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）：皮质脊髓束的皮质保留损伤是皮质下中风或多发性硬化症的可能结果，可导致严重的偏瘫或偏瘫。当损伤完全时，康复的预后极差。在这些情况下，鉴于下行皮质纤维已被破坏，受影响半球的皮质重组不太可能导致运动恢复。虽然将运动表征转移到未受影响的半球可能是此类患者运动康复的最可行途径，但这种转移可能会受到受影响一侧未受损害的皮质持续存在的半球间抑制（IHI）的限制。位于对侧半球皮质上。在正常状态下，这些连接被认为抑制了同侧半体上每个半球的潜在运动表征。这一系列研究的目标是开发一种基于神经调节的治疗方法来破坏这种抑制作用，从而解除对侧半球对受影响半体运动控制的潜在潜力并增强运动恢复。实验将针对两个具体目标进行。我们的方法涉及使用胼胝体的慢性电刺激来调节半球间通讯并从功能上破坏正在进行的 IHI。 具体目标 1 的目标是确定胼胝体慢性刺激对皮质脊髓/内囊完全损伤的灵长类动物模型运动恢复的影响。在放置胼胝体刺激电极和头侧记录室后，将单侧绘制内囊图并用穿过室放置的电极进行消融。将使用源自经颅磁刺激的运动诱发电位来确认病变的完整性。经过三个月的自然恢复后，将进行两个为期三个月的治疗组，动物被分配在两个组中的一个组中接受治疗，并在另一个组中接受假治疗。将使用改良的 Brinkman 板作为主要结果测量来监测运动功能。在目标 2 中，我们将确定胼胝体的慢性刺激是否与对侧运动皮层运动表征的变化相关。我们预计，慢性胼胝体刺激将导致对侧半球获得运动表征并控制身体受影响的一侧。从拟议实验中获得的初步数据将用于后续的临床前应用。 公共健康相关性：本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或其他类型脑损伤后运动缺陷患者的康复。在某些皮质下中风（一种损伤发生在大脑深处的中风）中，由于连接大脑与身体的纤维已被破坏，恢复的机会有限。有证据表明，大脑的另一侧可能具有在身体受损一侧承担运动功能的潜在能力，但是这种能力受到大脑两侧之间持续相互作用的限制胼胝体。为了解决这个问题，我们建议通过电刺激中风动物模型中的胼胝体来破坏大脑两侧之间的这种交流。随着时间的推移，将监测刺激对运动恢复和受中风影响的身体一侧的运动表征的影响。考虑到神经功能缺损的高发病率和普遍性以及普通人群中风带来的高昂经济成本，能够进一步促进中风后功能恢复的新疗法是必要的，如果被证明有效，将会产生巨大的影响。