Biomarker-Modulated Deep Brain Stimulation for Memory
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Solution Overview
Problem
Current deep brain stimulation (DBS) therapies for improving cognitive functions, such as memory encoding and recall, have shown inconsistent results and limited success in treating declarative memory deficits in neurological disorders, lacking robust and reproducible evidence, particularly in conditions like Alzheimer's disease and Lewy body dementia.
Innovation Solution
A system that modulates brain stimulation therapy based on theta-band biomarkers from electrical brain activity signals in the hippocampal and anterior nucleus of the thalamus regions, using data acquisition and signal analysis to determine parameters for stimulation, including frequency, timing, and site selection, to enhance cognitive processes like memory encoding and recall.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If DBS therapy is applied to treat cognitive functions, then memory function can be improved, but the results are inconsistent and not robust
Solution Approach 1:
The patent employs closed-loop feedback by detecting theta-band brain activity signals from the hippocampus and ANT regions and using these signals to dynamically adjust DBS stimulation parameters. This feedback mechanism ensures that stimulation is delivered only when beneficial theta activity is detected, improving the reliability of memory enhancement while avoiding inconsistent results from non-adaptive stimulation
Solution Approach 2:
The patent changes the parameter of stimulation frequency by delivering DBS at low frequencies (e.g., 2-10 Hz) that match the theta-band frequency range, rather than using traditional high frequencies. This parameter change aligns the stimulation with natural theta oscillations involved in memory processes, leading to more consistent and reliable memory improvement
2Adaptability or versatility
If DBS parameters are adjusted to improve memory, then cognitive function can be enhanced, but the stimulation may not be optimized for individual patients
Solution Approach 1:
The system continuously monitors theta-band activity from individual patients and uses this feedback to automatically adjust stimulation parameters in real-time. This personalized feedback loop ensures that each patient receives optimized stimulation tailored to their specific brain activity patterns, improving both adaptability and measurement precision of cognitive enhancement
Solution Approach 2:
The patent transitions from static, fixed DBS parameters to dynamic, adaptive parameters that change in response to real-time theta-band activity detection. This dynamic adjustment allows the therapy to adapt to individual patient variations and fluctuating brain states, improving both personalization and precision of cognitive improvement
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The system effectively improves memory performance by correlating theta-band activity with stimulation parameters, demonstrating chronic improvement in verbal memory with low-frequency DBS and predicting memory recall abilities, offering a more objective and efficient method for tracking cognitive processes and optimizing DBS therapy.
Implementation Method 1
A data acquisition system acquires electrical brain activity signals sensed by one or more electrodes in a brain of the patient, where the electrical brain activity signals include at least one signal indicative of electrical activity in a hippocampal region of the brain and at least one signal indicative of electrical activity in an anterior nucleus of the thalamus (ANT) region of the brain
Implementation Method 2
Brain stimulation therapy is then administered to the patient in accordance with the determined parameters. The patient may be diagnosed with epilepsy and the brain stimulation therapy can be administered at least in part to treat symptoms of epilepsy
Data Source
AI summary
Verbal memory impairment is a common symptom of temporal lobe epilepsy (“TLE”). The ability to encode and recall verbal memories can be probed with the classic free recall task. This study had three overarching hypotheses: 1) increased seizure frequency will lead to decreased verbal memory, 2) stimulation will modulate memory performance, and 3) stimulation will modulate the underlying neural correlates of memory. The study investigated these hypotheses in patients receiving chronic DBS to bilateral ANT. Recordings were obtained from individuals with drug resistant mesial TLE implanted with an investigational MEDTRONIC SUMMIT RC+S™ sensing and stimulation device. As patient seizure diaries are notoriously inaccurate, the patient's continuous local field potential (“cLFP”) was scored for seizures using a validated seizure classifier with trained epileptologist review, resulting in a reliable seizure diary. The subjects completed free recall memory tasks in their home environment with cLFP and behavioral data streamed to a handheld device and cloud repository.Through implementation of generalized linear mixed models (GLMM), the study was able to determine that ANT stimulation modulates memory performance, but changes in the seizure rate were not predictive of changes in memory performance. Analyzing the continuous local field potential recordings from these tasks, the study found that spectral power in the theta frequency band in the left ANT and hippocampus correlated with acute memory performance and chronic therapeutic stimulation frequency received.Not all patients are candidates for devices with chronic sensing capabilities, and this study indicates that changes in verbal memory performance can provide a suitable metric of therapy effectiveness in lieu of a reliable, objective seizure diary. But for those who do receive these and similar devices, thalamic-hippocampal spectral activities can be used to track and predict memory performance acutely and chronically, as well as predict the effect of therapeutic deep brain stimulation. Our study demonstrates chronic improvement of verbal memory with a new biomarker-based technology for remote task administration and modulation of the associated neural activities.