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[双语阅读] 大脑是恶性压力循环的罪魁祸首

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发表于 2010-2-27 00:06 | 显示全部楼层 |阅读模式

If after a few months’ exposure to our David Lynch economy, in which housing markets spontaneously combust, coworkers mysteriously disappear and the stifled moans of dying 401(k) plans can be heard through the floorboards, you have the awful sensation that your body’s stress response has taken on a self-replicating and ultimately self-defeating life of its own, congratulations. You are very perceptive. It has.

As though it weren’t bad enough that chronic stress has been shown to raise blood pressure, stiffen arteries, suppress the immune system, heighten the risk of diabetes, depression and Alzheimer’s disease and make one a very undesirable dinner companion, now researchers have discovered that the sensation of being highly stressed can rewire the brain in ways that promote its sinister persistence.

Reporting earlier this summer in the journal Science, Nuno Sousa of the Life and Health Sciences Research Institute at the University of Minho in Portugal and his colleagues described experiments in which chronically stressed rats lost their elastic rat cunning and instead fell back on familiar routines and rote responses, like compulsively pressing a bar for food pellets they had no intention of eating.

Moreover, the rats’ behavioral perturbations were reflected by a pair of complementary changes in their underlying neural circuitry. On the one hand, regions of the brain associated with executive decision-making and goal-directed behaviors had shriveled, while, conversely, brain sectors linked to habit formation had bloomed.

In other words, the rodents were now cognitively predisposed to keep doing the same things over and over, to run laps in the same dead-ended rat race rather than seek a pipeline to greener sewers. “Behaviors become habitual faster in stressed animals than in the controls, and worse, the stressed animals can’t shift back to goal-directed behaviors when that would be the better approach,” Dr. Sousa said. “I call this a vicious circle.”

Robert Sapolsky, a neurobiologist who studies stress at Stanford University School of Medicine, said, “This is a great model for understanding why we end up in a rut, and then dig ourselves deeper and deeper into that rut.”

The truth is, Dr. Sapolsky said, “we’re lousy at recognizing when our normal coping mechanisms aren’t working. Our response is usually to do it five times more, instead of thinking, maybe it’s time to try something new.”

And though perseverance can be an admirable trait and is essential for all success in life, when taken too far it becomes perseveration — uncontrollable repetition — or simple perversity. “If I were to try to break into the world of modern dance, after the first few rejections the logical response might be, practice even more,” said Dr. Sapolsky, the author of “Why Zebras Don’t Get Ulcers,” among other books. “But after the 12,000th rejection, maybe I should realize this isn’t a viable career option.”

Happily, the stress-induced changes in behavior and brain appear to be reversible. To rattle the rats to the point where their stress response remained demonstrably hyperactive, the researchers exposed the animals to four weeks of varying stressors: moderate electric shocks, being encaged with dominant rats, prolonged dunks in water. Those chronically stressed animals were then compared with nonstressed peers. The stressed rats had no trouble learning a task like pressing a bar to get a food pellet or a squirt of sugar water, but they had difficulty deciding when to stop pressing the bar, as normal rats easily did.

But with only four weeks’ vacation in a supportive setting free of bullies and Tasers, the formerly stressed rats looked just like the controls, able to innovate, discriminate and lay off the bar. Atrophied synaptic connections in the decisive regions of the prefrontal cortex resprouted, while the overgrown dendritic vines of the habit-prone sensorimotor striatum retreated.

According to Bruce S. McEwen, head of the neuroendocrinology laboratory at Rockefeller University, the new findings offer a particularly elegant demonstration of a principle that researchers have just begun to grasp. “The brain is a very resilient and plastic organ,” he said. “Dendrites and synapses retract and reform, and reversible remodeling can occur throughout life.”

Stress may be most readily associated with the attosecond pace of postindustrial society, but the body’s stress response is one of our oldest possessions. Its basic architecture, its linked network of neural and endocrine organs that spit out stimulatory and inhibitory hormones and other factors as needed, looks pretty much the same in a goldfish or a red-spotted newt as it does in us.

The stress response is essential for maneuvering through a dynamic world — for dodging a predator or chasing down prey, swinging through the trees or fighting off disease — and it is itself dynamic. As we go about our days, Dr. McEwen said, the biochemical mediators of the stress response rise and fall, flutter and flare. “Cortisol and adrenaline go up and down,” he said. “Our inflammatory cytokines go up and down.”

The target organs of stress hormones likewise dance to the beat: blood pressure climbs and drops, the heart races and slows, the intestines constrict and relax. This system of so-called allostasis, of maintaining control through constant change, stands in contrast to the mechanisms of homeostasis that keep the pH level and oxygen concentration in the blood within a narrow and invariant range.

Unfortunately, the dynamism of our stress response makes it vulnerable to disruption, especially when the system is treated too roughly and not according to instructions. In most animals, a serious threat provokes a serious activation of the stimulatory, sympathetic, “fight or flight” side of the stress response. But when the danger has passed, the calming parasympathetic circuitry tamps everything back down to baseline flickering.

In humans, though, the brain can think too much, extracting phantom threats from every staff meeting or high school dance, and over time the constant hyperactivation of the stress response can unbalance the entire feedback loop. Reactions that are desirable in limited, targeted quantities become hazardous in promiscuous excess. You need a spike in blood pressure if you’re going to run, to speedily deliver oxygen to your muscles. But chronically elevated blood pressure is a source of multiple medical miseries.

Why should the stressed brain be prone to habit formation? Perhaps to help shunt as many behaviors as possible over to automatic pilot, the better to focus on the crisis at hand. Yet habits can become ruts, and as the novelist Ellen Glasgow observed, “The only difference between a rut and a grave are the dimensions.”

It’s still August. Time to relax, rewind and remodel the brain.

