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》雜志“新聞與觀察”欄目的一則評(píng)論中，加利福尼亞大學(xué)神經(jīng)科學(xué)家Marin- I- Sereno認(rèn)為,，根據(jù)最新資料顯示,，成年動(dòng)物大腦可能比科學(xué)家所希望的可塑性更小。
馬薩諸塞州總醫(yī)院的霍華德·休斯醫(yī)學(xué)研究所（Howard Hughes Medical Institute）Stelios M.Smirnakis與馬克斯·普朗克生物控制論研究所（Max Planck Institute for Biological Cybernetics）的Nikos K. Logothetis一道,，使用功能性核磁共振成像技術(shù)（fMRI）對視網(wǎng)膜損傷后的成年猴子進(jìn)行為期7個(gè)半月的皮層活動(dòng)監(jiān)測。他們發(fā)現(xiàn),，原來的視覺皮層進(jìn)行了有限的重組,。
患有嚴(yán)重癲癇癥的兒童，在外科手術(shù)期間損傷整個(gè)大腦半球后,，仍然可能恢復(fù)對他們身體受到影響一側(cè)運(yùn)動(dòng)肌的控制,，并能夠發(fā)展正常的語言技能。 但是對于成年人,，大腦可塑性的實(shí)例已經(jīng)明顯減少,。
20世紀(jì)80年代和80年代的一系列研究表明，在成年動(dòng)物體內(nèi),，“填充”在運(yùn)動(dòng)肌和視覺皮層空白點(diǎn)的神經(jīng)元由于損傷而缺乏傳感輸入,，從而變得靜止。這引起一種猜測,，就是成年大腦可能能夠修復(fù)眼睛,、耳朵、皮膚甚至它本身的永久性損傷,。就對視網(wǎng)膜的損傷為例,，Smirnakis說：“占優(yōu)勢（但決不是普遍）的觀點(diǎn)認(rèn)為，早在原始視覺皮層時(shí)就已經(jīng)發(fā)生重大的視覺皮層重組,。”
但來自該團(tuán)隊(duì)的最新成像研究表明,，在猴子身上，情況并非如此,。Smirnakis說：“我們問：在視網(wǎng)膜損傷的原始視覺皮層附近的可見驅(qū)動(dòng)活動(dòng)能夠在損傷發(fā)生后的幾個(gè)月內(nèi)恢復(fù)到與損傷前相當(dāng)?shù)乃絾幔?答案為“是”,，在那個(gè)時(shí)間段，原始視覺皮層不能達(dá)到完全正常的敏感度,。”
要得出這一結(jié)論,，Smirnakis及其團(tuán)隊(duì)對四只猴子的視網(wǎng)膜進(jìn)行激光凝固，在視野的相同側(cè)面創(chuàng)建小盲點(diǎn),。 視網(wǎng)膜發(fā)送被大腦解釋為光,、顏色或物體的信號(hào),。在原始視覺皮層，視網(wǎng)膜的每一部分都相當(dāng)于一個(gè)特定區(qū)域,。 沒有任何可見信號(hào)需要譯解,，每只猴子相應(yīng)的盲點(diǎn)的皮層區(qū)就變得靜止，沒有任何活動(dòng),。
該研究團(tuán)隊(duì)測定了每個(gè)皮層靜止點(diǎn)的尺寸和形狀。 他們將輕度麻醉的猴子放在功能性核磁共振成像機(jī)器下,，用于測定血流量以及大腦活動(dòng),。 隨著猴子眼睛的睜開，該團(tuán)隊(duì)成員以凹處（視力最敏銳部分的視網(wǎng)膜上的小坳陷）為中心,，在動(dòng)物視網(wǎng)膜處聚焦各種柵格和圓形圖案,，并覆蓋盲點(diǎn)。 在進(jìn)行激光手術(shù)2到3小時(shí)之后,，測定皮層安靜區(qū)域的尺寸,，將其尺寸與每隔幾周所測到的尺寸相比,，直到七個(gè)半月,。
Smirnakis說：“如果猴子的視覺皮層確實(shí)重組了，那么關(guān)在籠子中進(jìn)行掃瞄時(shí),，它將會(huì)表現(xiàn)正常,。 然后，當(dāng)我們將它們帶回到掃描器時(shí),，其盲點(diǎn)皮層姆段Ы?崴跣?。′^?牽?導(dǎo)噬希?倉骨?虼笮∪勻幌嗤?Ｋ?芪У納窬??⒚揮薪?刑畛洹?/P>
由于功能性核磁共振成像的數(shù)據(jù)必須經(jīng)過譯碼,，研究人員用第二種方法檢驗(yàn)他們的結(jié)果,。 他們將微小的電極置于皮層上，并測定視覺皮層上電的活動(dòng),；映射出幾乎相同的皮層安靜區(qū)域,。 結(jié)果印證了功能性核磁共振成像技術(shù)的數(shù)據(jù)。
Smirnakis認(rèn)為,，在他進(jìn)行研究的2小時(shí)后到7個(gè)月之前的這一期間,，視覺皮層是有可能重組的。 其他研究已經(jīng)顯示,，有些視覺皮層修復(fù)在損傷發(fā)生后立即開始,，也可能在損傷后數(shù)年開始重組。
Smirnakis說：“因?yàn)樵谛碌拇竽X皮質(zhì)存在過類似的組織,，我們能推測,，新的調(diào)節(jié)視覺皮層重組的功能性聯(lián)系可能很難在其他地方形成,。 在這些區(qū)域的視覺皮層重組可能更加依賴現(xiàn)有圖案聯(lián)系的變化，它在皮質(zhì)下反饋,，或其他面到面的更寬的聯(lián)系,。 當(dāng)然，那只是進(jìn)行的高度推測,。 這也是可以想象的----雖然我們認(rèn)為可能性很小----在新皮層區(qū)而不是原始視覺皮層上,，新的功能聯(lián)系也許在更早的時(shí)間就已經(jīng)形成，而且神經(jīng)軸突的萌芽可能需要更長一段時(shí)間才能發(fā)生,。”
Smirnakis補(bǔ)充說：研究還確定,，功能性核磁共振成像技術(shù)（fMRI）是測定猴子大腦視覺皮層重組的有效方法。 將來可能會(huì)有類似的研究來展現(xiàn)科學(xué)家是如何幫助受損大腦恢復(fù)的,。 他說：“在人體上很難研究大腦皮層的重組,。皮層損傷并非以可控的方式發(fā)生，從而得到的數(shù)據(jù)很難解釋,。 但是,，我們卻可以在猴子身上設(shè)計(jì)所需要的損傷，并可以在腦卒中發(fā)生后測試藥品,，將大腦能夠進(jìn)行的視覺皮層重組歸類,。這是一個(gè)在將來可能有益的激勵(lì)和研究皮層重組的有效方法。”
