The criterion "Potential Isolation by Brain Damage" refers to the notion that distinct intelligences can be independently affected by brain damage. This means that a specific type of intelligence can be impaired or lost while others remain intact, indicating its unique neurological basis. For instance, a person might suffer damage to a part of the brain responsible for linguistic abilities, losing their capacity to use language, while their mathematical or musical abilities remain unaffected. This criterion supports Gardner's idea that multiple intelligences are separate from each other, each residing in different areas of the brain.

Phineas P. Gage (1823–1860) was an American railroad construction foreman remembered for his improbable  survival of an accident in which a large iron rod was driven completely through his head, destroying much of his brain's left frontal lobe, and for that injury's reported effects on his personality and behavior over the remaining 12 years of his life‍—‌effects sufficiently profound that friends saw him (for a time at least) as "no longer Gage".