Brain May Be Less Plastic Than Hoped
The visual cortex of the adult primate brain displays less flexibility in response to retinal injury than previously thought, according to a new study published in the May 19, 2005, issue of the journal Nature. This may have implications for other regions of the brain, and the approach the investigators used may be a key to developing successful neurological interventions for stroke patients in the future.
Stelios M. Smirnakis, a Howard Hughes Medical Institute physician-postdoctoral fellow at Massachusetts General Hospital, and colleagues including Nikos K. Logothetis of the Max Planck Institute for Biological Cybernetics used functional magnetic resonance imaging (fMRI) to monitor cortical activity for seven and one-half months after injury to the retina of adult monkeys. They found limited reorganization in the primary visual cortex.
Their results contradict previous thinking. In a “News and Views” commentary published in the same issue of Nature, Martin I. Sereno, a neuroscientist at the University of California, San Diego, says the latest data indicate that adult brains may be less plastic than scientists had hoped.
In children, the brain's ability to compensate for injuries is well known. Children with severe epilepsy who lose an entire hemisphere during surgery can regain motor control on the affected side of their body and go on to develop normal language skills. But in adults, the case for brain plasticity has been less clear.
A series of studies in the 1980s and 1990s seemed to show that, in adult animals, neurons “filled in” blank spots in the motor and visual cortex after these areas fell silent from lack of sensory input due to injury. This led to speculation that adult brains could compensate for permanent damage to the eyes, ears, skin, or even to itself. In the case of damage to the retina, Smirnakis said, “the predominant-but by no means universal-view was that significant reorganization occurred as early as it does in the primary visual cortex.”
But the latest imaging research from his team shows that, in monkeys, this is not the case. “We asked: Can visually driven activity in the region of the primary visual cortex that corresponds to the retinal injury recover to pre-lesional levels in the months following the lesion?” said Smirnakis. “The answer is, in that time interval the primary visual cortex did not achieve anything like normal responsivity.”
To arrive at this conclusion, Smirnakis and his group first photocoagulated the retinas of four monkeys with a laser, creating small blind spots on the same sides of the field of vision. The retina sends signals that the brain interprets as light, color, or objects. Each section of the retina corresponds to a specific location in the primary visual cortex. Without any visual signal to interpret, the cortical area corresponding to each monkey's blind spot fell silent, generating no activity.
The team measured the size and shape of each of these cortical quiet spots. They placed the lightly anesthetized monkeys into a fMRI machine, which measures blood flow, and hence, brain activity. With the monkey's eyes held open, the team focused various grid and circle patterns on the animal's retina, centered on the fovea—a small depression in the retina where vision is most acute—and covering the blind spot. They made baseline measurements of the cortical quiet zone two to three hours after the laser surgery and compared them to new readings taken every few weeks for up to seven and a half months.
“If the visual cortex of the monkeys did reorganize, it would happen as they were behaving normally in their cages in between scans,” said Smirnakis. “And then, when we brought them back to the scanner, the region of their cortex corresponding to the blind spot would have shrunk.” Instead, though, the silent region remained the same size each time. The neurons surrounding it did not reach out to fill it in.
Because fMRI data is subject to interpretation, the researchers checked their results with a second method. They placed tiny electrodes on the cortex and measured electrical activity in the visual cortex; mapping virtually the same cortical quiet zones. The results confirmed the fMRI readings.
Smirnakis said it is possible that the visual cortex could reorganize before or after the two- hour to seven-month time frame of his study. Other research has suggested that the visual cortex adapts somewhat immediately after injury. “And it is possible that, years after injury, the visual cortex could begin to reorganize,” he said.
“Since there is similar organization across the neocortex of the brain, we could speculate that functional new connections mediating reorganization may also be difficult to form elsewhere,” Smirnakis added. “Reorganization in these areas might then depend more on the modification of existing patterns of connectivity, be it subcortical, feedback, or other broad area-to-area connections. Of course, that is highly speculative. It is also conceivable—although in our opinion less likely—that in neocortical areas other than the primary visual cortex, new functional connections may have an easier time forming, and axonal sprouting may occur over longer distances.”
The study also establishes fMRI as a valid method to measure reorganization in the monkey brain, Smirnakis added. Similar studies could one day show scientists how to help the brain to recover from injuries. “In humans, studying brain reorganization is difficult. Cortical injuries are not happening in a controlled fashion, and resulting data consequently are difficult to interpret,” he said. “But in the macaque, you can design lesions and test pharmaceuticals to sort out what kind of reorganization the brain is capable of after, say, a stroke. It's a powerful way to stimulate and study reorganization that may turn out to be beneficial in the future.”
