Cognition, emotion and the cerebellum.

The following was presented at the 2008 NAF Annual Membership Meeting in Las Vegas, NV and edited for publication in Generations.

We're going to talk about a topic that is somewhat new in the ataxia world, new to doctors but not new to patients. And this is the notion of cognition, emotion and the cerebellum. Emotion we all understand what that is--what makes us feel things. Cognition is intellectual function--planning, reasoning, forming strategies, language formation, finding our way in space. That's the large understanding of what cognition entails. What I'm going to go through with you is a brief background of what it is about the cerebellum that lends itself to playing a role in cognition and emotion. I'm going to talk about the clinical phenomena that are important in this scenario, and then end off with some comments about how you can be proactive in thinking about these aspects of your everyday function in the setting of cerebellar disorders.

The cerebellum looks the same everywhere when you look at it under the microscope, but the connections of different parts of cerebellum to different parts of brain are quite importantly distinct. The part called the anterior lobe is linked up with the part of the brain that's important for movement, and the posterior lobe is linked up to part of the brain that are important for planning, reasoning, thinking, understanding, language and so on, and the middle line of the cerebellum which is called the vermus, is linked up to parts of the brain that are important for emotional processing. So there is a way for cerebellum to talk to the big brain upstairs not just in motor regions but to areas involved in cognition and emotion as well.

A different place in the cerebellum is active when one doesn't just speak words, but does a manipulation to words when one has to think of another word. For example, if I show you the picture of a chair, you have to say the word "sit" you're generating a verb for a noun so there's a language component, an intellectual process, that activates cerebellum but in a different place than the part of cerebellum involved in the actual formation of the words. There's a difference between language and speech and they activate different parts of cerebellum. The cerebellum is [also] important for love and emotional expression and certainly intensely held emotions.

When I went to the bedside and examined some of my patients who had a stroke in the cerebellum they've had some kind of problem either in the blood vessels in the neck or a problem in the heart. A piece of something flew up into the brain and caused a blockage of blood vessels and they had a stroke. This is an old-fashioned way of comparing structure in the brain to function. Those who had a stroke involving the anterior lobe in a blood vessel called the superior cerebellar artery, these people had ataxia on the same side as where the stroke took place. In-coordination of the arm and the leg, that was what one expects in the old-fashioned view of cerebellum. But when the people who had a stroke that involved not the anterior lobe but the bottom part, the posterior lobe, when I examined them their ataxia rating scale score was negative, was normal. And they didn't have problems with movement. So what was their problem? A number of patients who have strokes or tumors taken out or trouble in the back part of cerebellum called the posterior lobe, have a change in behavior.

When you look at this in a larger context, we described a syndrome in people who have cerebellar troubles which are called the cerebellar cognitive affective syndrome. And this is a constellation, a combination of troubles that include problems with executive function, spatial cognition, language deficits and personality changes. The executive function is what we think of generally as frontal lobe function (planning, organizing, strategy formation, verbal reasoning, holding something in mind and manipulating it). And it's also very important for multi-tasking, something that people consistently report to me as an issue when they have cerebellar difficulties. Spatial cognition involves awareness of where one is in space, ability to navigate in space. I've heard more than once from someone with a true motor ataxia who would report to me that they're bumping into the wall as they try to go into another room not because they can't control their motion, but because they seem to misjudge the distance. And that's a very interesting use of turn of phrase, to report what we see as motor in-coordination but what patients may describe as an inability to put together your sense of where the world is in terms of your own body. It has a sensory component to it.

Personality change happens (in the people that we saw in the clinic) when the mid-line of cerebellum was involved and this had a remarkable pattern. There was a blunting of their expression of emotion that made people look depressed and sometimes they in fact were, but at the same time they could be actually a little dis-inhibited in their behaviors, not quite checking their behaviors in a way one would expect in normal interactions. We found a similar kind of problem in children who'd had tumors taken out of the cerebellum. In the children that we looked at, there was a constellation of difficulties of failure to organize their own thinking, verbal and visual spatial material, their planning was impaired, language was troublesome, and memory for stories was troublesome. Again, when the mid-line was involved, some of these children had a dramatic change in their behaviors. Some of them (between 15 and 30% depending on the study) stopped talking, they get what's called cerebellar mutism--it's a posterior facisyndrome, which can go on for some weeks and even beyond that after a surgery taking a tumor out of the cerebellum. And in addition to that there's a change in their behavior, they can be impulsive and irritable and quite aggressive on one hand, and on the other hand sort of happy and giggly and playful--a marked change in their behavior from one moment to the next as you're with them in the room.

