A bigger role for the little brain?

In the early 19th century, neuroanatomist Franz Joseph Gall believed that the cerebellum, the little attachment to the brain that packs half of the neurons in our head, is the “organ of the instinct of reproduction.” The bigger it is the stronger our libido.

But if you’ve ever lost your balance, or staggered home from a party after a few too many drinks, you’ll know what happens when it isn’t working properly.

The cerebellum (meaning little brain in Latin) has critical roles in controlling and co-ordinating movement. Without a cerebellum, you would have a hard time walking in a straight line or learning to ride a bike – functions that it performs automatically and unthinkingly.

But some researchers now believe that the humble little brain has roles beyond just fine-tuning movement: It may also contribute to higher mental functions such as thought and emotions.

“Most neurologists are still convinced that the cerebellum does not do more than coordination of sensori-motor functions,” says Peter Mariën of Vrije Universiteit in Brussels, “but there are now thousands of well-designed studies that you can’t neglect, and I think that’s abundant evidence.”

A thinking cerebellum

The roles traditionally ascribed to the cerebellum come mostly from animal experiments performed throughout the 19th century, which showed that cerebellar lesions invariably caused some kind of motor disturbance on the same side of the body as the damage.

Later, the neurologist Gordon Holmes studied more than 40 soldiers who returned from World War one with cerebellar injuries due to gunshot wounds. He noted that the effects of the lesions “fall almost exclusively upon the motor system,” observations that confirmed the presumed role of the cerebellum and strengthened this traditional view.

Sitting behind the brainstem at the top of the spinal cord, the cerebellum is perfectly positioned to read movement-related information as it enters and leaves the brain. It has two hemispheres, each consisting of a single sheet of tissue that is tightly folded like an accordion from front to back. These contain a number of distinct cell types, including Purkinje neurons, the largest cells in the brain, and granule cells, the smallest. Despite accounting for just 10 percent of the total volume of the brain, it contains more cells than all the other parts put together.

Cells in the cerebellum are arranged in a highly orderly manner. Granule cells have a single fiber that runs from left to right, while Purkinje cells have a large, flat and elaborately branched dendritic tree positioned perpendicularly to them. Each granule cell fiber thus runs through and connects with the dendrites of numerous Purkinje cells, each of which forms connections with hundreds of thousands of granule cell fibers.

This arrangement of cells seems perfectly suited to co-ordinating the activities of muscle groups. The dense network of cells is the last step that smooths the rough, clumsy motor actions and allow for fine, precise moves.

But the organ could be doing the same thing to cognitive functions.

Evidence began to emerge about 25 years ago, when neuroscientists started using functional neuroimaging techniques such as fMRI and PET to study brain activity, and sometimes found that the cerebellum is activated during language and problem-solving tasks.

These findings were dismissed as anomalies, but since then, hundreds more such studies have reported activity in the cerebellum during mental tasks, leading one researcher to state that human functional neuroimaging has “generated compelling evidence that the human cerebellum responds to cognitive task demands… without setting out to do so.”

Another line of evidence comes from clinical studies of people born without a cerebellum. Conditions like this are extremely rare and, not surprisingly, children who lack a cerebellum have great difficulty learning to walk, keeping their balance and performing fine movements. But apparently they also exhibit some differences in their intellectual and emotional skills.

Neurologist Jeremy Schmahmann of Massachusetts General Hospital and his colleagues have studied several dozen patients with rare diseases that affect the cerebellum. Their research suggests that damage to the rear portion of the cerebellum can impair executive functions such as planning, abstract reasoning and working memory, whereas damage to the interior portion may lead to only small deficits in executive and visuo-spatial functions. They argue that these observations constitute a previously unrecognized condition, which they have named cerebellar cognitive affective syndrome.

A need for more evidence

Not everyone is taken by the idea of the thinking little brain, however.

“I’m not convinced by the clinical evidence,” says Mitchell Glickstein, emeritus professor of neuroscience at University College London. “The lesions aren’t restricted to the cerebellum, and these patients probably have vascular damage that’s being ignored.” He adds that he has seen clear data from children who have had cerebellar tumors removed: “They have a tendency towards more labile emotions, but there’s not a hint of any intellectual deficit.” 

Glickstein is also skeptical of the neuroimaging and connectivity data showing the cerebellum is lit-up during nonmotor tasks. “Many of the frontal areas connected to the cerebellum control eye movements,” he says. “Almost everything we do is preceded by eye movements, but nobody ever controls for that in their experiments.”

In other words, the cerebellum could be just looking out for the next motor function it has to manage, Glickstein said. “It wants to know what’s going to happen in the next few seconds of your life. It wants to organize, arrange and plan movements without thinking about them.”  

According to Glickstein, the evidence that the cerebellum plays a role in cognition is rather weak. “If I saw an unequivocal cerebellar lesion associated with an unequivocal cognitive deficit, then I’d believe it, but I haven’t seen anything like this so far.”

Mariën says the problem lies in how and when patients with cerebellar lesions are tested. “The brain might be able to compensate for cerebellar lesions quite quickly,” he says. “If you see patients one or two months after a cerebellar stroke, there’s a big chance that there’s already been some compensation.”

A little brain that does a little bit of everything

If the cerebellum has a role in cognition, it seems to be a discrete one. Patients show deficits that are too subtle to detect using conventional tests designed to assess cortical functions, Mariën says. “There’s a need to develop fine-grained tools that are able to discriminate its functional roles.”

More recent functional neuroimaging studies have found that multiple circuits connect the cerebellum to areas of the prefrontal cortex known to be involved in complex cognition, which suggests that the organ may be able to modify the activity of prefrontal areas.

And it is possible that a disconnect between the cerebellum and these areas could lead to cognitive symptoms. For example, Mariën and his colleagues recently reported the case of a patient with cognitive symptoms linked to a lesion in part of the brainstem that contains numerous pathways connecting the cerebellum to the rest of the brain.

“The cerebellum on itself does not have a seat for cognition,” Mariën said. “But parts of it are connected with primary areas in the brain involved in cognition. If you disconnect the cerebellum of input from these areas, then its modulatory role is lost.”

Looking at the cerebellum as part of a network rather than a stand-alone attachment to the brain could perhaps reveal the true nature of this old part of the brain.

He adds that cognitive deficits from cerebellar lesions are subtle, and that clinicians regularly overlook them, because they use tests designed to assess cortical function. “The cerebellum [probably has] a discrete modulatory role in cognition, so you have to look very carefully to look through the [movement] disorder,” he says. “There’s a need to develop fine-grained tools that are able to discriminate its functional roles.”

Mariën and his colleagues recently identified a similar syndrome. “We detected it by chance in a patient who I’d diagnosed with cerebellar cognitive affective syndrome, [who had a] brainstem lesion,” he explains, adding that the pons, the region damaged in these patients, contains numerous pathways connecting the cerebellum to many other parts of the brain. They have named the condition brainstem cognitive affective syndrome.

“The cerebellum is… the best connected structure in the brain, and when there’s a disconnection in the network and a loss of input from other areas, this gives rise to symptoms,” says Mariën. “I expect new diagnostic tools and the further development of neuroimaging techniques will further our insights into its cognitive functions.”

 

Originally posted on Brain Decoder, May, 2015.