior of rats with selective fimbria-fornix lesions and intrahippocampal fetal septal cell transplants.

Female Long-Evans rats were given electrolytic lesions of either the medial fimbria bilaterally (Fi, n = 24), the dorsal fornix (Fo, n = 24), or both structures (FF, n = 24) at 31 days of age. Ten rats were given sham-operations. Ten days later, half the rats with lesions received bilateral intrahippocampal grafts of embryonic septal cell suspensions (FiT, FoT, FFT, respectively). As already reported in a separate publication (J.C. Dalrymple-Alford, C.R. Kelche, J.C. Cassel, G. Toniolo, V. Pallage, & B.E. Will, 1987, Experimental Brain Research, 210, 115-128), 7 months after transplant surgery, grafted rats were found to be more impaired in an eight-arm radial maze than nongrafted rats. The present report concerns a pharmacological study carried out in the same rats 11 months after grafting. We examined the effects of ip injections of physostigmine (0.01, 0.05, 0.10 mg/kg) and then of d-amphetamine (1.6 mg/kg), as compared with baseline control injections of saline. Just prior to the drug treatments, performances of grafted and nongrafted rats did not differ significantly, but impairments in grafted rats reappeared during subsequent no-injection and saline control trials. Physostigmine failed to affect significantly the performances in rats of any group. d-Amphetamine improved performances in grafted rats with medial fimbria lesions, impaired performances in grafted rats with dorsal fornix lesions, and did not change performances in grafted rats with both lesions, as compared with their respective nongrafted counterparts. Histological analysis revealed variable reinnervation of the host structure and substantial graft-induced lesions of the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

PubMed1985

Pre-natal administration of diazepam improves radial maze learning in mice.

A number of studies have found that the peri-natal exposure of rodents to diazepam alters their adult behaviour. Adult male mice, treated with diazepam or appropriate controls during pregnancy, were examined in terms of their ability to learn a radial maze. Those animals receiving diazepam prior, but not after birth, learnt the maze significantly more rapidly. The results are discussed in terms of the possible involvement of the hippocampus in this influence of diazepam.

Age Factors↗

PubMed1984

Comparison in the mouse of the effect of the opiate delta receptor antagonist ICI 154129 and naloxone in tests of extinction, passive avoidance and food intake.

The effects of 30 and 80 mg/kg ICI 154,129, an opiate delta receptor antagonist, were compared with those of 0.1 and 10 mg/kg naloxone using tests of food-intake, passive avoidance and extinction in mice. Whereas naloxone depressed food intake and facilitated extinction, ICI 154,129 failed to affect food intake, passive avoidance or extinction although the mice reared significantly more during the test of food intake.

Animals↗

PubMed1984

Preoperative differential housing and dorsal hippocampal lesions in rats.

Rats housed in impoverished environments often show greater behavioral deficits after receiving brain lesions than to rats housed in standard or enriched environments. However, the resemblance between the effects of social isolation and those of hippocampal lesions in rats prompted the suggestion that rats socially isolated at weaning rather than grouped counterparts may show less behavioral change after sustaining dorsal hippocampal lesions when adult. In socially reared rats, hippocampal lesions produced increased ambulation and object contact in an open field, reduced passive avoidance in a runway task, and produced faster acquisition of active avoidance in a shuttle box, but there were no such differences in isolation-reared rats. Ambulation and object contact in isolates were intermediate to those of rats with lesions and intact group-housed rats, and the behavior of isolates during passive and active avoidance training was generally similar to that of grouped rats with lesions. The introduction of a distractor during approach training in an alley reduced running speeds more in rats with lesions than in controls. The several significant interactions between housing state and lesion state suggest that neural pathways associated with the hippocampal formation may mediate some behavioral effects of differential housing.

Animals↗