The Prefrontal Cortex

Where it is and what it connects to

The prefrontal cortex occupies the front third or so of each frontal lobe, lying ahead of the primary motor cortex and the premotor and supplementary motor areas. Anatomically it is defined by what it is not: it is the frontal cortex that is not devoted to producing movement. Cytoarchitecturally it is distinguished by a well-developed granular layer IV, which the motor areas lack, and it is often called the granular frontal cortex for this reason.

Its most telling feature is its connectivity. The prefrontal cortex is one of the most densely and widely connected regions of the brain. It receives input from every sensory modality, either directly or through association cortex; it exchanges signals with the posterior parietal cortex through the superior longitudinal fasciculus; it is reciprocally connected with the limbic structures that carry emotional and motivational information, including the amygdala and the hippocampus; it loops through the basal ganglia and back via the thalamus; and it projects downwards to motor systems and to the brainstem nuclei that release the neuromodulators dopamine, noradrenaline, serotonin, and acetylcholine.

This is also why the prefrontal cortex is the frontal node of the frontoparietal control network described on the cognition hub. Its function is inseparable from its partners, and the modern view treats prefrontal damage as damage to a network rather than the loss of a self-contained organ.

The four subdivisions

The prefrontal cortex is not homogeneous. Its different territories have different connections and different characteristic deficits when damaged. Four divisions are worth knowing, and they map roughly onto four kinds of control.

A useful, if crude, contrast runs between the dorsolateral and ventromedial or orbitofrontal territories. The dorsolateral surface is associated with the cold, abstract side of control: holding rules, manipulating information, planning a sequence. The ventral and medial surfaces are associated with the hot, valuational side: what things are worth, what feels right, what other people will think. Both are control, but they control different things, and lesions to the two produce recognisably different patients.

The brain's executive

The prefrontal cortex is often described as the brain's executive, and for once the metaphor earns its keep. An executive does not do the work of a company; it sets goals, allocates attention and resources, monitors progress, and overrides the reflexive response when it is the wrong one. That is a fair description of what prefrontal circuits contribute.

Physiologically, the signature discovery is delay-period activity. Recordings from the primate lateral prefrontal cortex show neurons that fire persistently throughout a delay while an animal holds a location or a stimulus in mind, and that stop firing when the response is made. This sustained firing appears to be the physical form of keeping something in mind when it is no longer in front of you, and it underpins working memory.

From that basic capacity, several higher functions follow.

The unifying theme is control over time. Almost everything the prefrontal cortex does involves bridging a gap between a goal set now and an action taken later, holding the relevant information across that gap, and suppressing whatever else the environment is urging you towards in the meantime.

The slowest region to mature

Cortical development does not proceed uniformly. Primary sensory and motor areas mature first; association cortex follows; and the prefrontal cortex finishes last, by a wide margin. Longitudinal magnetic resonance imaging studies that scan the same children repeatedly across adolescence show a characteristic sequence: an early wave of grey matter expansion, followed by a prolonged period of thinning as unused synapses are pruned, and a steady, continuing increase in white matter volume as prefrontal axons are myelinated. In the prefrontal cortex, this process runs through the teenage years and does not settle until roughly the mid-twenties.

The practical picture from developmental research is that the gap is widest when a decision is emotionally charged, socially observed, or made quickly. In calm, deliberate conditions adolescents perform close to adults. Under peer pressure and time pressure, the difference in impulse control shows. This is consistent with a picture in which limbic and reward systems come online earlier and prefrontal regulation of them arrives later. The brain development page treats this timetable in full.

Phineas Gage: the real record

On 13 September 1848, in Cavendish, Vermont, a twenty-five-year-old railway construction foreman named Phineas Gage was using a metre-long tamping iron to pack blasting powder into a hole in rock. The charge detonated early. The iron was driven upwards through his left cheek, behind the left eye, and out through the top of his skull, landing many metres away. It damaged principally the left frontal lobe, including orbitofrontal and ventromedial regions, with likely involvement of adjacent left prefrontal cortex.

