"Recovery of sensorimotor function after frontal cortex damage in rats: Evidence that the serial lesion effect is due to serial recovery": Correction.

Reports an error in "Recovery of sensorimotor function after frontal cortex damage in rats: Evidence that the serial lesion effect is due to serial recovery" by John M. de Castro and Mark C. Zrull (Behavioral Neuroscience, 1988[Dec], Vol 102[6], 843-851). The plate for this article appears on page 996. The information should read, "Plate B. Photographs of the dorsal side of the brains showing the minimum (top) and maximum (bottom) extent of the lesion produced unilaterally in the sham group (left) and bilaterally in the single- and two-stage groups (right)." (The following abstract of the original article appeared in record 1989-28759-001.) Multiple-staged brain lesions produce fewer and smaller behavioral effects than single surgery (the serial lesion effect, SLE). Two hypotheses were tested: the reduced deficit hypothesis and the serial recovery hypothesis. Effects of lesions of the medial frontal cortex on sensorimotor behavior were investigated in 7 rats that received bilateral damage in single surgery, 16 in 2 unilateral stages separated by 3 wks, or 5 with unilateral damage followed 3 wks later by sham surgery. Unilateral damage produced deficits on the contralateral side in response to visual, tactile, and olfactory stimuli and impairments in roll-over and paw withdrawal responses. All impairments except visual placement recovered over the next 3 wks. A 2nd unilateral lesion on the contralateral side produced the same symptoms on the opposite side. Bilateral damage incurred in a single stage produced the same deficits on both sides. Because the effects of the 2nd unilateral lesion in the 2-stage group produced comparable contralateral effects to those produced in the single-stage group, but no reinstatement of ipsilateral deficits, the reduced deficit hypothesis was rejected. It was concluded that SLE occurred as a result of serial recovery of the deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Quantitative behavioral study of the acute and long-term effects of two-stage bilateral 6-OHDA-induced lesions of the nigrostriatal dopaminergic system in monkeys.

Bilateral lesions of the nigrostriatal dopaminergic system (2-stage lesions separated by 5–6 months) were induced in 3 monkeys trained to initiate forelimb-reaching movements toward a visual target. After each lesion, analysis of the task performance over several months of regular testing showed that the latency to initiate the movement was permanently prolonged in monkeys showing 90% or more striatal dopamine depletion, whereas animals with less severe depletion completely recovered the task performance. Several months after a unilateral nigrostriatal damage, a lesion on the other side produced impairments only on the side of the body contralateral to that second lesion and did not reinstate the deficits on the side previously affected by the first lesion. This suggests that the remaining intact nigrostriatal dopaminergic system may not be involved in the long-term behavioral recovery observed in monkeys with a unilateral lesion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Food wrenching and dodging: A neuroethological test of cortical and dopaminergic contributions to sensorimotor behavior in the rat.

Sensorimotor behavior in unilateral decorticate and unilateral dopamine-depleted rats was studied in a naturally occurring social interaction in which rats compete for food with relatively stereotyped species-typical responses. In the interaction a "robber" attempts to wrest food from a feeding "victim," which in turn protects the food by making rapid contralateral dodges. Hemidecortication abolished dodging to food wrenching attempts made by a rat approaching contralaterally to the lesion, so that the food was stolen, but recovery occurred between 15 and 60 days after surgery. Use of the side contralateral to the lesion to wrest food was moderately impaired, and recovery of food wresting was more rapid than recovery of dodging. Unilateral dopamine depletion produced dodging impairments to food-wresting attempts that were made both ipsilateral and contralateral to the side of the lesion, and the deficits endured over 60 test days. The food was frequently lost to food-wrenching attempts made contralateral to the lesion, whereas the direction of dodges to approaches ipsilateral to the lesion was reversed. Food wresting was also bilaterally impaired. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Further analysis of sensory inattention following lateral hypothalamic damage in rats.

Reports results of 2 experiments with a total of 14 Sprague-Dawley albino, 17 Charles-River albino, and 8 Long-Evans hooded rats. Ss with lateral hypothalamic damage had severe impairments in orienting to sensory stimuli and in using their limbs. When damage was unilateral, these deficits occurred only on the side contralateral to the lesion. Bilateral damage caused bilateral sensorimotor impairments which were involved in the early postoperative deficits in feeding and killing. Sensorimotor capacities recovered gradually and in a predictable fashion. Several aspects of the sequence of recovery were parallel to the ontogeny of sensorimotor capacities. Finally, these impairments seemed to be associated with damage to an area in the ventrolateral hypothalamus-subcapsular area, where pallidohypothalamic and amygdalohypothalamic fibers reportedly pass. (61 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioural effects of subthalamic nucleus lesions in the hemiparkinsonian marmoset (Callithrix jacchus)

