Can Yesterday’s TRAUMA Become Tomorrow’s BRAIN Seizure?

As painful memories are repeatedly replayed, could the brain’s remarkable plasticity sometimes work against itself?

Umair Ashraf
Consider a medial temporal focal seizure. There may be no dramatic collapse and no violent convulsion. Awareness simply becomes altered. A person may suddenly lose track of where they are, forget what they were doing moments earlier, or fail to recognize an ordinary context. Then come repetitive, almost automatic behaviors: swallowing, chewing, lip-smacking, tongue movements or small stereotyped sounds. Within less than a minute, the episode may be over. Confusion, fatigue or headache can follow.

This familiar seizure pattern opens a much larger question. Why does a network normally responsible for memory, emotion and behavioural integration suddenly become capable of producing pathological hypersynchrony? Why does the temporal-limbic network appear so repeatedly in focal epilepsy when the brain contains countless other highly active circuits?

The conventional answers are important: hippocampal sclerosis, developmental abnormalities, tumours, previous injury, infection and genetic disorders can all create epileptogenic vulnerability. But if we temporarily put these established anatomical and genetic explanations aside, another question becomes possible. Could the brain’s own mechanism for learning and adapting sometimes participate in making a network seizure-prone?

The answer begins with neuroplasticity.

The brain is constantly converting experience into biology. A meaningful experience does not remain a psychological event floating above the neurons. Repeated neuronal activity changes synaptic strength, receptor expression, intracellular signalling and, eventually, gene expression. Glutamatergic transmission through AMPA and NMDA receptors can produce calcium entry into neurons. Calcium then activates signalling molecules including CaMKs. At the same time, metabotropic receptors can engage different intracellular routes: Gs-coupled receptors can increase cyclic AMP and activate PKA, while Gq-coupled receptors activate phospholipase C, generating IP3 and DAG and recruiting intracellular calcium and PKC. These pathways can converge upon transcriptional regulators such as CREB and influence neurotrophic signalling, including BDNF.

This is the molecular machinery through which experience becomes lasting change.

Long-term potentiation, or LTP, is one of its clearest examples. Repeatedly important activity can strengthen selected synapses so that a neural network becomes increasingly efficient at reproducing a pattern it has encountered before. The brain learns through repetition.

But plasticity does not ask whether the repeated experience is good for us.

A child learning a language repeatedly strengthens useful circuits. A musician repeatedly rehearsing a sequence modifies the networks required for that skill. But an individual trapped in persistent fear, obsession, emotional dependency, addiction, resentment or traumatic rumination can also repeatedly recruit the same neural systems. The hippocampus retrieves the memory. The amygdala gives it emotional significance. Prefrontal networks attempt to interpret and regulate it. Reward and motivational circuits can reinforce its salience. Sleep may deteriorate. Stress systems may remain activated.

Psychology has now crossed into molecular biology.

Persistent stress engages the hypothalamic-pituitary-adrenal axis and alters glucocorticoid signalling. It can influence glutamatergic transmission, calcium-dependent signalling, synaptic plasticity and neurotrophic mechanisms. Chronic stress can also affect astrocytes and microglia and alter the inflammatory environment surrounding neurons.

This becomes particularly relevant to epilepsy because neuroinflammation is not simply an innocent bystander. Molecules such as IL-1β and HMGB1 can activate inflammatory signalling through IL-1 and Toll-like receptor pathways. Experimental studies show that these pathways can enhance NMDA-receptor function, increase neuronal calcium influx, disturb inhibitory GABAergic signalling and activate transcriptional mechanisms associated with persistent neuronal and network changes. In experimental models, IL-1β and HMGB1 can lower the threshold for focal ictal activity.

Now the question becomes more interesting. If psychological experience can alter stress hormones, glutamate signalling, calcium-dependent pathways, gene expression, BDNF, glial activity and inflammatory signalling, could prolonged psychological stress also influence the biological conditions under which epileptogenic plasticity develops?

Experimental epilepsy provides a striking clue.

