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The study of the clinical course of methamphetamine (MAP) psychosis yields insights into the biological aspect of the relapse of the paranoid psychotic state with hallucination in schizophrenia. A series of MAP psychosis studies in Japan conducted over a period of more than four decades revealed three types of clinical courses of MAP psychosis after discontinuation of MAP: transient type, prolonged type, and persistent type. Identification of the latter two indicates a lasting change in the brain that produces and maintains a schizophrenia-like paranoid psychotic state without MAP. The characteristic course seen in the transient type is acute recurrence of the psychotic state after a long remission period, almost identical to the initial episode, due to reuse of MAP or to psychological stressors. Such lasting vulnerability of the brain to schizophrenia-like psychotic symptoms may be caused by a lasting sensitization of the brain to the psychotogenic action of MAP resulting from its chronic abuse. Experimental studies using animals sensitized to MAP-induced stereotypy suggest that lasting enhancement of MAP-induced dopamine release in the striatum and nucleus accumbens is related to the development and expression of brain vulnerability to schizophrenic symptoms.

Dopamine transporter knockout (DAT KO) mice display deficits in sensorimotor gating that are manifested by reduced prepulse inhibition (PPI) of the acoustic startle reflex. Since PPI deficits may model some of the cognitive dysfunctions identified in certain neuropsychiatric patients, we have studied the effects of transporter blockers on PPI in wild-type and DAT KO mice. Treatments with High dose psychostimulants that block DAT as well as the norepinephrine (NET) and serotonin (SERT) transporters (60 mg/kg cocaine or methylphenidate) significantly impaired PPI in wild-type mice. By contrast, these treatments significantly ameliorated the PPI deficits observed in untreated DAT KO mice. In studies with more selective transport inhibitors, the selective NET inhibitor nisoxetine (10 or 30 mg/kg) also significantly reversed PPI deficits in DAT KO mice. By contrast, while the SERT inhibitor fluoxetine (30 mg/kg) normalized these PPI deficits in DAT KO mice, citalopram (30 or 100 mg/kg) failed to do so. The 'paradoxical' effects of cocaine and methylphenidate in DAT KO mice are thus likely to be mediated, at least in part by the ability of these drugs to block NET, although serotonin systems may also have some role. Together with recent microdialysis data, these results support the hypothesis that prefrontal cortical NET blockade and consequent enhancement of prefrontal cortical extracellular dopamine mediates the reversal of PPI deficits in DAT KO mice.

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Summary:Purpose: To examine the effects of cognitive-motor function on EEG discharges and the neuropsychological mechanisms of seizure induction in patients sensitive to cognitivemotor tasks.Methods: Four hundred eighty patients with epilepsies were subjected to cognitive tasking, termed "neuropsychological EEG activation (NPA)." It consisted of reading, speaking, writing, written calculation, mental calculation, and spatial construction. Furthermore, patients showing a provocative NPA effect were subjected to a detailed NPA protocol to identify the possible precipitating factors, which consisted of simple hand movements, action programming requiring hand movement, and thinking activity not requiring hand movement.Results: NPA had an inhibitory effect on EEG discharges in 133 (63.9%) of 208 patients with discharges in the awake EEG. Conversely, NAP had a provocative effect in 38 (7.9%) of 480 patients. In 32 of the 38 patients, the precipitating factor was action programming. Among them, five showed a precipitating factor restricted to linguistic activity, and the remaining 27 were affected by various action-programming factors including both linguistic and praxic activities. In four of 38 patients, the precipitating factor was thinking, predominantly linguistic tasks in one patient and spatial tasks in three patients. No patient had a precipitating factor identified as motor activity.Conclusions: These results suggest that cognitive-motor function has an inhibitory effect on EEG discharges in the majority of epilepsy patients and a provocative effect in some patients, and that seizures of the patients showing a provocative NPA effect are precipitated by action programming or thinking activity. Key Words: Action programming-Juvenile myoclonic epilepsyNeuropsychological EEG activation-Reflex epilepsy.The impact of higher mental activities on each type of epilepsy or seizure remains unclear, because standard EEGs record changes during sleep, hyperventilation, photic stimulation, and opening and closing of the eyes, but not in systematic cognitive tasks. Reflex epilepsies induced by cognitive-motor activities such as reading, calculation, speaking, writing, and thinking have been described in the literature, but such triggers are considered to be uncommon. For example, standard EEG recordings at the Mayo Clinic in the United States included a mental arithmetic calculation task, and only one of >100,000 recordings showed an EEG effect (1). Conversely, various daily mental activities have been shown to facilitate or inhibit seizure occurrence in patients with epilepsy (2).This study was designed to examine how much cognitive-motor activities influence epileptic EEG disAddress correspondence and reprint requests to Dr. H. Matsuoka at Department of Psychiatry, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. E-mail: mtok@psy.med.tohoku.ac.jp charges by using a special EEG activation protocol for testing various mental activities, which we called "neuropsychological EEG a...