Behavioral deficits induced by local injection of bicuculline and muscimol into the primate motor and premotor cortex.

1. The role of intracortical GABAergic inhibition in the performance of hand movements was studied in macaque monkeys while they performed two behavioral tasks: a raisin pick-up test and a visual reaction-time task. A gamma-aminobutyric acid (GABA) agonist, muscimol (MUS; 1-5 microgram), and an antagonist, bicuculline methiodide (BMI, 1-10 micrograms), were injected at various sites in the precentral motor cortex (MC), at which single-unit activity was related to the manual aspects of the performance of the reaction-time task. 2. Manual dexterity in the raisin pick-up task was severely disturbed by injections of either MUS or BMI into the hand MC. The effect was less severe after injections into the postarcuate premotor cortex (PM). 3. Performance of the reaction-time task was unstable after injection of BMI. The instability was caused by increased electromyogram (EMG) activity and by cocontractions of agonistic and antagonistic muscles of the arm during the pressing or release of the lever. 4. Reaction time was increased by injection of MUS, although the effect was temporary and decayed within 60 min. These deficits were consistent with the time course of the decrease in the total amount of EMG activity of hand muscles related to the task. As in the case of the raisin pick-up task, performance deficits were greater when MUS and BMI were injected into the hand MC and smaller when they were injected into the PM. 5. After injection of BMI, the animals gradually began to display muscle activity in response to a green warning signal that did not require a behavioral response. The muscle activity accelerated to spontaneous muscle twitches without any external stimulus, and the animals were unable to continue the task. These BMI-induced twitches were eliminated by injection of barbiturate. 6. Appropriate levels of GABAergic inhibition in the MC appear, therefore, to be important for the regulation of spatiotemporally organized ensembles of muscle activity, in particular for reciprocal contraction at the task-related joints.