We know from studies of people who have a variety of cerebellar degeneration disorders that there is a high incidence of what the group at Johns Hopkins called non-cognitive psychiatric disorders, the commonest of which was mood disorder. Depression is a major problem in people who have a variety of ataxias from the neurodegenerative disorders including the SCA's and sporadic ataxias and so on. We also know from a large body of literature now that autism, which is a common problem as you know, schizophrenia, attention deficit disorder, dyslexia, and even children who are born very pre-term when you study them with time, and you look at the brains of some of these folks who have passed on we see that there are changes in the cerebellum sometimes in conjunction with changes elsewhere. But we know that these are behaviorally defined disorders. Not ataxia, but problems in behavior in which there is a cerebellar abnormality. This relationship of cerebellum to behavior comes from both angles.

Over the last 15-20 years as people have come to spend time with us in the clinic they have reported a variety of impairments that I then looked at in a more systematic manner to see what is the nature of the affective change in the cerebellar cognitive affective syndrome? Cognition being intellect, affective being emotional expression and experience.

The symptoms together divide up into five major groups of difficulty: attentional control, emotional control, along the spectrum of autistic behaviors, psychosis spectrum, and social skill set which is actually quite a common issue. The symptoms in these categories can be divided as I've looked at them. In one category the symptoms are down or depressed; in another they're actually exaggerated or enhanced. And this is somewhat like the problem of movement control in cerebellum, the dysmetria of movement where there's an overshoot and undershoot in the movement domain. One tries to reach for something and you overshoot or you reach and you don't quite get there. The same thing seems to apply to the domains of cognition and emotion.

In the range of attentional control: distractibility, hyper-activity, compulsive behaviors, ritualistic behaviors, these can be problems that one experiences in some people who have cerebellar difficulties. Rumination is the opposite, getting stuck and set, staying with the same kind of thinking pattern, obsessional thoughts may be a problem in folks with cerebellar pathologies [as well as] emotional control, impulsive, dis-inhibition, sometimes in feelings being incongruence to the state of mind that you're in. This happens for example, in multiple system atrophy, probably 30 to 40 percent of patients who have cerebellar type MSA have what's called pathologic laughing and crying. Where there may be exaggerated expression of emotion even in the absence of the feeling state that goes along with that, crying or laughing when one doesn't feel sad or happy or doing it in a manner exaggerated or inappropriate to the context. There can be a sense of depression, sadness, hopelessness that goes along with this emotional control difficulty.

In the children that we've seen the autistic spectrum behaviors are really quite striking and they include just like autistic kids stereotypical behaviors head rocking and banging behaviors. They don't like sensory contact so you get this avoidant behavior and tactile defensiveness. A couple of cases I'll describe had this psychosis spectrum, illogical thought, paranoid thinking, a lack of empathy or an apathy, an inability to engage appropriately in emotional interactions. Then finally, the social skill set, where there can be difficulty in interacting with people in the playground that these children have. For example, inability to control the anger, irritability, sometimes overly territorial, overly possessive. On the other side of that, overly passive or immature, not understanding social boundaries and being too gullible and too trusting.

