LH Lesions Research Articles

Spatial attention in children with perinatal stroke

Spatial neglect is a common feature of right hemisphere damage in adults, but less is known about spatial inattention following early brain damage. We used a Posner-based cueing task to examine hemispatial neglect and aspects of attention in children with perinatal stroke in either left (LH) or right hemisphere (RH) and controls. A visual perception task assessed the speed of visual perception. A spatial attention cueing task (the E-task) measured the ability to discriminate the direction of a target stimulus (“E”), when presented on the left or right side of the screen. This task provided indices of performance for attention orienting, disengagement and reorienting. Children with LH lesions had slowed visual perception compared to controls. Children with RH lesions did not demonstrate similar deficits. On the E-task, groups with both LH and RH lesions demonstrated lower accuracy on both left and right sides compared to controls. Children with LH lesions also showed impaired attention orienting and disengagement on left and right sides compared to controls, while children with RH lesions were most impaired in orienting and disengagement on their contralesional side. Children with LH lesions demonstrated more extensive attentional deficits than children with RH lesions. These results suggest that development of spatial attention may require different neural networks than maintenance of attention.

Role of the lateral hypothalamus in submandibular salivary secretion during feeding in rats

To evaluate the role of the lateral hypothalamic area (LH) in the masticatory-salivary reflex, we investigated submandibular salivary secretion and the electromyographic (EMG) activity of the jaw-closer masseter muscle in sham-operated rats and rats with unilateral LH lesions. One week prior to surgery and recording, the rats were given daily experience of eating pellets; powder; or hard, medium or soft mash, all of which were composed of laboratory chow. Salivary secretion was induced during eating and grooming behavior. During eating, the powdered food induced the highest salivary flow rate, and the soft (wet) mash induced the lowest salivary flow rate. Conversely, the amount of food consumed (dry weight) was greatest when soft mash was provided and lowest when the powder or pellets (a dry diet) were provided. The EMG activity of the masseter muscle during eating was greatest during consumption of the pellets and weakest during consumption of the powder. LH lesions that were ipsilateral to the examined submandibular gland reduced salivary secretion to about 20–30% of the control value, whereas contralateral LH lesions reduced it to about 40–50% of the control value. Neither masseter muscle EMG activity nor food consumption was markedly affected by the presence of an LH lesion. These results suggest that the texture of food, especially its water content, affects the flow rate of saliva and that the LH is heavily involved in the masticatory-salivary reflex.

Differential impact of posterior lesions in the left and right hemisphere on visual category learning and generalization to contrast reversal

Hemispheric differences in the learning and generalization of pattern categories were explored in two experiments involving sixteen patients with unilateral posterior, cerebral lesions in the left (LH) or right (RH) hemisphere. In each experiment participants were first trained to criterion in a supervised learning paradigm to categorize a set of patterns that either consisted of simple geometric forms (Experiment 1) or unfamiliar grey-level images (Experiment 2). They were then tested for their ability to generalize acquired categorical knowledge to contrast-reversed versions of the learning patterns. The results showed that RH lesions impeded category learning of unfamiliar grey-level images more severely than LH lesions, whereas this relationship appeared reversed for categories defined by simple geometric forms. With regard to generalization to contrast reversal, categorization performance of LH and RH patients was unaffected in the case of simple geometric forms. However, generalization to contrast-reversed grey-level images distinctly deteriorated for patients with LH lesions relative to those with RH lesions, with the latter (but not the former) being consistently unable to identify the pattern manipulation. These findings suggest a differential use of contrast information in the representation of pattern categories in the two hemispheres. Such specialization appears in line with previous distinctions between a predominantly lefthemispheric, abstract-analytical and a righthemispheric, specific-holistic representation of object categories, and their prediction of a mandatory representation of contrast polarity in the RH. Some implications for the well-established dissociation of visual disorders for the recognition of faces and letters are discussed.

Sex-dependent body weight changes after iontophoretic application of kainic acid into the LH or VMH

Body weight changes and food and water intakes were studied in CFY male and female rats after kainic acid (KA)-induced destruction of the lateral hypothalamic area (LH) or the ventromedial hypothalamic nucleus (VMH). To minimize the extent of damages, KA was iontophoretically applied by means of glass micropipettes. KA was ejected in 50 or 80 mM concentrations with 5–15 μA current for 5 min. Tip diameter of pipettes varied between 10–20 μ.m. Lesions were restricted to the LH or VMH. Effects were sex-dependent. LH lesions resulted in hypophagia, hypodipsia and body weight loss only in male rats. On the other hand, only female animals exhibited hyperphagia and weight increase when the VMH was destroyed. The role of sex-dependence in hypothalamic body weight regulation is discussed.

