Understanding Brain Function through Lesions and Ablation: Insights from Neuropsychology

How do scientists figure out which part of the brain controls which function? One of the most direct – and revealing – methods in the history of neuropsychology involves studying what happens when brain tissue is removed or damaged. Known as lesion and ablation techniques, these approaches have helped build the foundation of modern brain science. By observing deficits that follow brain damage – whether from accidents, disease, or controlled surgical procedures – researchers have mapped cognitive and behavioral functions onto specific brain regions with remarkable precision.

What are lesions and ablation?
Experimental ablation in animals
Localization of function: mapping the brain through damage
Paul Broca and language localization
The frontal lobe and personality: the case of Phineas Gage
Memory and the hippocampus: lessons from Patient H.M.
Ablation as a clinical tool
Strengths and limitations of lesion and ablation methods
The brain’s remarkable adaptability

What are lesions and ablation?

A brain lesion refers to any area of damaged or abnormal brain tissue. In neuropsychology, lesions may arise naturally through strokes, tumors, infections, or traumatic injuries – or they may be experimentally induced in animal research. Ablation, by contrast, refers to the deliberate surgical destruction or removal of brain tissue. The word itself derives from the Latin ablatus, meaning “carried away.” Despite that description, ablation usually destroys tissue in place rather than physically removing it.

Lesions are typically classified by their scope. A focal lesion affects one discrete brain region, while a diffuse lesion spreads across multiple areas. The impact of a lesion depends heavily on where it occurs. Damage to the frontal lobe tends to affect decision-making and personality; damage to the hippocampus disrupts memory; and damage to the occipital lobe can impair vision.

Experimental ablation in animals

Ablative brain surgery was first pioneered by Pierre Flourens (1794-1867), a French physiologist who removed parts of the nervous system in animals and carefully observed the behavioral consequences. If an animal could no longer move a limb after a specific region was removed, it was inferred that the region controlled that movement. This method – termed experimental ablation – allowed researchers to draw systematic links between brain regions and their functions.

Modern experimental ablation involves drilling small holes in an animal’s skull and inserting electrodes or cannulas using a stereotactic apparatus – a device that allows precise targeting of brain coordinates. Electricity passed through an electrode destroys the targeted tissue, or chemicals are delivered via the cannula to damage the area of interest. By comparing the animal’s behavior before and after the procedure, researchers infer the function of the damaged region. Such research is considered unethical on humans due to the irreversible nature of the damage – but nature and medical necessity have, over time, provided plenty of accidental and surgical human cases to study.

Localization of function: mapping the brain through damage

One of the central aims of lesion and ablation research is to establish the localization of function – the idea that specific brain regions are responsible for specific cognitive or behavioral tasks. Lesion studies have been foundational in elucidating the neural substrates of higher cognitive functions, including perception, attention, decision-making, social cognition, and emotional processing. Early investigations demonstrated that focal brain damage could dissociate complex cognitive processes – such as language – into distinct components tied to different brain regions.

This logic is straightforward: if a particular brain region participates in a particular function, that function should be impaired when the region is damaged or removed. The typical inference is that if a brain region participates in a function, its removal or damage should impair that function – though researchers acknowledge that alternative explanations exist. Brain lesions can, for instance, trigger reorganization of function or even release previously inhibited capacities.

Paul Broca and language localization

One of the earliest breakthroughs came from French physician Paul Broca in the 19th century. Studying patients who had lost the ability to produce speech, Broca traced their deficits to a specific region in the left frontal lobe – now known as Broca’s area. This was among the first clear demonstrations that a higher cognitive function like language was tied to a discrete anatomical location. Modern lesion studies often include hundreds of patients, enabled by neuroimaging technology and advanced statistical methods that allow much more rigorous mapping of lesion-induced deficits to brain anatomy than early single-case reports permitted.

The frontal lobe and personality: the case of Phineas Gage

No lesion case has captured the scientific imagination more than that of Phineas Gage. In 1848, Gage – a 25-year-old railroad foreman in Vermont – survived a freak explosion that drove a metal tamping rod through his skull, destroying much of his left frontal lobe. His case was perhaps the first to suggest the role of brain areas in determining personality and to indicate that specific parts of the brain, when affected, can induce specific mental changes.

Before the accident, Gage was described by his employers as their most capable and efficient foreman. Afterward, his personality shifted dramatically. His contractors considered the change in his mind so marked that they could not give him his place again; he was described as fitful, irreverent, and impatient of restraint. This change pointed researchers toward the frontal lobe’s critical role in personality, social behavior, and executive function – insights that remain central to neuropsychology today.

It is worth noting that Gage’s story is sometimes overstated. Only a minority of scientific articles covering the case mention that Gage eventually recovered and resumed something resembling normal life, including working as a stagecoach driver in Chile – a demanding job requiring planning and focus. His partial recovery foreshadowed later understanding of the brain’s plasticity.

Memory and the hippocampus: lessons from Patient H.M.

If Phineas Gage illuminated the frontal lobe’s role in personality, then Patient H.M. – Henry Molaison – did the same for memory and the hippocampus. In the 1950s, Molaison underwent surgery to treat severe epilepsy resistant to all available medication. Neurosurgeon William Scoville removed the anterior two-thirds of the hippocampus, along with the amygdala and the entorhinal cortex. The seizures improved, but the consequences for memory were catastrophic.

