Anesthetics and electroconvulsive therapy seizure duration: implications for therapy from a rat model.

The anesthetic agents methohexital (Brevital), Innovar, and ketamine (Ketaject) were examined for their effect on seizure duration following electroconvulsive stimulation in a rat model of electroconvulsive therapy (ECT). Compared to unanesthetized control animals, methohexital anesthesia shortened seizure duration by 42%, ketamine anesthesia tended to increase seizure duration, and Innovar anesthesia had no effect on duration of seizures.

Electroencephalographic recording during bitemporal and unilateral non-dominant hemisphere (Lancaster Position) electroconvulsive therapy.

electrical seizure activity induced by ECT appears in three phases: Phase I initial 18-22 Hz. (beta-like) activity, Phase II arrhythmic polyspike activity, and Phase III rhythmic 2 1/2-3 1/2 Hz. spike/polyspike-wave activity. With bitemporal ECT, Phase II activity appears simultaneously in all leads. With unilateral non-dominant hemisphere ECT, there is an orderly march on Phase II polyspikes from the right anterior temporal region. After termination of a seizure, there is symmetrical suppression of normal activity with bitemporal ECT, but with unilateral non-dominant hemisphere ECT there is less suppression of normal activity in the unstimulated side.

Performance of children with ADHD on tests sensitive to frontal lobe dysfunction.

The performances of 20 children with attention deficit hyperactivity disorder (ADHD) were compared with those of 20 matched normal controls on a battery of neuropsychological tests. The ADHD children exhibited impaired function in reading comprehension, verbal learning and memory, and on the Information, Arithmetic, Digit Span, Block Design, and Coding subtests of the Wechsler Intelligence Scale for Children-Revised, but they performed nearly normally on measures of verbal and design fluency and on the Wisconsin Card Sorting Test. The hypothesis that disturbances in frontal lobe function related to impulse control may be responsible for the cognitive impairments observed in ADHD was not supported. Inability to control and direct attention appears to be more central to the pathophysiology of this disorder.

Reduplicative paramnesia: a disconnection syndrome of memory.

A case of post-traumatic reduplicative paramnesia (Capgras syndrome) is presented in which the patient experiences duplications in all three spheres of orientation (time, place, person). We postulate that these duplications are the result of a disconnection of new memory registration from past memory stores. The patient is unable to integrate present cues with premorbid experience, and bases judgments of his present orientation upon recollections from the past. A deep lesion at the right posterior hippocampus and temporo-parieto-occipital junction is suggested as the site of this postulated primary memory disconnection, based upon neuropsychological testing and CAT scan results. This right temporal atrophy and memory disconnection appears to have induced immature personality changes.

Cognitive disturbances in Parkinson's disease.

To test the hypothesis that the cognitive impairments that accompany Parkinson's disease (PD) arise from frontal lobe dysfunction, patients with idiopathic PD and controls were tested on a neuropsychological battery that included measures of anterograde memory, visuospatial perception, and naming, as well as several tests that are known to be sensitive to lesions of the frontal lobes. PD patients of normal mental status as measured by the Mini-Mental State Examination performed normally on the naming, line orientation, and verbal recognition memory tests but exhibited deficits on verbal recall. On tests of frontal lobe function, these patients showed mild deficits on a category fluency task and on the Wisconsin Card Sorting Test. However, their errors on the latter were not typical of patients with frontal lesions, and they performed normally on a letter fluency task and exhibited normal release from proactive interference. Patients of lower than normal mental status performed poorly on nearly all of the cognitive tasks including confrontational naming, line orientation, and recognition memory, suggesting that their cerebral dysfunction extended beyond subcortical-frontal circuits. The present study supports the usefulness of the Mini-Mental State Examination for cognitive screening of PD patients, but does not support the hypothesis that the cognitive impairments in PD arise principally from disruption of frontal lobe functioning.

The electroencephalographic pattern during electroconvulsive therapy: V. Observations on the origins of phase III delta energy and the mechanism of action of ECT.

