Modulation of interhemispheric inhibition for the treatment of subcortical stroke

调节半球间抑制治疗皮质下中风

• 批准号: 8127346
• 负责人: KENNETH B BAKER
• 金额: $ 21.49万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8127346
• 关键词: Stroke

DESCRIPTION (provided by applicant): Cortex-sparing damage to the corticospinal tract, a possible outcome in cases of subcortical stroke or multiple sclerosis, can result in severe hemiparesis or hemiplegia. When the damage is complete, the prognosis for rehabilitation is extremely poor. In these cases, cortical reorganization of the affected hemisphere is unlikely to result in motor recovery given that the descending corticofugal fibers have been destroyed. And while transfer of motor representation to the non-affected hemisphere may be the most viable route to motor rehabilitation for such patients, such a transfer is likely to be limited by the persistence of interhemispheric inhibition (IHI) from the spared cortex of the affected side upon the contralesional hemispheric cortex. In the normal state, these connections are thought to suppress the latent motor representation of each hemisphere over the ipsilateral hemibody. The goal of this line of research is to develop a neuromodulation-based treatment approach to disrupt this suppressive effect, leading to disinhibition of the contralesional hemisphere's latent potential for motor control over the affected hemibody and enhance motor recovery. Experimentation will be carried out in two specific aims. Our approach involves the use of chronic, electrical stimulation of the corpus callosum to modulate interhemispheric communication and functionally disrupt on-going IHI. In specific aim 1, the goal is to determine the effect of chronic stimulation of the corpus callosum on motor recovery in a primate model of complete corticospinal/internal capsule lesion. Following placement of the corpus callosum stimulation electrode and a cephalic recording chamber, the internal capsule will be mapped unilaterally and ablated with electrodes placed through the chamber. The completeness of the lesion will be confirmed using motor evoked potentials derived from transcranial magnetic stimulation. Following three months of natural recovery, two three-month treatment blocks will take place with animals assigned to receive treatment during one of the two blocks and sham treatment in the other block. Motor function will be monitored using the modified Brinkman board as the primary outcome measure. In aim 2, we will determine whether chronic stimulation of the corpus callosum is associated with changes in motor representation of the contralesional motor cortex. We expect that chronic corpus callosum stimulation will lead the contralesional hemisphere to acquire motor representation and control over the affected side of the body. The preliminary data acquired from the proposed experimentation will be used for a subsequent pre-clinical application. PUBLIC HEALTH RELEVANCE: The goal of this study is to determine whether electrical stimulation of certain brain regions can be used to improve recovery in patients with motor deficits following stroke or other types of brain damage. In some cases of subcortical stroke, a type of stroke where the damage occurs deep in the brain, there is limited opportunity for recovery as the fibers that connect the brain to the body have been destroyed. There is evidence that the opposite side of the brain may have a latent ability to assume motor function over the side of the body that is impaired, however this ability is limited by on-going interactions that occur between the two sides of the brain by way of the corpus callosum. To address this, we propose to disrupt this communication between the two sides of the brain by electrically stimulating the corpus callosum in an animal model of stroke. The effect of stimulation on both motor recovery and the motor representation of the side of the body affected by the stroke will be monitored over time. New treatments that can further enhance recovery of function after strokes are necessary and, if proven efficacious, will have a dramatic impact given the combined high incidence and prevalence of neurological deficits and the high economic cost from stroke in the general population.

描述（由申请人提供）：皮质脊髓束的损害是皮层中风或多发性硬化症的可能结果，可能会导致严重的半肉食或偏瘫。损害完成后，康复的预后极为差。在这些情况下，鉴于降级皮层纤维已被破坏，受影响半球的皮质重组不太可能导致运动恢复。虽然将运动表示向不受影响的半球转移可能是此类患者运动康复的最可行的途径，但这种转移可能受到对相反半球皮层受影响的一侧的持续性皮层的持续性限制。在正常状态下，这些连接被认为可以抑制每个半球在同侧半体体上的潜在运动表示。这一研究的目的是开发一种基于神经调节的治疗方法，以破坏这种抑制作用，从而抑制了对侧半球对受影响的半身控制运动的潜在潜在的潜在潜力并增强运动恢复。实验将以两个特定的目的进行。我们的方法涉及使用慢性，对call体的慢性电刺激来调节半球间的通信并在功能上破坏正在进行的IHI。 在特定的目标1中，目标是确定call体慢性刺激对完全皮质脊髓/内囊病变的灵长类动物模型中的运动恢复的影响。在放置call体刺激电极和头膜记录室后，内部胶囊将单方面映射，并用放置在腔室的电极上擦拭。使用从经颅磁刺激衍生出的电动电势确认病变的完整性。在自然恢复三个月后，将在两个区块之一中分配的动物进行两个三个月的治疗块，在另一个区块中进行假治疗。将使用修改后的Brinkman板作为主要结果度量来监视运动功能。在AIM 2中，我们将确定对call体的慢性刺激是否与相反运动皮层的运动表示变化有关。我们预计，慢性call体刺激将导致对侧半球获得运动的表现并控制人体受影响的一侧。从提出的实验中获得的初步数据将用于随后的临床前应用。 公共卫生相关性：这项研究的目的是确定某些大脑区域的电刺激是否可用于改善中风后运动缺陷或其他类型的脑损伤的运动缺陷患者的恢复。在某些情况下，皮层中风，损害在大脑深处发生的一种中风，恢复的机会有限，因为将大脑与人体连接到人体的纤维已被破坏。有证据表明，大脑的相对侧可能具有潜在的能力，可以在身体的侧面假设运动功能受损，但是这种能力受到大脑双方通过call体之间的持续相互作用的限制。为了解决这个问题，我们建议通过在动物的中风模型中电力刺激call体，以破坏大脑双方之间的这种通信。随着时间的推移，刺激对受冲程影响的身体侧的运动恢复和运动侧的运动表示影响。鉴于神经系统缺陷的高发病率和流行率以及普通人群中中风的高经济成本，可以在中风后进一步增强功能恢复的新治疗方法。