Brenda Milner: Pioneer of the Study of the Human Frontal Lobes

Although the behavioral effects of damage to the frontal lobes date back to at least the late 19th century even midway through the 20th century very little was known about human frontal lobe function and there was a general consensus that the frontal lobe did not play a key role in cognition. This all changed when Brenda Milner published a chapter in a 1964 volume entitled: The Frontal Granular Cortex and Behavior. Milner’s chapter, “Some effects of frontal lobectomy in man,” was the first systematic study of the effect of frontal lobe excisions on cognition in human patients. Milner had access to a unique population of frontal excision patients at the Montreal Neurological Institute that were being treated by Wilder Penfield and his associates for a wide range of neurological disorders, including intractable epilepsy. Milner and her colleagues engaged in a more than 50-year study that has had a formidable impact on our understanding of frontal lobe function. Paralleling studies of frontal lobe function in non-humans they influence on understanding the evolution and function of the prefrontal cortex of mammals. Thus, although Brenda Milner is best known for her studies of human memory, she has had an equally important contribution to our understanding of the frontal lobes.

The early argument for prefrontal leucotomy: the collision of frontal lobe theory and psychosurgery at the 1935 International Neurological Congress in London

The pathophysiology of mental illness and its relationship to the frontal lobe were subjects of immense interest in the latter half of the 19th century. Numerous studies emerged during this time on cortical localization and frontal lobe theory, drawing upon various ideas from neurology and psychiatry. Reflecting the intense interest in this region of the brain, the 1935 International Neurological Congress in London hosted a special session on the frontal lobe. Among other presentations, Yale physiologists John Fulton and Carlyle Jacobsen presented a study on frontal lobectomy in primates, and neurologist Richard Brickner presented a case of frontal ablation for olfactory meningioma performed by the Johns Hopkins neurosurgeon Walter Dandy. Both occurrences are said to have influenced Portuguese neurologist Egas Moniz (1874–1955) to commence performing leucotomies on patients beginning in late 1935. Here the authors review the relevant events related to frontal lobe theory leading up to the 1935 Neurological Congress as well as the extent of this meeting’s role in the genesis of the modern era of psychosurgery.

Neuropsychological outcome following frontal lobectomy for pharmacoresistant epilepsy in adults

Objective:This retrospective cohort study characterized cognitive and motor outcomes in a large sample of adults who underwent frontal lobe resections for treatment of pharmacoresistant epilepsy.Methods:Ninety patients who underwent unilateral frontal lobe resection for epilepsy (42 language-dominant hemisphere/48 nondominant hemisphere) between 1989 and 2014 completed comprehensive preoperative and postoperative neuropsychological evaluations that included measures of verbal and nonverbal intellectual functioning, attention/working memory, processing speed, language, executive functioning, verbal and visual memory, and motor functioning. Objective methods were used to assess meaningful change across a wide range of abilities and to identify factors associated with neuropsychological decline following frontal lobectomy. Detailed postoperative neuroimaging analysis was conducted to characterize region, extent, and volume of resection.Results:Forty-eight percent of patients did not demonstrate meaningful postoperative declines in cognition and an additional 42% demonstrated decline in 1 or 2 cognitive domains. When cognitive decline was observed, it usually occurred on measures of intelligence, visuomotor processing speed, or executive functioning. Side and site of resection were unrelated to cognitive outcome, but played a role in decline of contralateral manual dexterity following supplementary motor area resection. Higher preoperative ability, older age at surgery, absence of a malformation of cortical development on MRI, and poor seizure outcome were related to cognitive decline on some measures, but had poor sensitivity in identifying at-risk patients.Conclusions:The vast majority of patients who undergo frontal lobectomy for treatment of pharmacoresistant epilepsy demonstrate good cognitive and motor outcomes.