Deep brain stimulation system and method with multi-modal, multi-symptom neuromodulation
Described here is a deep brain stimulation (“DBS”) approach that targets several relevant nodes within brain circuitry, while monitoring multiple symptoms for efficacy. This approach to multi-symptom monitoring and stimulation therapy may be used as an extra stimulation setting in extant DBS devices, particularly those equipped for both stimulation and sensing. The therapeutic efficacy of DBS devices is extended by optimizing them for multiple symptoms (such as sleep disturbance in addition to movement disorders), thus increasing quality of life for patients.
1. A method for controlling a deep brain stimulator (DBS) implanted in a brain of a subject, comprising the steps of:
receiving electrical data obtained from a DBS implanted in a subcortical structure including a globus pallidus of the brain of the subject;
determining that the subject is in an awake state based on analyzing the electrical data from the subcortical structure based on first phase amplitude coupling (PAC) data from the globus pallidus;
determining that the subject is in an NREM sleep stage based on analyzing the electrical data from the DBS implanted in the subcortical structure to identify second PAC data which is reduced compared to the first PAC data from the awake state and at least one of a K complex or a spindle; and
adjusting control of the DBS based on determining that the subject is in an NREM sleep stage.
2. The method of claim 1 , wherein the globus pallidus includes at least one of a globus pallidus internal (GPI) segment, a globus pallidus external (GPe) segment, and the subcortical structure further includes one of: a subthalamic nucleus (STN) or a thalamus.
3. The method of claim 1 , wherein the electrical data comprises a plurality of frequency bands, and
wherein determining that the subject is in the NREM sleep stage further comprises:
determining that the subject is in the NREM sleep stage based on calculating a relative power associated with each of the plurality of frequency bands.
4. The method of claim 3 , wherein adjusting control of the DBS further comprises:
reducing therapeutic stimulation of the DBS based on determining that the subject is in the NREM sleep stage.
5. The method of claim 4 , further comprising:
receiving further electrical data obtained from the subcortical structure of the brain of the subject,
determining that the subject is no longer in the NREM sleep stage based on analyzing the further electrical data, and
resuming the therapeutic stimulation of the DBS based on determining that the subject is no longer in the NREM sleep stage.
6. The method of claim 1 , wherein determining the that the subject is in the NREM sleep stage based on analyzing the electrical data further comprises:
determining that the sleep stage of the subject is asleep during a preprogrammed waking period, and
wherein adjusting control of the DBS based on determining that the subject is in the NREM sleep stage further comprises:
transmitting a signal from the DBS to alert the subject to wake up.
7. A method for modulating sleep in a subject, comprising:
receiving electrical data obtained from a deep brain stimulator (DBS) implanted in a subcortical structure including a globus pallidus of a brain of the subject;
determining that the subject is in an awake state based on analyzing the electrical data from the subcortical structure based on first phase amplitude coupling (PAC) data from the globus pallidus;
determining that the subject is in an NREM sleep stage based on analyzing the electrical data from the DBS implanted in the subcortical structure to identify second PAC data which is reduced compared to the first PAC data from the awake state and at least one of a K complex or a spindle;
stimulating the subcortical structure of the brain of the subject using the DBS implanted in the brain of the subject to alter the NREM sleep stage of the subject based on determining that the subject is in the NREM sleep stage,
stimulating comprising applying a patterned stimulation to the subcortical structure using the DBS.
8. The method of claim 7 , wherein the patterned stimulation comprises:
a charge balanced pulse train comprising a maximal energy delivered at a center frequency Fc to amplify oscillations having the center frequency Fc.
9. The method of claim 8 , further comprising:
receiving feedback signals obtained from the brain of the subject,
the feedback signals comprising the electrical data obtained from the DBS,
identifying a phase angle of the feedback signals associated with a maximum amplification of oscillations with center frequency Fc, and
stimulating the subcortical structure of the brain of the subject at the identified phase angle using at least one electrode of the DBS.
10. The method of claim 9 wherein receiving the feedback signals obtained from the brain of the subject further comprises:
removing electrical stimulation artifacts from the feedback signals.
11. The method of claim 9 , wherein receiving the feedback signals obtained from the brain of the subject further comprises:
receiving the feedback signals from at least one of: a scalp electrode, an implanted electrocorticography (ECoG) array, a spinal cord lead, or an electromyography (EMG) electrode.
