Computer assisted tomography of focal cerebral radiation necrosis in the monkey.

The right occipital lobe in a series of pubescent monkeys was exposed to 3500 rads of orthovoltage radiation in a single dose. Sixteen to 38 weeks later the irradiated region broke down, rather abruptly. The visual evoked response, funduscopic photography, cerebral spinal fluid determinations for protein and lactic dehydrogenase, and computer assisted tomography (CAT) were used to anticipate and reflect the breakdown in neural tissue. CAT scanning demonstrated the two main effects of focal delayed radiation necrosis in this model (in a representative monkey): pronounced vasogenic edema from a break in the blood brain barrier, and contralateral hydrocephalus from brain distortion with obstruction of cerebral spinal fluid circulation. These findings were confirmed by postmortem examinations.

Memory during subclinical hippocampal seizures.

We performed neuropsychological testing in 2 patients during subclinical hippocampal seizures recorded with depth electrodes. Neither subject showed impairment of consciousness, orientation, motor skills, or verbal fluency. The rapidity of recall of a well-learned word list was impaired in 1 subject during ictal fast spiking in the left hippocampus. Subclinical seizure activity may be responsible for a portion of the memory deficits found in patients with epilepsy.

Memory in a case of bilateral thalamic infarction.

The role of individual structures within the diencephalon for memory functioning is unknown. We present anatomic localization of lesions and a longitudinal neuropsychological profile of a young man who had a bilateral diencephalic stroke in the interpeduncular profundus arterial territory. MRI localized the lesions to the mamillothalamic tracts and inferior thalamic peduncle. The amnesia was characterized by severe impairment in explicit recall of new facts and events, while word-completion priming and remote memory were intact. We suggest that the memory deficit results from a disconnection of the diencephalon from the medial temporal region.

Temporal lobectomy outcome in older versus younger adults.

A total of 340 patients age 50 years and older were compared with 30 patients younger than 50 years, all of whom had anterior temporal lobectomy for refractory epilepsy. Seizure outcome, neuropsychological test scores, and change in driving status were analyzed. Age and duration of epilepsy were related independently to outcome, but laterality of interictal sharp waves (an early epilepsy risk factor) and presence of tumor were not. Sixteen patients (52%) in the older group and 257 patients (75.6%) in the younger group (p < 0.008) were seizure free. Postoperative neuropsychological outcome and driving status were similar in older and younger patients.

Monkeys with combined amygdalo-hippocampal lesions succeed in object discrimination learning despite 24-hour intertrial intervals.

Monkeys with combined amygdalo-hippocampal removal show severe impairments on visual memory tasks after delays of only a minute or two, yet they learn visual discrimination habits about as quickly as normal animals with intertrial intervals of the same duration. In an attempt to resolve this discrepancy between abnormally rapid forgetting and successful retention, tests were conducted to determine whether discrimination learning would be prevented in animals with limbic lesions if intertrial intervals lasted 24 hr. The results showed that as long as the lesion did not encroach on inferior temporal cortex, the operated animals could acquire concurrent sets of 20 object discrimination habits at the same rate as normal animals, in an average of about 10 trials per set. The findings suggest that learning and retention processes are divisible into a mechanism for memory formation that is dependent on the limbic system and a mechanism for habit formation that is not.

Dissociation of the effects of inferior temporal and limbic lesions on object discrimination learning with 24-h intertrial intervals.

Monkeys with bilateral ablations of the inferior temporal cortical area TE were trained on a visual discrimination task thought to measure non-cognitive habit formation. The task consisted of 20 object discriminations presented concurrently, but at the rate of only one trial on each per day; successive trials on a given discrimination were thus separated by 24-h intertrial intervals. Performance on this task by the animals with TE lesions was compared to that of both normal control monkeys and monkeys that had sustained bilateral removals of the amygdala and hippocampus. In contrast to the latter animals, which learned the 24-h intertrial interval task about as quickly as the normal controls, monkeys with area TE removals were markedly impaired. Taken together with earlier findings demonstrating that ablation of area TE impairs visual recognition memory, the present results suggest that area TE contributes not only, like limbic structures, to a cognitive memory system, but also, unlike limbic structures, to a non-cognitive habit system. Evidence is reviewed suggesting that this latter system may involve a corticostriatal circuit.

Further analyses of clock drawings among demented and nondemented older subjects.

In a previous article we described a 10-point scoring system (i.e., scale 1) to grade clock drawings to command and copy with hands set for "ten after 11" among demented patients. Alzheimer's subjects (AD) improved from the command to copy conditions, whereas subjects with ischaemic vascular dementia (IVD) did not. To investigate the underlying cognitive deficits responsible for this profile, an additional scale was developed (scale 2) that tallied errors in graphomotor functioning, hand/number placement, and executive control. On an independent sample of subjects, AD subjects, again, made significant improvement on scale 1 from the command to copy condition, whereas no such improvement occurred among the IVD subjects. On scale 2, IVD subjects made more graphomotor errors in the command condition, and more executive control and more total errors in the copy conditions than AD subjects. A number of positive correlations were noted between tests of language and memory on scale 1. By contrast, scores on tests of executive control declined as scale 2 errors increased. In addition, a principal component analysis indicated that scale 2 test performance loaded on a factor with other tests related to executive control. These results suggest that impairment in frontal systems functioning may explain why IVD subjects do not improve from the command to copy conditions on scale 1. Such a pattern of performance in clock drawing may also be helpful in making a differential diagnosis between AD and IVD.

Does the brain actively maintain itself?

