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Why Neuroscientists Should Be Careful About Making Conclusions From Single Patients

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By Gary Stix
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Our current understanding of how the brain works often borrows from observations of the anomalous patient. The iron rod that penetrated Phineas Gage’s head made the once emotionally balanced railroad foreman impulsive and profane. But it gave neurologists clues as to the role of the brain’s frontal lobes in exercising self-control. The epilepsy surgery that removed Henry Molaison’s hippocampus opened a whole new line of research about memory.

Still, conclusions about mental processes from single patients arrive freighted with unavoidable risk. Neuroscientists can’t replicate what they find in neurologically damaged patients by removing a frontal lobe or hippocampus from other research subjects without planning for significant downtime in a state or federal prison.

That means that what we think we learn from an initial examination of a Gage or a Molaison may be less than meets the eye. The cautionary lessons of single-case neuroscience were underlined in a recent paper in Neuropsychologia by Marc Himmelbach and two colleagues at the Hertie-Institute for Clinical Brain Research, part of Eberhard Karls University in Tübingen, Germany.

The team took another look at the well-known case of D.F., a woman who suffered brain damage more than 20 years ago from carbon monoxide. D.F.’s entry into the case history annals came about because, as a result of her injuries, she could not recognize everyday objects, a condition called visual agnosia, yet she was still able to grasp them.

The observed disparity between recognition and motor skill control is the basis for what is called “action-perception dissociation.” This separation of visual processing purports to explain why, for instance, even though you cannot perceive a fly ball decelerating, your motor control system still responds accordingly so that you can snag it in your glove.

In D.F.’s case, after her visual cortex, located at the back of your head, receives inputs from the eye, it appears to relay a faulty signal to the temporal lobes on both sides of the brain, which impedes recognition of an object. By contrast, a second signal seems to travel unimpaired from the visual cortex to the parietal lobe at the top of the head, enabling the object to be grasped.

Himmelbach and his collaborators reran the experiment by taking 20 healthy women and putting them through the same set of tests administered to D.F., including tasks such as grasping blocks. They then compared the results from these new experiments with the original tests on D.F. and discovered that she was substantially impaired, not just on recognition, but on tasks involving motor skills as well. That finding undercuts the theory that the two pathways function independently and suggests that there may be significant overlap between them. “The problem was that the main motif of the theory built on D.F., the action vs. perception disassociation, is so simple and straightforward that it can be easily be communicated to a wider non-specialist audience,” Himmelbach says in an e-mail. The paper adds that there has been other work that confirms this neurophysiological model. But, again, the case of D.F. complicates this picture as well. “…many of these findings do not provide unequivocal evidence in favor of or against the dual visual steam hypothesis without reference to D.F. and could also be integrated by alternative models that do not explicitly state an action-perception disassociation,” the authors write.

Other famous single-cases have also come up for second looks. Molaison, often referred to as simply HM, could generally not store new memories of an event or a building’s spatial layout, but could learn new skills. Himmelbach pointed out that a reassessment of Molaison’s impairment showed that he eventually learned to negotiate the rooms of the house he lived in, proof that he could sometimes form spatial memories. “He had problems whenever he had to learn something in a limited time with a limited number of repetitions and he was better whenever he was allowed to learn the very same thing over and over again for a long time,” Himmelbach says. Similarly, Gage’s accident-acquired social ineptness reportedly diminished as time passed, though he was never adequately examined to determine the extent of change in his cognitive abilities.

In every instance, the outcome was probably not as clear-cut as the textbook accounts suggest. “The main problem of single-case research lies in the selective reporting of data and simplification of equivocal findings, Himmelbach says. “This is a problem for all research techniques, but for single-case research the independent replication of original findings is a particular problem as it is very unlikely that an independent group of researchers gets access to another single case with more or less identical characteristics.” The message conveyed: Looking at a single individual, though often vitally useful, can turn perilous if over-reliance on these observations becomes the foundation for new models of how complex brain circuits function.

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