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The neurobiological basis of bipolar disorders (BD) has received increased attention and several brain regions and brain circuits have been correlated with clinical symptoms. These brain regions and circuits may represent targets for neuromodulation techniques such as transcranial Direct Current Stimulation (tDCS). We systematically reviewed the literature to explore the risks and benefits of tDCS in BD and examined all mood states. Following the PRISMA guidelines, a systematic literature search using several databases was performed from April 2002 to June 2017. From the 135 eligible studies, we retained 19 relevant articles for the systematic review, including 170 patients with BD treated by tDCS. Data from 10 studies suggest that tDCS improves depressive symptoms in BD. One case report of add-on-tDCS reported a significant positive response on manic symptoms. In 4 studies, tDCS impacted specific neurocognitive functions in euthymic patients. There is also preliminary evidence that tDCS improves neurological soft signs and sleep quality in euthymia. Side effects were predominantly transient and low-intensity, although 6 cases of hypomanic/manic affective switches have been reported. The majority of studies have been open trials with few patients. More sufficiently powered randomized controlled trials are needed to clarify the effectiveness of tDCS. Preliminary data suggests that tDCS holds promise as a treatment for BD, especially during depressive episodes. Perhaps most promising are emerging data suggesting tDCS may impact neurocognition and sleep quality in euthymia and be useful for relapse prevention.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation approach in which low level currents are administered over the scalp to influence underlying brain function. Prevailing theories of tDCS focus on modulation of excitation-inhibition balance at the local stimulation location. However, network level effects are reported as well, and appear to depend upon differential underlying mechanisms. Here, we evaluated potential network-level effects of tDCS during the Serial Reaction Time Task (SRTT) using convergent EEG- and fMRI-based connectivity approaches. Motor learning manifested as a significant ( p <.0001) shift from slow to fast responses and corresponded to a significant increase in beta-coherence ( p <.0001) and fMRI connectivity ( p <.01) particularly within the visual-motor pathway. Differential patterns of tDCS effect were observed within different parametric task versions, consistent with network models. Overall, these findings demonstrate objective physiological effects of tDCS at the network level that result in effective behavioral modulation when tDCS parameters are matched to network-level requirements of the underlying task.

To date, no measures are available that permit differentiation of discrete, clinically distinct subtypes of schizophrenia (SZ) with potential differential underlying pathophysiologies. Over recent years, there has been increasing recognition that SZ is heterogeneously associated with deficits in early auditory processing (EAP), as demonstrated using clinically applicable tasks such as tone-matching task (TMT). Here, we pooled TMT performances across 310 SZ individuals and 219 healthy controls (HC), along with clinical, cognitive, and resting-state functional-connectivity MRI (rsFC-MRI) measures. In addition, TMT was measured in a group of 24 patients at symptomatic clinical high risk (CHR) for SZ and 24 age-matched HC (age range 7–27 years). We provide the first demonstration that the EAP deficits are bimodally distributed across SZ subjects ( P < 0.0001 vs. unimodal distribution), with one group showing entirely unimpaired TMT performance (SZ-EAP+), and a second showing an extremely large TMT impairment (SZ-EAP−), relative to both controls ( d = 2.1) and SZ-EAP+ patients ( d = 3.4). The SZ-EAP− group predominated among samples drawn from inpatient sites, showed higher levels of cognitive symptoms (PANSS), worse social cognition and a differential deficit in neurocognition (MATRICS battery), and reduced functional capacity. rsFC-MRI analyses showed significant reduction in SZ-EAP− relative to controls between subcortical and cortical auditory regions. As opposed to SZ, CHR patients showed intact EAP function. In HC age-matched to CHR, EAP ability was shown to increase across the age range of vulnerability preceding SZ onset. These results indicate that EAP measure segregates between discrete SZ subgroups. As TMT can be readily implemented within routine clinical settings, its use may be critical to account for the heterogeneity of clinical outcomes currently observed across SZ patients, as well as for pre-clinical detection and efficacious treatment selection.

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Deficits in auditory processing contribute significantly to impaired functional outcome in schizophrenia (SZ), but mediating factors remain under investigation. Here we evaluated two hierarchical components of early auditory processing: pitch-change detection (i.e. identifying if 2 tones have "same" or "different" pitch), which is preferentially associated with early auditory cortex, and serial pitch-pattern detection (i.e. identifying if 3 tones have "same" or "different" pitch, and, if "different", which one differed from the others), which depends also on auditory association regions.Deficits in pitch-change detection deficits in SZ have been widely reported and correlated with higher auditory disturbances such as Auditory Emotion Recognition (AER). Deficits in serial pitch-pattern discrimination have been less studied. Here, we investigated both pitch perception components, along with integrity of AER in SZ patients vs. controls using behavioral paradigms. We hypothesized that the deficits could be viewed as hierarchically organized in SZ, with deficits in low-level function propagating sequentially through subsequent levels of processing.Participants included 27 SZ and 40 controls. The magnitude of the deficits in SZ participants was large in both the pitch-change (d = 1.15) and serial pitch-pattern tasks (d = 1.21) with no significant differential task effect. The effect size of the AER deficits was extremely large (d = 2.82). In the SZ group, performance in both pitch tasks correlated significantly with impaired AER performance. However, a mediation analysis showed that serial pitch-pattern detection mediated the relationship between simpler pitch-change detection and AER in patients.

Further studies are needed to strengthen the level of evidence for antidepressive approaches in PWS. The inclusion of PWS as stakeholders is also considered to be a major issue for future guideline development.

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