Temporal factors in recovery of function after brain damage

doi:10.1016/0014-4886(75)90079-5

Experimental Neurology

Volume 47, Issue 3, June 1975, Pages 470-480

https://doi.org/10.1016/0014-4886(75)90079-5 Get rights and content

Abstract

Although many experiments have shown that serial lesions of the CNS often result in behavioral sparing, there have also been reports of failure to obtain recovery with the seriatum technique. One factor which might account for the succes or failure of sequential lesion experiments could be the duration of the interoperative interval. Thus, a minimum period may be required between operations in order to initiate the recovery process, and it was the purpose of the present experiment to explore this possibility. We have found that rats given sequential (two-stage) frontal aspiration lesions with either a 30 or 20 day interoperative interval were not disrupted on acquistion of a spatial alternation task when compared with sham-operated controls; animals with two-stage lesions spaced 10 days apart were impaired when contrasted to the latter groups although they performed significantly better than rats given simultaneous, bilateral operations. Because of this finding two groups of rats receiving either two-stage sham operations or two saline injections were also tested as controls for surgical stress. No differences in performance between these two groups of rats were observed. Thus, the severity of the deficit and subsequent behavioral recovery may be related to the interval of time between successive operations. Since all subjects had at least 5 weeks of postoperative recovery prior to training in spatial alternation, it is unlikely that postoperative factors would play as as important a role in functional recovery as the interval between successive lesions.

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Cited by (32)