In a phenomenon known as kindling, repeated stimulation of particular neural circuits progressively increases their susceptibility to seizures. A network that initially tolerates stimulation can, after repeated activation, become increasingly capable of generating abnormal synchronous activity. Molecular changes involving synaptic transmission, inhibition, excitability and network connectivity accompany this process. While kindling is robustly demonstrated in rodent models—and epileptologists note it is notoriously difficult to replicate definitively in human brains—it serves as a powerful conceptual model for how repetitive activation might fundamentally alter a network’s baseline excitability over time.

But psychological repetition is not electrical kindling. Replaying a traumatic relationship in one’s mind is not equivalent to electrically stimulating the hippocampus. It would therefore be scientifically unjustified to say that rumination itself creates an epileptic focus.

The more defensible question is whether prolonged psychological stress can influence some of the same biological machinery that determines how neural networks adapt.

A 2026 review in Revue Neurologique has brought this possibility directly into contemporary epilepsy research under the term “psychoepileptogenesis.” Bartolomei and colleagues reviewed evidence from animal models and clinical studies suggesting that psychological stress or trauma may not merely precipitate seizures in someone who is already vulnerable, but may potentially contribute to epileptogenic network reorganisation. Their discussion particularly implicates limbic structures such as the hippocampus and amygdala, together with HPA-axis dysregulation and BDNF-related mechanisms. Importantly, the authors present this as an emerging field rather than an established explanation for human epilepsy.

At this point, a crucial clinical distinction must be made. Neurology has long recognised Psychogenic Non-Epileptic Seizures (PNES)—often understood today within the framework of Functional Neurological Disorder (FND)—where severe stress and trauma manifest as observable, physically real seizures without abnormal cortical electrical discharges. In PNES, the psychological burden drives a functional, network-level phenomenon. Psychoepileptogenesis, however, proposes something fundamentally different: that chronic stress and trauma-induced neuroinflammation might physically alter the brain’s structural and electrical thresholds, contributing to true, electrographic hypersynchrony.

The medial temporal lobe makes this hypothesis particularly intriguing. The hippocampus is deeply involved in memory formation, contextual processing and experience-dependent plasticity. The amygdala attaches emotional significance to experiences. Their connections allow an emotionally charged event to become a powerful, repeatedly retrievable memory. These same limbic networks are deeply implicated in temporal-lobe epilepsy.

This overlap does not prove that emotional trauma creates temporal-lobe epilepsy. It does, however, give neuroscience a specific network in which the interaction between stress, memory, plasticity and epileptogenic vulnerability can be investigated.

There is another remarkable feature of focal seizures: the abnormal activity does not necessarily remain confined to the place where it begins. A seizure is a network event. Depending on its origin and propagation, activity can recruit the temporal cortex, insula, thalamus, frontal networks, basal ganglia and brainstem.

This helps explain why a person can perform an apparently organised action while conscious awareness is impaired. Swallowing, chewing and other repetitive behaviours do not require the prefrontal cortex to consciously command every individual muscle. The brain contains organised pattern-generating circuitry, particularly in the brainstem, capable of coordinating complex motor sequences. Higher cortical and subcortical systems normally initiate and regulate these programmes. During a seizure, abnormal activity can recruit these existing circuits.

The behaviour therefore may look purposeful while actually being an automatic manifestation of abnormal network recruitment.

This is where the popular idea of the “reptilian brain” can become tempting, but it needs to be handled carefully. Modern neuroscience does not support a literal division between a primitive animal brain and a newer human brain. Higher cortical networks continuously interact with evolutionarily conserved subcortical and brainstem systems. The more accurate concept is not that the “animalistic brain” bypasses the human brain, but that abnormal cortical or limbic activity can recruit automatic networks whose execution does not depend on conscious executive control.

The insula adds another layer to the puzzle. Parts of the insular cortex are agranular or dysgranular, but the granular layer is not an electrical shield. Its absence does not automatically make the insula hyperexcitable. The significance of the insula in epilepsy is better understood through its dense connections with temporal, frontal, limbic, thalamic and autonomic networks. When these networks become involved in a seizure, the resulting symptoms can include striking visceral, laryngeal, autonomic and behavioural phenomena.