12. The method of claim 8 , further comprising:
changing the center frequency Fc using an outer loop scheduler of the DBS to generate an updated patterned stimulation, the updated patterned stimulation designed to stimulate the subcortical structure of the brain of the subject to enter at least one of a REM sleep stage or the NREM sleep stage, and
wherein stimulating the subcortical structure of the brain of the subject further comprises:
stimulating the subcortical structure of the brain of the subject by applying the updated patterned stimulation to the subcortical structure.
13. The method of claim 12 , further comprising:
receiving feedback signals obtained from the brain of the subject,
the feedback signals comprising the electrical data obtained from the DBS,
analyzing the feedback signals to determine that the brain of the subject has been in at least one of the REM sleep stage or the NREM sleep stages for a target period of time, and
wherein changing the center frequency Fc further comprises:
changing the center frequency Fc based on analyzing the feedback signals to determine that the brain of the subject has been in at least one of the REM sleep stage or the NREM sleep stage for the target period of time.
14. A deep brain stimulation (DBS) system, comprising:
a controller including a processor and instructions that, when executed by the processor, configure the DBS system to:
receive electrical data obtained from a DBS implanted in a subcortical structure including a globus pallidus of a brain of a subject;
determine that the subject is in an awake state based on analyzing the electrical data from the subcortical structure based on first phase amplitude coupling (PAC) data from the globus pallidus;
determine that the subject is in an NREM sleep stage based on analyzing the electrical data from the DBS implanted in the subcortical structure to identify second PAC data which is reduced compared to the first PAC data from the awake state and at least one of a K complex or a spindle; and
adjust therapeutic stimulation of the DBS to at least one of induce sleep or awaken the subject based on determining that the subject is in the NREM sleep stage.
15. The system of claim 14 , wherein the controller is further configured to:
receive further electrical data obtained from the subcortical structure of the brain of the subject,
determine that the subject is no longer in the NREM sleep stage based on analyzing the further electrical data, and
resume the therapeutic stimulation of the DBS based on determining that the subject is no longer in the NREM sleep stage.
16. The system of claim 14 , wherein the electrical data comprises a plurality of frequency bands, and
wherein the controller, when determining that the subject is in the NREM sleep stage, is further configured to:
determine that the subject is in the NREM sleep stage based on calculating a relative power associated with each of the plurality of frequency bands.
17. The system of claim 14 , wherein the controller is further configured to:
modulate sleep in the subject by stimulating the subcortical structure of the brain of the subject using the DBS.
18. The system of claim 14 , wherein the therapeutic stimulation of the DBS includes a stimulation frequency of greater than or equal to 10 Hz and less than 30 Hz.
19. The system of claim 18 , wherein the therapeutic stimulation of the DBS includes a stimulation frequency of 10 Hz.
20. The system of claim 14 , wherein the therapeutic stimulation of the DBS includes a stimulation frequency of greater than or equal to 0.1 Hz and less than or equal to 30 Hz.
21. A deep brain stimulation (DBS) system, comprising:
a controller including a processor and instructions that, when executed by the processor, configure the DBS system to:
receive electrical data obtained from the DBS implanted in a subcortical structure including a globus pallidus of a brain of a subject;
determine that the subject is in an awake state based on analyzing the electrical data from the subcortical structure based on first phase amplitude coupling (PAC) data from the globus pallidus;
determine that the subject is in an NREM sleep stage based on analyzing the electrical data from the DBS implanted in the subcortical structure to identify second PAC data which is reduced compared to the first PAC data from the awake state and at least one of a K complex or a spindle;
stimulate the subcortical structure of the brain of the subject to alter the NREM sleep stage of the subject based on determining that the subject is in the NREM sleep stage,
stimulating comprising applying a patterned stimulation to the subcortical structure.
22. The system of claim 21 , wherein the patterned stimulation comprises:
a charge balanced pulse train comprising a maximal energy delivered at a center frequency Fc to amplify oscillations with center frequency Fc.
23. The system of claim 22 , wherein the controller is further configured to:
receive feedback signals obtained from the brain of the subject,
the feedback signals comprising the electrical data obtained from the DBS,
identify a phase angle of the feedback signals associated with a maximum amplification of oscillations with center frequency Fc, and
stimulate the subcortical structure of the brain of the subject at the identified phase angle using at least one electrode of the DBS.