Inter-hemispheric synchronicity and symmetry: The functional connectivity consequences of stroke and neurodegenerative disease
2022, NeuroImage: Clinical
Citation Excerpt :
Previous research has provided clear evidence of the relevance of the temporal characteristics of lesion for overall recovery of function. Studies comparing behavioral recovery in rats subjected to successive resections varying in the number of stages and inter-lesion intervals have consistently shown that more gradual lesions were associated with better functional recovery (Patrissi & Stein, 1975; Stein et al., 1977). A review (Desmurget et al., 2007) of human studies of progressive damage (slow growing tumors) and acute damage (stroke) confirmed that gradually progressing damage generally yielded better cognitive outcomes and produced more neurotopographically distributed re-organization.
Stroke and neurodegenerative diseases differ along several dimensions, including their temporal trajectories -abrupt onset versus slow disease progression. Despite these differences, they can give rise to very similar cognitive impairments, such as specific forms of aphasia. What has been scarcely investigated, however, is the extent to which the underlying functional neuroplastic consequences are similar or different for these diseases. Here, for the first time, we directly compare changes in the brain’s functional network connectivity, measured with resting-state fMRI, in stroke and progressive neurological disease. Specifically, we examined two groups of individuals with chronic post-stroke aphasia or non-fluent primary progressive aphasia, matched for their behavioral profiles and distribution of left-hemisphere damage. Using previous proposals regarding the neural functional connectivity (FC) phenotype of stroke as a starting point, we compared the two diseases in terms of homotopic FC, intra-hemispheric FC changes and also the symmetry of the FC patterns between the two hemispheres. We found, first, that progressive disease showed significantly higher levels of homotopic connectivity than neurotypical controls and, further, that stroke showed the reverse pattern. For both groups these effects were found to be behaviorally relevant. In addition, within the directly impacted left hemisphere, FC changes for the two diseases were significantly correlated. In contrast, in the right hemisphere, the FC changes differed markedly between the two groups, with the progressive disease group exhibiting rather symmetrical FC changes across the hemispheres whereas the post-stroke group showed asymmetrical FC changes across the hemispheres. These findings constitute novel evidence that the functional connectivity consequences of stroke and neurodegenerative disease can be very different despite similar behavioral outcomes and damage foci. Specifically, stroke may lead to greater independence of hemispheric responses, while neurodegenerative disease may produce more symmetrical changes across the hemispheres and more synchronized activity between the two hemispheres.
Medial frontal lesions, postoperative treatment with an ACTH(4-9) analog, and acquisition of a win-shift spatial strategy
1991, Behavioural Brain Research
Forty adult rats of both genders were randomly assigned to one of four factorial groups and prepared with either medial frontal or sham lesions. On the day of surgery osmotic mini-pumps that had been prepared to deliver either 12.5 μg of ACTH(4–9) analog per 24 h or saline for the next 14 days were installed in a subcutaneous location. One month following surgery, these animals were studied in an avoidance conditioning experiment. Four to 6 months later their abilities to learn a water maze win-shift spatial strategy was investigated. The brain-damaged rats were found to be deficient on all behavioral measures examined: errors to criterion, days to criterion, and perseverative errors. Although post-neurosurgical administration of the ACTH 4–9 analog has been shown to improve behavioral recovery from brain damage in some studies, the peptide failed to improve the behaviors examined here.
Arginine vasopressin 4-9 retards spatial alternation learning
1989, Neuropeptides
Thirty adult male rats were randomly divided into three groups and prepared with either posterior parietal, medial frontal or sham neocortical injuries. After a 10–12 day recovery interval, access to water was restricted to a 30-min period per day and the rats were trained to run in a T-maze for a reward of sweetened water. After reaching a pre-training criterion, osmotic mini-pumps (Alzet 2002) were installed subcutaneously. For the next 14 to 15 days, the pumps delivered chronically either 0 or 1.2 μg of arginine vasopressin 4–9 (AVP 4–9) dissolved in bacteriostatic saline while the animals were trained on a reinforced spatial alternation task. Analysis of variance on the number of errors committed to a criterion of at least 80% correct alternations in two consecutive training sessions, or a ceiling of 50 errors (attained by two rats with parietal lesions), revealed a significant retardation in animals administered AVP 4–9 during training. These results demonstrate that this centrally active metabolite of vasopressin can interfere with the acquisition of a cognitive learning task when administered concomitantly with training.
Constraints on water maze spatial learning in rats. Implications for behavioral studies of brain damage and recovery of function
1988, Behavioural Brain Research
In an effort to develop spatial learning tasks not requiring food or water deprivation for use in studies of recovery of function after brain damage, T-maze spatial alternation learning was examined in intact rats using water maze swim-escape procedures. Consistent with previous studies, rewarded spatial alternation involving food or water deprivation was readily learned by intact rats. However, none of the groups of rats trained in the swim-escape tasks learned to alternate goal arm choices in the water maze at reliable rates. This was true regardless of whether non-correction or correction procedures were used, and regardless of intertrial delay intervals. Although average alternation rates over sessions did increase from chance levels, the majority of the rats did not reach criterion levels, even with as many as 38 consecutive days of testing. In contrast, a conditional spatial alternation task in the water maze, using a win-shift procedure, was readily learned. Surprisingly, a win-stay version of this conditional spatial task was not learned over 21 days of testing. These unexpected constraints on spatial learning and memory processes in rats cannot be attributed simply to failure of spatial information processing, nor to strict limitations on working memory in swim-escape tasks, since excellent spatial navigation abilities have been documented, and mastery of at least some working-memory tasks have now been demonstrated in swim-escape tasks.
Choline acetyltransferase immunopositive pyramidal neurons in the rat frontal cortex
1988, Brain Research
The putative cholinergic neurons of the rat's frontal cortex (Krieg's area 10) were studied using monoclonal antibody to choline acetyltransferase (ChAT). This paper reports two novel findings which might be very important to logicize the function of the frontal cortex. Firstly, the immunopositive cells were distributed in layers II, IV, V and VI around the rostral half, and layers IV, V and VI around the caudal half of Krieg's area 10. Secondly, the majority of immunopositive neurons in layer V was pyramidal cell.
The role of trophic factors in behavioral recovery and integration of transplants
1988, Progress in Brain Research
Transplants may stimulate vascularization, remove toxic substances, or promote neuronal survival and growth through neurotrophic interactions between host and transplant. This chapter discusses the relative contributions of trophic factors vs. circuitry restoration in recovery of function. It appears that the brain responds to injury by producing trophic factors that increase cell survival and they promote growth of neuritis. While transplants can apparently restore function by providing trophic support to remaining host tissues, or by replacing non-specific neuromodulatory or neurohumoral systems, their ability to restore function via the reconstitution of specific circuits and the subsequent restoration of information flow and processing may be much more limited. The anatomical and electrophysiological data still suggest that the restoration of specific functional connections may be possible, if sufficient numbers of appropriate connections can be established. Further progress in the transplant-induced functional recovery is anticipated as new and better ways of facilitating the establishment of graft-host interconnections are discovered.

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^☆: This research was conducted under the guidelines of the American Psychological Association's Principles for the Care and Use of Animals adopted by the Association in 1968.

²: Mr. Patrissi is currently a First Lieutenant in the United States Air Force, Biomedical Science Corps at Clark University under sponsorship of the Air Force Institute of Technology, Wright Patterson AFB, Ohio.

¹: The authors thank Dr. Antoinette Gentile, Mr. Arthur Firl, Mr. Alec Pearsall, and Ms. Alfhild Bassett for their assistance, advice and technical aid in various phases of this research.

³: This work was supported in part by NINDS Grant NS-08606, and by a Research Career Development Award, Type II, to the second author. This research served as partial fulfillment for the requirements of the M.A. Degree at Clark University for the first author, and we are particularly grateful to Clark University for its continued support and encouragement of basic research in these difficult times.

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Temporal factors in recovery of function after brain damage☆

Abstract

Brain Res.

Brain Res.

Brain Res.

Behav. Biol.

Brain Res.

Effects of successive and simultaneous lesions of somatosensory cortex on tactile discrimination in the rat

J. Comp. Physiol. Psychol.

Comparative recovery following simultaneous- and successive-stage frontal brain damage in mice

J. Comp. Physiol. Psychol.