Frontal lobe neglect in man. 1972.
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Biomedical subjects
Publications and source records attributed to E Valenstein.
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A patient with a discrete lesion of the left, intralaminar thalamic, nuclei exhibited a paradoxical finding with regard to finger-tapping. Normal subjects typically reduce their tapping rate when performing simultaneous verbal activity. Tapping was impaired in our patient's contralesional hand on baseline trials; however, performing the controlled oral word association (COWA) task, while finger-tapping, normalized her deficit. Subsequent experiments showed that motoric tasks rather than cognitive aspects of the COWA task were critical in potentiating finger-tapping performance. A SPECT study performed at rest revealed focal perfusion asymmetries in motor and premotor cortices. Because the caudal intralaminar nuclei project heavily to the striatum, striatal deafferentiation may account for these asymmetries. These observations provide some insight into the influences of the caudal intralaminar thalamic nuclei on basal ganglia function and the basal ganglia's influence on motor gating.
Using a crossed-response task, monkeys with neglect induced by frontal lesions appear to have motor rather than sensory neglect. However, the crossed-response task may not reveal sensory neglect (inattention) if no perceptual discrimination is required. We therefore trained two monkeys in a perceptually complex crossed-response task. Following unilateral frontal (arcuate gyrus) ablation, we found no contralateral perceptual disorders or sensory neglect in either monkey but did find a failure to respond with the contralateral arm (motor neglect) in both monkeys. We also found that the monkeys made more incorrect responses with the arm ipsilateral to the lesion than they did with the contralateral arm. The errors made by the ipsilateral arm could be a compensatory strategy or a disinhibition phenomenon. Because these incorrect responses were not rewarded and became more frequent as motor neglect improved, the incorrect responses of the ipsilateral arm are not a compensatory strategy, but rather a defect we term "disinhibition hyperkinesia" or "allokinesia."
OBJECTIVE: In humans and monkeys, the intraparietal sulcus separates the superior parietal lobule from the inferior parietal lobule (IPL). Whereas in humans Brodmann's area 7 is above this sulcus, in monkeys it is below and therefore part of the IPL. In humans, the IPL consists of Brodmann's areas 39 and 40. Some investigators contend that the monkey homologue of the human IPL (areas 39 and 40) is the monkey's IPL (area 7). Others contend that it is, at least in part, in the monkey's superior temporal sulcus (STS). In humans, IPL lesions induce neglect. Although IPL lesions in monkeys also have been reported to induce neglect, the STS was involved in these lesions. We sought to learn which of these two areas, when ablated, produces neglect. DESIGN: Study of five adult stump-tailed macaque monkeys by making five isolated STS and six IPL lesions. RESULTS: Inferior parietal lobule lesions were associated with misreaching but not with unilateral neglect. Neglect was observed in association with five of the six STS lesions. CONCLUSIONS: With regard to neglect, STS may be the monkey homologue of the human IPL. Animals with STS lesions and humans with IPL lesions may manifest unilateral neglect because these areas are necessary for normal awareness of external stimuli. This awareness may result from the integration of the areas important in stimulus localization (the "where is it?" system) and stimulus identification (the "what is it?" system), as well as the areas important in defining the biologic importance of stimuli, such as the frontal lobes and limbic areas.
A patient complained of memory disturbance after a small left thalamic infarction. Neuropsychological testing revealed her memory to be normal provided that she was allowed to rehearse or use semantic encoding strategies. When these strategies were prevented, her performance was impaired. Mapping of the lesion demonstrated involvement of the caudal intralaminar nuclei (centre médian and parafascicular nuclei), and portions of the medial nuclei (medioventral [reuniens], centromedial, and the most inferior aspect of the mediodorsal nucleus). The majority of mediodorsal nucleus, the mammillary bodies, the mammillothalamic tract, and the anterior thalamic nuclei, were spared. A comparison among our patient's performances and those of alcoholic Korsakoff patients, patient NA, and amnestic patients with circumscribed diencephalic lesions suggests that there are two distinct behavioral and anatomic types of memory impairment associated with diencephalic lesions. The severe amnesia associated with damage to the mammillary bodies, midline nuclei, mammillothalamic tract, and/or dorsomedial nucleus of the thalamus (eg, Korsakoff and NA) is characterized by encoding deficits that never approximate normal performance. The memory disturbance associated with damage to the intralaminar and medial nuclei of the thalamus is milder and is characterized by severe distractibility.
A patient with verbal amnesia and a propensity to direct his attention to the right following a retrosplenial area lesion was studied with positron emission tomography using [F-18] fluorodeoxyglucose. These studies showed that the left thalamus was hypometabolic, and the anterior 2/3 of the left hemisphere was hypermetabolic when compared with the right. There were no significant differences seen in the medial temporal lobes. Based on this study, it is posited that interruption of hippocampal input into the anterior thalamus was responsible for the amnesia, and the left frontal hyperactivity was associated with the propensity to attend contralaterally.
In this paper we describe the performance of an amnesic with a left retrosplenial lesion on three memory tasks assessing his ability to judge when a previously learned event had occurred. This patient was dramatically impaired in acquiring temporal information about new stimuli, and this defect could not be attributed to recognition failures or to frontal lobe dysfunction. In contrast to his impaired acquisition of temporal information, he had no difficulty judging the temporal order of remote historical events. The pattern of performance displayed by this patient suggests a specific defect in "time-tagging" of new incoming information.