Recent studies in non-human primates support a role for the subthalamic nucleus in the expression of parkinsonian symptomatology, and it has been proposed that subthalamic lesions may provide a surgical treatment for the symptoms of Parkinson's disease in humans. We have applied a broad range of behavioural tests to characterize the effects of lesions of the subthalamic nucleus on parkinsonian symptoms in the unilateral 6-hydroxydopamine (6-OHDA) lesioned marmoset (Callithrix jacchus). Thirteen marmosets were trained on a battery of behavioural tasks that were conducted at regular intervals before and after surgery. All received unilateral 6-OHDA lesions to the medial forebrain bundle. Seven animals were then given an additional N-methyl-D-aspartate lesion of the ipsilateral subthalamic nucleus, whereas the remaining six animals received a variety of control or sham lesions to the nucleus. The 6-OHDA lesions induced a strong ipsilateral bias in head position; mild-moderate ipsilateral rotation spontaneously and after injection of saline or amphetamine; and contralateral rotation after injection of apomorphine. Hemineglect was evident as delayed initiation of reaches on the contralateral side on the staircase reaching task. Additional subthalamic lesions significantly reversed the bias in head position from ipsilateral to contralateral and decreased neglect as evidenced by improved latencies to initiate reaching on the contralateral side at the staircase. However, deficits in skilled movements persisted in the subthalamic nucleus lesion group in that they did not complete the staircase task any faster than the control group and remained impaired on another task which required reaching into tubes. These behavioural effects demonstrate that excitotoxic lesioning of the subthalamic nucleus can ameliorate some, but not all, parkinsonian-like deficits in the unilateral 6-OHDA lesioned marmoset.     

Effects of dorsal noradrenergic bundle lesions on recovery after sensorimotor cortex injury

Several lines of evidence suggest that the recovery of the ability of rats to traverse a narrow beam after unilateral injury to the sensorimotor cortex is noradrenergically mediated. We tested the hypotheses that the influence of norepinephrine on beam-walking recovery occurs, at least partially, through effects in the contralateral and/or ipsilateral cerebral cortex. Rats had either a selective left or right 6-hydroxydopamine lesion or sham lesion of the dorsal noradrenergic bundle (DNB) 2 weeks before suction-ablation or sham injury of the right sensorimotor cortex. The rats' abilities to perform the beam-walking task were measured over the 10 days following cortex surgery. DNB lesions did not affect the initial severity of the beam-walking deficit and had no effect on the performance of the task in rats with sham cortex injuries. Lesions of the contralateral but not ipsilateral DNB significantly impaired recovery. Further, in cortically lesioned rats with contralateral DNB lesions, norepinephrine content in the cerebral cortex opposite to the sensorimotor cortex lesion was significantly correlated with recovery. These data suggest that the effect of norepinephrine on recovery of beam-walking ability may be partially exerted in the cerebral cortex contralateral to the injury.     

Unilateral labyrinthectomy downregulates glutamate receptor delta-2 expression in the rat vestibulocerebellum

Subcortical damage in neonates often has more severe consequences than in adults. Unilateral electrolytic hippocampal lesions in adult rats typically result in transient memory deficits, whereas neonatal lesions cause lasting memory impairments. We hypothesized that unilateral lesions made at birth may affect synaptic physiology in the contralateral hippocampus. Consequently, the ability to sustain long-term potentiation (LTP), a form of synaptic plasticity believed to underlie certain forms of memory, was compared between slices from the remaining hippocampus of rats lesioned as newborns and as adults. Initial studies showed that a train of 10 stimulation bursts patterned after the hippocampal theta rhythm produced robust and stable LTP both in slices from controls and rats lesioned at birth. However, a theta burst pattern of stimulation closer to intrinsic physiology (five burst pairs separated by 30 s each), induced significantly less LTP in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults. To investigate possible mechanisms underlying the deficit, the degree of paired-pulse facilitation (PPF) as well as the amount of depolarization occurring between two successive theta bursts were analyzed. The lesion did not detectably change PPF characteristics, suggesting that presynaptic mechanisms are normal. However, the extent to which a burst response was increased by a prior burst was significantly diminished in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults, indicating that postsynaptic factors involved in the initial triggering events of LTP are affected by the lesion. Reduced ability to sustain LTP in the remaining hippocampus may contribute to impaired memory function after unilateral neonatal hippocampal lesion.     