The generation of the spike-wave activity of Phase III of ECT seizures is attributed to the recurrence of synchronized, prolonged periods of intense inhibitory current flow (hyperpolarization), and associated rebound spike bursts, produced by the inhibitory circuit relationships and intrinsic electrophysiological properties of thalamic neurons. An anatomical and neurophysiological model of the development of generalized, synchronous 3-Hz spike-wave seizure activity is proposed which outlines the origin, maintenance, slowing, and termination of this fundamental seizure rhythm. Phase III inhibitory current flow (delta energy) and/or spike bursts may bring about therapeutic benefit by initiating a chain of agonist-independent and agonist-dependent events which results in long-term augmentation of serotonergic and noradrenergic neurotransmission and diminution of cholinergic neurotransmission in the forebrain. A specific anatomical and functional model of the mechanism of action of ECT is proposed, in which: (1) adrenergic and cholinergic pathways in the forebrain are assumed to be massively stimulated during ECT seizures, whereas serotonergic pathways are assumed to be inhibited during these seizures; (2) the beneficial effects of ECT are considered to be more dependent upon ECT-induced changes in 5-HT neurotransmission than upon alteration of noradrenergic function; (3) these beneficial effects involve up-regulation of 5-HT2 and down-regulation of M1- and M2-muscarinic receptor densities by both agonist-independent and agonist-dependent mechanisms, coupled with functional augmentation of noradrenergic neurotransmission; and (4) these effects may be brought about by Phase III inhibitory current flow- and/or spike burst-induced alteration of the function of second-messenger generator systems.

The electroencephalographic pattern during electroconvulsive therapy. IV. Spectral energy distributions with methohexital, innovar and ketamine anesthesias.

During Phase III of nondominant unilateral ECT seizures, total energy, total peak energy, total delta energy, and 1/2-power duration of total delta energy are all less (shorter) in the unstimulated, dominant hemisphere than they are in the stimulated hemisphere. Interhemispheric differences in total energy are greatest in the lateral frontotemporal cortex, where they average 40 percent with both methohexital and ketamine anesthesias in F8 greater than F7 and T4 greater than T3. This circumstance probably explains the characteristic memory sparing associated with nondominant unilateral ECT. The magnitudes of total and peak energies in each frequency band decrease in the order: delta greater than theta greater than alpha greater than beta. Delta energy constitutes approximately three-fourths of the unilateral ECT seizure's total energy, and Phase III delta energy may be the therapeutically effective agent in this treatment. Seizures induced during ketamine anesthesia are associated with a higher percentage of delta energy, with higher magnitudes of total energy and of total and peak delta energy, and with longer 1/2-power durations of delta energy. Nondominant unilateral ECT with ketamine anesthesia offers promise as the treatment of choice for patients resistant to ECT administered with methohexital anesthesia.

The electroencephalographic pattern during electroconvulsive therapy II. Preliminary analysis of spectral energy.

Computer assisted energy-spectral analyses were obtained on EEG recordings of unilateral non-dominant hemisphere ECT-induced seizures using the different pre-ECT anesthetic agents methohexital (Brevital), Innovar, and ketamine (Ketalar). The previously postulated predominance of electrical energy over the stimulated (right) hemisphere early in ECT-induced seizures is confirmed. There appears to be marked reduction in total seizure energy with methohexital anesthesia, whereas ketamine anesthesia appears to be associated with increased overall seizure energy. The greatest right to left energy transfer during the seizure occurred with Innovar anesthesia.

The electroencephalographic pattern during electroconvulsive therapy. III. Analysis of frontotemporal and nasopharyngeal spectral energy.

This study analyzes the frontotemporal and nasopharyngeal spectral energy of an ECT-induced seizure, in order to investigate the origin of the final Phase III activity, which contains most of the seizure's energy. Data supports these findings: energy in the delta frequency band is responsible for the generation, propagation, and maintenance of Phase III of the ECT-induced seizure; the synchronous "delta-firing" depolarizations of Phase III are recurrently initiated by an ECT-induced "generator" process; higher magnitudes of energy are generated centrally than are generated laterally during Phase III; and the lessened memory impairment associated with nondominant unilateral ECT is attributable to the markedly lower peak and total energies observed in the unstimulated temporal lobe.

Comparative effects of long-term ethanol consumption and forebrain lesions on maze learning and active avoidance behavior in rats.

Male rats consumed a liquid diet containing 10.7% ethanol as their only source of food and fluid for 6.5 months, beginning at 2 months of age. During withdrawal, there were no differences between the alcohol group and their pair-fed or free-fed controls on EEG, body temperature, irritability and tremor measures. In behavioral tests begun 4-5 weeks after withdrawal, the rats that had consumed alcohol acquired accurate spatial behavior in a cross maze task more slowly than controls, but were unimpaired in shuttle-avoidance learning. In concurrent studies with groups of rats that had sustained lesions of the dorsal hippocampus, the mamillary bodies (MMB), or the mediodorsal thalamus, the pattern of behavioral deficits after MMB lesions was found to be qualitatively similar to that observed after the cessation of long-term alcohol consumption. These findings provide renewed hope that a useful rodent model for studying the neuropsychology of cognitive deficits associated with human alcoholism can be developed.