From Howard Hughes Medical Institute
2005年5月19日刊登在《自然》杂志“新闻与观察”栏目的一则评论中，加利福尼亚大学神经科学家Marin- I- Sereno认为，根据最新资料显示，成年动物大脑可能比科学家所希望的可塑性更小。
马萨诸塞州总医院的霍华德·休斯医学研究所（Howard Hughes Medical Institute）Stelios M.Smirnakis与马克斯·普朗克生物控制论研究所（Max Planck Institute for Biological Cybernetics）的Nikos K. Logothetis一道，使用功能性核磁共振成像技术（fMRI）对视网膜损伤后的成年猴子进行为期7个半月的皮层活动监测。他们发现，原来的视觉皮层进行了有限的重组。
患有严重癫痫症的儿童，在外科手术期间损伤整个大脑半球后，仍然可能恢复对他们身体受到影响一侧运动肌的控制，并能够发展正常的语言技能。 但是对于成年人，大脑可塑性的实例已经明显减少。
20世纪80年代和80年代的一系列研究表明，在成年动物体内，“填充”在运动肌和视觉皮层空白点的神经元由于损伤而缺乏传感输入，从而变得静止。这引起一种猜测，就是成年大脑可能能够修复眼睛、耳朵、皮肤甚至它本身的永久性损伤。就对视网膜的损伤为例，Smirnakis说：“占优势（但决不是普遍）的观点认为，早在原始视觉皮层时就已经发生重大的视觉皮层重组。”
但来自该团队的最新成像研究表明，在猴子身上，情况并非如此。Smirnakis说：“我们问：在视网膜损伤的原始视觉皮层附近的可见驱动活动能够在损伤发生后的几个月内恢复到与损伤前相当的水平吗？ 答案为“是”，在那个时间段，原始视觉皮层不能达到完全正常的敏感度。”
要得出这一结论，Smirnakis及其团队对四只猴子的视网膜进行激光凝固，在视野的相同侧面创建小盲点。 视网膜发送被大脑解释为光、颜色或物体的信号。在原始视觉皮层，视网膜的每一部分都相当于一个特定区域。 没有任何可见信号需要译解，每只猴子相应的盲点的皮层区就变得静止，没有任何活动。
该研究团队测定了每个皮层静止点的尺寸和形状。 他们将轻度麻醉的猴子放在功能性核磁共振成像机器下，用于测定血流量以及大脑活动。 随着猴子眼睛的睁开，该团队成员以凹处（视力最敏锐部分的视网膜上的小坳陷）为中心，在动物视网膜处聚焦各种栅格和圆形图案，并覆盖盲点。 在进行激光手术2到3小时之后，测定皮层安静区域的尺寸，将其尺寸与每隔几周所测到的尺寸相比，直到七个半月。
Smirnakis说：“如果猴子的视觉皮层确实重组了，那么关在笼子中进行扫瞄时，它将会表现正常。 然后，当我们将它们带回到扫描器时，其盲点皮层姆段Ы?崴跣 ！钡?牵?导噬希?仓骨?虼笮∪匀幌嗤?Ｋ?芪У纳窬??⒚挥薪?刑畛洹?/P>
由于功能性核磁共振成像的数据必须经过译码，研究人员用第二种方法检验他们的结果。 他们将微小的电极置于皮层上，并测定视觉皮层上电的活动；映射出几乎相同的皮层安静区域。 结果印证了功能性核磁共振成像技术的数据。
Smirnakis认为，在他进行研究的2小时后到7个月之前的这一期间，视觉皮层是有可能重组的。 其他研究已经显示，有些视觉皮层修复在损伤发生后立即开始，也可能在损伤后数年开始重组。
Smirnakis说：“因为在新的大脑皮质存在过类似的组织，我们能推测，新的调节视觉皮层重组的功能性联系可能很难在其他地方形成。 在这些区域的视觉皮层重组可能更加依赖现有图案联系的变化，它在皮质下反馈，或其他面到面的更宽的联系。 当然，那只是进行的高度推测。 这也是可以想象的----虽然我们认为可能性很小----在新皮层区而不是原始视觉皮层上，新的功能联系也许在更早的时间就已经形成，而且神经轴突的萌芽可能需要更长一段时间才能发生。”
Smirnakis补充说：研究还确定，功能性核磁共振成像技术（fMRI）是测定猴子大脑视觉皮层重组的有效方法。 将来可能会有类似的研究来展现科学家是如何帮助受损大脑恢复的。 他说：“在人体上很难研究大脑皮层的重组。皮层损伤并非以可控的方式发生，从而得到的数据很难解释。 但是，我们却可以在猴子身上设计所需要的损伤，并可以在脑卒中发生后测试药品，将大脑能够进行的视觉皮层重组归类。这是一个在将来可能有益的激励和研究皮层重组的有效方法。”