Gage did not lose consciousness for long, spoke within minutes, and walked with assistance. He survived, an outcome so improbable that his physician, John Harlow, was widely disbelieved. Harlow's later report, published in 1868, is the primary source for what happened next, and it is the report that made Gage famous. Harlow described a man who had been an efficient and capable foreman, well liked by his crew, and who after the injury was, in the phrase that has echoed ever since, "no longer Gage": profane, capricious, impatient of restraint, unable to settle on a plan.

That much is the record. What the record does not support is the caricature that grew up afterwards. Gage did not become a violent brute or a derelict. Careful historical work, notably by the psychologist Malcolm Macmillan, has shown that the popular accounts drifted steadily further from Harlow's testimony with each retelling, acquiring details that appear in no primary source. What the documentary evidence actually shows is a man who worked in a livery stable, then travelled to Chile and worked for several years as a long-distance stagecoach driver, a demanding job requiring route planning, punctuality, handling of teams of horses, and dealing with passengers. He later returned to the United States and worked on a farm in California before dying in 1860, some twelve years after the accident, of complications from epileptic seizures.

So what should the case be taken to show? Three things, none of them the popular moral. First, that damage to ventromedial and orbitofrontal cortex can alter personality, social conduct, and self-regulation while leaving basic intellect, language, and memory broadly intact, a dissociation that was genuinely new and important in 1848. Second, that the brain is capable of considerable functional recovery, particularly with structure and demand. Third, and not least, that a single case, retold often enough, will accumulate details that nobody ever observed. Gage is a lesson about the frontal lobes and a lesson about how neuroscience folklore is made.

Frontal lobe syndromes

Clinically, prefrontal damage, from stroke, tumour, traumatic injury, or degenerative disease such as frontotemporal dementia, produces recognisable patterns rather than one uniform deficit. Three broad syndromes are conventionally described, and they map loosely onto the subdivisions above. They overlap in real patients, since lesions rarely respect anatomical boundaries.

1. Dysexecutive syndrome

   Associated chiefly with dorsolateral damage. The patient is disorganised, distractible, and perseverative: they repeat a strategy that has stopped working, fail to plan multi-step tasks, and struggle to hold a rule in mind. Formal IQ scores may be entirely normal, which is the diagnostic trap.

2. Disinhibited syndrome

   Associated with orbitofrontal and ventromedial damage. The patient is impulsive, socially inappropriate, tactless, and poor at anticipating consequences. They may know the rules of conduct perfectly well when asked and still fail to apply them. This is the Gage pattern.

3. Apathetic or abulic syndrome

   Associated with medial frontal and anterior cingulate damage. The patient shows reduced spontaneous behaviour, flattened initiative, and, in severe cases, akinetic mutism: awake, apparently aware, but neither speaking nor moving of their own accord.

The most instructive feature of all three is the dissociation between knowing and doing. Patients with prefrontal damage frequently pass standard tests of knowledge and reasoning yet fail to organise their lives. The neuropsychologist's phrase for this is a deficit in the application of intact abilities. It is one of the clearest demonstrations that intelligence, as measured by tests, and control of behaviour, are not the same thing.

The prefrontal cortex and intelligence

Where does the prefrontal cortex sit in relation to measured intelligence? The evidence supports a strong but carefully bounded claim.

On the strong side: prefrontal circuits are central to working memory and to executive function, and both correlate substantially with performance on tests of fluid reasoning. The lateral prefrontal cortex is one of the two anchors of the frontoparietal network that Jung and Haier's P-FIT synthesis identified as central to individual differences in intelligence, and it is reliably engaged by matrix reasoning and other tests of the kind used in an IQ test.

On the bounded side: prefrontal damage does not reliably lower IQ. This is the finding that most needs stating plainly, because it is so counter-intuitive. Patients with substantial frontal lesions, including patients with the disinhibited pattern, often score within the normal range on standard intelligence batteries while their lives fall apart. The reason is instructive. A test session is a highly structured environment: the goal is given to you, the task is segmented, distractions are removed, and someone tells you when to start and stop. In other words, the test supplies exactly the executive scaffolding that the damaged prefrontal cortex would otherwise have to provide. Take away the scaffolding, and the deficit appears.

The right conclusion is that the prefrontal cortex is essential to intelligent behaviour without being identical to test-measured intelligence. It is the difference between having the capacity and deploying it. Our page on crystallised and fluid intelligence covers the psychometric side of that distinction.

Correcting the Gage caricature

Related topics