Charles E. Olmstead

Effects of caudate nuclei or frontal cortex ablations in cats. II. Sleep-wakefulness, EEG, and motor activity ☆

Abstract The effects of caudate nuclei ablation or frontal cortex removal on the percentages of wakefulness and sleep stages, spontaneous motor activity, and the EEG were studied in cats by means of 24-hr polygraphic recordings for a 6-month period. A significant, permanent, reduction of sleep (particularly REM sleep) and an increase in motor activity were observed in cats with removal of most of the frontal tissue in front of the A22 stereotaxic plane. A similar decrease in sleep was also observed in animals with bilateral, almost total, removal of the caudate nuclei, but this reduction almost fully recovered after the second postlesion month. Motor hyperactivity was more marked in cats with caudate ablations than in cats with frontal ablations and persisted indefinitely. No marked or lasting effects on the EEG were observed. Sham-operated cats and those with unilateral caudate removal behaved like intact cats. It is concluded that both the frontal cortex and the caudate nuclei are parts of a postulated, complex, forebrain system modularing brain stem activating-deactivating central nervous system mechanisms.

Recovery of function after neonatal or adult hemispherectomy in cats: I. Time course, movement, posture and sensorimotor tests

Cats with removal of the left hemitelencephalon (hemispherectomy) as neonates (n = 12) or in adulthood (n = 14), were compared using a battery of 16 neurological and behavioral tests given when they were young adults (kittens) or at least 5 months after the lesion (adults). The neonatal-lesioned subjects grew normally and performed markedly and significantly better than adult-lesioned cats in 13 tests covering the wide range of movement, posture and sensory functions which were assessed. None of the animals recovered tactile placing of the right forelimb or a normal vision in the right visual field. However, the overall recovery was outstanding for all cats such that the neonatal-lesioned were hard to differentiate from intact controls in their spontaneous, daily activities. Because the lesions were similar in the two age-at-lesion groups, and since numerous functions were followed for prolonged, comparable postlesion time, we conclude that, after hemispherectomy in the cat, there definitely is greater functional recovery if the lesion is sustained early in life. We propose that the enhanced recovery of function in neonatal-lesioned cats is largely due to the extensive anatomical reorganization which we have demonstrated in ongoing studies, and which contrasts with a lesser remodeling in adult-lesioned cats.

Hippocampal theta rhythm persists in the permanently isolated forebrain of the cat

In cats with high mesencephalic transections surviving for up to 90 days, the hippocampal EEG shows exaggerated percentages of 3-5 Hz theta activity. The theta rhythm has similar waveform and frequency characteristics to that seen in the intact cat and can be selectively enhanced or abolished by systemic physostigmine or atropine respectively. These data demonstrate (1) that the caudal brainstem is not essential for the spontaneous appearance of the hippocampal theta rhythm, and (2) the integrity of a major cholinergic system in the chronically isolated forebrain.

Pediatric Low-grade Gliomas: Prognosis with Proton Magneti Resonance Spectroscopic Imaging

OBJECTIVE Our aim was to assess the correlation between the low-grade glioma (LGG) metabolic profile and tumor progression. Using in vivo proton magnetic resonance spectroscopic imaging, we specifically asked whether and which metabolic features are associated with tumor regrowth or recurrence. METHODS Eleven pediatric patients with histologically proven partially resected (<20% resection) midline LGG were treated and followed up for a period of 2 years. All patients underwent proton magnetic resonance spectroscopic imaging studies before any management was determined. Tumor progression was defined as radiological evidence of mass enlargement (>25%) during the follow-up period. Proton magnetic resonance spectroscopic imaging was performed using a PRESS-CSI sequence on a General Electric 1.5-tesla scanner (General Electric Medical System, Waukesha, WI). The signal intensities of N-acetylaspartate, choline (CHO), and creatine from the tumor and the normal brain were used to calculate normalized metabolite intensities and metabolite ratios. RESULTS Tumors that progressed during a 2-year period displayed higher normalized CHO than those that remained stable (Mann-Whitney test, P < 0.03). The majority (five of six) of the rapidly growing LGG showed values of normalized CHO of at least 1, whereas the nonprogressors had a normalized CHO value of less than 1. CONCLUSION In association with pediatric LGG, high normalized CHO values seem to herald the potential for rapid tumor growth. These observations may be valuable for defining subsets of patients with LGG who may benefit from early therapeutic interventions.

