Realistic Human Perception of Spatio-Temporal Thalamic Microstimulation

描述（由申请人提供）：事实证明，在人类丘脑刺激后，很难重建感知上准确和真实的触摸和压力感觉。以前的人体实验主要使用单部位微刺激和有规律的刺激模式，这始终会导致刺痛或感觉异常的感觉，偶尔才会有更自然的感觉。我们建议在进行丘脑DBS手术的同时，在术中实验中对人类感觉丘脑进行多部位微刺激。在这些实验中，我们将首先测试16或32通道Adtech微线阵列和Tucker- Davis急性切换头级的电极对。我们开发了一种开关装置，可以快速连接各种电极对进行微刺激。使用这个连接到头级的开关单元，我们可以快速评估多对电极的诱发感觉反应。这些实验是我们在复杂行为任务中使用运动丘脑和丘脑下核的微线阵列进行记录的丰富经验的自然延伸（n = 52例患者）。然后，我们接下来将在感觉丘脑的双或多微线组合上应用图案微刺激（10 - 50 5A），以重现引起的实际机械皮肤输入。模式最初将包括一个脉冲间隔增加的减速刺激（就像一个适应性的初级感觉反应），一个脉冲间隔逐渐缩短的加速刺激，以及一个恒定的脉冲序列，在1秒的周期内施加相同数量的脉冲。然后，患者对丘脑刺激的感知将根据这三种模式进行严格评估，同时逐步改变刺激的幅度、持续时间（从100毫秒到1000毫秒）和刺激的位置（到不同的对）。这些实验将有助于揭示感觉丘脑自然诱发反应的关键模式，并为开发感觉假肢装置提供现实感觉输入的潜在基础。R21机制将用于开发程序化的多部位微刺激方案，并评估患者衍生的现实感知概念，直接与分级触摸信号进行比较。进一步的测试将使用DBS宏观电极，但采用图案微刺激，以评估是否有可能将微线数据扩展到更大的油田。

DESCRIPTION (provided by applicant): It has proven difficult to recreate perceptually accurate and realistic touch and pressure sensation following thalamic stimulation in humans. Previous human experiments have used primarily single-site microstimulation with regular patterns of stimulation, which consistently results in a perception of tingling or paresthesias, and only occasionally a more natural sensation. We propose to perform multi-site microstimulation in human sensory thalamus during intra-operative experiments, while performing thalamic DBS surgery. During these experiments we will first test pairs of electrodes in a 16 or 32-channel Adtech microwire array and a Tucker- Davis acute, switching headstage. We have developed a switching unit to rapidly connect various pairs of electrodes for microstimulation. Using this switching unit connected to the headstage we can rapidly evaluate multiple pairs of electrodes for the evoked sensory response. These experiments are a natural extension of our large experience in recording with these microwire arrays from motor thalamus and subthalamic nucleus during a complex behavioral task (n = 52 patients). Then, we will next apply patterned microstimulation (10 - 50 5A) at dual or multiple microwire combinations in the sensory thalamus, to recreate the evoked actual mechanical skin input. Patterns will initially consist of a decelerating stimulus with an increasing interpulse interval (like an adapting primary sensory response), an accelerating stimulus with progressively shorter interpulse intervals, and a constant pulse sequence, with the same number of pulses applied over a 1 sec period. The patient's perception of the thalamic stimulation will then be critically assessed for these three patterns, while progressively altering the amplitude, the duration (from 100 to 1000 msec) and the location of the stimulation (to different pairs). These experiments will both help reveal the critical patterning of the natural evoked responses in sensory thalamus, as well as provide a potential substrate for insertion of realistic sensory inputs for development of a sensory prosthetic device. The R21 mechanism will be used to develop the programmed multisite microstimulation protocols and to assess the patient-derived concept of realistic perception, in direct comparison to a graded touch signal. Further tests will use a DBS macro-electrode, but with patterned microstimulation, to assess whether it is possible to extend the microwire data to a larger field. PUBLIC HEALTH RELEVANCE: This project will study how the brain processes sensation and the perception of sensation, in the human thalamus. This study will be important to understanding diseases where sensation is abnormally altered, such with nerve damage. This research may help to understand how an artificial sensory signal could be interpreted as a normal sensation, if the proper spatial and temporal pattern can be recreated. These results may lead to a sensory prosthesis to replace sensation where the nervous system has been damaged, for restoration of function.