Schizophrenic Deficits: Neuroleptics and the Prefrontal Cortex

Abstract

Modern techniques have been applied to brain modeling, based on recent approaches in the artificial intelligence field that use brain-like "connectionistic" computational architectures. The model proposed by Cohen and Servan-Schreiber uses a gain parameter which they identify with dopamine function. They apply their model to neuroleptically treated schizophrenia patients who show improved task performance which they link to increased dopamine function and increased gain in the prefrontal cortex. However, evidence indicates that antipsychotic medications block dopamine (especially D2) receptors, decreasing mesolimbic and mesocortical dopamine function. If therapeutic dosages of neuroleptics diminish dopamine function, this would decrease gain in context modules needed for adequate task performance. Schizophrenia patients would perform more poorly by further reducing gain in their already compromised context modules. The current investigators suggest three possible ways to resolve this difficulty, to explain why normals perform more poorly when taking neuroleptics, although acute schizophrenia patients' performance may be enhanced in several areas. Evidence would suggest that multiple processes occur simultaneously in neuroleptically treated patients with some processes counterbalancing others.

Comprehensive review: Computational modelling of schizophrenia

“…hypo-dopaminergic to hyperdopaminergic states), the models addressed the validity of different dopamine dysfunctions leading to the observed reduced performance. All these models reached the same conclusions, namely that prefrontal DA hypo-function was responsible for the deficient cognitive performance observed in patients (Amos, 2000;Carter and Neufeld, 2007;Servan-Schreiber, 1992, 1993;Jobe et al, 1994;Monchi et al, 2000;Peled and Geva, 2000). With respect to working-memory, low DA levels are thought to result in a signal that is easily corrupted by internal cortical noise which in turn becomes incapable of transmitting and maintaining meaningful contextual information about the ongoing task Servan-Schreiber, 1992, 1993).…”

“…This directly influences the activation pattern and the stochastic activity of the neurons in the system. SNR models traditionally focused on modelling cognitive symptoms and the performance of patients in tasks where they usually show deficits (e.g., Continuous Performance Task, Stroop Task, Rorschach inkblots, Wisconsin Card Sort Test (WCST), Facial Affect - Amos, 2000;Carter and Neufeld, 2007;Servan-Schreiber, 1992, 1993;Jobe et al, 1994;Monchi et al, 2000;Peled and Geva, 2000). In these models, poor performance on cognitive tasks stems from working-memory deficits in units representing the prefrontal cortex (PFC), due to a low signal-to-noise ratio.…”

Noradrenergic terminals are the primary source of α2-adrenoceptor mediated dopamine release in the medial prefrontal cortex

“…Dopaminergic and noradrenergic projections from the ventral tegmental area (VTA) and locus coeruleus (LC), respectively, converge to the prefrontal cortex (PFC), where they play key roles in cognitive, emotional, and motivational functions (Descarries et al, 1987;Van Eden et al, 1987;Seguela et al, 1990). In humans, impaired catecholamine transmission in the PFC has been implicated in the cognitive and emotional deficits observed in schizophrenia (Bird et al, 1979;Jobe et al, 1994 antidepressants (Invernizzi and Garattini, 2004), and antiparkinsonian treatment (Langer, 2015). α 2 -Adrenoceptor antagonists possibly enhance NE output via α 2 -autoreceptor inhibition (Langer, 1981).…”

Schizophrenic Deficits: Neuroleptics and the Prefrontal Cortex--A Reply

“…It is a sincere pleasure to see that our article on connectionist models of dopamine effects and schizophrenic deficits has attracted the attention of an established and respected group of researchers interested in schizophrenia, and opened a discussion of such models and their implications for this illness. Jobe et al (1994, this issue) correctly summarize one of the central ideas of our article (Cohen and Servan-Schreiber 1993)—the relation between “gain,” dopamine, and cognitive deficits—and appropriately point out some of its limitations. They also suggest alternative hypotheses within the framework laid out by our models.…”

“…The focus of their commentary is on how the effects of neuroleptic medication on dopamine activity relate to our hypothesis concerning reductions of dopamine activity in the prefrontal cortex (PFC). Jobe et al (1994, this issue) correctly point out that it is difficult to reconcile the fact that neuroleptics block dopamine activity while at the same time improving (or at least not further impairing) schizophrenic cognitive performance if, as we have hypothesized, performance deficits are due to a reduction of dopamine activity in the first place. In this context, Jobe et al (1994, this issue, p. 414) state that we predicted “medicated schizophrenia patients should perform better than unmedicated schizophrenia patients on the [Continuous Performance Test] CPT [Rosvold et al 1956],” and justifiably question this prediction.…”