One thing former President Bill Clinton was often noted for was feeling other people’s pain and anguish. But how did he do it, biologically speaking, that is?

Apparently by activating the anterior insular cortex and anterior cingulate cortex areas of the brain, in light of considerable brain-imaging data suggesting that those are the brain regions that we activate when we empathize with others’ pain and suffering. However, the evidence comes from cross-sectional studies and thus does not constitute proof that this is the case.

Now a small, but intriguing new study published in the September Brain does seem to constitute such proof—however, only for the anterior insular cortex, not for the anterior cingulate cortex.

The lead scientist was Xiaosi Gu, Ph.D., a postdoctoral fellow at the Institute of Neurology in London. The senior scientist was Jin Fan, Ph.D., an assistant professor of psychiatry and neuroscience at Mount Sinai School of Medicine in New York.

Gu and her colleagues identified three individuals who had brain damage limited to the anterior insular cortex and three individuals who had brain damage limited to the anterior cingulate cortex—something that happens rarely—and who were willing to participate in their study. All of the subjects had experienced such damage from surgical removal of low-grade gliomas.

The scientists then used a perceiving-another-person’s-pain paradigm to test feelings of empathy in these six subjects, in six other subjects with damage to other areas of the brain, and in 14 neurologically intact matched control subjects.

The paradigm consisted of 216 digital color photos showing someone’s left or right hand or foot in painful or nonpainful situations. The scientists then analyzed the subjects’ behavioral responses.

The subjects with anterior insular cortex damage—but not the subjects with anterior cingulate cortex damage—showed a significantly diminished ability to discriminate painful from non-painful stimuli compared with subjects with other types of brain damage or with neurologically intact control subjects.

Moreover, viewing an individual in pain did not interfere with judgment in subjects with anterior insular cortex damage, whereas it did so in subjects with anterior cingulate cortex damage, in neurologically intact control subjects, and in subjects with other types of brain damage.

So it looks as if the anterior insular cortex, but not the anterior cingulate cortex, is the main neural network subserving empathy.

“We were surprised by the result,” Gu told Psychiatric News. “Both the anterior insular cortex and the anterior cingulate cortex have been traditionally considered to be involved in empathy based on previous neuroimaging studies. Consequently, one would predict that lesions in either region would impact empathy processing. However, by comparing patients with focal lesions in either the anterior insular cortex or the anterior cingulate cortex, we found that only anterior insular cortex lesions, but not anterior cingulate cortex lesions, significantly impaired a patient’s ability to understand and empathize with others’ emotions. The finding challenges previous neuroimaging studies by showing that only the anterior insular cortex, but not the anterior cingulate cortex, is critical for human empathy.”

The scientists believe that their findings have implications for a swath of neuropsychiatric illnesses characterized by prominent deficits in social functioning, they said in their report—for instance, antisocial personality disorder, autism, borderline personality disorder, conduct disorder, frontotemporal dementia, and schizophrenia.

In addition, Gu pointed out, “Empathy deficits in patients with brain damage to the anterior insular cortex are surprisingly similar to the empathy deficits found in people with the aforementioned psychiatric disorders, suggesting potentially common neural deficits in those psychiatric populations.”

Their findings also have clinical implications, Gu believes. For example, since the brain is highly plastic, behavioral and cognitive therapies might be developed to compensate for empathy deficiencies arising from the anterior insular cortex. And more into the future, it might be possible to pinpoint the cellular and molecular mechanisms in the anterior insular cortex that give rise to empathy and to use such knowledge to develop medications that could foster empathy in individuals who lack it.

The study was funded by the National Institutes of Health, the James S. McDonnell Foundation, and the Brain and Behavior Research Foundation.

An abstract of “Anterior Insular Cortex Is Necessary for Empathetic Pain Perception” is posted at http://brain.oxfordjournals.org/content/135/9/2726.abstract.