All living systems have special mechanisms for combatting entropy; however, the brain has dimensions of organized complexity beyong those manifest in the anatomical structure and physiology of the rest of the body. Reasons are given in support of the notion that the brain therefore must have a special, intrinsic "homeostatic" system for its information bearing structures, and, further, that slow electroencephalographic activity has properties which might make it useful for such an order-maintaining function. Recovery from brain damage is hypothesized to be a byproduct of this process, which may involve a cruder sort of information processing than occurs with such functions as perception and learning. Synchronized EEG activity may be adequate to handle this sort of information processing. Speculations are offered about possible mechanics, on the neuronal level, of slow wave participation in plasticity; for example, one such suggestion is based on findings that electrical fields can influence cellular orientation. The methodology of discovering the distribution within the brain of the hypothetical maintenance system is discussed briefly.

Verbal and figural recognition memory: task development and age associations.

The goal of the present study was to develop and validate parallel tests of verbal and figural delayed-recognition memory with similar task demands and difficulty levels. Such tasks would allow examination of age differences and longitudinal age changes in visual recognition memory for two types of stimuli, activate divergent neural systems, and allow us to use the same procedures within the confines of functional neuroimaging as those we use in standard neuropsychological administration. The tasks introduced here include a delay between target presentation and test phase, are matched in difficulty, and yield moderate levels of performance. Individual and group differences in task performance were examined in 80 cognitively normal men and women in two older age groups: 60 to 69 and 70 to 85. Accuracy averaged 74% in both tasks, with lower performance in the oldest age group. Although accuracy was equivalent between tasks, subjects had a more liberal response bias in the figural than verbal task. Performance on the new recognition-memory tests was significantly related to Benton Visual Retention Test (BVRT; Benton [1963]. New York: The Psychological Corporation) and California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober [1987]. New York: The Psychological Corporation) performance measures. The absence of floor or ceiling effects, wide range of individual variability, and demonstrated concurrent validity of the present tasks suggest their potential utility in functional neuroimaging studies and in the early detection of cognitive decline.

Local cerebral glucose utilization in newborn and pubescent monkeys during focal motor seizures.

The [14C]deoxyglucose method was used to determine the rate of local cerebral glucose utilization (LCGU) in newborn and pubescent monkeys during focal motor seizures induced by injecting penicillin into the face-hand area of the right motor cortex. Seizures were studied in 3 newborn and 6 pubescent monkeys, and 3 newborn and 4 pubescent monkeys were used as controls. In controls, the pattern of glucose utilization within structures of the sensorimotor system was quite differenet at the two age levels; newborns showed far less activity, especially in the neocortex and striatum. In the monkeys with seizures, the unilateral increase in LCGU relative to the controls was greater in newborn than in pubescent monkeys except in the cerebral and cerebellar cortices. The increased glucose utilization in cortical and subcortical structures of the newborns was ipsilateral to the discharging lesin and lacked the well-defined pattern seen in the pubescent monkeys. In general, newborn brain was capable of supporting a focal motor seizure but lacked the precise clinical and electrographic expressions or efficient energy metabolism that accompany maturation of the brain at puberty.

Propagation of focal motor seizures in the pubescent monkey.

The rate of local cerebral glucose utilization was determined for quantification of energy metabolism in macrostructures of the sensorimotor system during propagation of focal motor seizures in 24-month-old monkeys. The rate was measured in 4 control animals and in 4 monkeys each with seizures limited to the contralateral face, seizures of the contralateral face and upper extremity, and bilateral expression of seizures. Glucose utilization increased significantly, primarily unilaterally, with propagation. The increase was greatest in the sensory and motor cerebral cortices, putamen, and globus pallidus, was somewhat less in sensory and motor thalamic relay nuclei, and was least in the cerebellar cortex.

Effects of manipulation of the sensorimotor system on focal motor seizures in the monkey.

During focal motor seizures induced by injecting penicillin into the face-hand area of the right motor cortex of 24-month-old monkeys, the sensorimotor system was manipulated by three methods. Elimination, by a paralytic agent, of proprioceptive input from contracting muscles and joints did not alter the electrographic expression of the seizure or the pattern of local glucose utilization in cortical or subcortical components of the sensorimotor system. An overall increase in the rate of energy metabolism occurred in the paralyzed monkeys with electrographic seizures. Cryogenic destruction of up to 90% of the ipsilateral ventral caudal globus pallidus had no effect on electrographic or clinical expression of the seizure. Electrical stimulation of the ipsilateral ventral caudal globus pallidus caused reproducible maximum expression of electrographic and clinical seizure phenomena for the 90-second duration of the stimulus.

Outcome after temporal lobectomy in bilateral temporal lobe epilepsy.

We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.

Normative neuropsychological test performance: effects of age, education, gender and ethnicity.

Normative data on neuropsychological test performance for a sample of 131 adults (ages 18-49) is presented. All subjects were native speakers of English screened for past or present medical, neurological and psychiatric disorders, including substance abuse. A broad-based battery including measures of intellectual skills, memory and learning, receptive and expressive language, auditory and visual information processing and attention, sensory processing, motor skills, and self-reported anxiety and depression was administered. Means, standard deviations and percentile rankings for all tests are reported. Regression analyses were computed to consider the concurrent influence of sociodemographic factors on all tests. Significant effects of age (M=27.1 yrs), education (M=14.6 yrs), gender (58% male), and ethnicity (62% white) were observed for relatively few test scores. Younger age at testing was associated with better continuous performance test scores. Higher education levels were associated with higher vocabulary and reading scores. Males had higher WAIS-R Information scores and faster Finger Tapping scores compared to females Ethnicity was associated with Full-scale IQ, and additional tests with a verbal component, e.g., Boston Naming Tests, and non-verbal component, e.g., Drawing Tests. We conclude that sociodemographic factors infrequently account for more than 10% of the variance for many neuropsychological test scores.