Old age and cognition: enhancement of recent memory in aged rats by the calcium channel blocker nimodipine.

Aged hooded rats were given extensive training on an 8-arm radial arm maze task. The testing procedure was so designed as to maximally challenge each animal's trial specific memory capacities. After performance had stabilized, the animals were administered different dosages of the dihydropyridine calcium channel blocker nimodipine. In all animals, the drug improved performance in the 8-arm maze but, more importantly, it did so in a dose-related manner. These results, along with other findings, support the notion that calcium homeostasis may be an important factor determining the behavioral consequences of aging and particularly memory dysfunctions.

Aging and cognition: facilitation of recent memory in aged nonhuman primates by nimodipine.

Impairments of recent memory are a common complaint associated with aging and especially with respect to certain neural pathological conditions that may accompany aging. While this is well recognized, there is little clear evidence for a viable therapeutic treatment. Recently, however, certain investigations have suggested that blocking neuronal calcium channels may be an effective treatment for the memory impairments that are associated with brain injury as well as the memory failures that may occur during aging. The present research supports this suggestion by demonstrating that the dihydropyridine calcium channel blocker, nimodipine, will significantly improve the stabilized performance of 28-29-year-old rhesus monkeys when they are tested on a delayed-response task which depends upon trial-specific, or recent, memory.

Recovery of function after brain damage: the chronic consequence of large neocortical injuries.

In the present experiment we addressed the common clinical finding that subsequent to recovery of function, there is often a lingering chronic dysfunction associated with extensive neocortical injury. We have confirmed this observation in the laboratory setting, and the data is compatible with the theoretical position that brain injury induces a shift in dominance of functional neural systems that normally control behavior. Although the present data do not suggest how this shift in dominance may be reversed, it does, nonetheless, demonstrate that the persistent chronic dysfunctions associated with neocortical injury may be effectively moderated within certain environmental situations.

Recovery of function after brain damage: facilitation by the calcium entry blocker nimodipine.

Large neocortical injuries can interfere with the initial performance of many previously learned behaviors. This dysfunction, however, may not be attributable to the loss of the memories of learned behaviors but to a failure to access memories that are spared. The results of this experiment support this hypothesis by demonstrating that the calcium entry blocker nimodipine, which prevents trauma-induced retrograde amnesia in a 1-trial passive learning situation, will also facilitate the recovery of pre-operatively learned brightness discrimination in rats with visual neocortical injuries.

Frontal decortication in rhesus monkeys: a test of the interference hypothesis.

Four monkeys with dorsolateral frontal ablations and 3 unoperated controls were run on discrimination problems which sequentially presented both relevant and irrelevant visual stimuli prior to the opportunity for a choice response. As previously reported, monkeys with undamaged brains performed significantly better on those problems presenting relevant information first, being unaffected by later occurring irrelevant stimuli. Contrary to the behavior of the normal monkeys, monkeys with lesions of the dorsolateral frontal cortex were severely impaired when irrelevant stimuli were presented after the relevant stimuli had been processed, but before the opportunity to respond had occurred. In other words, the frontal monkeys performed just the opposite of the normals in these procedures, even though the relevant and irrelevant stimuli were manipulated within the usual temporal definitions of the two-choice discrimination trial. These data demonstrate that the presentation of irrelevant stimuli before the choice response can significantly impair frontally decorticated monkeys and that this impairment does not require the use of a long temporal delay preceding the opportunity to respond. For this reason the data were interpreted as rather direct support of the interference hypothesis of frontal dysfunction. On the basis of these and other data discussed, it was concluded that one function of the dorsolated frontal cortex involves the suppression of interfering stimulus events interposed between the information necessary to guide behavior and the behavior itself.

Recovery of function after brain damage: the extrinsic stimulus specificity of spared neural traces.

Previous research has demonstrated that while primary visual cortex lesions in rats will disrupt performance of a learned brightness discrimination, the neural traces associated with this discrimination are spared. Moreover, the spared neural traces may, in certain instances, influence the postoperative reinstatement of a brightness discrimination. The present research was designed to determine the generality of this postoperative influence. The results indicate that while the normal rat and the visual decorticate rat may readily transfer learning between discriminations involving different discriminative cues, a visual lesion between two discriminations prevents this transfer. These data are interpreted as indicating that the postoperative influence of a spared neural trace is dependent upon the reoccurrence of specific extrinsic stimulus cues.

Recovery of function after brain damage: differential effects of blocking calcium uptake during the recovery of a learned behavior and the performance of the recovered behavior following neocortical brain injury.

The recovery of a learned behavior following brain damage is typically considered to have occurred when the brain-injured individual reattains the performance criterion that defined original preoperative learning. While this is obviously correct from an operational point of view, it does not necessarily mean that the consequences of the brain injury have been reversed, particularly with regard to the sustained performance of the supposedly recovered behavior. The present research attempted a more comprehensive evaluation of the behavioral effects of localized neocortical injury by investigating how a calcium channel blocker would effect (a) the original preoperative acquisition, (b) the initial postoperative recovery, and (c) the subsequent long-term performance of a brightness discrimination learned by rats subjected to injuries of their visual neocortex. The results demonstrated that notwithstanding the brain-injured rat's ability to reattain the performance criterion used to define preoperative learning, its long-term performance of this recovered behavior was significantly inferior to that of a normal rat. More importantly, the present data suggest that there are important differences between the initial postoperative recovery of a behavior and its long-term performance since the same drug that will facilitate initial recovery has just the opposite effect with respect to the animals long-term postoperative performance of the behavior.

Arousal from sleep: the physiological and subjective effects of a 15 dB(A) reduction in aircraft flyover noise.

The present research was concerned with whether or not a 15 dB(A) reduction in overall noise level would lessen the sleep disturbing properties of jet aircraft flyover noise and, if less disturbing, whether this would be subjectively appreciated by the sleeping individual. The results indicate that a reduction of 15 dB(A) does result in less sleep disruption but only during sleep characterized by fast-wave electroencephalographic activity. During sleep characterized by slow-wave electroencephalographic activity, such a reduction in the sleep-disturbing properties of jet aircraft noise has little effect. Moreover, even when effective during fast-wave sleep, the decreased arousal produced by the lower noise levels is not subjectively appreciated by the individual in terms of his estimate of the quality of his night's sleep. Thus, reducing the overall noise level of jet aircraft flyovers by some 15 dB(A), is, at best, minimally beneficial to sleep.