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Hemispherectomy Leaves Brain Networks Intact and Strengthens Their Connections

Article In Brief

Researchers found that in six patients who had undergone a hemispherectomy as children, their cognitive abilities were high-functioning despite the fact that they were missing half of the brain tissue.

Figure

Six adult participants with left (n=2, HS2 and HS3) or right (n= 4, HS1, HS4, HS5, and HS6) hemispherectomy. Axial slices were taken minimally above the anterior/posterior commissure line.

Brain networks that underly cognition, emotion, movement, and other functions develop normally after childhood hemispherectomy, despite the loss of half the brain's volume, according to a study published November in the journal Cell Reports.

The findings, which were drawn from functional MRI data, provide support for clinical studies showing that young hemispherectomy patients can maintain or regain important cognitive and motor function after surgery, and may provide physicians more information when counseling families about surgical options for intractable seizures.

“Despite missing an entire brain hemisphere, we found all the same major brain networks that you find in healthy brains with two hemispheres,” lead study author Dorit Kliemann, PhD, a postdoctoral scholar in the laboratory of Ralph Adolphs, PhD, professor of psychology, neuroscience, and biology, and the director of the Caltech Brain Imaging Center, said in a statement accompanying the publication of the study.

The findings provide an important message for families of patients who undergo hemispherectomy, independent experts agreed.

“I think this paper will help us with the messages that families need to know before epilepsy surgery,” commented Ajay Gupta, MD, section head of pediatric epilepsy at the Cleveland Clinic in Ohio, who was not involved in the study.

“Early intervention and stopping seizures does matter, and after surgery a good form of brain plasticity continues to operate, and is further enhanced by long-term rehabilitation, learning, and support after surgery, which is important for making the most of that plasticity.”

Hemispherectomy can be an effective treatment for selected children with intractable seizures due to significant hemispheric lesions of diverse etiologies and low risk of new unacceptable neurologic deficits, Dr. Gupta said.

In a 2013 long-term follow-up study in Epilepsia of 186 children who underwent hemispherectomy, he and his team showed that at a mean of six years post-surgery, 56 percent were seizure-free, while 36 percent had recurrence of their seizures. Of this combined group (n=115), 83 percent walked independently, and 70 percent had satisfactory spoken language skills.

“Some patients will become seizure free or have a rare triggered seizure, while others benefit partially,” Dr. Gupta said. “If we stop seizures and treat early, there is a good chance the brain will learn those functions, and that they will reside somewhere else in the brain, in area we did not affect through surgery.”

Study Design, Findings

A network is a group of regions distributed across the brain that are engaged together during specific types of activities, such as cognition, emotion, movement, and attention, the study authors explained. Since their discovery, networks have emerged as the likely substrate for complex tasks, and not only their existence, but their anatomical locations, have been shown to be consistent across thousands of individuals.

The dramatic nature of hemispherectomy raises the question of how the normal networks of brain activity are affected by the loss of a full hemisphere, especially since the activity of most networks is inter-hemispheric.

To explore that question, Dr. Kliemann and colleagues performed brain scans of six individuals up to 22 years after their surgeries. Three individuals had Rasmussen syndrome, two had perinatal stroke, and one had cortical dysplasia. Onset was between birth and 10 years, and age at operation was between three months and 11 years.

The authors first showed that a standard fMRI atlas, derived from normal controls, could be meaningfully applied to the brains of hemispherectomy patients. By comparing various properties of the fMRI signals from the brain at rest in the two groups, they found that the atlas was in fact applicable to the patients.

Next they examined the coordinated signals from each network and compared those of hemispherectomy patients to those of a set of controls run in the same scanner with the same parameters. “Given that most resting-state networks are bilaterally distributed across both hemispheres, we expected to find possibly profoundly rearranged networks in the single remaining hemisphere of the hemispherectomy participants,” the authors wrote.

They found instead that, within the remaining hemisphere, the patients' network topography matched those of the controls, regardless of whether it was the right or left hemisphere that remained.

There was, however, one potentially important difference between the two groups: the functional connectivity between different networks was stronger in the hemispherectomy patients than in the controls, a finding that was true for all of the networks in most of the patients.

“It appears that the networks are collaborating more,” Dr. Kliemann said. “The networks themselves do not look abnormal in these patients, but the level of connections between the networks is increased in all six patients.”

“It's truly amazing what these patients can do,” Dr. Kliemann said. “Yes, they have challenges, but their cognitive abilities are still remarkably high functioning given that they are missing half of the brain tissue. We need to understand how this is possible with only a single brain hemisphere—an important question about plasticity, reorganization, and compensation.”

Expert Commentary

The finding of preserved networks in these patients is not completely surprising, said Michael D. Fox, MD, PhD, associate professor of neurology at Harvard Medical School and director of the Laboratory for Brain Network Imaging and Modulation at Beth Israel Deaconess Medical Center in Boston.

“Given that these patients are, overall, functioning normally, I would have expected relatively normal networks. Prior work in patients with callosotomy is also consistent with the current results,” Dr. Fox said.

“This finding could eventually be clinically relevant and help us understand how the brain responds to injury, but many questions remain,” Dr. Fox added.

“Among the most prominent questions is what the functional significance of this increased between-network connectivity is. The authors noted that some recent work suggests it may subserve executive cognitive abilities such as working memory, but much more remains to be learned about this extra connectivity. All the measurements in the current study were done with the brain at rest, not engaged in specific tasks. Future studies will examine how the networks respond to sensory input or during cognitive challenges.”

Figure

“I think this paper will help us with the messages that families need to know before epilepsy surgery. Early intervention and stopping seizures does matter, and after surgery a good form of brain plasticity continues to operate...”—DR. AJAY GUPTA

For most of the children in this study, the interval between symptom onset and surgery was relatively short, which usually correlates with a better outcome, since long-term seizure exposure can induce maladaptive plasticity, Dr. Gupta, of the Cleveland Clinic, noted.

“I think this study shows us how remarkably plastic the brain can be,” Dr. Gupta said, given that the same networks used by the whole brain can function in only half of it. The extra connectivity between networks may reflect “a higher level of ‘teamwork,’” he suggested, “and that is very encouraging, because it tells us how and why, once we do the surgery, rehabilitation might be very helpful for achieving the best potential these patients have.

“When we see these families post-surgery, they are worried about the return of seizures, but they are just as much worried about the child's socialization, learning, attention, and memory when the seizures controlled, and we have to attend to those things as well.”

Disclosures

Drs. Kliemann, Gupta, and Fox have no relevant disclosures.

Link Up for More Information

• Kliemann D, Adolphs R, Tyszka JM, et al. Intrinsic functional connectivity of the brain in adults with a single cerebral hemisphere https://www.sciencedirect.com/science/article/pii/S2211124719313816. Cell Rep 2019;29(8):2398–2407
    • Moosa AN, Jehi L, Marashly A, et al. Long-term functional outcomes and their predictors after hemispherectomy in 115 children https://onlinelibrary.wiley.com/doi/full/10.1111/epi.12342. Epilepsia 2013;54(10):1771–1779