Wireless Implantable Device for Major Depressive Disorder

 

Mental health is one of the major health issues costing more than $57B annually. Depressive disorder is a major disease of psychiatric disorders. For those patients who failed current behavioral and pharmacological treatment, one option is the deep brain stimulation. The objective of this proposal is to develop an implantable wireless close-loop feedback system that enables the detection of neural signals in the targeted brain site(s) and use these neural signals to trigger electrical stimulation for depression management. Electrical stimulation of neural substrates will increase the set of neurotransmitters (serotonin, norepinephrine, dopamine) that are determinants for mood. The final goal of the project is to design an implantable system that can be used for clinical treatment of depression.

During the one year funding period, we have developed wireless devices for closed-loop neural recording and stimulation. The multi-channel wireless recording modules have been designed, fabricated and assembled. The modules are programed to communicate with a custom-made graphic user interface based on Labview for real time monitoring and data recording. The devices and system passed bench tests under various scenarios. The data communication errors were minimized at various distances while in the laboratory setting the data error rates were tested as zero within 3 m distances. The system also integrated the simulator modules with a single control interface and automatic control that can be programmed with specific algorithms.

Wireless Implantable Closed-Loop DeviceIn vivo animal experiments were conducted using the wireless system with designed scenarios. The experiments were validated with control and statistical analysis. Recordings also were compared between our wireless system and the gold standard wired method showing better performance in the digital wireless system. Recording modules were also used to record ECoG signals. Recorded data by our wireless recording system contain less noises and power-line interferences compared to those by the conventional wired system CED 1401. Stimulation of the ventral tegmental area in the brain has shown pain relief effect in awake animals. This effect has also been verified by recording single spinal cord dorsal horn neurons. On the contrary, stimulation of the primary somatosensory cortex tend to make objects more sensitive to peripheral mechanical and thermal stimuli. Exampled experiments investigated behavioral tests with or without electrical stimulation in the brain for mechanical Von Frey filament withdrawal threshold tests at the plantar surface of the paw and thermal paw withdrawal tests by Infrared thermal stimulator aimed at the plantar surface of the paw. By utilizing the wearable recording modules to remove stress of constrain from the objects, the medial prefrontal cortex showed decrease of field potentials when electrical stimulation were applied in the skin in anesthetized animals. An increase of local field potential in the ventral tegmental area has been found correlated to the increase of locomotion in animals after drug injection.

These experimental results were made possible and accomplished with the wearable digital multichannel modules, with the integrated stimulators in the closed-loop system, and provided empirical data for further animal and possibly clinical experiments in the future.

Current Status of the project

The proposed goal has been completed. The project remains to be active for the ultimate goal of clinical applications. Optimization of the multichannel recording modules, integrated stimulators, and the control system will further be refined and updated. Further animal tests are needed to establish database for clinical studies.

Publications, Patents filed, additional funding secured

1. “A Wearable Telemetric Neural/EMG/ECoG Activity Acquisition Platform for Small Freely Moving Animals,” C. Zuo, X. Yang, Y. Wang, A.L. Li, Y.B. Peng and J.-C. Chiao, Asia-Pacific Microwave Conference, APMC2012, Kaohsiung, Taiwan, Dec. 4-7, 2012. Full paper.

2. “A Digital Wireless System for Closed-loop Inhibition of Nociceptive Signals,” C. Zuo, Y. Wang, C.E. Hagains, A.L. Li, X. Yang, Y. B. Peng and J.-C. Chiao, Journal of Neural Engineering, Vol. 9, No. 5, 056010, 2012.

3. Ai-Ling Li, Chao Zuo, Yang Wang, Xiaofei Yang, J-C Chiao, Yuan B Peng: The inhibition of the field potential activity in medial prefrontal cortex by nocicpetion. SfN, 2013.

4. Amber L Harris, Ai-Ling Li, Jiny E. Sibi, Samara A Morris-bobzean, Yuan B. Peng, Linda I. Perrotti: Local field potentials in the ventral tegmental area correlate with cocaine-induced locomotor activation: measurements in freely moving rats. SfN, 2013.

5. Kelly Bullock, Ai-Ling Li, Chao Zuo, Yang Wang, Xiaofei Yang, J.-C. Chiao, Yuan B. Peng: Effect of primary somatosensory cortex stimulation on mechanical and thermal thresholds in freely moving rats. Society for Neuroscience Abstract, 2012.

6. Jiny Sibi, Ai-Ling Li, Chao Zuo, Yang Wang, Xiaofei Yang, J.-C. Chiao, Yuan B. Peng: Stimulation of ventral tegmental area increases mechanical pain threshold and thermal pain latency in rats. Society for Neuroscience Abstract, 2012.

7. Ai-Ling Li, Chao Zuo, Yang Wang, Xiaofei Yang, J.-C. Chiao, Yuan B. Peng: Stimulation of the ventral tegmental area inhibits spinal cord dorsal horn neuronal activity. Society for Neuroscience Abstract, 2012.

8. Ruben Najera, Jiny E Sibi, Ai-Ling Li, Christopher McNabb, Perry N Fuchs, Yuan B Peng, Heekyeong Park: Deep Brain Stimulation of Entorhinal Cortex Enhances Spatial Memory in Rats. Society for Neuroscience Abstract, 2012

“We are grateful that TexasMRC Grant has provided us not only connection with clinicians, but valuable resources to continue the improvement and modification of our wireless recording and stimulating modules. Technologies under the support of this grant will benefit research and development in various future directions to target depression, pain, drug addition, and other psychiatric and neurological disorders. The grant also enabled us to obtain preliminary data for applications of research grants to study the disease models in a larger scale in order to establish clinically-relevant databases for future human uses.”

Primary Investigator:

Dr. Yuan Bo Peng, UTA
Associate Professor-Psychology
ypeng@uta.edu // (817) 272-5222 // Biography

Team Members:

J.-C Chiao Ph.D., UTA
Alan Podawiltz, D.O., UNTHSC
Beverly Wu, MD., UNTHSC
Sabatino Bianco, MD. FAANS., THR-AMH

 

 

 

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