The same caution applies to the prefrontal cortex. Hypometabolism and altered connectivity can occur in cortical regions beyond the seizure focus, particularly in chronic epilepsy. But this should not be reduced to the idea that the DLPFC becomes metabolically exhausted and therefore loses control over a lower “animalistic” brain. Hypometabolism is evidence of altered network function and adaptation, not proof of a simple one-way failure of executive regulation.

There is, however, a useful conceptual contrast here. The healthy brain continuously regulates its automatic systems through distributed cortical and subcortical networks. A seizure represents a temporary state in which abnormal synchrony can recruit networks without following their ordinary functional hierarchy. The brain is not necessarily executing a new programme; it can be forcing an existing programme to run under pathological circumstances.

Childhood provides another window into the question of how intense neuronal activity can leave a lasting mark.

Fever itself should not be described as simply “burning” neurons or producing hippocampal sclerosis. Most febrile seizures are benign. But prolonged febrile status epilepticus is different. FEBSTAT studies have shown that a subset of children develop acute hippocampal abnormalities following prolonged febrile status, and those with acute hippocampal T2 abnormalities have a substantially increased risk of later hippocampal sclerosis and mesial temporal epilepsy. In the long-term FEBSTAT follow-up, 10 of 14 children with acute hippocampal T2 hyperintensity who had follow-up imaging developed definite hippocampal sclerosis, and mesial temporal epilepsy occurred disproportionately in those with the initial hippocampal injury.

The important lesson is not that fever alone causes epilepsy. It is that sustained pathological neuronal activity during a vulnerable developmental period can trigger molecular, inflammatory and structural changes that may persist long after the original event. Experimental and human studies increasingly implicate neuroinflammation, altered gene expression and changes in hippocampal synaptic connectivity in this process.

Now bring this back to psychological experience.

Suppose a young brain repeatedly encounters an emotionally charged pattern. The same memory is retrieved again and again. The same fear is anticipated. The same reward is pursued. The same anger is rehearsed. The same cue repeatedly activates the same behavioural response. Sleep becomes poor. Stress hormones remain elevated. Dopaminergic reinforcement strengthens the salience of the behaviour. Glutamatergic signalling repeatedly activates calcium-dependent plasticity. Gene expression adapts. BDNF and other neurotrophic pathways participate in remodeling. Glial and inflammatory systems respond.

Could such repeated activation, under particular circumstances, gradually shift a network from adaptive plasticity toward maladaptive excitability?

That is the hypothesis we should be careful not to overstate—but also not dismiss without investigation.

Because the distinction between learning and epileptogenesis may be less absolute than it first appears. Both involve activity-dependent changes in synapses, receptors, intracellular signalling and gene expression. The difference lies in the pattern, intensity, duration, cellular environment and network consequences of that plasticity.

Normal plasticity makes a circuit better at something useful.

Maladaptive plasticity may make a network increasingly efficient at doing something it should not do.

A seizure is ultimately not simply “too much electricity.” It is the abnormal recruitment and synchronisation of neuronal populations within a network whose excitability and inhibitory controls have become sufficiently disturbed to permit pathological activity.

That is why the question of psychological stress is scientifically interesting. It is not necessary to claim that trauma directly creates epilepsy. The more sophisticated possibility is that prolonged psychological stress may act as a modifier of epileptogenic vulnerability, interacting with other biological factors and changing the environment in which neural plasticity takes place.

This is also why the word “trigger” may be insufficient. A trigger explains why a seizure happens today. Epileptogenesis asks a deeper question: why did this network become capable of producing the seizure at all?

Perhaps the brain does not simply remember what happened to us.
It adapts to what happens repeatedly.
And sometimes, the most important story in epilepsy may not begin with the seizure itself.
It may begin years earlier, when a particular neural network was repeatedly asked to remember, fear, desire, compensate, adapt and fire.

The unresolved question is whether, under some circumstances, yesterday’s psychological experience can become tomorrow’s biological vulnerability—and eventually, tomorrow’s seizure.
(The author is a Counsellor,Member of ISSUP. Aims to bridge psychology with advanced biology & neuroscience towards public welfare)