Abstract: Apparatus is provided that includes a two-dimensional arrangement (70) of extracranial electrodes (30), configured to be placed outside and in electrical contact with a skull of a subject identified as at risk of or suffering from a disease; and a cerebrospinal fluid (CSF) electrode (32), configured to be implanted in a ventricular system of a brain of the subject. Control circuitry is configured to drive the extracranial and the CSF electrodes (30, 32) to clear a substance from brain parenchyma of the subject into at least one region of the brain selected from the group consisting of: a subarachnoid space of the brain and dural sinuses of the brain. Other embodiments are also described.

Abstract: An electrical brain treatment system includes a parenchymal electrode, configured to be implanted in direct physical contact with brain parenchyma or meninges of the brain of a subject identified as at risk of or suffering from a disease; and a cerebrospinal fluid (CSF) electrode, configured to be implanted in a CSF-filled space selected from a ventricular system and a subarachnoid space. Control circuitry is electrically coupled to the parenchymal electrode and the CSF electrode, and is configured to clear a substance from the brain parenchyma into the CSF-filled space of the brain by applying direct current between the parenchymal electrode and the CSF electrode as a series of pulses, with an average amplitude of between 0.25 and 0.5 mA, an average pulse width of between 0.5 and 2 ms, and an average frequency of between 1 and 5 Hz. Other embodiments are also described.

Abstract: A method is provided that includes implanting a first electrode in a cerebrospinal fluid (CSF)-filled space of a brain of a subject identified as at risk of or suffering from Alzheimer's disease. One or more second electrodes are implanted superficial to brain parenchyma of the subject, such that the brain parenchyma is spatially disposed between a ventricular system of the brain and the one or more second electrodes. Control circuitry is activated to drive the first and the one or more second electrodes to clear amyloid beta and/or tau protein from the brain parenchyma into the ventricular system by applying current between the first electrode and the one or more second electrodes using an average voltage of less than 1.2 V. Other embodiments are also described.

Abstract: A method is provided that includes implanting a first electrode in a cerebrospinal fluid (CSF)-filled space of a brain of a subject identified as at risk of or suffering from Alzheimer's disease. One or more second electrodes are implanted superficial to brain parenchyma of the subject, such that the brain parenchyma is spatially disposed between a ventricular system of the brain and the one or more second electrodes. Control circuitry is activated to drive the first and the one or more second electrodes to clear amyloid beta and/or tau protein from the brain parenchyma into the ventricular system by applying current between the first electrode and the one or more second electrodes using an average voltage of less than 1.2 V. Other embodiments are also described.

Abstract: A method is provided that includes implanting (a) a parenchymal electrode in or in contact with an outer surface of brain parenchyma of a subject identified as at risk of or suffering from a disease, and (b) a cerebrospinal fluid (CSF) electrode in a CSF-filled space of a brain of the subject, the CSF-filled space selected from the group consisting of: a ventricular system and a subarachnoid space. A midplane treatment electrode is disposed in or over a superior sagittal sinus. Control circuitry is activated to drive the parenchymal electrode and the CSF electrode to drive a substance from the brain parenchyma into the CSF-filled space of the brain, and apply a treatment current between the CSF electrode and the midplane treatment electrode to drive the substance from the CSF-filled space of the brain to the superior sagittal sinus. Other embodiments are also described.

Abstract: Apparatus is provided that includes an extracranial electrode, configured to be placed outside and in electrical contact with a skull of a subject identified as at risk of or suffering from a disease; and a cerebrospinal fluid (CSF) electrode, configured to be implanted in a ventricular system of a brain of the subject. Control circuitry is configured to drive the extracranial and the CSF electrodes to clear a substance from brain parenchyma of the subject into the ventricular system of the brain. Other embodiments are also described.

Abstract: A method is provided that includes implanting (a) a parenchymal electrode in or in contact with an outer surface of brain parenchyma of a subject identified as at risk of or suffering from a disease, and (b) a cerebrospinal fluid (CSF) electrode in a CSF-filled space of a brain of the subject, the CSF-filled space selected from the group consisting of: a ventricular system and a subarachnoid space. A midplane treatment electrode is disposed in or over a superior sagittal sinus. Control circuitry is activated to drive the parenchymal electrode and the CSF electrode to drive a substance from the brain parenchyma into the CSF-filled space of the brain, and apply a treatment current between the CSF electrode and the midplane treatment electrode to drive the substance from the CSF-filled space of the brain to the superior sagittal sinus. Other embodiments are also described.