Molaison was left with profound anterograde amnesia – he could no longer form new long-term memories. Yet his intelligence and personality remained largely intact, and he could still learn new motor skills. His case suggested that the hippocampus is not the site of long-term memory storage, but is essential to encoding and transferring memories to other parts of the brain. It also clarified the distinction between explicit memory (conscious recall of facts and events, which was lost) and implicit memory (procedural and skill-based memory, which remained intact) – a distinction now foundational to memory research.

After early surgical cases resulted in profound amnesia, the critical role of the hippocampus and associated medial temporal lobe structures in declarative memory became evident, and surgical approaches were quickly changed to become unilateral and more precise, reducing the risk of severe cognitive consequences for future epilepsy patients.

Ablation as a clinical tool

Beyond research, ablation techniques have genuine therapeutic applications. The evolution of therapeutic lesions in functional neurosurgery has moved from large, imprecise procedures – such as the prefrontal leucotomy – to highly targeted interventions using modern technology. Today, MRI-guided laser ablation allows neurosurgeons to destroy tissue with extraordinary precision, causing minimal damage to surrounding areas. This technique is used to treat epileptic foci, brain tumors, and other neurological conditions.

Another modern approach is magnetic resonance-guided focused ultrasound (MRgFUS), which uses multiple ultrasound beams to heat and destroy a specific target within the brain without any incision. MRgFUS is currently used clinically to treat tremor in essential tremor and Parkinson’s disease as an alternative to deep brain stimulation, with its effectiveness confirmed in large randomized controlled trials.

Ablation is also valuable in epilepsy surgery. When seizures originate from a discrete brain region and cannot be controlled by medication, surgical ablation of that region can dramatically reduce or eliminate seizure frequency. The outcomes of such surgeries have, in turn, generated further insights about brain function – essentially turning clinical necessity into neuropsychological discovery.

Strengths and limitations of lesion and ablation methods

A key strength of lesion studies is their ability to provide causal evidence. Unlike neuroimaging methods that reveal correlational patterns of brain activity, lesion studies directly demonstrate that a region is necessary for a particular function. Chronic lesion studies provide unique, vital insights into brain function that cannot be achieved via temporary inactivation methods or correlational studies of brain activity, and integrating these insights with other methods is crucial for advancing neuroscience.

However, the method has real limitations. Localization of cognitive function is not as straightforward as motor or sensory functions – individual differences, hierarchical organization of cognitive systems, and functional networks all complicate interpretation. Brain lesions rarely respect anatomical boundaries, and the etiology of damage (stroke, tumor, trauma) affects which regions are likely to be involved. Furthermore, sample sizes in neuropsychological studies of patients tend to be low, constrained by the difficulty of recruiting and testing special populations.

There is also the issue of plasticity. The brain does not simply lose function when a region is damaged – it sometimes adapts. The central nervous system retains an innovative ability to recover and adapt through secondary compensatory mechanisms. Neuroplasticity – the brain’s capacity to reorganize itself structurally and functionally – means that the behavioral deficits observed after a lesion may not perfectly reflect the original role of the damaged region. Some functions may shift to intact areas, and recovery can occur over time, as Phineas Gage’s own story illustrated.

The brain’s remarkable adaptability

One of the most important lessons from lesion research is that the brain is not a static, rigidly wired machine. When one region is damaged, others can sometimes compensate. Mapping studies in nonhuman primates demonstrated that after behavioral recovery from brain injury, the original injured cortical region’s functions could localize to an adjacent territory. In humans, neuroimaging studies after stroke or injury show similar patterns of cortical reorganization, where neighboring or even contralateral regions take over lost functions.

This adaptability does not mean lesion effects are trivial – severe and permanent deficits can and do occur, as Patient H.M.’s case demonstrates. But it does mean that the relationship between a brain region and a behavior is often more dynamic and distributed than a simple one-to-one mapping. Lesion studies identify brain regions essential to function, while neuroimaging studies identify regions that are involved in, but not necessarily essential to, a particular brain function – a distinction that matters enormously for interpreting the evidence.

Together, lesion and ablation methods – spanning centuries from Flourens’s animal experiments to today’s MRI-guided neurosurgery – have given neuropsychology some of its most enduring and foundational insights. They reveal not only where functions live in the brain, but also how remarkably the brain can reorganize when those places are lost.

What do you think? If a person recovers cognitive function after a brain lesion, does that mean the damaged region wasn’t truly necessary – or does it tell us something more interesting about how the brain distributes its work? And given the ethical limits on experimental lesion studies in humans, how much can we rely on accidental injuries to build a complete picture of brain function?

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Table of Contents

What are lesions and ablation? 🔗

Experimental ablation in animals 🔗

Localization of function: mapping the brain through damage 🔗

Paul Broca and language localization 🔗

The frontal lobe and personality: the case of Phineas Gage 🔗

Memory and the hippocampus: lessons from Patient H.M. 🔗

Ablation as a clinical tool 🔗

Strengths and limitations of lesion and ablation methods 🔗

The brain’s remarkable adaptability 🔗