Medial-Frontal Stimulation Enhances Learning in Schizophrenia by Restoring Prediction Error Signaling.
Posterror learning, associated with medial-frontal cortical recruitment in healthy subjects, is compromised in neuropsychiatric disorders. Here we report novel evidence for the mechanisms underlying learning dysfunctions in schizophrenia. We show that, by noninvasively passing direct current through human medial-frontal cortex, we could enhance the event-related potential related to learning from mistakes (i.e., the error-related negativity), a putative index of prediction error signaling in the brain. Following this causal manipulation of brain activity, the patients learned a new task at a rate that was indistinguishable from healthy individuals. Moreover, the severity of delusions interacted with the efficacy of the stimulation to improve learning. Our results demonstrate a causal link between disrupted prediction error signaling and inefficient learning in schizophrenia. These findings also demonstrate the feasibility of nonpharmacological interventions to address cognitive deficits in neuropsychiatric disorders.


CONCLUSIONS
When there is a difference between what we expect to happen and what we actually experience, our brains generate a prediction error signal, so that we can map stimuli to responses and predict outcomes accurately. Theories of schizophrenia implicate abnormal prediction error signaling in the cognitive deficits of the disorder. Here, we combine noninvasive brain stimulation with large-scale electrophysiological recordings to establish a causal link between faulty prediction error signaling and learning deficits in schizophrenia. We show that it is possible to improve learning rate, as well as the neural signature of prediction error signaling, in patients to a level quantitatively indistinguishable from that of healthy subjects. The results provide mechanistic insight into schizophrenia pathophysiology and suggest a future therapy for this condition.
Department of Psychology, Center for Integrative and Cognitive Neuroscience, Vanderbilt Vision Research Center, Vanderbilt University, Nashville, Tennessee 37240.
Robert M G
RM
Reinhart
Department of Psychology, Center for Integrative and Cognitive Neuroscience, Vanderbilt Vision Research Center, Vanderbilt University, Nashville, Tennessee 37240.
Julia
J
Zhu
Department of Psychology, Center for Integrative and Cognitive Neuroscience, Vanderbilt Vision Research Center, Vanderbilt University, Nashville, Tennessee 37240 sohee.park@vanderbilt.edu geoffrey.f.woodman@vanderbilt.edu.
Sohee
http://orcid.org/0000-0003-3797-4776
S
Park
Department of Psychology, Center for Integrative and Cognitive Neuroscience, Vanderbilt Vision Research Center, Vanderbilt University, Nashville, Tennessee 37240 sohee.park@vanderbilt.edu geoffrey.f.woodman@vanderbilt.edu.
Geoffrey F
GF
Woodman
D000328:Adult; D001703:Biophysics; D003265:Contingent Negative Variation / Q000502:physiology*; D004558:Electric Stimulation; D004569:Electroencephalography; D005071:Evoked Potentials; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology* / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications*
error-related negativity; executive control; learning; medial–frontal cortex; schizophrenia; transcranial direct-current stimulation