We evaluated neurologic function in 18 patients, ages 5 to 26 years, with cystic fibrosis. Eight were deficient in vitamin E. Sural nerve conduction latency was increased and nerve action potential amplitude decreased in the vitamin E-deficient group in comparison with the vitamin E-sufficient group. Two vitamin E-deficient patients had absent deep tendon reflexes; findings of clinical neurologic examinations were otherwise normal. We recommend early supplementation with vitamin E for patients with cystic fibrosis who have pancreatic insufficiency, to prevent neurologic dysfunction.
Four monkeys were trained to open a door with either the right or left hand in response to a tactile stimulus to either leg. After unilateral frontal arcuate ablation inducing unilateral neglect, the response time on this task increased most when the monkey responded with the hand contralateral to the lesion, but also increased when the monkey used the hand ipsilateral to the lesion. The side of stimulation had no effect on response time. Control (anterior superior temporal) lesions did not cause neglect and only affected response time slightly in one monkey (using the limb contralateral to the lesion). We conclude that response time is increased in animals with unilateral neglect and that the increase results from a defect in intention to act (motor neglect) rather than from sensory neglect.
A 39-year-old man developed retrograde and anterograde amnesia following haemorrhage from an arteriovenous malformation situated near the splenium of the corpus callosum. MRI studies demonstrated damage to the splenium, and to a region containing the retrosplenial cortex and the cingulate bundle. The fornix was anterior and inferior to the site of maximal damage, but may have been involved; the stria terminalis was probably spared. Structures known to be important in memory but spared by the lesion included the hippocampus, thalamus, and basal forebrain. The retrosplenial cortex receives input from the subiculum and projects to the anterior thalamus, thus providing an alternative route between hippocampus and thalamus. Perhaps more importantly, medial temporal structures involved in memory receive anterior thalamic input directly via the cingulate bundle and indirectly through a relay in the retrosplenial cortex. We suggest that this thalamocortical portion of Papez' circuit may be important in memory, and that lesions of the cingulum and retrosplenial cortex may cause amnesia by disrupting this pathway.
Lesions of ascending dopaminergic pathways induce neglect in animals. Apomorphine, a dopamine receptor agonist, decreases the magnitude of neglect in rats with cortical lesions. We treated two patients with 15 mg of bromocriptine daily for 3 to 4 weeks, one with chronic (longer than 6 months) and one with relatively more acute disabling neglect. Tests for neglect that significantly improved on therapy and worsened after its withdrawal included line, letter, and geometric figure cancellation tasks. Neither patient noted any untoward effects. Based on this open trial of dopamine agonist therapy in humans with neglect, larger controlled studies may be warranted.
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Neglect is a disorder in which the response to stimulation is diminished or absent on the side of the body contralateral to the lesion in the absence of an elemental sensory or motor defect. Most cases of neglect in humans are induced by cortical damage, but there have been no investigations of the pharmacologic basis of neglect induced by cortical damage. We examined the role of the dopamine system in polymodal neglect caused by a unilateral lesion of the medial precentral prefrontal cortex of the rat. A dose-response examination of the effect of apomorphine on neglect revealed that apomorphine, at 0.5 mg/kg, the highest dose examined, significantly improved the orientation scores of subjects in all modalities tested and significantly decreased the total number of allesthetic responses. The therapeutic effect of apomorphine was mediated by dopamine receptors as the therapeutic effect of apomorphine was blocked by prior administration of spiroperidol. These results demonstrate the important role of disruption of dopamine mechanisms in neglect induced by a lesion of medial precentral cortex.
For normal writing it is essential that both motoric and linguistic competence be present; disruption of one or the other of these faculties may result in qualitatively different types of agraphia. Two right-handed patients became agraphic after left hemisphere lesions; pure apraxic agraphia in the absence of limb apraxia developed in one patient and pure linguistic agraphia in association with severe ideomotor limb apraxia in the other. The performance of these patients not only serves to illustrate the dissociation between the motoric and linguistic faculties that underlie writing but also confirms that ideomotor limb apraxia and apraxic agraphia are distinct and dissociable entities.
To learn whether animals with parietotemporal lesions have sensory inattention or defective intention, we trained monkeys to respond with the contralateral limb to a threshold tactile stimulus. After parietotemporal lesions that induced neglect, the monkeys continued to respond normally to threshold stimuli on the side opposite the lesion (the neglected side), but made errors when stimulated on the normal side (ipsilateral to the lesion), often failing to use the contralateral extremity. On this learned task, there was no abnormality of sensory input or sensory attention. The problem was attributed to an impaired preparation to respond (intention).
In the past two to three decades, clinicians and neuroscientists have been studying the functions of the right hemisphere. Neither hemisphere seems to be dominant in the absolute sense. Each appears to be specialized and is dominant for different functions. However, most functions require the cooperation of both hemispheres. When one is damaged, the other can often compensate for the damaged one. Lesions of the left hemisphere are associated with language (speech, reading, and writing) and praxic disorders, and lesions of the right hemisphere can result in visuospatial, attentional, and emotional disorders. The authors review some of the major behavior disorders associated with right hemisphere dysfunction and concentrate on three major types of disorders--visuospatial, attentional, and emotional. Although not all the behavioral defects associated with right hemisphere damage can be subgrouped under these three types, they are the ones most often associated with right hemisphere lesions.