Leonard W. Hamilton

Secondary brain changes following lesions: A new paradigm for lesion experimentation

Abstract The surgically-induced lesion has traditionally been used to study the localization of functions in the brain. The basic tenets for its use are that (1) functions are represented in discrete brain structures such as nuclei and fiber tracts and that (2) lesions disrupt function by removal of functional tissue in circumscribed sites in the brain. Contrary to this traditional view, there is growing evidence that the secondary changes in the brain which are induced by a lesion, both directly (necrosis, anterograde and retrograde degeneration) and indirectly (transneuronal degeneration, regeneration and sprouting, denervation supersensitivity, alteration of neurochemical pools, vascular disruption, diaschisis), may comprise the more significant neurological changes which can account for alteration of behavior in a lesion experiment. This evidence is reviewed and a new strategy of research utilizing lesions is proposed, suggesting that greater emphasis be placed on the a posteriori assessment of secondary changes in the brain as they are correlated with changes in behavior. The implications of such considerations for establishing brain-behavior relationships are discussed.

Behavioral effects of unilateral and bilateral septal lesions in rats

Abstract Unilateral and bilateral septal lesions produced: (a) impaired reversal of a T-maze position habit; (b) changes in water consummatory behavior following deprivation; and (c) enhanced shuttle-box avoidance responding. The rats with unilateral lesions were superior to those with bilateral lesions in acquiring the avoidance response, but were intermediate to control rats and rats with bilateral lesions on the reversal task. Some brain mechanisms which could account for these data are discussed.

Increased conditioned gustatory aversion following VMH lesions in rats

Abstract Rats with ventromedial hypothalamic (VMH) lesions and sham operated animals were allowed 20 min of access to a solution of sweetened condensed milk. After drinking the substance, the animals received intraperitoneal injections of either saline or methylatropine (1.0 mg/kg). The rats injected with methylatropine demonstrated reduced intake of the test solution when it was next presented. This conditioned gustatory aversion was more pronounced and more resistant to extinction in the rats with VMH lesions. The results support the hypothesis that VMH lesions increase responsivity to interoceptive cues associated with illness as well as to exteroceptive cues associated with consummatory responding.

Septal lesion, sex, and incentive shift effects on open field behavior of rats.

Abstract Rats with lesions of the septum and control rats were placed in an open field for 5 min per day under three conditions: Habituation (3 days); Preshift (10 days), in which half of the animals were given access to 32% sucrose and half to 4% sucrose; and Postshift (4 days), in which all rats received 4% sucrose. Lesioned animals tended to spend less time in motion and engage in less rearing behavior than controls; showed a negative contrast in lick rate equivalent to the controls subsequent to the shift; showed an exaggerated increase in ambulatory behavior subsequent to the shift; and were more ‘conservative’ than controls in sampling from novel sources of sucrose present during the postshift period. Female rats engaged in more activity than males; were less affected by sucrose concentration differences during preshift; showed negative contrast effects equivalent to the males; but female rats with septal lesions showed the slowest rate of recovery from contrast and spent the most time in motion during postshift.

Effect of septal lesions on retention of negative contrast

Abstract In three experiments rats were trained to lick either 32% or 4% sucrose solutions for five min per day. Following acquisition training, the 32% rats were shifted to 4%. A negative contrast effect was found in control rats with retention intervals of 1, 4, or 5-days inserted between shift phases, but not with a 17-day retention interval. The effect of septal lesions was to accelerate the forgetting so that contrast effects were found with a 1-day, but not with 4-, or 5-day retention intervals.

Faster acquisition of an olfactory discrimination following septal lesions in male albino rats

Normal rats and rats with septal lesions were maintained on a 23.5-hr water deprivation schedule and trained to bar press for water reinforcement, which was available during the presentation of one odor (SD) but not another (Sdelta). Vanilla and vinegar were the olfactants. Both groups showed evidence of discrimination within the first 2-hr of training and reached asymptotic discrimination ratios greater than 90 percent, but the rats with septal lesions reached successively higher levels of discrimination faster than the controls. The results suggest a septal inhibitory influence on the olfactory bulbs.

Responsivity to decreasing sucrose concentrations following septal lesions in the rat

Abstract The effect of septal lesions on consummatory responding for sucrose was examined in two experiments. In both experiments it was found that the lesion did not prevent the occurrence of an abrupt decrement in consummatory responding subsequent to a decrease in sucrose concentration. The results also indicated that the opportunity for comparison among different concentrations may be an important factor in determining whether a septal rat licks more or less than a control for a given concentration of sucrose. A third aspect of the results indicated that septal rats are less sensitive than controls to the post-ingestive consequences of sucrose intake. The data are discussed in terms of an incentive model of septal effects.

Partitioning of behavioral arousal

Abstract Rats given continuous access to running wheels exhibited depressed stabilimeter and rearing activity in novel environments. Whereas starvation increased running wheel activity, it depressed stabilimeter activity markedly and increased rearing slightly, but not significantly. Relative to animals fed ad lib, starved rats exhibited an absence of intersession habituation of stabilimeter responses and diminished intrasession habituation of rearing responses. Whereas running wheel behavior was correlated with percent body weight loss, stabilimeter and rearing responses were not. These data accentuate the heterogeneity of so-called behavioral arousal.

Effects of interruption of limbic system pathways on different measures of activity

Abstract Activity levels were measured following selective knife-cuts of the fornix, medial forebrain bundle or diagonal band. Each of these manipulations increased running-wheel activity, but only fornix transection increased activity in the stabilimeter. The stabilimeter activity declined following diagonal band cuts, and did not change following medial forebrain bundle cuts. None of these manipulations changed open field or rearing activity. The different patterns of effects suggest different anatomical systems that control activity, and emphasize the heterogeneity of activity indices.

The effect of minor tranquilizers on psychomotor performance

The effect of a standard daily regimen of chlordiazepoxide, prazepam (a new benzodiazepine tranquilizer), and placebo were examined in a three way double-blind comparison for a sample of normal volunteers. The criteria include a limited spectrum of psychomotor functions.A learning effect was conspicuous for all drugs on all criteria during the day-long sequence of ten trials. For the most part the differences between the drug groups were insignificant, but there were distinctive modifications in the performance of the chlordiazepoxide group.The clearest effect of the tranquilizer medications was found in the time estimation tests. Paradoxically, the drugs correct a naturally occurring perceptual error.