Abstract: Apparatus is provided that includes an extracranial electrode, configured to be placed outside and in electrical contact with a skull of a subject identified as at risk of or suffering from a disease; and a cerebrospinal fluid (CSF) electrode, configured to be implanted in a ventricular system of a brain of the subject. Control circuitry is configured to drive the extracranial and the CSF electrodes to clear a substance from brain parenchyma of the subject into the ventricular system of the brain. Other embodiments are also described.

Abstract: Apparatus is provided that includes a parenchymal electrode, configured to be implanted in brain parenchyma of a subject identified as at risk of or suffering from a synucleinopathy; and a cerebrospinal fluid (CSF) electrode, configured to be implanted in a CSF-filled space of a brain of the subject, the CSF-filled space selected from the group consisting of: a ventricular system and a subarachnoid space. Control circuitry is configured to drive the parenchymal and the CSF electrodes to clear alpha-synuclein (aSyn) from the brain parenchyma into the CSF-filled space of the brain. Other embodiments are also described.

Abstract: A method is provided that includes positioning electrodes in or in contact with a head of a subject identified as in need of enhanced microglial cell activation. Control circuitry is activated to drive the electrodes to apply an electrical current to a brain of the subject in pulses having an average pulse duration of between 0.1 ms and 10 ms, and to configure the electrical current to enhance microglial cell activation for taking up amyloid beta or tau protein from brain parenchyma. The control circuitry is activated to apply the electrical current with an average amplitude of between 0.1 and 5 mA, or with an average voltage that results in between 0.1 and 5 mA current. Other embodiments are also described.

Abstract: A method is provided that includes positioning electrodes in or in contact with the head of a subject identified as in need of enhanced microglial cell activation. Control circuitry is activated to drive the electrodes to apply an electrical current to the brain of the subject, and to configure the electrical current to enhance microglial cell activation for taking up a substance from brain parenchyma. Other embodiments are also described.

Abstract: An electrical brain treatment system includes a parenchymal electrode, configured to be implanted in direct physical contact with brain parenchyma or meninges of the brain of a subject identified as at risk of or suffering from a disease; and a cerebrospinal fluid (CSF) electrode, configured to be implanted in a CSF-filled space selected from a ventricular system and a subarachnoid space. Control circuitry is electrically coupled to the parenchymal electrode and the CSF electrode, and is configured to clear a substance from the brain parenchyma into the CSF-filled space of the brain by applying direct current between the parenchymal electrode and the CSF electrode as a series of pulses, with an average amplitude of between 0.25 and 0.5 mA, an average pulse width of between 0.5 and 2 ms, and an average frequency of between 1 and 5 Hz. Other embodiments are also described.

Abstract: A method is provided that includes implanting (a) a parenchymal electrode in or in contact with an outer surface of brain parenchyma of a subject identified as at risk of or suffering from a disease, and (b) a cerebrospinal fluid (CSF) electrode in a CSF-filled space of a brain of the subject, the CSF-filled space selected from the group consisting of: a ventricular system and a subarachnoid space. A midplane treatment electrode is disposed in or over a superior sagittal sinus. Control circuitry is activated to drive the parenchymal electrode and the CSF electrode to drive a substance from the brain parenchyma into the CSF-filled space of the brain, and apply a treatment current between the CSF electrode and the midplane treatment electrode to drive the substance from the CSF-filled space of the brain to the superior sagittal sinus. Other embodiments are also described.

Abstract: Apparatus is provided that includes a parenchymal electrode, configured to be implanted in brain parenchyma of a subject identified as at risk of or suffering from a synucleinopathy; and a cerebrospinal fluid (CSF) electrode, configured to be implanted in a CSF-filled space of a brain of the subject, the CSF-filled space selected from the group consisting of: a ventricular system and a subarachnoid space. Control circuitry is configured to drive the parenchymal and the CSF electrodes to clear alpha-synuclein (aSyn) from the brain parenchyma into the CSF-filled space of the brain. Other embodiments are also described.

Abstract: A method is provided that includes positioning electrodes in or in contact with the head of a subject identified as in need of enhanced microglial cell activation. Control circuitry is activated to drive the electrodes to apply an electrical current to the brain of the subject, and to configure the electrical current to enhance microglial cell activation for taking up a substance from brain parenchyma. Other embodiments are also described.