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Attentional deficits are core symptoms of
schizophrenia, contributing strongly to disability.
Prefrontal dysfunction has emerged as a candidate
mechanism, with clinical evidence for prefrontal
hypoactivation and disinhibition (reduced GABAergic
inhibition), possibly reflecting different patient
subpopulations.
Researchers tested in rats whether imbalanced
prefrontal neural activity impairs attention.
To induce prefrontal hypoactivation or disinhibition,
scientists microinfused the GABA-A receptor agonist
muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or
antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side),
respectively, into the medial prefrontal cortex.
Using the five-choice serial reaction time (5CSRT)
test, scientists showed that both muscimol and
picrotoxin impaired attention (reduced accuracy,
increased omissions).
Muscimol also impaired response control (increased
premature responses).
In addition, muscimol dose dependently reduced
open-field locomotor activity, whereas 300 ng of
picrotoxin caused locomotor hyperactivity;
sensorimotor gating (startle prepulse inhibition)
was unaffected.
Therefore, infusion effects on the 5CSRT test can be
dissociated from sensorimotor effects.
Combining microinfusions with in vivo
electrophysiology, researchers showed that muscimol
inhibited prefrontal firing, whereas picrotoxin
increased firing, mainly within bursts.
Muscimol reduced and picrotoxin enhanced bursting
and both drugs changed the temporal pattern of
bursting. Picrotoxin also markedly enhanced
prefrontal LFP power.
Therefore, prefrontal hypoactivation and
disinhibition both cause attentional deficits.
Considering the electrophysiological findings, this
suggests that attention requires appropriately tuned
prefrontal activity.
Apart from attentional deficits, prefrontal
disinhibition caused additional neurobehavioral
changes that may be relevant to schizophrenia
pathophysiology, including enhanced prefrontal
bursting and locomotor hyperactivity, which have
been linked to psychosis-related dopamine
hyperfunction.
See also
Brain stimulation may reduce anorexia symptoms
(2016-03-29)
Link...
For more information
JNeurosci
The Journal of Neuroscience
Too Little and Too Much: Hypoactivation and
Disinhibition of Medial Prefrontal Cortex Cause
Attentional Deficits
Link...
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