Effects of caudate nuclei or frontal cortex ablations in cats. IV. Bar pressing, maze learning, and performance.

Abstract Bar pressing, maze learning, and passive avoidance acquisition were examined, before and/or after surgery, in cats with extensive unilateral or bilateral ablations of the caudate nuclei or frontal cortices and in sham-operated cats. The caudate ablations were by aspiration using a midline transcallosal approach. In a two-bar lever-pressing situation the acaudate animals showed specific defects consisting of difficulties in shaping the use of the paws, tendency to persist at the response producing the last reward, inability to execute two concurrent motor acts, and peculiar postural adjustments. These changes contributed to slow rates of responding, markedly impaired ability to alternate, and interfered with all phases of acquisition and performance. Frontal cats, conversely, exhibited markedly irregular behavior, inability to sustain performance, and slow rates of bar pressing without the other response peculiarities of acaudate cats. The unilaterally ablated animals exhibited only fragments of these defects. In a standard T-maze, on spatial alternation and black-white discrimination tasks, acaudate cats showed errors of perseveration while frontal cats produced mainly randomly distributed errors. Such defects were not seen in unilaterally lesioned animals. The above deficits did not manifest any marked recovery even in cats studied for up to 16 months. Passive avoidance was normal in all animals except the cat with the largest caudate removal. Sham-operated cats behave like intact animals. In conclusion: (i) Stable, chronic cats with caudate removal and absence of dorsofrontal cortical damage are capable of learning, retention, and performance far beyond previous suggestions; (ii) The discrete behavioral deficits resulting from extensive caudate or frontal lesions are different, suggesting that these structures play different functional roles. The deficits resulting from caudate destruction are discussed in terms of interference with high level sensory motor processess; their similarities with some clinical manifestations of human basal ganglia pathology are noted.

Effects of caudate nuclei or frontal cortex ablations in cats: III. Recovery of limb placing reactions, including observations in hemispherectomized animals.

This is a long-term study of the time course of impairments of the limb placing reactions in cats following bilateral removal of the frontal cortical areas (n = 9), bilateral (n = 11), or unilateral (n = 10), ablation of the caudate nuclei or removal of one cerebral hemisphere (n = 5). In addition the effects of d-amphetamine and of removal of the remaining frontal cortex on the placing reactions of the limbs contralateral to the hemispherectomy were assessed. The main results were: (i) a substantial recovery of the contact placing reactions was observed in frontal cats; the recovery started very late (third or fourth month) and was considered as complete within 6 to 9 months in four cats. (ii) A variable degree of impairment of the contact placing reactions occurred in caudatectomized cats; both the magnitude of the impairments and the length of the recovery period (up to 4 months) were proportional to the extent of the ablation. (iii) No recovery of the contact placing reactions was observed in limbs contralateral to the hemispherectomy either spontaneously, under the action of d-amphetamine (producing a transient enhancement of proprioceptive components and a pseudocontact placing reaction), or following removal of the remaining frontal cortex. The meaning of the above findings in the context of pertinent literature, the mechanisms of compensation following frontal ablation, and the possible participation of the caudate in the physiological control of the contact placing reactions are discussed.

Tumor Volume and Growth Kinetics in Hypothalamic-Chiasmatic Pediatric Low Grade Gliomas

Pediatric low grade gliomas evidence a tendency towards quiescent growth, thus complicating the clinical management of nonresected tumors whose clinical behavior may be difficult to predict. We decided to explore the hypothesis of possible correlation in pediatric low grade glioma between tumor volume and growth rate. We identified 6 children with hypothalamic chiasmatic lesions. Five of these patients were treated only with biopsy and 1 with repeated partial tumor resection. All of 6 patients had 10–15 sequential brain MRI over a time span of 3–8 years. Tumor volume was determined using Sigma Scan Image® software. The results were analyzed utilizing two equations for modeling tumor growth: exponential and Gompertz. In 4 patients whose tumor volume was approximately 80–100 cm3 at the time of diagnosis, slow spontaneous partial regression was observed. In the other patients deceleratory or exponential tumor growth was volume-dependent. Our results suggest that growth of pediatric low grade glioma decelerates as tumor becomes large and that the Gompertz model for tumor growth is useful for understanding the growth kinetics of pediatric low grade glioma.

