From Cells to Circuits, from Vision to Cognition, from Monkeys to Humans: Leslie Ungerleider's Pioneering Neuroscience

Perhaps the most influential contribution of Leslie's career was the development of the two cortical pathways framework in collaboration with Mort Mishkin (Figure 1). The identification of distinct dorsal and ventral pathways originating in primary visual cortex (V1) subserving “where” or “what” processing, respectively, relied on careful and systematic brain lesion studies combined with elegant behavioral paradigms (Baker & Kravitz, 2024). Such an approach provides direct insight into the function of the neural substrate (Richmond & Eldridge, 2024). The critical contribution of the two pathways framework was that it grounded our understanding of behavior and physiology in the underlying neuroanatomy.

It is impossible to overstate the significance of the two pathways framework and how it fueled subsequent work. Much debate has focused on how best to characterize the functional roles of the two pathways (Vaziri-Pashkam, 2024), interactions between the pathways (Puce, 2024), as well as why there should be segregation at all (Han & Sereno, 2024) and how best to define what a “pathway” is (Ritchie, Montesinos, & Carter, 2024). One of Leslie's final contributions was to propose the existence of a third visual pathway critical for social perception, which includes the motion-selective middle temporal area and regions in the banks of the STS, with distinct functional properties from the dorsal and ventral pathways (Küçük, Foxwell, Kaiser, & Pitcher, 2024).

Although the identification of the two pathways provided a critical framework, the details of the underlying neuroanatomy needed to be characterized. In a series of intricate and definitive neuroanatomical studies, Leslie identified projections of visual areas along the two pathways, highlighting major cortical and subcortical targets such as regions in the banks of STS, the pulvinar nucleus, and the basal ganglia. Such anatomical information revealed the complexity of the visual pathways and provided a critical foundation for interpreting the neurophysiological data that she also started to acquire in awake, behaving nonhuman primates, often in collaboration with Bob Desimone who joined National Institute of Mental Health in 1980. Leslie always emphasized the importance of considering the underlying anatomy both for elucidating the role of individual areas, such as V1 (Marcondes et al., 2024) or amygdala (John, Wang, Bullock, & Barbas, 2024; Pujara & Murray, 2024), and for understanding the larger scale networks that support complex behavior (Pessoa, 2024). Even in later years, Leslie's eyes always lit up when asked a question about specific anatomical connections. To her, neuroanatomy was the foundation on which functional studies could be built.

In the early 1990s, Leslie refashioned her research program and turned her hand to human neuroimaging, a move facilitated by the unique environment within the intramural program at National Institutes of Health. Initially, she focused on finding evidence for the separate dorsal and ventral pathways in humans using PET and collaborating with Jim Haxby. The success of this endeavor led her to embark on a whole series of highly influential studies with the less invasive fMRI in the newly founded Laboratory of Brain and Cognition. At this time, the utility of fMRI was being seriously questioned and the involvement of Leslie, with her background in nonhuman primate anatomy and neurophysiology, was critical for providing credibility to the technique and advancing the field. This turned out to be an extremely productive period for Leslie's career, with numerous highly influential neuroimaging articles covering diverse topics including selective attention, face perception, emotion, and perceptual decision-making. For example, Leslie and Susan Courtney¹ were able to show that the distinction of “what” and “where” could also be applied to frontal cortex and working memory (Courtney & Hinault, 2024).

Throughout this period, Leslie maintained both nonhuman primate and human laboratories, with each informing the other—one of the very few research programs running parallel studies across species. It was not long before she started conducting fMRI in nonhuman primates.

One of the major areas of interest of Leslie's nonhuman primate fMRI research was face perception and, in particular, facial expression processing (Taubert & Japee, 2024) and social interaction (Kovacs-Balint et al., 2024). In typical Leslie fashion, she pursued a multimodal approach with work that often combined electrical stimulation or reversible inactivation lesions with fMRI (Liu, Avidan, Turchi, Hadj-Bouziane, & Behrmann, 2024) to understand the underlying circuits and not just the functional properties of isolated regions. With a rapidly growing fMRI literature on human face perception, this work created a bridge between our detailed understanding of nonhuman primate functional neuroanatomy and the functional architecture observed in humans. This work even extended into studies of facial expression perception in people with Moebius Syndrome, a condition that causes facial paralysis (Japee, 2024).

Although we have highlighted four major areas of Leslie's research, we have not covered all her interests and her impact by any means. Leslie's research not only covered all levels of visual processing from retina to frontal cortex (Zhang et al., 2024), but she also made major contributions to our understanding of working memory, emotional processing, and motor learning and plasticity (Oren, Korman, & Karni, 2024). Leslie's influence extends across multiple fields, and her impact will stay with our field for many years to come.

Corresponding author: Chris Baker, Laboratory of Brain and Cognition, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, 10/416, Bethesda, MD 20892, or via e-mail: [email protected].

Chris Baker: Conceptualization; Writing—Original draft; Writing—Review & editing. Sabine Kastner: Conceptualization; Writing—Review & editing.

S. K. is funded by the National Institutes of Health (https://dx.doi.org/10.13039/100000002), grant numbers: 1P50MH132642, 2RO1 EY017699, and R01 MH137624. C. B. is funded by the Intramural Research Program of NIMH, grant numbers: ZIAMH002893 and ZIAMH002909.

Retrospective analysis of the citations in every article published in this journal from 2010 to 2021 reveals a persistent pattern of gender imbalance: Although the proportions of authorship teams (categorized by estimated gender identification of first author/last author) publishing in the Journal of Cognitive Neuroscience (JoCN) during this period were M(an)/M = .407, W(oman)/M = .32, M/W = .115, and W/W = .159, the comparable proportions for the articles that these authorship teams cited were M/M = .549, W/M = .257, M/W = .109, and W/W = .085 (Postle and Fulvio, JoCN, 34:1, pp. 1–3). Consequently, JoCN encourages all authors to consider gender balance explicitly when selecting which articles to cite and gives them the opportunity to report their article's gender citation balance.