Attributions (beliefs) and job satisfaction associated with back pain in an industrial setting

Transient cerebral ischemia can produce irreversible neuronal damage and permanent learning and memory impairments in humans. This study examined whether ischemia-induced brain damage in rats results in impairments on the delayed nonmatching-to-sample (DNMS) task, a nonspatial recognition task analogous to tests on which amnesic patients display impairments. Male Wistar rats received either sham surgery or 20-min forebrain ischemia induced by bilateral carotid occlusion and hypotension. Four weeks after surgery, ischemic rats were significantly impaired in both learning and performing the DNMS task at retention intervals up to 5 min. Extensive presurgical training did not reduce this impairment. Observable cell loss in ischemic rats was limited to CA1 pyramidal neurons and a subset of cells in the dentate gyrus. The results indicate that ischemic damage to the hippocampus in rats results in recognition memory deficits similar to those produced by ischemic damage in humans.     

Impaired object recognition memory in rats following ischemia-induced damage to the hippocampus.

Transient cerebral ischemia can produce irreversible neuronal damage and permanent learning and memory impairments in humans. This study examined whether ischemia-induced brain damage in rats results in impairments on the delayed nonmatching-to-sample (DNMS) task, a nonspatial recognition task analogous to tests on which amnesic patients display impairments. Male Wistar rats received either sham surgery or 20-min forebrain ischemia induced by bilateral carotid occlusion and hypotension. Four weeks after surgery, ischemic rats were significantly impaired in both learning and performing the DNMS task at retention intervals up to 5 min. Extensive presurgical training did not reduce this impairment. Observable cell loss in ischemic rats was limited to CA1 pyramidal neurons and a subset of cells in the dentate gyrus. Results indicate that ischemic damage to the hippocampus in rats results in recognition memory deficits similar to those produced by ischemic damage in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preoptic area and substantia nigra interact in the control of maternal behavior in the rat.

Investigated the influence of the lateral connections of the medial preoptic area (MPOA) on maternal behavior via the substantia nigra (SN). In Exp I, conducted with 45 postpartum lactating Charles River CD rats, the effects of large and small bilateral electrolytic lesions of SN were investigated. Large lesions severely disrupted maternal behavior and caused stereotyped activity in Ss. A 2nd experiment employed an asymmetrical lesion design and 37 Ss. Ss that received a unilateral knife cut severing the lateral connections of the MPOA and a contralateral lesion of the SN showed larger deficits in maternal behavior than either sham Ss or Ss that received a unilateral preoptic cut paired with an ipsilateral SN lesion. Measurements of body weights, body temperatures, and stereotyped behavior indicated that the differences in maternal behavior between the ipsilateral and contralateral groups could not be explained on the basis of nonspecific effects. (57 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chemical senses involved in garter snake prey training.

Trained 8 garter snakes to follow earthworm-extract trails in a multiple-choice maze and then subjected them to either sham surgery or complete bilateral vomeronasal nerve transection. Ss with sham surgery trailed and ate at preoperative levels; Ss lacking a functional vomeronasal system developed a feeding deficit and trailed at chance levels. In Exp II 16 Ss were preoperatively tested for ability to follow a battery of trails including a range of trail concentrations and 2 trail manipulations. After baseline testing, 2 Ss were subjected to sham surgery, 7 to olfactory nerve transection, and 7 to vomeronasal nerve transection. Ss with vomeronasal nerve lesions demonstrated trailing and feeding deficits commensurate with the extent of nerve damage. Ss with olfactory nerve cut and sham surgery followed all trails at preoperative levels and maintained high tongue-flick rates when following stronger extract trails. Four Ss (2 with sham lesions, 1 with olfactory nerve lesion, and 1 with a partial vomeronasal nerve lesion) were tested with the vomeronasal ducts sutured closed. These Ss were unable to follow any trails at better than chance levels, but most continued to attack and ingest earthworm bits. Results suggest that garter snakes are heavily dependent on the vomeronasal system for following chemical prey trails. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Taste perception in patients with insular cortex lesions.