Where one takes all of this observation is that we hear from you, our patients, who teach us what it is that we need to understand about the cerebellum, is that the cerebellum is not involved only in motor control. Ataxia certainly is a movement disorder; it's a problem as nobody else can know better than you can. But in addition to that, it appears that different parts of the cerebellum regulate different kinds of functions. We know that the motor cerebellum is predominantly in the top part, the anterior lobe, and there's another part down at the bottom called lobial eight that also has a representation for movement. But what are expanded massively through evolution are the lateral parts, the big posterior lateral parts of cerebellum [and] we now know from studies of imaging and anatomy, are important for higher order function. So the way that we think about this is the damage to the motor parts of cerebellum produces the dysmetria (Greek term for the in-coordination with timing) of movement, or the ataxia that you know well. The other aspect that we're learning more about as we go is that damage to the posterior lobe of the cerebellum the new part that's evolved with evolution, when that is damaged you get the dysmetria of cognition and emotion and that's the cerebellar cognitive affective syndrome. Now the reason that this seems to work and I've put this together as the dysmetria of thought theory, dysmetria again being the word we've used to describe movement in ataxia. In the same way that the cerebellum regulates all the movements that go on, rate, rhythm and the force and the accuracy of all of our movements whether it's breathing or speech or eye movements, so does it regulate the mental capacities (the way that we can think rapidly and clearly, how consistently, our capacity to think and to keep emotions in check and how appropriate are our interactions in the environment). This is the dysmetria of thought theory--that the cerebellum does. We think it optimizes behavior, it produces a behavior that is appropriate to context, and we can do it automatically without our awareness. So when you lose that, when you have to bring things to consciousness, and pay attention to what used to happen automatically without a conscious awareness but now is an issue where we need to change the way that we develop our strategies for managing that.

This results in a series of appreciations that have indications for therapy. It can be tough to say to folks who are dealing with ataxia there are emotional and cognitive problems and this is always a sensitive issue ... but what it does is it empowers you to recognize that if these issues arise they are problems that are not in your head, they're in your brain. And that's the "need to know" imperative. So when you walk into your doctor's office and your doctor says "oh that's ataxia, it has nothing to do with emotion or intellectual function," you can take this information and say "I beg to differ."

One caveat here, bear in mind that some of these disorders like SCA 1 for example, would involve parts of the brain that are outside of cerebellum. So we have to be careful about how much we ascribe to the cerebellum in these particular disorders. That's why when I study this question I'm trying to focus on people who we know have problems confined to cerebellum because that then can inform our knowledge of other disorders that have cerebellum and maybe other problems as well.

So some aspects to bear in mind at the clinical level that matter for you in your daily lives--depression, anxiety and panic disorder may occur, [and] they're all treatable. There are medications for each of these symptoms and syndromes, they're not specifically for ataxia, but they're specific for quality of life improvement in problems that may be plaguing you or your family. Executive function, the planning, the organizing, the strategy formation, the multitasking that fails apart in many situations and people tell me of their stories, this is something that one can deal with [through] cognitive rehabilitation. [For example] taking one step at a time, focusing on one task at a time before moving onto the next. The multi-tasking applies as much to the motor domain as to the cognitive domain.

Memory impairment can be an issue, but this is not Alzheimer's disease. People do not forget who they are or forget what happened to them in the recent past. What the memory impairment consists of in folks who have cerebellar troubles is the ability to pull things up. The memories aren't gone, they're difficult to access, there is a tip-of-the-tongue phenomenon, trouble pulling things up but the information is still in there. Strategies to get around that can be helpful.

The MSA patients who kick and scream and shout in the middle of the night and throw their partners out of bed as a consequence with bruising and injury--there's a neurology behind that, they're not just being mean. That happens, and there are treatments for this, you can actually treat the REM sleep behavior disorders. This laughing and crying that can be embarrassing to MSA patients can be treated with medications.

Importantly for the children who have developmental abnormalities, or the kids who've survived tumors, or those who have onset of disease in early childhood where that affects the way the brain is developing, we need to recognize that the developmental and language delays need to be managed actively with physical therapy, occupational therapy, rehabilitation services, working with the school counselors addressing these issue head-on. And all the other aspects of autism spectrum disorders, psychosis spectrum disorders there have not yet been any studies that clearly identify which medications for which patients, for which symptoms. I think that having recognized this as an issue, you'll be able to move forward and come up with answers to these questions.

So recognizing the problem is a need to know imperative. We can bring actions to conscious awareness to try to minimize the difficulties that you're having. Use medications that are appropriate to each of the symptoms, and then consider sometimes the physical rehabilitation that you're engaged in may be helpful not only for the motor control but for its overflow affect on the rest of our mood and our general well-being.

By Jeremy Schmahmann, MD