Understanding tDCS effects in schizophrenia: a systematic review of clinical data and an integrated computation modeling analysis

Brunoni, André R.; Shiozawa, Pedro; Truong, Dennis Q.; Javitt, Daniel C.; Elkis, Hélio; Fregni, Felipe; Bikson, Marom

doi:10.1586/17434440.2014.911082

Cited by 63 publications

(39 citation statements)

References 93 publications

(119 reference statements)

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“…During tDCS an extracellular field is generated in the brain affecting cortical and subcortical structures including deep brain structures such as the hippocampus [36], also affecting hippocampus-dependent tasks [37], [38]. Local stimulation can be recreated in vitro by applying uniform electric fields across hippocampal slices, which allow micro-recording from the dendritic and somatic layers independently (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Direct Current Stimulation Alters Neuronal Input/Output Function

et al. 2017

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Background Direct current stimulation (DCS) affects both neuronal firing rate and synaptic efficacy. The neuronal input/output (I/O) function determines the likelihood that a neuron elicits an action potential in response to synaptic input of a given strength. Changes of the neuronal I/O function by DCS may underlie previous observations in animal models and human testing, yet have not been directly assessed. Objective Test if the neuronal input/output function is affected by DCS Methods Using rat hippocampal brain slices and computational modeling, we provide evidence for how DCS modulates the neuronal I/O function. Results We show for the first time that DCS modulates the likelihood of neuronal firing for a given and fixed synaptic input. Opposing polarization of soma and dendrite may have a synergistic effect for anodal stimulation, increasing the driving force of synaptic activity while simultaneously increasing spiking probability at the soma. For cathodal stimulation, however, the opposing effects tend to cancel. This results in an asymmetry in the strength of the effects of stimulation for opposite polarities. Conclusions Our results may explain the asymmetries observed in acute and long term effects of transcranial direct current stimulation.

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Section: Resultsmentioning

confidence: 99%

Direct Current Stimulation Alters Neuronal Input/Output Function

et al. 2017

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“…Therefore, there is a dire need for effective and noninvasive treatment options without the side effects. Over the past decade, tDCS has come into the spotlight, showing some promise as a drug-free intervention for neuropsychiatric illnesses, such as schizophrenia (58). Compelling rationales for using tDCS in schizophrenia include the fact that NMDA receptor dysfunction is implicated in schizophrenia pathophysiology (59) and NMDA antagonists abolish tDCS effects, whereas NMDA agonists enhance tDCS effects (60,61).…”

Section: Discussionmentioning

confidence: 99%

Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain

Reinhart

Zhu

Park

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Executive control and flexible adjustment of behavior following errors are essential to adaptive functioning. Loss of adaptive control may be a biomarker of a wide range of neuropsychiatric disorders, particularly in the schizophrenia spectrum. Here, we provide support for the view that oscillatory activity in the frontal cortex underlies adaptive adjustments in cognitive processing following errors. Compared with healthy subjects, patients with schizophrenia exhibited low frequency oscillations with abnormal temporal structure and an absence of synchrony over medialfrontal and lateral-prefrontal cortex following errors. To demonstrate that these abnormal oscillations were the origin of the impaired adaptive control in patients with schizophrenia, we applied noninvasive dc electrical stimulation over the medial-frontal cortex. This noninvasive stimulation descrambled the phase of the low-frequency neural oscillations that synchronize activity across cortical regions. Following stimulation, the behavioral index of adaptive control was improved such that patients were indistinguishable from healthy control subjects. These results provide unique causal evidence for theories of executive control and cortical dysconnectivity in schizophrenia.oscillations | neural synchrony | adaptive control | schizophrenia | transcranial direct current stimulation N etworks involving frontal cortex allow us to adapt our actions to dynamic environments and adjust information processing following errors (1). This adaptive control is a hallmark of healthy goal-directed behavior, but it is dysfunctional in a variety of psychiatric and neurological disorders (2-4). In particular, the adaptive-control deficits that are a central feature of schizophrenia are highly predictive of poor functioning in daily life (5). In the laboratory, a canonical signature of adaptive control is the magnitude of posterror slowing of reaction time (RT), in which healthy subjects respond more slowly after making an error (6, 7). Patients with schizophrenia show an impaired ability to slow down their responses after errors (4, 8-13, but also 14, 15), providing a laboratory index that captures the rigid, perseverative, and maladaptive behavior that is characteristic of the disorder (8, 16).Adaptive control in the healthy brain is hypothesized to depend partly on the low-frequency EEG oscillations measured over medial-frontal cortex. The low-frequency oscillations are thought to reflect coordinated activity across the diverse set of brain areas recruited to perform a task (1,(17)(18)(19)(20)(21)(22). In addition, medial-frontal theta (4-8 Hz) oscillations appear to signal the need for adaptive control across a variety of tasks and situations. Situations that call for adaptive control include stimulus novelty, response conflict, negative feedback, and behavioral errors, with all of these situations sharing a common medial-frontal spectral signature in the theta band (21). However, the functional significance of medial-frontal theta may be much broader than simply ...

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“…Some stimulation modalities, like the conventional tDCS approach, inevitably influence regions across the brain-and interpretation of behavioral changes based on any single node is an assumption (Seibt et al, 2015). Alternatively, direct action on multiple nodes in a network can be embraced as inherent to the net actions of stimulation (Brunoni et al, 2014;Dasilva et al, 2012;Douglas et al, 2015;Senco et al, 2015) where connectivity parameters can be informed by functional imaging or tractography (Sweet et al, 2014). This analysis has been particularly advance for DBS (McIntyre and Hahn, 2010).…”

Section: Step 4: From Network To Behaviormentioning

confidence: 99%