Research on nonhuman primates suggests that the primary taste cortex in humans is located in the rostrodorsal insula. Qualitative and quantitative assessment of taste perception was performed on 6 patients with unilateral damage to the insula, 3 patients with brain damage outside the insula, and 11 age-matched, normal subjects. Each subject identified the quality and intensity of the gustatory stimuli applied separately to the left and right sides of the anterior tongue. Damage to the right insula produced ipsilateral taste recognition and intensity deficits. Damage to the left insula caused an ipsilateral deficit in taste intensity but a bilateral deficit in taste recognition. The unexpected deficit in the left-hemispheric stroke patients for taste recognition on the right side of the tongue suggests that taste information from both sides of the tongue passes through the left insula. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unilateral internal carotid arterial occlusion: special considerations

Cases of patients with unilateral internal carotid arterial occlusion and contralateral internal carotid arterial stenosis are reviewed. Forty-two percent presented with a fixed neurological deficit. The deficit was referable to the side of occlusion in 92% and to the side of stenosis in 8%. Eleven percent had a neurological complication following carotid endarterectomy on the side of the stenotic lesion. The neurological complication was referable to the side of stenosis in 67% and to the side of occlusion in 33%. Patients have been followed for an average of 19 months and have not developed any additional TIA's or strokes in the followup period. There may be a role for an extracranial-intracranial bypass (ECIC) on the occluded side prior to an endarterectomy on the stenotic side if a poor collateral situation exists. An ECIC should be done in patients who remain symptomatic following carotid endarterectomy on the stenotic side. These data do not support doing ECIC in asymptomatic patients with unilateral carotid arterial occlusion.     

A case of unilateral gustatory disturbance produced by the contralateral midbrain lesion

We reported a case of unilateral gustatory disturbance produced by a lesion in the contralateral midbrain. A 37-year-old man first noticed dysesthesia in the left side of his face. Later, the patient developed dysesthesia of the left part of the lip, muscular weakness on the left lower extremity and gustatory disturbance on the left side. MR scan disclosed a lesion in the tegmentum of the right midbrain, which showed low intensity on a T1-weighted image and high intensity on a T2-weighted image. This lesion could be due to multiple sclerosis. This case suggests that the unilateral gustatory information ascends via the contralateral pathway at the midbrain level. It is suggested that the central gustatory pathways above the ipsilateral pontine taste are ascend via the contralateral projections to the thalamic taste area (parvicellular portion of the ventral posteromedial thalamic nucleus, VPMpc).     

Comparison of the effects of frontal cortical and thalamic lesions on measures of olfactory learning and memory in the rat

Rats were trained on an olfactory continuous delayed nonmatching-to-sample (DNMTS) task and then given 1 of 4 treatments: sham surgery or radio-frequency lesion of the lateral internal medullary lamina of the thalamus or of the frontal cortex along the medial wall or dorsal to the rhinal sulcus. Thalamic lesions produced persistent deficits on the continuous DNMTS task, and both the cortical lesions resulted in transient impairments that disappeared with continued training. Manipulations of stimulus set size and the delay between trials affected continuous DNMTS performance but did not exacerbate group differences. All 3 lesion groups performed normally when next trained on a discrimination task with odorants and go-no-go procedures comparable to continuous DNMTS. These results indicate that lesions did not affect ability to perform go-no-go procedures, to discriminate among odorants, or to use reference memory to respond on the basis of a fixed stimulus-response rule.     

Amnesia and neglect: beyond the Delay-Brion system and the Hebb synapse

Hippocampal damage in people causes impairments of episodic memory, but in rats it causes impairments of spatial learning. Experiments in macaque monkeys show that these two kinds of impairment are functionally similar to each other. After any lesion that interrupts the Delay-Brion system (hippocampus, fornix, mamillary bodies and anterior thalamus) monkeys are impaired in scene-specific memory, where an event takes place against a background that is specific to that event. Scene-specific memory in the monkey corresponds to human episodic memory, which is the memory of a unique event set in a particular scene, as opposed to scene-independent human knowledge, which is abstracted from many different scenes. However, interruption of the Delay-Brion system is not sufficient to explain all of the memory impairments that are seen in amnesic patients. To explain amnesia the specialized function of the hippocampus in scene memory needs to be considered alongside the other, qualitatively different functional specializations of other memory systems of the temporal lobe, including the perirhinal cortex and the amygdala. In all these specialized areas, however, including the hippocampus, there is no fundamental distinction between memory systems and perceptual systems. In explaining memory disorders in amnesia it is also important to consider them alongside the memory disorders of neglect patients. Neglect patients fail to represent in memory the side of the world that is contralateral to the current fixation point, in both short- and long-term memory retrieval. Neglect was produced experimentally by unilateral visual disconnection in the monkey, confirming the idea that visual memory retrieval is retinotopically organized; patients with unilateral medial temporal-lobe removals showed lateralized memory impairments for half-scenes in the visual hemifield contralateral to the removal. Thus, in scene-memory retrieval the Delay-Brion system contributes to the retrieval of visual memories into the retinotopically organized visual cortex. This scene memory interpretation of hippocampal function needs to be contrasted with the cognitive-map hypothesis. The cognitive-map model of hippocampal function shares some common assumptions with the Hebb-synapse model of association formation, and the Hebb-synapse model can be rejected on the basis of recent evidence that monkeys can form direct associations in memory between temporally discontiguous events. Our general conclusion is that the primate brain encompasses widespread and powerful memory mechanisms which will continue to be poorly understood if theory and experimentation continue to concentrate too much, as they have in the past, on the hippocampus and the Hebb synapse.     

