Methods and Materials
The DISCERN Model
- I was a doctor
- I worked in New-York
- I liked my job
- I was good doctor
- Tony was a gangster
- Tony worked in Chicago
- Tony hated his job
- Tony was a bad gangster
- 1Working memory (WM) disconnection was prompted by neuroimaging studies suggesting cortical disconnection, especially involving WM networks, in schizophrenia (47,48,49,50). Disconnection was simulated by pruning excitatory and inhibitory WM connections in the story generator if their absolute connection strength fell below a specified threshold (
Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: Relationship with impaired cognition, behavioral disorganization, and global function.Am J Psychiatry. 2008; 165: 1006-101451). An extended version of disconnection also pruned connections between the hidden → output layer of the story generator.
- Yoon J.H.
- Minzenberg M.J.
- Ursu S.
- Ryan Walter B.S.
- Wendelken C.
- Ragland J.D.
- Carter C.S.
- 2Noise added to WM networks was prompted by reports indicating excessive cortical noise, reduced signal-to-noise ratio, and inefficiency in frontal WM cortical systems in persons with schizophrenia (52,53,54). These conditions were simulated by adding Gaussian noise to story generator WM neuron outputs.
- 3Working memory network gain reductions were prompted by a connectionist model of hypodopaminergic cortical neuromodulation in patients with schizophrenia expressed as reduced neural response (36) and neuroimaging studies showing reduced activation in WM circuits during task performance in patients with disorganization symptoms (55,56). This alteration was modeled as reduced gain (i.e., slope) of the response curve of neurons in the hidden and recurrent layers of the story generator module (36).
- 4Response bias shifts. Elevated arousal, which could produce overactivation at neuronal level, was simulated as lateral shifts in the response curve of WM layer story generator neurons (57). This manipulation, in theory, could also simulate a failure to deactivate the superior temporal gyrus when performing a WM task detected in early-phase patients with schizophrenia (58).
- 5Semantic network distortion demonstrated by lexical categorization, priming, and fluency tasks has been statistically linked to language disorganization and schizophrenia (11,12,13). These abnormalities were simulated by adding noise to word representations in the semantic memory.
- 6Excessive activation in semantic networks. Increased temporal and prefrontal activity during semantic associations and increased activation of the cingulate cortex during object naming has been reported in schizophrenia (14,59). These disturbances were simulated by increasing output activation of neurons in the semantic network.
- 7Heightened semantic priming. Studies have suggested heightened spread of activation in semantic networks in patients with schizophrenia based on word association data, especially among patients with language disorganization (10,15,16,17). This disturbance was simulated by blurring semantic network outputs so that words semantically linked to a target word were co-activated.
- 8Exaggerated prediction-error signaling (hyperlearning). Elevated brain response to prediction error during learning has been linked statistically to delusion formation (25). Moreover, prediction-error coding and other salience-driven aspects of learning appear to be mediated, at least in part, by dopaminergic pathways (60,61,62); elevated dopamine release is associated with schizophrenia (Figure 1A).
Human Story Recall
In one seat of the bus a wispy old man sat holding a bunch of fresh flowers. Across the aisle was a young girl whose eyes came back again and again to the man's flowers. The time came for the man to get off. He thrust the flowers into the girl's lap. “I can see you love flowers,” he explained, “and I think my wife would like you to have them. I'll tell her I gave them to you.” The girl accepted the flowers and watched the man get off the bus and walk through the gate of an old cemetery.
I hitched into town. A wispy old man driving a pick-up truck with his frail wife gave me a ride. I sat in the back and watched the tires kick up dust. We stopped and waited for a traffic light. I turned around and peered into the rear window. I hadn't eaten all day and my eyes came back again and again to a bag of Fritos on the dashboard. The man got out of the truck and walked around to the back. “My wife noticed that you kept looking at the Fritos,” he explained, “and she wanted you to have them.”
