Table 2.

Main findings of recent PET studies in epilepsy

Group	Target	Main findings in epilepsy patients	Author’s interpretation
GABA	GABAA receptor	Inverse correlation of seizure frequency with uptake in the frontal piriform cortex in patients with different sites of seizure onset [4].	The prepiriform cortex might represent a common epileptogenic area independent of the localization of seizure onset.
Glutamate	NMDA receptor	Increased global uptake in patients not on antidepressants. [13••]	Global increase of NMDA receptor activation might reflect ongoing epileptogenesis.
Multidrug transporters	P-glycoprotein	Increased P-glycoprotein activity in pharmacoresistant patients, particularly in mesiotemporal areas [21••, 22]	Increased P-glycoprotein activity could contribute to multidrug resistance by reducing the intracellular concentration of antiepileptic drugs.
Inflammation	TSPO	Increased uptake in ipsilateral temporal lobe and, to a lesser extent, in ipsilateral thalamus and contralateral temporal lobe. [36••, 37]	Increased TSPO expression points to activation of microglia and an inflammatory reaction in epilepsy patients that could induce epileptogenesis.
Serotonin, inflammation	Tryptophan metabolism	Increased uptake in epileptic vs. non-epileptic brain tubers in TSC. Increased uptake in the epileptic focus of children with intractable epilepsy. Low sensitivity but high specificity of these findings [44••, 45•, 46, 47]	[11C]AMT-PET adds valuable information on the location of the epileptic focus. It might reflect increased tryptophan metabolism that indicates the local production of proconvulsants.
Serotonin	5-HT1A receptor	Reduced uptake ipsilaterally to seizure focus, particularly in the hippocampus. Decreased uptake in insular cortex and anterior cingulate in depressed epilepsy patients [50–59]	Adds lateralizing information with higher specificity than FDG-PET. A widespread reduction of serotonin receptors extending beyond the temporal lobe might indicate a pathomechanism of comorbid depression.
	Serotonin transporter	Reduced uptake in ipsilateral insula in epilepsy patients with depression [49•]	Decreased serotonin reuptake might represent a compensatory mechanism for low serotonin levels in comorbid depression.
Dopamine	Presynaptic dopamine, D1/D2/D3 receptor, dopamine transporter	Bilaterally reduced uptake in basal ganglia, particularly striatum and substantia nigra [65–75]	An altered dopaminergic neurotransmission might impair termination of seizures.
Cannabinoids	CB1 receptor	Increased uptake in ipsilateral temporal lobe; decreased uptake in bilateral insula [82]	Supports dysregulation of cannabinoids in epilepsy that could represent a pro or anticonvulsive phenomenon.
Opioids	μ, δ. and κ opioid receptors	Reduced radioligand uptake during absence and reading-induced seizures. Increased uptake 8 h after spontaneous seizures [84–87]	Opioid release during seizures might contribute to seizure termination. This is likely followed by an early interictal overexpression of opioid receptors.
Acetylcholine	Nicotinic ACh receptor	Increased uptake in epithalamus, ventral mesencephalon, and cerebellum in ADNFLE patients. Decreased uptake in prefrontal cortex [90]	Thalamic and mesencephalic findings may indicate a unique mechanism of nocturnal seizures in ADNFLE. Reduced prefrontal receptor density could be due to neuronal loss.