Medial prefrontal cortex lesions and spatial delayed alternation in the developing rat: Recovery of sparing?

In Exp 1, Long-Evans rat pups received medial prefrontal cortex (PFC) aspirations or sham surgery on Postnatal Day 10 (PND10) and were then trained on PND23 to perform 1 of 2 T-maze tasks: discrete-trials delayed alternation (DA) or simple position discrimination. Early PFC damage produced a selective failure to learn the DA task. In Exp 2, pups given the same lesion or sham surgery were trained on DA on PND19, PND27, or PND33. In relation to sham-operated controls, pups with PFC damage were impaired on PND19, somewhat impaired on PND27, and entirely unimpaired when tested on PND33. In Exp 3, pups given larger lesions of the frontal cortex on PND10 were impaired on DA when tested on PND23 but not when tested on PND33. These findings indicate that early PFC lesions result in a memory deficit around the time of weaning, which then recovers over the next 10–24 days of development. Moreover, the early deficit is selective for a late developing cognitive process (or processes) that is involved in acquisition of DA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lesions in the mesial frontal cortex on bimanual co-ordination in monkeys

The hypothesis was tested that the mesial frontal cortex, including the supplementary motor area, is engaged in bimanual co-ordination. Three monkeys, trained in a well-co-ordinated bimanual pull-and-grasp task, were subjected to unilateral or bilateral lesions of the mesial frontal cortex. With unilateral lesions, the deficit consisted in a delay in movement initiation of the contralateral arm. With a bilateral lesion, the deficit was more pronounced with marked bilateral delays in movement onset and slowing in reaching. However, in the three monkeys bimanual co-ordination at the moment of goal achievement remained intact with an excellent temporal co-variation of the two limbs. In the two unilateral cases, an adaptive strategy developed after a few sessions, either by catching up during reaching with the limb contralateral to the lesion (monkey M1) or by delaying movement initiation of the limb ipsilateral to the lesion (monkey M2). This outcome is discussed in terms of Lashley's principle of motor equivalence, i.e. invariant goal achievement with variable means. Bilateral lesions led to a transient and near-total impairment in movement self-initiation when all external cues were absent. It is concluded that in monkeys the mesial frontal cortex does not play a crucial role in bimanual co-ordination but rather in movement initiation, especially when sensory cues are absent.     

Early cerebellar lesions impair eyeblink conditioning in developing rats: Differential effects of unilateral lesions on Postnatal Day 10 or 20.

Experiment 1 demonstrated that the ipsilateral cerebellar hemisphere is essential for the acquisition of eyeblink conditioning in infant rats and that cerebellar lesions given on Postnatal Day 10 (PND10) produced deficits in eyeblink conditioning when given to either hemisphere. For both hemispheres, lesions that were restricted to the cerebellar cortex produced less severe deficits than lesions that included the deep nuclei. Experiment 2 showed that the age at which the cerebellar lesions occurred determined whether damage to the contralateral cerebellar hemisphere impaired conditioning. Lesions of either the ipsilateral or contralateral hemisphere that included the deep nuclei disrupted eyeblink conditioning when given on PND10. In contrast, when lesions were given on PND20, ipsilateral lesions that included the deep nuclei abolished conditioning, while the same lesion given to the contralateral hemisphere had no effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of serial unilateral and serial bilateral visual cortex lesions on brightness discrimination relearning in rats.

In Exp I, 32 male Long-Evans hooded rats with serial unilateral (SU), serial bilateral (SB), or 1-stage bilateral (B) visual cortex lesions were compared in their retention of a preoperatively learned brightness discrimination. Groups SU and SB showed substantial savings of the brightness discrimination after the completed bilateral visual cortex removals, while Group B showed a complete postoperative loss. In Exp II with 34 rats, the effects of 2 additional types of serial bilateral visual cortex lesions were investigated. These involved the medial and then lateral aspects of visual cortex in 2 stages (ML), or vice versa (LM). Once again, the serial bilateral lesion groups (SB, ML, and LM) showed substantial savings of the discrimination after the completed lesion, while Group B showed a complete postoperative loss. Results indicate that the serial lesion effect is not specific to interhemispheric relationships. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)