Dysfunctional Neural Plasticity in Patients With Schizophrenia

Daskalakis, Zafiris J.; Christensen, Bruce K.; Fitzgerald, Paul B.; Chen, Robert

doi:10.1001/archpsyc.65.4.378

Cited by 123 publications

(84 citation statements)

References 41 publications

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“…Despite the consistent reduction of cortical plasticity in schizophrenia patients following different types of plasticity-inducing non-invasive brain stimulation (Hasan et al, 2013a;Daskalakis et al, 2008a;Frantseva et al, 2008;Oxley et al, 2004) and the association of smoking with functional and symptomatic improvements (D'Souza and Markou, 2012), the impact of nicotine intake via smoking on neuroplasticity in schizophrenia has not yet been investigated. To determine the physiological basis of the association between nicotine and neuroplasticity, we applied LTD-like plasticity-inducing cathodal tDCS to smoking and nonsmoking schizophrenia patients.…”

Section: Introductionmentioning

confidence: 99%

Smoking Restores Impaired LTD-Like Plasticity in Schizophrenia: a Transcranial Direct Current Stimulation Study

Strube

Bunse

Nitsche

et al. 2014

Neuropsychopharmacol

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Impaired neuroplastic responses following noninvasive brain stimulation have been reported repeatedly in schizophrenia patients. These findings have been associated with deficits in GABAergic, glutamatergic, and cholinergic neurotransmission. Although various neurophysiological studies have indicated a relationship between nicotine and neuroplasticity in healthy individuals, the present study is the first investigation into the impact of nicotine on LTD-like plasticity in patients with schizophrenia. Cortical excitability and cortical plasticity were explored in 30 schizophrenia patients (17 smoker, 13 nonsmoker) and 45 healthy controls (13 smoker, 32 nonsmoker) by using single-pulse transcranial magnetic stimulation (TMS) before and following cathodal transcranial direct current stimulation (tDCS) applied to the left primary motor cortex. Our analysis revealed abolished LTD-like plasticity in nonsmoking schizophrenia patients. However, these plasticity deficits were not present in smoking schizophrenia patients. In healthy controls, significant MEP reductions following cathodal tDCS were observed in nonsmoking individuals, but only trend-level reductions in smokers. In smoking schizophrenia patients, the severity of negative symptoms correlated positively with reduced neuroplasticity, whereas nonsmoking patients displayed the opposite effect. Taken together, the data of our study support the notion of an association between chronic smoking and the restitution of impaired LTD-like plasticity in schizophrenia patients. Although replication and further research are needed to better understand this relationship, our findings indicate that nicotine intake might stabilize the impaired inhibition-facilitation balance in the schizophrenic brain through a complex interaction between cortical plasticity, and GABAergic and cholinergic neurotransmission, and might explain the reduced prevalence of negative symptoms in this population.

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Section: Introductionmentioning

confidence: 99%

Smoking Restores Impaired LTD-Like Plasticity in Schizophrenia: a Transcranial Direct Current Stimulation Study

Strube

Bunse

Nitsche

et al. 2014

Neuropsychopharmacol

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“…The resulting changes in synaptic strength occur secondary to simultaneous activation of coactive cells (as theorized by Hebb 3 ), manifesting as LTP or LTD. There is strong neurophysiological evidence that plasticity is disrupted in schizophrenia, 1,8 a disorder that is commonly associated with deficits in learning and memory, in addition to delusions, hallucinations, and disorganization. 9 In the following sections, we outline the neural components of plasticity in the brain.…”

Section: Hebbmentioning

confidence: 99%

“…46 Deficits of neural plasticity involved with the main inhibitory neurotransmitter, GABA, have been documented in the brains of patients with schizophrenia. 1,47,48 Studies in memory processing (mediated in the amygdala and hippocampus) have shown abnormalities in schizophrenia, with altered PFC activation, decreased hippocampal volume, 49,50 and decreased GABAergic activity, particularly in hippocampal regions, demonstrated in postmortem studies. 51,52 These results have led to the hypothesis that there may not be adequate inhibition between the amygdala and hippocampus, especially in GABAergic interneurons in these regions, 51 resulting in disrupted LTP.…”