Lateral and medial hypothalamic lesions do not acutely affect brown adipose tissue thermogenesis

The acute effect of lateral (LH) and medial (MH) hypothalamic lesions on mitochondrial GDP binding in brown adipose tissue (BAT) (an index of thermogenic state) was studied one and two days postlesion. Groups of rats were lesioned, sham-lesioned, or unoperated and were all fasting. An additional group of unoperated rats had access to food throughout the study. The objective was to determine whether the hypermetabolic state and rapid weight loss known to be induced by LH lesions were attributable to the activation of BAT thermogenesis, and, if so, whether these effects were specific for LH lesions. No effect of either lesion on BAT thermogenic state could be detected at either time studied. Despite that fact, LH-lesioned rats, but not MH-lesioned rats, were hyperthermic at both times. We conclude that the prolonged hyperthermia which occurs shortly after LH lesions is not due to an activation of BAT thermogenesis. Instead, it can be likened to the febrile state in which an initial and brief activation of both nonshivering thermogenesis in BAT and shivering thermogenesis in muscles occurs only during the rising phase of the fever and is suppressed as soon as a stable hyperthermic state is reached. It thus appears unlikely that substantial and prolonged activation of BAT thermogenesis is a major mechanism that promotes exaggerated short-term weight loss in the LH-lesioned rat.

Lateral hypothalamic feeding mechanisms: Iontophoretic effects of kainic acid, ibotenic acid and 6-hydroxydopamine

In order to study hunger motivated behavior kainic acid (KA), ibotenic acid (IB) and 6-hydroxydopamine (6-OHDA) were iontophoretically applied to the lateral hypothalamus of rats. Neurotoxins at concentrations between 20–120 mMol were applied with 5–20 μA current for 5–10 min. Tip diameter of glass micropipettes varied between 10–50 μ. Application of KA, IB and 6-OHDA caused temporary body weight loss, hypophagia and hypodipsia. Effects were dose dependent: correlation was found between current strength, tip diameter of pipettes, concentrations of neurotoxins and the extent of cellular damage. Aphagic and adipsic symptoms and the death of animals were only observed after extensive LH lesions. There was no significant difference in food consumption after 24 hr deprivation among groups. Water deprivation and extracellular or intracellular dehydration resulted in a considerable increase in water intake in all animals, however, consumption in lesioned rats was lower than that of controls. These water regulatory disturbances in 6-OHDA treated animals were somewhat less severe. Results show that the bilateral cellular microlesions of the LH and damage of dopaminergic (DA) elements with 6-OHDA both cause disturbances of feeding behavior. Although the severity of symptoms in some respects depends upon the nature of neurotoxic treatment, the basic consequences are essentially similar. It is suggested that the LH “feeding center” and the ascending DA pathways represent a single system involved in the organization of hunger motivated behavior.

Lateral hypothalamic lesions and activity of the sympathetic nervous system

The firing rate of efferent sympathetic nerves to brown adipose tissue was measured on 18 h and 18 d following lateral hypothalamic lesions (LH). Eighteen hours following acute lateral hypothalamic lesions, sympathetic firing rate was significantly increased. Following chronic LH lesions there was a decrease in food intake and a fall in body weight which had stabilized by four days. Eleven days after surgery a group of control animals were food restricted and subsequently pair fed twice daily to maintain a body weight comparable to that of the LH lesioned animals. Food intake was lower in the pair-gained animals on all but one day of the experiment. When studied 18 days following LH lesions, sympathetic firing rates were significantly higher than in either the ad lib or pair-fed controls. Sympathetic firing rate in pair fed rats, on the other hand, was significantly lower than in the sham lesioned rats. These data are consistent with the hypothesis that the LH lesion removes an inhibitory control over sympathetic firing rate both acutely and in chronically lesioned animals and that this increased sympathetic firing rate may play an important role in the maintenance of a lower body weight.

