Understanding the Intricacies of the Human Brainstem: Individual Variability, Bilateral Asymmetry, and Unexpected Species Differences


The brainstem is a vital and complex part of the brain, responsible for interconnecting the cerebral cortex with the spinal cord and the cerebellum. There are three main divisions of the brainstem, the midbrain, the pons, and the medulla. Each is made up of numerous nuclei, defined by neuroanatomists as groupings of nerve cell bodies. These nerve cells, or neurons, then send information, via long fibers called axons, to other brain regions. Different brainstem nuclei are important for different functions. Some nuclei are involved in the processing of sensory information; visual, vestibular, auditory and somatosensory information are analyzed in different brainstem nuclei. Other brainstem nuclei are involved in the control of movement,  providing critical input to the cerebellum, a large structure with many neurons that mediates the coordination of movement, generation of eye movements, and some aspects of cognitive function. Another important aspect of brainstem function is the presence of specific nuclei that are rich in neurotransmitters like dopamine, serotonin, and norepinephrine. These transmitters are critical for motor control, attention, sleep-wake cycles, and mood.  Classically, it has been suggested that over evolution it is the cerebral cortex that enlarges and changes in function, while, in contrast,  the brainstem remains largely conserved. By that view, the brainstem in the mouse would have the same organization and function as the brainstem in humans.

This view has been challenged by the work of Professors Joan S. Baizer from the University at Buffalo and Sandra F. Witelson from McMaster University. They have explored the characteristics of four crucial brainstem nuclei, three of which are involved in motor control via connections with the cerebellum, and the fourth in auditory processing. These nuclei are the nucleus paramedianus dorsalis (PMD), the principal nucleus of the inferior olive (IOpr), the arcuate nucleus of the medulla (Arc), and the dorsal cochlear nucleus (DC). The results of their research were published in the journal Frontiers in Neuroanatomy.

The researchers analyzed postmortem brain tissue from the Witelson Normal Brain Collection, as well as archival sections from other species. Their findings revealed significant individual differences, left-right asymmetry, and species differences in the size, shape, and appearance of these nuclei. They observed cases with extremely large or small nuclei, unusual configurations of nuclei, and distinct variations in organization between the left and right sides of the brainstem. Moreover, they discovered that two of these nuclei, the PMD and the Arc, were unique to the brainstem of humans and were not found in other mammals. These findings revealed significant differences in brainstem organization in humans compared to many other species.

Based on these findings, the researchers proposed that these distinct characteristics of the human brainstem nuclei might reflect human-specific adaptations allowing complex cognitive functions, such as language, music, and social cognition and also for motor control, especially of the hands and fingers, critical for the use of tools, skills well-developed in humans. They also noted that genetic factors, such as gene duplication, gene expression, and epigenetic regulation, could affect the development of these brainstem nuclei.

The study concluded by emphasizing the need for further comparative studies on human brainstem organization. Such research would contribute to a more comprehensive understanding of the brainstem and its possible involvement in human-specific neurological and psychiatric disorders.

In summary, the research conducted by Baizer and Witelson sheds new light on the complexity and individual variability of the human brainstem. The organization of the brainstem has changed significantly over evolution. This study highlights the significance of studying the human brainstem and its variations to further our understanding of brain function and highlights the importance of developing personalized medical interventions.


Baizer JS, Witelson SF. Comparative analysis of four nuclei in the human brainstem: Individual differences, left-right asymmetry, species differences. Frontiers in Neuroanatomy. 2023;17.

Go To Frontiers in Neuroanatomy.