Abstract: A pharmaceutical composition includes an active agent capable of reducing dihydroorotate dehydrogenase (DHODH) enzyme activity in the central nervous system (CNS), and a pyrimidine nucleobase or an intermediate in the de novo synthesis thereof. A method for treating a disease or disorder associated with cortico-hippocampal hyperactivity in a subject in need thereof, or for preventing or delaying onset of the disease or disorder in a subject diagnosed as suffering from an elevated cortico-hippocampal activity or being at genetic risk for developing the disease or disorder. The method includes administering to the subject a therapeutically effective amount of the pharmaceutical composition above.

Abstract: The present invention provides pharmaceutical compositions and methods for preventing, delaying onset of, or treating diseases or disorders associated with cortico-hippocampal hyperactivity such as epilepsy, using an active agent capable of reducing dihydroorotate dehydrogenase (DHODH) enzyme activity in the central nervous system, optionally together with a pyrimidine nucleobase or an intermediate in the de novo synthesis thereof.

Abstract: The present invention provides pharmaceutical compositions and methods for preventing, delaying onset of, or treating diseases or disorders associated with cortico-hippocampal hyperactivity such as epilepsy, using an active agent capable of reducing dihydroorotate dehydrogenase (DHODH) enzyme activity in the central nervous system, optionally together with a pyrimidine nucleobase or an intermediate in the de novo synthesis thereof.

Abstract: A method of treating Alzheimer's disease (AD) is disclosed. The method comprises electrically stimulating a nerve pathway in a brain region of a subject with at least two high frequency spike bursts of electrical currents, the bursts comprising between 2-20 spikes, wherein a frequency of the spikes in the bursts is between 5-200 msec.

Abstract: A method of treating Alzheimer's disease (AD) is disclosed. The method comprises electrically stimulating a nerve pathway in a brain region of a subject with at least two high frequency spike bursts of electrical currents, the bursts comprising between 2-20 spikes, wherein a frequency of the spikes in the bursts is between 5-200 msec.

Abstract: The present invention provides compositions and methods for enhancing cognitive function and synaptic plasticity. According to the method, Ca++ influx into excitatory neurons (nerve cells) is decreased by treatment with a number of different agents including divalent cations (e.g., Mg++), GABAB agonists, GABAA agonists, calcium channel blockers, and/or compounds that decrease action potential firing such as sodium channel blockers. Decreasing Ca++ influx results in increased synaptic plasticity and enhanced cognitive function. In particular, decreasing Ca++ influx associated with uncorrelated neural activity results in long-lasting increases in synaptic plasticity and cognitive function. This is achieved by administration of agents that cause a voltage-dependent block of NMDA receptors (e.g., divalent cations such as Mg++) or by administration of GABAB agonists such as baclofen.