Preoperative experience with insulin enhances glucoprivic feeding in rats with lateral hypothalamic lesions

Adult male Sprague-Dawley rats received either one injection per week of regular insulin (IP, 5 Units) or saline for 4 weeks prior to destruction of the LH or sham-operations. During this preoperative period, animals given insulin consumed significantly more food in a 6-hr test period than animals given saline. Following surgery, animals were given 3 weeks to recover from the acute effects of LH lesions and then tested for responsiveness to glucoprivic challenges. Sham-operated animals from both pre-operative injection groups consumed significantly more food during a 6-hour period when injected with either insulin (5 and 7.5 Units) or 2-DG (400 mg/kg) than when given saline injections. Similarly, LH-lesioned rats with preoperative experience with insulin significantly increased food intake when given insulin or 2-DG. In contrast, LH-lesioned rats without preoperative experience with insulin failed to increase feeding in response to the administration of either insulin or 2-DG. Differnnces in feeding responses following glucoprivation between LH-lesioned rats with and without preoperative exposure to insulin were not a function of differences in the extent of central nervous system damage. The present data indicate that experimental conditions play an important role in determining the presence or absence of regulatory deficits following brain damage.

Development of acute feeding disorders, hyperactivity, and stomach pathology after medial and lateral hypothalamic lesions in rats

The acute effects of medial (VMH) and lateral (LH) hypothalamic lesions on stomach morphology, motor activity, and feeding behavior were compared in two experiments. Rats received VMH or LH lesions and were sacrificed 4, 8, or 24 h later. Both lesions produced high activity counts at 4 h and a comparable number of ulcers, starting at the earliest interval tested. Neither VMH nor LH lesions produced acute changes in other organs, such as the adrenals, thymus, or spleen. In a second experiment, quantitative measures of stomach pathology did not indicate significant differences between ulceration produced by VMH and LH lesions in 24 h. A separate group receiving VMH lesions showed pronounced hyperphagia and hyperdipsia immediately after the lesion, while LH rats were aphagic and adipsic. Motor activity levels after the lesions correlated positively with ulcer incidence and severity. Possible relations between these acute behavioral and visceral effects of hypothalamic lesions are discussed.

Transection of fibers crossing the lateral border of the lateral hypothalamus: Fragmented spontaneous ingestive patterns and reanalysis of “regulatory deficits” in rats with sagittal knife cuts

Rats bearing sagittal knife cuts lateral to the LH showed fragmented meal patterns. Both drinking and locomotor activity occurred during the interruptions in dry chow meals. This fragmented pattern resembles that found in rats with LH lesions, yet it is anatomically unlikely these knife cut animals sustain damage to any known salivary pathway. The cut animals were also found to show delayed drinking responses after intracellular or extracellular dehydration, yet they increased their water intake normally when offered a salty chow. They showed impaired glucoprivic feeding. The similarities of these findings to those in LH and other preparations are discussed.

Saliva hypersecretion during aphagia following lateral hypothalamic lesions

Using a new and simple technique, saliva output was measured in rats with lesions in the lateral hypothalamic area (LH). While aphagic and adipsic during the first several days after surgery, the LH rats showed a dramatic hypersecretion of saliva relative to control rats subjected to sham operations and food and water deprivation. In contrast, rats recovered from aphagia for several months showed a hyposecretion of seliva, both in room temperature and in a hot environment. The results are discussed as they relate to the emphasis on autonomic consequences of LH lesions.

Impairment in a T-maze task following unilateral lateral hypothalamic lesions

Rats with unilateral LH lesions showed great difficulty performing a contraversive turn to escape shock in a T-maze. Rats that were required to turn to the side ipsilateral to the side of their lesion did not show this performance deficit. The impairment in contraversive responding was shown to dissipate over time. It is proposed that animals with LH lesions do not suffer learning disabilities in escape-avoidance tasks, but can not activate motor behavior directed toward the side contralateral to their lesion.

Post-prandial EEG synchronization in normal and hypothalamically lesioned rats

Electrical activity of the anterior cortex of rats was recorded following injection of nutritive or non-nutritive material directly into the stomach. In normal animals, significantly more EEG synchronization was observed following injections of nutritive eggnog, than following an equal volume of isotonic saline. This nutrient-specific EEG synchronization response was studied in subsequent experiments to evaluate the motivational state of rats with ventromedial and lateral hypothalamic lesions. Rats with VMH lesions continued to show nutrient-specific EEG synchronization which was not significantly different from that seen in normal rats. Rats with LH lesions failed to show nutrient-specific EEG synchronization. It was proposed that LH contains structures which are critical to the rats' ability to show nutrient-specific EEG synchronization, whereas VMH does not. Further, it was noted that nutrient-specific EEG synchronization did not reappear with the recovery of voluntary feeding. It was hypothesized that destruction of a receptor, or related mechanism, resulted from LH lesions.