Treating Seizures Leads to Face Blindness Discovery: Q&A with Josef Parvizi

When Josef Parvizi set out to treat a patient with uncontrollable seizures, he was not expecting the serendipitous turn of events that would lead to a new discovery: the critical importance of two nerve clusters for perception of faces. The findings, recently published in the Journal of Neuroscience, may help researchers better understand a clinical condition known as prosopagnosia – the inability to distinguish on person’s face from another – also known as face blindness.

Working as the Director of the Stanford Program for Drug-Resistant Epilepsies, Parvizi specializes in treating people who have difficult-to-treat seizures. Ron Blackwell of Santa Clara, Calif., had been experiencing seizures since he was 11, but until 2012, they had been under control with medication. To help locate the source of the seizures, Parvizi and his colleagues used a combination of fMRI, intracranial recording, and electrical brain stimulation.

The target of the investigation was the fusiform gyrus, on the underside of the temporal lobe. The researchers placed electrodes, as is customary, about 1 centimeter apart, which was almost precisely at the positions of two nerve clusters, pFus and mFus. Upon application of the electrical stimulation, Blackwell was no longer able to recognize Parvizi’s face. His face instantly became distorted to Blackwell (see a video of the encounter). Parvizi talked to CNS about this work, which has received wide press coverage in the past couple weeks.

CNS: How did you meet Ron Blackwell, the subject in your study?

Parvizi: I saw him in my clinic and after the failure of new medications, and with several runs of diagnostic tests that suggested a clear seizure focus, we decided to go for invasive monitoring with the hope of being able to resect the presumed seizure focus.

CNS: Were you expecting your treatment of Blackwell’s seizures to yield results related to visual perception in the fusiform gyrus? Did you set out to study facial recognition?

Parvizi: Initially, given the visual nature of his auras and seizures, and given the strong scalp EEG evidence for focality of his seizures in the right posterior quadrant of the head, we planned to cover the occipital and inferior temporal regions. After the implantation we recorded from all electrodes and we performed electrical brain stimulation, which is a routine clinical procedure for two reasons: 1) localizing the source of seizures by weak electrical stimulation of that region and causing the patient’s same epileptic auras, and 2) functional mapping of the cortex (to avoid harming them during surgery). What we happened to discover from the electrical stimulation of the fusiform gyrus in Ron Blackwell was not expected.

CNS: What got you interested in this line of research?

Parvizi: In Norway, where I received my medical degree, everyone had to take six months of philosophy. I became so fascinated by the philosophy lectures during my medical school that Istarted doing research with a philosopher/doctor, Reidar Lie, who became the most significant person in my career. One day, he returned from a trip to Chicago and brought me a gift, Descartes Error by Antonio Damasio, a behavioral neurologist in Iowa. I read it in route Israel and Egypt for vacation, and it was aboard a boat on the Red Sea where I decided that I had to do behavioral neurology and help patients in need while at the same time let them teach me about their brain. That is how I was brought to this line of research, namely trying to practice medicine and help patients with uncontrolled seizures become seizure free and at the same time let them (and the serendipity) teach us about our own brains. Learning about the brain, from its molecules in petri dishes to rodent circuitries, and human subjective reports is the way to go to understand the ancient philosophies about the meaning of life.

CNS: What are the implications of the study for the most people?

Parvizi: “We are our brains.” We see the world with our brain and we learn about the world with our brains. Artificial (or pathological) alteration of the activity of the brain will make our view of the reality very distorted. Small pulse of electricity made Ron Blackwell see my face as a totally different person’s. In some patients, seizures distort their facial perception and that is most likely due to the pathological activities in the fusiform areas and their cortical and subcortical networks.

CNS: What promise does this research hold for use of intracranial recording?

Parvizi: Neuroimaging method is perfect for its global resolution (i.e., whole brain study), but it only gives correlative evidence. It also suffers from poor individual anatomical resolution if you do group analysis and spatial smoothing and it has a poor temporal resolution. So intracranial recordings combined with imaging methods that help localize functional hubs of the brain and the precise location of each electrode location gives us an immensely useful tool.

The recordings are done in clinical setting so the electrodes are implanted where the clinical needs are, and everyone should know that the clinical setting makes it extremely hard and challenging to run these kinds of studies. Our focus is to put the patient safety and clinical care at the forefront and, many times we have to abort our experiments because of clinical events and or needs.

CNS: What are you working on next? Do you have future work planned on facial recognition and prosopagnosia?

Parvizi: Now we are working on deciphering the brain activity as it unfolds in real life setting and in real time from the early visual perception to the latest moment of a decision when the subject clicks a button. I am very fortunate to have great colleagues at Stanford and Berkeley (Kalanit Grill-Spector, Jaimie Henderson, Bob Knight, Bill Newsome, Krishna Shenoy, Anthony Wagner, Brian Wandell) who have joined their forces with me to establish the Stanford Human Intracranial Cognitive Electrophysiology Program (SHICEP) where we tackle many different outstanding questions of neuroscience. I am also very fortunate that the collaborative and collegial environment in SHICEP has made it very easy for postdocs and students in my lab and in my colleagues’ labs to share their experience and pool their extraordinary talent together to solve challenging scientific methods and questions.

Media contact: Lisa M.P. Munoz, CNS Public Information Officer, cns.publicaffairs@gmail.com