Right hemisphere involvement in learning disability, attention deficit disorder, and childhood major depressive disorder.

Learning disability, attentional disorder and childhood major depression are frequent diagnoses in children with behavioral disturbances and impaired school performance. All three disorders are associated with right cerebral hemisphere dysfunction. Anatomical disturbance of right hemisphere function results in learning disability and/or attentional disorder. The physiological disturbance of right hemisphere function produced by a major depressive episode results in additional learning disability and/or attentional disorder.

Myotonic dystrophy as a disease of abnormal membrane receptors: an hypothesis of pathophysiology and a new approach to treatment.

Muscle weakness, clinical myotonia, and multiple systemic organ disturbances characterize myotonic dystrophy. Many of these systemic disturbances involve target organ insensitivity to aminergic or peptidergic (hormonal) stimulation. Reduced density or impaired function of aminergic and peptidergic (hormonal) receptors throughout the body may underlie this disorder. Tricyclic antidepressant augmentation of aminergic function ameliorates depressive symptoms, increases strength, and improves clinical myotonia in myotonic dystrophy patients.

Use of serotonergic drugs for treating depression in older patients.

The selective serotonin reuptake inhibitors (SSRIs) offer a relatively new alternative to traditional tricyclic antidepressants (TCAs) in the treatment of depression in older adults. The two drug classes are equally effective, but SSRIs tend to cause fewer sedating, anticholinergic, or hypotensive effects and are unlikely to affect cardiac conduction. SSRIs also have a wider therapeutic window and are safer in cases of overdose. Potential side effects include GI distress, worsening of headaches, insomnia, and sexual dysfunction. Drawbacks of using SSRIs are their potential for drug interactions and relatively high cost.

An hypothesis regarding the commonality of right-hemisphere involvement in learning disability, attentional disorder, and childhood major depressive disorder.

Learning disability, attentional disorder, and childhood major depression are frequent clinical diagnoses for children who show behavioral disturbances and impaired school performance. We suggest that all three of these conditions may be associated with dysfunction of the right cerebral hemisphere. Anatomical disturbance of right-hemisphere function is often associated with learning disability or attentional deficits. The physiological disturbance of right-hemisphere function by a major depressive episode may produce or exacerbate learning disability or attentional disorder.

Non-specificity of motor hyperactivity as a diagnostic criterion.

The relationship between motor hyperactivity and childhood depression was investigated in a group of 178 children referred for evaluation of school problems. 60% (n = 107) of the children fulfilled the modified Feighner criteria for primary childhood depression. 44% (n = 78) of the children had motor hyperactivity and 75% (n = 59) of these also showed depression. Terminal insomnia, somatic complaints, self-deprecation, episodic loss of interest in school and usual activities, social withdrawal, and preoccupation with death and dying were the symptoms which significantly differentiated depressed from non-depressed children.

Cognitive improvement associated with tricyclic antidepressant treatment of childhood major depressive illness.

11 children fulfilling DSM-III criteria for major depressive illness were administered detailed neuropsychological batteries prior to and 3 to 6 mo. after starting tricyclic antidepressant treatment. Remission of depressive illness in children with melancholic major depression was associated with significant improvement in WISC-R Verbal IQ and Performance IQ, and on the Similarities, Comprehension, Block Design, and Coding subtests. In addition, there were significant improvements on the Halstead Categories test, on the Visual Reception subtest of the Illinois Test of Psycholinguistic Abilities, and in response latencies on the Matching Familiar Figures test. Two children with evidence of mild left hemiparesis showed amelioration of hemiparesis during tricyclic antidepressant treatment.

Neuropsychological study of children during and after remission of endogenous depressive episodes.

2 children experiencing endogenous depressive episodes show impaired cognitive functioning. Following tricyclic antidepressant-induced remission of depression, there was significant improvement in psychometric test performance.

Antidepressant treatment of children: clinical relapse is unrelated to tricyclic plasma concentrations.

Plasma concentrations of imipramine and amitriptyline and their desmethylated metabolites were measured in 20 children being treated for major depressive illness 2 wk. and 5 to 10 wk. after achieving drug dosages of 2.25 mg/kg body weight. At 2 wk. all children had exhibited clinical improvement, but by 10 wk. 4 of the 10 children treated with imipramine and 5 of the 10 children treated with amitriptyline had experienced clinical relapse of depressive symptoms. Tricyclic antidepressant plasma concentrations and ratios were comparable in the subgroups of children who maintained their clinical improvement and those who relapsed. There was no evidence of a systematic decline in plasma tricyclic antidepressant concentrations in those children who relapsed.