The Triple Helix @ UChicago

Spring 2018

"Unsung Heroes: Case Studies of Patients with Neurological Anomalies" by Lindsey Jay


Some of the most enlightening scientific findings regarding the functions of different brain regions have come from in-depth studies of people who have lived with damage to specific brain regions. Due to limitations in technology, scientists prior to the 20thcentury could only fully study the brain in dissections after the patient died. It was otherwise impossible to fully understand what went on underneath the skull of a living human.

When scientists began studying cases of people who had damaged specific parts of their brains in accidents, they could observe what functionalities these patients lacked. While lab rats also provide a way for us to look at brain functionality, case studies can more directly inform us of how the human brain works. Phineas Gage, Patient RB, and Patient DF are three such case studies that contributed to the advancement of neuroscience research.

Phineas Gage: Personality


Fig. 1. Phineas Gage following his accident (left) and a reconstruction of the iron rod through his skull (right).

Phineas Gage (1823-1860) was a white male who worked as the foreman of a railway construction group.  In 1848, however, an explosion at the construction site caused a 1.25” diameter iron rod to plunge into his face under his left cheekbone and out through the top of his head.[1] The blow did not cause him to lose consciousness; however, it destroyed the left part of his frontal lobe. 

Although his bodily functioning remained fully intact, his personality did not. Formerly known as a calm, thoughtful man, Gage became irritable, impatient, and profane. It also became difficult for him to follow through on any plans he made. 

Gage’s personality change appeared to last for only about two or three years, since he was able to take up a job as a long-distance stagecoach driver in Chile that required both focus and planning.[2] This reversal may point to the potential rewiring in his brain that allowed him to regain the ability to plan, although no scientists followed up on Gage for further study.

These changes in Gage’s behavior were some of the first pieces of modern evidence that the prefrontal cortex may be responsible for impulsivity control and executive functioning, the skills that appeared to be compromised in Gage. Gage’s miraculous recovery also provided an early piece of evidence for neuroplasticity, or the ability for the brain to rewire itself and regain functionality.

Patient RB: Memory


Fig. 2. Photomicrographs of left (L) and right (R) coronal sections of Patient RB’s hippocampus. Asterisks indicate evidence of complete loss of pyramidal cells in CA1 of the hippocampus but normal densities in the other regions.
[Source: Zola-Morgan, S, et al. “Human Amnesia and the Medial Temporal Region: Enduring Memory Impairment Following a Bilateral Lesion Limited to Field CA1 of the Hippocampus.” The Journal of Neuroscience, vol. 6, no. 10, Jan. 1986, pp. 2950–2967., doi:10.1523/jneurosci.06-10-02950.1986.]

RB (1926-1983) was a white male who worked as a postal worker before retiring in 1976 due to a medical disability. Two years later, he was hospitalized and underwent a coronary bypass operation. After the surgery, a sudden atrial tear occurred and, in the two minutes before it was repaired, led to a massive loss of blood.[3] RB was then properly treated before his discharge from the hospital. 

After this sudden blood loss, or ischemia, his family members noticed that he was often forgetful of things recently mentioned in conversation and commonly misplaced his belongings. Doctors suspected that the ischemia led to this memory impairment, and it was confirmed post-mortem that there was severe damage limited to the hippocampal region in his brain responsible for converting short-term into long-term memories. This was the first studied case of brain damage isolated completely to the hippocampus. 

With his consent, neuroscientists conducted a battery of neurological examinations on RB to better understand the role of the hippocampus in memory. He had a normal IQ on the Wechsler Adult Intelligence Scale but exhibited severe verbal and nonverbal memory impairments; most notably, RB demonstrated anterograde amnesia in tests of recognition and recall. His retrograde memory appeared to be intact, however, as he could recall most events that occurred before his ischemic episode, including famous faces and autobiographical information. 

Scientists were able to fully section his brain following his death and found that only the CA1 region of the hippocampus was damaged, while the rest of the brain appeared completely normal. These findings helped neuroscientists isolate behaviors specific to CA1 hippocampal functionality.

Patient DF: Visual Agnosia


Fig. 3. Ventral stream lesions in Patient DF shown in contrast to the expected location of the lateral occipital complex (LOC) in healthy participants. (A) Lesions in DF were traced on slices that indicated tissue damage in pale blue. The rightmost image shows a slice through the lesions. (B) The expected location of LOC based on group data from seven neurologically intact participants. The activation in the slice is also outlined in orange in panel A for comparison.
[Source: Whitwell, Robert L., et al. “Patient DF’s Visual Brain in Action: Visual Feedforward Control in Visual Form Agnosia.” Vision Research, vol. 110, 2015, pp. 265–276., doi:10.1016/j.visres.2014.08.016.]

DF (age and race unknown) is a woman who suffered irreversible brain damage from carbon monoxide poisoning in 1988, causing her to develop visual form agnosia, a profound loss of visual form perception.[4] It is believed that her lateral occipital cortex, which is responsible for initial processing of visual stimuli, was bilaterally damaged.[5]

These first observations that DF could not identify objects visually but could still accurately grasp objects differently depending on their shape led to the two-streams hypothesis.[5] According to this hypothesis, there are two paths of processing visual input: 1) the “ventral stream,” or the “what” stream, which processes the physical characteristics of the object such as color and shape, and 2) the “dorsal stream,” or the “where” stream, which helps locate where something is in space. 

When asked to identify pictures of objects such as cars or chairs, DF could not recognize them. On the other hand, when she had to reach for objects such as a magnet, her hand would form the correct shape to grasp the object despite not being able to recognize it. Researchers thus proposed that DF’s “ventral stream,” the visual pathway that processes what objects are, was damaged, while her “dorsal stream,” the pathway that processes where objects are located in space, was intact.  

An fMRI study on DF confirmed the activation of the occipitoparietal system during grasping tasks but not object identification tasks, providing evidence that the dorsal stream may exist along the parietal lobe. Moreover, the occipitotemporal system was activated during visual identification tasks in normal subjects but not in DF, further confirming that a ventral stream may exist in the temporal lobe separately. The two-streams hypothesis has since been widely accepted. 


These case studies served as foundations in understanding the functional organization of the brain. Phineas Gage helped establish the role of the prefrontal cortex in impulsivity control, while RB provided a unique opportunity to study the hippocampus and revealed its importance in memory consolidation. Finally, DF’s specific loss of visual functionality allowed scientists to develop the two-streams hypothesis. Thus, these case studies provided us our first glimpse into the complex functioning of the human brain. 



[1] “The Phineas Gage Story.” School of  

[2] Hamilton, Jon. “Why Brain Scientists Are Still Obsessed With The Curious Case Of Phineas Gage.” NPR, NPR, 21 May 2017,  

[3] Zola-Morgan, S, et al. “Human Amnesia and the Medial Temporal Region: Enduring Memory Impairment Following a Bilateral Lesion Limited to Field CA1 of the Hippocampus.” The Journal of Neuroscience, vol. 6, no. 10, Jan. 1986, pp. 2950–2967., doi:10.1523/jneurosci.06-10-02950.1986. 

[4] James, Thomas W., et al. “Ventral Occipital Lesions Impair Object Recognition but Not Object‐Directed Grasping: an FMRI Study.” Brain, vol. 126, no. 11, 2003, pp. 2463–2475., doi:10.1093/brain/awg248. 

[5] Whitwell, Robert L., et al. “Patient DF’s Visual Brain in Action: Visual Feedforward Control in Visual Form Agnosia.” Vision Research, vol. 110, 2015, pp. 265–276., doi:10.1016/j.visres.2014.08.016. 

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