Section: Schizophrenia and Plasticitymentioning

confidence: 99%

A Review of Evidence Linking Disrupted Neural Plasticity to Schizophrenia

et al. 2013

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The adaptations resulting from neural plasticity lead to changes in cognition and behaviour, which are strengthened through repeated exposure to the novel environment or stimulus. Learning and memory have been hypothesized to occur through modifications of the strength of neural circuits, particularly in the hippocampus and cortex. Cognitive deficits, specifically in executive functioning and negative symptoms, may be a corollary to deficits in neural plasticity. Moreover, the main excitatory and inhibitory neurotransmitters associated with neural plasticity have also been extensively investigated for their role in the cognitive deficits associated with schizophrenia. Transcranial magnetic stimulation (TMS) represents some of the most promising approaches to directly explore the physiological manifestations of neural plasticity in the human brain. Three TMS paradigms (use-dependent plasticity, paired associative stimulation, and repetitive TMS) have been used to evaluate neurophysiological measures of neural plasticity in the healthy brain and in patients with schizophrenia, and to examine the brain's responses to such stimulation. In schizophrenia, deficits in neural plasticity have been consistently shown which parallel the molecular evidence appearing to be entwined with this debilitating disorder. Such pathophysiology may underlie the learning and memory deficits that are key symptoms of this disorder and may even be a key mechanism involved in treatment with antipsychotics. W W W Une revue des données probantes liant la plasticité neuronale déréglée à la schizophrénieLes adaptations issues de la plasticité neuronale entraînent des changements de la cognition et du comportement, lesquels sont renforcés par l'exposition répétée au nouvel environnement ou stimulus. Une hypothèse veut que l'apprentissage et la mémoire surviennent par des modifications de la force des circuits neuronaux, particulièrement dans l'hippocampe et le cortex. Les déficits cognitifs, spécifiquement ceux du fonctionnement exécutif et des symptômes négatifs, peuvent être un corollaire des déficits de la plasticité neuronale. En outre, les principaux neurotransmetteurs excitateurs et inhibiteurs associés à la plasticité neuronale ont également fait l'objet de recherches poussées quant à leur rôle dans les déficits cognitifs associés à la schizophrénie. La stimulation magnétique transcrânienne (SMT) représente certaines des approches les plus prometteuses qui explorent directement les manifestations physiologiques de la plasticité neuronale dans le cerveau humain. Trois paradigmes de la SMT (plasticité activité-dépendante, stimulation couplée associative, et SMT répétitive) ont servi à évaluer les mesures neurophysiologiques de la plasticité neuronale dans le cerveau en santé et chez les patients souffrant de schizophrénie, et à examiner les réponses du cerveau à cette stimulation. Dans la schizophrénie, les déficits de plasticité neuronale ont été constamment démontrés, ce qui correspond aux éléments de preuve moléculaires qui semblent êtr...

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“…Both GABA and NMDA receptormediated neurotransmission play an important role in use-dependent plasticity. 105 Daskalakis and colleagues 111 evalu ated use-dependent plasticity in 14 medicated and 6 unmedicated patients with schizophrenia and 12 healthy partici pants. A significant reduction of use-dependent plasticity was demonstrated in those with schizophrenia compared with healthy participants.…”

Section: Functional Consequences Of Disordered Inhibitionmentioning

confidence: 99%

Inhibition of the cortex using transcranial magnetic stimulation in psychiatric populations: current and future directions

Radhu

Ravindran

Levinson

et al. 2012

J Psychiatry Neurosci

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Dysfunctional Neural Plasticity in Patients With Schizophrenia

Abstract: It is possible that in schizophrenia, these deficits in neural plasticity are related to disturbances of gamma-aminobutyric acid, N-methyl-D-aspartate neurotransmission, or dopamine that may potentially account for the aberrant motor performance of these patients.

Cited by 123 publications

References 41 publications

Smoking Restores Impaired LTD-Like Plasticity in Schizophrenia: a Transcranial Direct Current Stimulation Study

Smoking Restores Impaired LTD-Like Plasticity in Schizophrenia: a Transcranial Direct Current Stimulation Study

A Review of Evidence Linking Disrupted Neural Plasticity to Schizophrenia

Inhibition of the cortex using transcranial magnetic stimulation in psychiatric populations: current and future directions

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