 

如果你能在大卫林奇经济状况下呆上几个月,这的房屋自发燃烧,办公室的人谜一般的消失,充斥着耳膜的是人们面对致人死地的工作计划时发出的让人窒息的呻吟声,这时候,你身体的压力反应系统已经启动了自我修复机制,但最终还是自暴自弃。恭喜你,你很敏感。的确如此。

如果说长期的压力导致血压上升,动脉硬化,免疫系统抑制,高糖尿病患病率,抑郁,阿尔茨海默症和使人变成恶性竞争者还不是太糟的话,现在研究者们发现长期处在压力状态下能够使大脑重建来提高它的恶性的承受力。

今年初夏的科学杂志上报到,波多黎各Minho大学生命健康研究所的Nuno Sousa 和他的同伴描述了这样一项实验:在长期高压下生活的大鼠失去了他们狡猾的本性,它们宁愿拒绝吃东西,也不会尝试回到熟悉的路线和回忆曾经通过死记硬背掌握的反应,例如强制性的按食物盘子的按钮。

另外,老鼠的行为干扰还反映为它们的基本神经回路中出现了一对互补的改变。一方面,与大脑执行决策制定和目标导向行为有关的区域萎缩,另一方面,与习惯形成有关的大脑的区域却增加了。

换句话说,啮齿类目前被认为先天喜欢重复的做同一件事,他们会在同一个死胡同似的大鼠田径场上跑圈而不愿意寻找一个通往更方便的下水道处的输油管道。“行为在有压力的动物中比在对照组能够更快的变成习惯,更糟的是,当有更好的选择时,有压力的动物不能重新回到目标导向行为的状态。”Sousa博士说。“我管这个叫恶性循环。”

在斯坦福大学医学院研究压力的神经学家Robert Sapolsky说,“这个模型可以很好的解释为什么我们总是在刻板乏味的生活中混沌而终,并且在这种生活中越陷越深。”

事实上,Dr. Sapolsky 说,“当我们标准的应付模式玩不转时,我们在认知方面简直是一团糟。相比于思考,在做一件事时我们自发的反应会重复这件事5次,可能是时候试试新玩意了。”

尽管恒心毅力是个令人羡慕的品质并且是成功必不可少的要素,但是一旦过度它就变成了固执--不可控制的重复--或者简单的坚持。“如果我正在尝试进入现代舞的世界--在开始的几次失败之后,逻辑反应可能是更多的练习。Dr. Sapolsky说,他是“为什么斑马不得溃疡”一书的作者。“但是在遭到第12000次拒绝以后,可能我会认识到这对我来说不是一个有前景的职业。”

很高兴,行为和大脑中压力诱导的的改变可能能够恢复。为了使大鼠的压力反应达到最活跃点,研究者让实验动物在不同的压力环境中生存如温和的机械振动,和吵闹的大鼠关在同一只笼子里,延长在水中浸泡的时间。将长期压抑的动物和没有压力的动物相比。受到压力的大鼠在学习某些任务时,诸如按按钮取得食物或者从一个鞘里得到糖水,但是他们在决定何时停止压按钮的时候比普通的大鼠要困难。

但是在为期四周没有欺负没有噪声的假期后, 从前受到压力的大鼠看起来很像对照组,能够创造,辨别和停止按按钮。大脑前额皮层的决定区域内萎缩的突出连接重新生长,而习惯倾向感应纹状体中过度生长的树突则萎缩了。

根据洛克菲勒大学神经内分泌实验室的首席科学家Bruce S. McEwen的研究,新的发现为研究者刚刚开始研究的理论提供了优异的解释。“大脑是一个安静有可塑性的器官,”他说。树突和突触可以回缩和重建,可回复的模型在整个生命进程中都可发生。

压力可能与后工业社会快节奏的生活有关,但是身体的压力反应系统自古便已存在。它的基本体系结构,与神经和分泌刺激抑制的荷尔蒙的内分泌器官相连的网状结构和其他的必须的因素,在金鱼和红斑蝾螈中与在人类中看起来没什么两样。

压力反应系统对于在动力学世界中生存是必不可少的---对于逃避捕猎者,或追捕猎物,在树丛里摇来摇去或者抗击疾病--它自身就是一种动力系统。在今天,McEwen博士说,压力系统的生化干扰因素升高和降低。“皮质醇和肾上腺素升高和降低,”他说。“我们的煽动性的细胞因子升高和降低。”

压力荷尔蒙的目标器官类似于和着节拍起舞:血压升高和降低,心脏跳得快跳得慢,肠胃紧缩和放松。这个系统叫做拮抗平衡,即在永恒的变化中保持平衡,与将pH值和血液中氧气的浓度保持在一个狭窄不变的范围内的体内平衡机制是相反的。

不幸的是,我们的压力控制系统的动力机制使之变得容易被打破,尤其是当其超负荷工作时。在大多数动物中,严重的威胁存生压力反应系统刺激,同情和“或打或逃”功能的激活。但是当危险过去,平静的副交感神经通路将所有的反应都清零。

在人类中,尽管大脑可以思考,将阴魂不散的恐惧和与他人的见面,高校舞会分开,压力反应系统长时间处于高活力状态会将整个反馈的环打破。可取的范围内和目标量以内的反应在滥用的情况下会成为灾难。当人们跑步的时候,身体为了更快的向肌肉中输送氧气,会使血压达到峰值。但如果血压长期属于升高状态,有可能引起一系列的疾病。

为什么有压力的头脑倾向于形成某种习惯?可能是为了将尽量多的行为转变成自动发出的,从而更好的面对危机。然而习惯可能b变成使人裹足不前的绊脚石。就像小说家Ellen Glasgow观察到的那样,“在停止和死亡之间的唯一不同就是他们的程度。

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