Behavioral neurology is a field with tremendous clinical opportunities to change the life trajectory of children as well as to discover new knowledge, at the interface of neuroscience and many other biological, technological, theoretical, and social fields, about how our brains work. In recognition of the importance of behavioral neurology, the Martha Bridge Denckla Award, established by the Child Neurology Society just recently in 2021, honors Dr. Denckla’s legacy as a pioneer in behavioral neurology research as well as her influence as a master clinician, mentor, and educator.
This year’s recipient, Dr. Stewart Mostofsky, is not only an internationally recognized translational neuroscientist in behavioral neurology, but he is also one of Dr. Denckla’s most renowned and prolific mentees. As a result, Dr. Mostofsky’s nomination was quickly and enthusiastically supported by 13 PhDs, 8 MDs, and 3 MD PhDs, representing specialties such as neuroimaging, neurophysiology, and motor phenotyping in academic institutions, private institutes, governmental organizations, and industry, spanning three continents.
Stewart Mostofsky grew up in Long Island, New York, where his parents were not physicians, but where some formative experiences may have primed his neural circuits to enter behavioral neurology. He recalls an early fascination with the character Tommy Westphall, an iconic autistic character on the television show St. Elsewhere and with Raun Kaufman, a young boy with severe Autism, portrayed compulsively spinning plates with his parents on the television docudrama Son-Rise: A Miracle of Love, and he wonders whether this set the stage for his scientific interests.
After his decision to become a physician, Dr. Mostofsky’s fascination with higher cognition grew through clinical experience and reading. During a medical school clerkship at Albany Medical College, a bedside examination of a patient with the rare disconnection syndrome, alexia without agraphia, compelled him to seek neurobiological understanding at the medical library, where he read a book chapter by the trailblazing behavioral neurologist Norman Geschwind. While this piqued an interest in adult medicine, ultimately, his adult neurology clerkship helped persuade him that he would rather work with children. He matched at the University of Minnesota for general pediatrics, and was then convinced by his attendings to stay for his child neurology residency.
One reason for his affinity with Ken Swaiman’s training program was its interdisciplinary nature: the pediatric neuropsychology department was embedded in child neurology. This allowed him to continue to explore his interests with another giant, Dr. Elsa Shapiro, whose rigorous work illuminated neurocognitive and neurobehavioral phenotypes in rare genetic diseases.
The academic expectations of his residency also propelled and directed Dr. Mostofsky’s career toward discovery. Self-study was a key driver. After reading about the Marr and Albus computational model of cerebellar function and subsequent experimental validation by Masao Ito, he gave a memorable, and somewhat iconoclastic, talk to his faculty mentors about the role of the cerebellum in cognitive function and behavior, with the help of about 30 handwritten transparencies and an overhead projector. His residency research project, assessing motor coordination and response times in children with ASD, further guided him toward the possibility of an academic career.
Attending scientific meetings as a child neurology resident and networking with many other leaders in the field also proved crucial to this emerging academic mindset. It was around this time that Dr. Mostofsky met Dr. Denckla at a conference in Cincinnati. He shared his ideas with her and ultimately decided to move to Baltimore, Maryland, to the Kennedy Krieger Institute (KKI), where he has worked for 30 years.
In addition to the fantastic opportunities for mentorship and collaboration from Dr. Denckla and numerous colleagues at the KKI and Johns Hopkins, the support of US tax dollars for early-career clinician scientists provided critical support. Dr. Story Landis helped direct the NINDS priorities toward supporting early investigators, including Dr. Mostofsky. Building on great mentoring and high productivity during a T32, a K08, and a K02 award, Dr. Mostofsky gained rigorous scientific training, a large network of collaborators, research methodology expertise, and deep knowledge of the interface of cognitive and motor systems in Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and Tourette syndrome. Funding for his subsequent research has come through a broad portfolio, not only multiple NIH R01s but also grants from patient advocacy organizations such as the National Alliance for Autism Research (now Autism Speaks) and the Tourette Association of America.
Jumping forward to the present, Dr. Mostofsky maintains very high academic productivity while also directing the Center for Neurodevelopmental and Imaging Research at the Kennedy Krieger Institute. He also serves as medical director for the Center for Autism and Related Disorders at the Kennedy Krieger Institute and is Professor of Neurology and Psychiatry at Johns Hopkins University. The Kennedy Krieger Institute’s Center for Neurodevelopmental and Imaging Research (CNIR) is comprised of numerous outstanding faculty, postdoctoral fellows, and psychological associates engaged in the mission of understanding and finding better treatments for neurodevelopmental disorders in children. Under Dr. Mostofsky’s able direction, current research at the center is improving our understanding of ADHD, ASD, Tourette Syndrome, and traumatic brain injury. This work involves multiple novel and innovative methodologies including but not limited to functional and volumetric magnetic resonance imaging, magnetic resonance spectroscopy, transcranial magnetic stimulation, electroencephalography, tactile sensory quantification, and blood and cerebrospinal fluid biomarkers. All these techniques are being utilized to advance our understanding of motor, cognitive, and emotional development and to identify improved treatments in high-impact, highly prevalent developmental disorders. Critically, the domains of impaired function studied by Dr. Mostofsky and colleagues in idiopathic developmental disorders are also pervasive and highly impairing throughout the common and rare diseases managed by child neurologists.
Dr. Mostofsky himself has made substantial, internationally-recognized contributions to the neuroscience of behavioral disorders in children. As a clinical investigator studying motor and cognitive dysfunction of the developing brain, his research integrates motor skill and cognitive assessment, neuroimaging approaches, and neurophysiological/neural stimulation. He employs these diverse methods to elucidate neural mechanisms underlying developmental brain disorders and to use the knowledge gained to inform diagnosis, to guide clinical intervention, and to develop novel therapeutic approaches. While many important (and unimportant) scientific papers written by child neurologists languish, unread and uncited, Dr. Mostofsky’s over 200 publications in PubMed are widely read and clearly influence behavioral neurology. As evidence of this, his work has been cited more than 2,000 times per year every year since 2016, he has an H Index of 90, and an I-10 index of 234. He is most well-known for his translational work using neuroimaging with a strong emphasis on development of the motor system in children, work that creatively and systematically expanded work by his mentor Dr. Denckla. Perhaps less well known, his work also includes high impact studies characterizing psychosocial predictors of neurobehavioral development, novel treatment studies, and statistical approaches to modeling cognitive and behavioral disorders.
Dr. Mostofsky’s impact outside of academia and science is also noteworthy. Not surprisingly, his involvement in the arts mirrors his involvement in behavioral neurology: not content with the works of the past, done by others, Dr. Mostofsky supports experimental, groundbreaking music. He co-founded a Baltimore-based independent record label, Ehse Records, and co-founded the Fields Festival, an immersive arts and music camping event in rural Maryland. As a strong supporter and performer in Baltimore’s experimental and improvisational music scene, he performed at Baltimore’s High Zero Festival and documented the local experimental music scene as a photographer. Significantly, he has passed on his love for the arts to both of his sons.
Dr. Mostofsky’s career, like Dr. Denckla’s, has been one of curiosity, path finding, and persistence. He has shown how neurologists can contribute to better understanding of the developing brain in Autism and ADHD. He has found new ways to integrate clinical observation of motor development with neuroscience and cognitive psychology. His work continues to be instrumental in creating and refining the research domains of sensorimotor function and cognitive control, thereby exerting a large impact on the direction of neurodevelopmental investigations across the country.