RT info:eu-repo/semantics/article
T1 Impaired prefrontal synaptic gain in people with psychosis and their relatives during the mismatch negativity
A1 Ranlund, Siri
A1 Adams, Rick A.
A1 Díez, Álvaro
A1 Constante, Miguel
A1 Dutt, Anirban
A1 Hall, Mei‐Hua
A1 Maestro Carbayo, Amparo
A1 McDonald, Colm
A1 Petrella, Sabrina
A1 Schulze, Katja
A1 Shaikh, Madiha
A1 Walshe, Muriel
A1 Friston, Karl
A1 Pinotsis, Dimitris
A1 Bramon, Elvira
AB The mismatch negativity (MMN) evoked potential, a preattentive brain response to a discriminable change in auditory stimulation, is significantly reduced in psychosis. Glutamatergic theories of psychosis propose that hypofunction of NMDA receptors (on pyramidal cells and inhibitory interneurons) causes a loss of synaptic gain control. We measured changes in neuronal effective connectivity underlying the MMN using dynamic causal modeling (DCM), where the gain (excitability) of superficial pyramidal cells is explicitly parameterised. EEG data were obtained during a MMN task--for 24 patients with psychosis, 25 of their first-degree unaffected relatives, and 35 controls--and DCM was used to estimate the excitability (modeled as self-inhibition) of (source-specific) superficial pyramidal populations. The MMN sources, based on previous research, included primary and secondary auditory cortices, and the right inferior frontal gyrus. Both patients with psychosis and unaffected relatives (to a lesser degree) showed increased excitability in right inferior frontal gyrus across task conditions, compared to controls. Furthermore, in the same region, both patients and their relatives showed a reversal of the normal response to deviant stimuli; that is, a decrease in excitability in comparison to standard conditions. Our results suggest that psychosis and genetic risk for the illness are associated with both context-dependent (condition-specific) and context-independent abnormalities of the excitability of superficial pyramidal cell populations in the MMN paradigm. These abnormalities could relate to NMDA receptor hypofunction on both pyramidal cells and inhibitory interneurons, and appear to be linked to the genetic aetiology of the illness, thereby constituting potential endophenotypes for psychosis.
SN 1065-9471
YR 2015
FD 2015
LK https://uvadoc.uva.es/handle/10324/66449
UL https://uvadoc.uva.es/handle/10324/66449
LA spa
NO Human Brain Mapping 37: 351-365
DS UVaDOC
RD 17-jul-2024