Evidence for Impaired Cortical Inhibition in Schizophrenia Using Transcranial Magnetic Stimulation

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

doi:10.1001/archpsyc.59.4.347

Cited by 284 publications

(222 citation statements)

References 66 publications

Supporting

Mentioning

184

Contrasting

Unclassified

Order By: Relevance

“…Although robust changes in cortical GAD67 mRNA are not typically found in the PFC of individuals with depression (Thompson et al, 2009;Sibille et al, 2011), significant decreases in somatostatin suggest that interneuron deficits may be especially prominent in a subset of interneurons shown to directly contribute to cortical plasticity (Lazarus and Huang, 2011). As inhibitory interneuron deficits are shared among those with depression, bipolar disorder, and schizophrenia (Thompson et al, 2009(Thompson et al, , 2011Fung et al, 2010;Hashimoto et al, 2008;Daskalakis et al, 2002), cortical plasticity deficits would also be expected to be found in multiple forms of psychopathology.…”

Section: Discussionmentioning

confidence: 99%

Neuroplasticity in Depressed Individuals Compared with Healthy Controls

Player

Taylor

Weickert

et al. 2013

Neuropsychopharmacol

106

View full text Add to dashboard Cite

Several lines of evidence suggest that neuroplasticity is impaired in depression. This study aimed to compare neuroplasticity in 23 subjects with DSM-IV major depressive episode and 23 age-and gender-matched healthy controls, using an objective test that is independent of subject effort and motivation. Neuroplasticity was assessed in the motor cortex using a brain stimulation paradigm known as paired associative stimulation (PAS), which induces transient changes in motor cortical function. Motor cortical excitability was assessed before and after PAS using single-pulse transcranial magnetic stimulation (TMS) to induce motor evoked potentials (MEPs) in a hand muscle. After PAS, MEP amplitudes significantly increased in healthy controls compared with depressed subjects (P ¼ 0.002). The functional significance of motor cortical changes was assessed using a motor learning task-a computerized version of the rotor pursuit task. Healthy controls also performed better on motor learning (P ¼ 0.02). BDNF blood levels and genotype were assayed to determine any relationship with motor cortical plasticity. However, PAS results did not correlate with motor learning, nor appear to be related to BDNF measures. The significance of these findings is that it provides one of the first direct demonstrations of reduced neuroplasticity in depressed subjects, using an objective test.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuroplasticity in Depressed Individuals Compared with Healthy Controls

Player

Taylor

Weickert

et al. 2013

Neuropsychopharmacol

106

View full text Add to dashboard Cite

show abstract

“…Thus, the methods presented in this paper can be used to directly evaluate inhibition from specific cortical regions (eg, DLPFC) whose dysfunction has been associated with the pathophysiology leading to several neurological and psychiatric disorders. For example, it has previously been demonstrated that unmedicated patients with schizophrenia have impaired CI, and that such inhibitory deficits can be rectified through treatment with antipsychotic medications (Daskalakis et al, 2002a;Fitzgerald et al, 2002). However, these studies were limited by the fact that such findings were from the motor cortex, a cortical region that is perhaps less relevant to the pathophysiology of schizophrenia compared with the DLPFC.…”

Section: Discussionmentioning

confidence: 99%

“…One advantage to recording inhibition directly from the cortex, however, will be that future source localization studies may uncover the origins of such inhibitory potentials. We anticipate that such future work will also be invaluable in helping to identify the pathophysiological origins of a variety of disorders associated with disrupted CI (Cantello et al, 2002;Daskalakis et al, 2002a). In this regard, future pharmacological studies and molecular studies attempting to clarify the link between these EEG recordings of LICI to GABA B receptor-mediated mechanisms in the cortex are needed.…”

Section: Discussionmentioning

confidence: 99%

Long-Interval Cortical Inhibition from the Dorsolateral Prefrontal Cortex: a TMS–EEG Study

Daskalakis

Farzan

Barr

et al. 2008

Neuropsychopharmacol

Self Cite

218

194

View full text Add to dashboard Cite

Several studies have demonstrated that cortical inhibition (CI) can be recorded by paired transcranial magnetic stimulation (TMS) of the motor cortex and recorded by surface electromyography (EMG). However, recording CI from other cortical regions that are more closely associated with the pathophysiology of some neurological and psychiatric disorders (eg, dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously unattainable. This study, therefore, was designed to investigate whether CI could be measured directly from the motor cortex and DLPFC by combining TMS with electroencephalography (EEG). Long-interval CI (LICI) is a TMS paradigm that was used to index CI in the motor cortex and DLPFC in healthy subjects. In the motor cortex, LICI resulted in significant suppression (32.8 ± 30.5%) of mean cortical evoked activity on EEG, which was strongly correlated with LICI recorded by EMG. In the DLPFC, LICI resulted in significant suppression (30.1±26.9%) of mean cortical evoked activity and also correlated with LICI in the motor cortex. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurological and psychiatric disorders.

show abstract

“…From circumstantial evidence of an association of schizophrenia with a lowered threshold for seizures, 40 recent studies have found direct evidence of impaired cortical inhibition (i.e. enhanced excitability), 41 and reduced transcortical inhibition of motor circuitry. 42 Studies of molecular markers of GABA signaling in post-mortem brain of patients with schizophrenia have provided consistent evidence of diminished GABA activity.…”

Section: Introductionmentioning

confidence: 99%

Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression

et al. 2007

View full text Add to dashboard Cite

Cortical GABAergic dysfunction has been implicated as a key component of the pathophysiology of schizophrenia and decreased expression of the gamma-aminobutyric acid (GABA) synthetic enzyme glutamic acid decarboxylase 67 (GAD 67 ), encoded by GAD1, is found in schizophrenic post-mortem brain. We report evidence of distorted transmission of single-nucleotide polymorphism (SNP) alleles in two independent schizophrenia family-based samples. In both samples, allelic association was dependent on the gender of the affected offspring, and in the Clinical Brain Disorders Branch/National Institute of Mental Health (CBDB/NIMH) sample it was also dependent on catechol-O-methyltransferase (COMT) Val158Met genotype. Quantitative transmission disequilibrium test analyses revealed that variation in GAD1 influenced multiple domains of cognition, including declarative memory, attention and working memory. A 5 0 flanking SNP affecting cognition in the families was also associated in unrelated healthy individuals with inefficient BOLD functional magnetic resonance imaging activation of dorsal prefrontal cortex (PFC) during a working memory task, a physiologic phenotype associated with schizophrenia and altered cortical inhibition. In addition, a SNP in the 5 0 untranslated (and predicted promoter) region that also influenced cognition was associated with decreased expression of GAD1 mRNA in the PFC of schizophrenic brain. Finally, we observed evidence of statistical epistasis between two SNPs in COMT and SNPs in GAD1, suggesting a potential biological synergism leading to increased risk. These coincident results implicate GAD1 in the etiology of schizophrenia and suggest that the mechanism involves altered cortical GABA inhibitory activity, perhaps modulated by dopaminergic function.

show abstract

Evidence for Impaired Cortical Inhibition in Schizophrenia Using Transcranial Magnetic Stimulation

Abstract: These results suggest that schizophrenia is associated with deficits in CI and that antipsychotic medications may increase CI.

Cited by 284 publications

References 66 publications

Neuroplasticity in Depressed Individuals Compared with Healthy Controls

Neuroplasticity in Depressed Individuals Compared with Healthy Controls

Long-Interval Cortical Inhibition from the Dorsolateral Prefrontal Cortex: a TMS–EEG Study

Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression

Contact Info

Product

Resources

About