Proton magnetic resonance spectroscopic imaging of pediatric low-grade astrocytomas

Despite their uniform histologic appearance, pediatric lowgrade astrocytomas (LGA) often exhibit a rather unpredictable clinical course. It is presently unclear whether certain specific genetic, immunologic and/or metabolic features underlie these observed variations. In order to address this question we examined the tumor distribution of choline compounds (Cho), creatine (Cr) and N-acetyl aspartate (NAA) in seven children with midline LGA by means of proton magnetic resonance spectroscopy imaging (H-MRSI). Studies were performed with a 1.5 T GE Signa Scanner equipped with the standard head coil; nominal voxel size was 7.5×7.5×15 mm. This spatial resolution allowed us to select and independently evaluate multiple regions of interest (ROI) in the tumor as well as in areas of normal brain from the same individual. Normalized values of the observed signal intensities demonstrated a lower NAA and Cr content in the tumors than in the surrounding normal brain. Intratumoral Cho signals were also below normal values in all but one patient. The average Cho: NAA ratio was consistently higher in the tumor than in the normal brain. However, there was a wide variation (up to fourfold) in the Cho: NAA ratios of different ROIs, even within the same tumor. Our results clearly indicate that pediatric LGAs are metabolically heterogeneous, a feature that may be relevant to the understanding of their variable biologic behavior. Inasmuch as unique metabolic patterns were observed in some LGAs, we believe that systematic HMRSI studies of these patients may help define subsets within the group with specific therapeutic requirements.

Effects of caudate nuclei or frontal cortical ablations in kittens: responsiveness to auditory stimuli and comparisons with adult-operated littermates.

Abstract These experiments assess the behavioral responsiveness of adult cats with extensive caudate nuclei or frontal cortical ablations, sustained either neonatally or in adulthood, to presentations of cat vocalizations or of tones. Each subject received 27 presentations, at 1-min intervals, of a 12 s sequence of taped vocalization (calls) on 2 successive days and, 1 week later, a similar series of 2-kHz tones of the same duration and intensity. The behavioral responses were scored using a six-point rating scale and the data were analyzed to compare responsiveness of the groups within each testing day, decrement of responsiveness across the trials of each session (habituation), and retention of habituation across successive days. We found that (a) all acaudate and afrontal cats persisted in responding at higher levels than intact animals in all three testing sessions; (b) the cats with caudate ablations were more responsive than those with frontal ablations to both calls and tones; (c) the hyperresponsiveness was more marked for adult-operated in relation to kitten-operated preparations; (d) in general, the responsiveness of all kitten groups decreased progressively across the three testings; and (e) for the adult-operated cats, there was a decrement between the two call sessions and an increase between the call and the tone sessions. These findings suggest that both the caudate nucleus and the frontal cortex participate in processes controlling the organisms responsiveness to external stimuli with the caudate removal producing the largest defect; they also indicate that, with some qualifications, the lesions sustained by the kitten result in less marked later effects than those sustained by the adult. Furthermore, they may help to explain some of the behavioral changes which we described previously for cats with caudate ablations.

Limited (L4-S1, L5-S1) Selective Dorsal Rhizotomy for Reducing Spasticity in Cerebral Palsy

Summary Selective posterior rhizotomy is effective for relieving spasticity associated with cerebral palsy. In current techniques dorsal roots from L1/L2 to S1/S2 are selectively divided. With transoperative electromyography (EMG) significant sensory loss has been prevented, but postoperative hypotonia following excessive reduction of the fusimotor drive is still of concern for surgeons and therapists. To decrease the volume of deafferentiated rootlets we proposed a limited selective posterior rhizotomy (LPSR) that limits the extent of the surgery to three (L4-S1) or two (L5-S1) dorsal roots. We present the results of two group of spastic children; group 1 (n=59, 32 quadriplegic and 27 diplegic) who had a L4-S1 LPSR. and group 2 (n=12) in whom L5 and S1 were selectively rhizotomized. Posture, passive movilization, range of joint movement, and muscle tone in hip flexors, adductors, leg flexors and plantar flexors were graded according to the method proposed by Sindou and Jeanmonod. In all groups there was a significant reduction of the mentioned parameters (Friedman test p<0.001) at 6, 12 and 18 months after surgery. The preoperative and postoperative ability to ambulate was classified into five grades. In all groups there was a significant (χ2 between p<0.01 and p<0.001) improvement in the quality of their gait. A third of the patients achieved some form of independent ambulation. Our results suggest that extensive selective deafferentation of the lower limbs is not an absolute requisite for reducing muscle tone or achieving functional improvement in spastic children.