Realistic Human Perception of Spatio-Temporal Thalamic Microstimulation

描述（由申请人提供）：已经证明，在人类丘脑刺激后，难以重建感知上准确和逼真的触摸和压力感觉。先前的人体实验主要使用具有规则刺激模式的单部位微刺激，这始终导致刺痛或感觉异常的感知，并且仅偶尔产生更自然的感觉。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急性切换头台中的电极对。我们开发了一种开关单元，用于快速连接各种电极对进行微刺激。使用这个连接到头台的开关单元，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的行为任务（n = 52例患者）期间用这些来自运动丘脑和丘脑底核的微丝阵列记录的大量经验的自然延伸。然后，我们接下来将在感觉丘脑中的双或多个微导线组合处施加模式化微刺激（10 - 50 5A），以再现诱发的实际机械皮肤输入。模式最初将包括具有增加的脉冲间间隔的减速刺激（如适应性初级感觉反应），具有逐渐缩短的脉冲间间隔的加速刺激，以及恒定的脉冲序列，在1秒的时间内施加相同数量的脉冲。然后将针对这三种模式严格评估患者对丘脑刺激的感知，同时逐渐改变刺激的幅度、持续时间（从100到1000毫秒）和位置（对不同的对）。这些实验将有助于揭示感觉丘脑中自然诱发反应的关键模式，并为插入逼真的感觉输入以开发感觉假体装置提供潜在的基底。R21机制将用于开发编程的多部位微刺激方案，并与分级触摸信号直接比较，评估患者衍生的真实感知概念。进一步的测试将使用DBS宏电极，但带有模式化微刺激，以评估是否可以将微导丝数据扩展到更大的视野。 公共卫生相关性：该项目将研究大脑如何在人类丘脑中处理感觉和感觉的感知。这项研究对于理解感觉异常改变的疾病（如神经损伤）非常重要。这项研究可能有助于理解如何将人工感觉信号解释为正常感觉，如果可以重新创建适当的空间和时间模式。这些结果可能会导致感觉假体来取代神经系统受损的感觉，以恢复功能。

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.