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Early Cerebral Perfusion of the Language-Dominant Hemisphere Is Tied to Recovery of Reading Ability After Stroke

Article In Brief

New findings point to the importance of restoring blood flow to left hemispheric language areas of the brain after stroke to restore reading ability.

Figure

The distribution of brain coverage (A) by lesions within the patient sample; (B) Group-averaged left-brain perfusion; (C) Differences in left-brain perfusion relative to right-brain perfusion on initial assessment. For each patient, continuous perfusion values were used in a subtraction of life-right perfusion and vice-versa, into a group subtraction map.

Increased cerebral blood flow perfusion in the reading network of the language-dominant hemisphere in the period shortly after left-brain stroke was associated with reading ability three months or longer after the stroke, researchers reported in the August 29 online edition of Human Brain Mapping.

The investigators at the Kessler Foundation Center for Stroke Rehabilitation Research in New Jersey also found, conversely, that increased perfusion of similarly positioned areas in the right, or non-language-dominant, hemisphere was associated with decreased reading ability.

The study found that reading function was not dependent on increased blood flow around the stroke lesion, said Olga Boukrina, PhD, a research scientist at the Kessler Foundation.

“For some, reading deficits may be the main obstacle to regaining their expected quality of life,” the researchers said. “These data suggest that early activation and re-perfusion of the left reading network is essential for better chronic reading performance. This finding could ultimately have prognostic value for stroke recovery.”

Study Design, Findings

For the study, the researchers measured cerebral blood flow using arterial spin labeling MRI in 31 right-handed patients who had had a left-hemisphere supratentorial stroke in the previous five weeks, or the subacute period. They also tested their reading ability and phonology competence. Fifteen of the patients had the same assessments performed in the chronic period at least three months after the stroke.

When researchers looked at the homologous regions in the right and left reading networks, they found that perfusion of the left reading network was positively associated with reading accuracy (p< .05), while perfusion of the right reading network was negatively associated with reading accuracy (p< .001).

“Subacute right brain activation is sometimes seen as a necessary transition step in stroke recovery,” researchers said. “Our findings challenge this view.”

Interestingly, researchers found that perfusion of the reading networks was more predictive of chronic reading ability than lesion volume.

“While lesion volume and overlap of lesion with the left-hemisphere reading network predicted subacute performance, perfusion, rather than lesion load, was a better predictor of chronic performance,” they said. “Thus, information about cerebral perfusion explained unique variance in chronic reading outcomes not accounted for by lesion load alone.”

Researchers found that perfusion in the area of the lesion on the left wasn't associated with chronic word reading accuracy (p= 0.27), but perfusion of the region's counterpart on the right side was negatively associated with chronic reading accuracy (p< .01)

“While we observed lower subacute perilesional perfusion compared to the non-lesioned contralateral homologue, perilesional perfusion did not increase in the chronic period,” researchers said. “Therefore, it seems that subacute perilesional perfusion does not contribute to improved function.”

Dr. Boukrina said that the findings might point to the need for selectively stimulating one hemisphere and not the other. For instance, interventions focused on phonological processing would selectively stimulate the left hemisphere since this function is limited to the left. A non-invasive approach with transcranial magnetic stimulation is another potential avenue, she said.

She said she is looking into neural-based feedback, using participants' own brain activation as feedback in real-time and altering it for therapeutic ends, adding that she hopes the findings clarify the value of neuroimaging in helping to guide stroke recovery.

“I've heard this expressed a number of times by clinicians, that neuroimaging really was not helpful in predicting what kinds of outcomes or what kinds of impairments the patients will have,” she said. “I hope our work and that of others helps to contribute to a more detailed understanding of how neuroimaging informs the current profile of impairment of the patient by showing that it's not just the location of the stroke itself, but also of other areas that may be affected by events related to stroke that predict the outcomes. It's not a random relationship between lesion (and) location that's shown in neuroimaging, and the outcomes of the patients.”

There are many details that are not understood yet, but “characterizing those details and how they affect brain function in general can help us get closer and narrow that gap between looking at neuroimaging and being able to predict both the initial set of impairments (and) long-term outcomes—how are patients likely to do long-term, how they're able to recover,” she said.

Neuroimaging can also have a role in marking the progress of therapy by “helping us see if a given therapy produces this pattern of brain activity that we know is beneficial,” Dr. Boukrina added.

Expert Commentary

Argye E. Hillis, MD, MA, professor of neurology at Johns Hopkins University School of Medicine, said the study findings are new but they are also consistent with previous work showing that language recovery is associated with left hemisphere language areas, not right hemisphere homologs.

The results “mostly have practical implications for stroke neurologists caring for patients in the acute to subacute stage—it underscores the importance of restoring blood flow to left hemisphere language areas,” she said. “If these areas progress to infarction, it is much less likely that patients will be able to recover important functions like reading.”

Figure

“I hope our work and that of others helps to contribute to a more detailed understanding of how neuroimaging informs the current profile of impairment of the patient by showing that its not just the location of the stroke itself, but also of other areas that may be affected by events related to stroke that predict the outcomes. Its not a random relationship between lesion (and) location thats shown in neuroimaging, and the outcomes of the patients.”—DR. OLGA BOUKRINA

She added that “it remains unclear in the patients in this study whether increased left hemisphere perfusion led to better reading recovery, or whether better reading recovery led to increased activation—and, thus, blood flow—to left hemisphere reading areas. In either case, it is clear that (the) left temporal/fusiform cortex is more important for accurate phonological processing and reading than right hemisphere areas.”

H. Branch Coslett, MD, FAAN, professor of neurology at the University of Pennsylvania, said the study's methodology was sound but that it's limited, as are most studies on the topic, by the relatively small sample size, especially the 15 studied in the chronic period. He said the findings are not surprising and that he suspects there is a consensus “that reading and other language functions would be better post-stroke to the extent that the brain regions that support language in the normal (pre-stroke) state are utilized.”

“Those of us who believe that the right hemisphere may be crucial for language recovery in some individuals will not be dissuaded by this study,” he said. “One version of the right hemisphere hypothesis is that in patients with severe language deficits—usually from large lesions—the right hemisphere has the capacity to mediate language function; the claim is not that the right hemisphere develops the full range of linguistic capabilities that the normal language network provides, but that the right hemisphere may contribute to language recovery in some subjects and that the contribution is likely to be greater to the extent that the left hemisphere language circuits are disrupted.”

Testing this would require comparing left and right hemisphere blood flow in patient subgroups defined by language deficit severity, he said.

The prediction, he said, would be that those with larger language deficits would show increases in blood flow in the right hemisphere in the chronic period, while patients with milder deficits—usually those with smaller lesions—would show improvement in left hemisphere blood flow that correlates with the preserved left hemisphere language network resuming function.

This comparison would require a much larger sample size, though, he said.

“The bottom line in my view is that the study supports the claim that the left hemisphere language network is optimized for language and to the extent that it is preserved (as judged by blood flow), language performance should be better. This is an unsurprising conclusion but one that is important to demonstrate.”

Disclosures

Drs. Boukrina and Coslett had no disclosures.

Link Up for More Information

• Boukrina O, Barrett AM, Graves WW. Cerebral perfusion of the left reading network predicts recovery of reading in subacute to chronic stroke https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.50854. Hum Brain Mapp 2019; Epub 2019 Aug 26.