Comparing Human and DISCERN Story Recall
|Subject Recall: “I remember a whispering man that had flowers on a bus and he saw a girl and she wanted them … ”|
Out of maximum score of 5, this segment assigned a score of 3. Partial credit given for (iv) because it could be inferred that the girl was riding on the bus. Only partial credit was given to (v) because there is no statement or inference that the girl paid special attention to the flowers. Insertion of term, “whispering,” received no credit and was scored as a lexical misfire (see Methods and Materials).
|(i) A (man) sat in a seat on the bus||1 (“man on a bus . . . ”)|
|1. a man rode or is on a bus|
|.5. there was a man in some sort of vehicle|
|(ii) man was a wispy/old||0|
|1. old man + indication of frailty|
|.5. old man or frail man|
|(iii) (man) was hold a bunch of flowers||1 (”[man] had flowers”)|
|1. (man) possessed, holding or carrying flowers|
|.5. (man) possessed something|
|(iv) A young girl was/sat across the aisle from the man||.5 (“he saw a girl”)|
|1. female sitting next to, near, or across from man|
|.5. female riding in the same vehicle as man|
|(v) The girl's eyes came back again and again to the man's flowers.||.5 (“[girl] wanted [the flowers]”)|
|1. female paid special attention to the flowers|
|.5 female noticed or wanted something|
The girl gave the old man the flowers as a gift
The cop arrested me for speeding
“wispy old man” → “whispering man”
Kate was interested in guns (substituting for books, in DISCERN stories, both terms referred to objects of interest)
A girl was sitting on the bus near him and he noticed her looking at his eyes.
I remember the generosity of the flowers. I remember that he gave her flowers and she gave, she put the flowers on the tombstone. And I remember there was a truck involved, I believe it was a flatbed.
- Joe was my boss.
- I hated Joe.
- Joe was in his 30s.
- Joe had a beard.
- Joe liked baseball.
- Mary was the fiancée of Joe.
- I liked talking to Mary.
- I gave a kiss good-bye to Mary.
|Age||Gender (M/F)||Parental Education (Grades)|
|WAIS Scaled Vocabulary Score|
|Healthy Control Subjects (n = 20)||36.6 (9.0)||(11/9)||13.7 (4.0)||12.2 (3.0)|
|Persons with Schizophrenia (n = 37)||41.5 (9.6)||(16/21)||15.1 (7.6)||9.9 (4.6)|
|Significance Test (two-tailed)||t(55) = 1.51, p = .14||χ2 = .72, p = .40||t(53) = .77, p = .44||t(55) = 2.04, p = .046|
|Recall Success||Agent Slotting Error Penetrance||Lexical Misfire Penetrance||Derailment Penetrance|
|Healthy Control Subjects (n = 20)||.67 (.12)||.023 (.033)||.051 (.064)||.011 (.040)|
|Persons with Schizophrenia (n = 37)||.41 (.23)||.086 (.121)||.065 (.085)||.122 (.226)|
|Significance Test (two-tailed, uncorrected)||t(55) = 4.9, p = .00001||t(44.8) = 3.0, p = .004||t(49.3) = .70, p = .49||t(50.7) = 3.8, p = .0004|
|2-D Hyperlearning||2-D WM Disconnection|
|t Test||p Value||t Test||p Value|
|WM Noise (2)||3.9||<.0001||3.6||.0004|
|WM Gain Reduction (3)||7.8||<.0001||7.2||<.0001|
|Altered WM Bias (4)||14.7||<.0001||13.3||<.0001|
|Semantic Network Distortion (5)||9.9||<.0001||9.2||<.0001|
|Excessive Semantic Network Activation (6)||8.2||<.0001||7.7||<.0001|
|Semantic Blurring/Overpriming (7)||9.5||<.0001||8.8||<.0001|
- Vito (substituting for Joe) was in his 30s.
- Joe was a doctor.
- Joe worked in New York
- Joe was my boss.
- I hated Joe.
- Vito was a famous gangster.
- Vito was the boss of Tony
- Tony hated Vito.
- Tony feared Joe (substituting for Vito).
- Vince went to Starbucks.
- Vince sat at a table.
- Vince liked Vito.
- Vince feared Joe (substituting for Vito).
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