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Background: Dysfunctional neuroplasticity may be one of the pathophysiological mechanisms underlying major depression. We have previously established methods to assess neuroplasticity from the dorsolateral prefrontal cortex (DLPFC) using a paired associative stimulation (PAS) paradigm, which pairs a preceding peripheral nerve stimulation with subsequent transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG). We aimed to investigate neuroplasticity through the PAS paradigm in the DLPFC in patients with depression compared to healthy subjects.Methods: Twenty-nine patients with depression and 28 healthy controls participated in this study. There were no significant age or sex differences between the two groups. All participants received PAS paradigm in the DLPFC. We analyzed PAS induced potentiation from the DLPFC in both groups calculating the power of TMS-evoked potentials (TEP). A two-way ANOVA with PAS effect as a within-subject factor and diagnostic group as a between-subject factor was performed to examine the group differences in the PAS paradigm.Results: DLPFC-PAS induced a significant potentiation at the stimulation site in both patients and healthy subjects (mean ± SD: 1.24 ± 0.33 [μV] vs. 1.48 ± 0.28 [μV]). However, when we compared PAS potentiation between patients and healthy subjects, there were significant main effects of PAS (F1,53  = 68.63, p < 0.0001) and PAS-by-diagnostic group interaction (F1,53  = 25.05, p < 0.0001). Post hoc analysis demonstrated that patients had a significantly lower PAS potentiation compared to healthy subjects (t55  = 3.128, p = 0.003).Conclustions: Our findings provide evidence for impaired neuroplasticity in DLPFC in patients with depression compared to healthy subjects. Such findings may ultimately help us understand the pathophysiology of MDD and mechanisms involved in its treatment. [ABSTRACT FROM AUTHOR]

Over 350 million people worldwide suffer from depression, a third of whom are medication-resistant. Seizure therapy remains the most effective treatment in depression, even when many treatments fail. The utility of seizure therapy is limited due to its cognitive side effects and stigma. The biological targets of seizure therapy remain unknown, hindering design of new treatments with comparable efficacy. Seizures impact the brains temporal dynamicity observed through electroencephalography. This dynamicity reflects richness of information processing across distributed brain networks subserving affective and cognitive processes. We investigated the hypothesis that seizure therapy impacts mood (depressive symptoms) and cognition by modulating brain temporal dynamicity. We obtained resting-state electroencephalography from 34 patients (age = 46.0 ± 14.0, 21 females) receiving two types of seizure treatments-electroconvulsive therapy or magnetic seizure therapy. We used multi-scale entropy to quantify the complexity of the brain's temporal dynamics before and after seizure therapy. We discovered that reduction of complexity in fine timescales underlined successful therapeutic response to both seizure treatments. Greater reduction in complexity of fine timescales in parieto-occipital and central brain regions was significantly linked with greater improvement in depressive symptoms. Greater increase in complexity of coarse timescales was associated with greater decline in cognition including the autobiographical memory. These findings were region and timescale specific. That is, change in complexity in occipital regions (e.g. O2 electrode or right occipital pole) at fine timescales was only associated with change in depressive symptoms, and not change in cognition, and change in complexity in parieto-central regions (e.g. Pz electrode or intra and transparietal sulcus) at coarser timescale was only associated with change in cognition, and not depressive symptoms. Finally, region and timescale specific changes in complexity classified both antidepressant and cognitive response to seizure therapy with good (80%) and excellent (95%) accuracy, respectively. In this study, we discovered a novel biological target of seizure therapy: complexity of the brain resting state dynamics. Region and timescale dependent changes in complexity of the brain resting state dynamics is a novel mechanistic marker of response to seizure therapy that explains both the antidepressant response and cognitive changes associated with this treatment. This marker has tremendous potential to guide design of the new generation of antidepressant treatments. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation is an emerging protocol for repetitive transcranial magnetic stimulation that takes 1-3 min to administer, yet offers equal/superior potency to conventional protocols lasting 30-60 min. However, preclinical evidence suggests that D2 receptor blockade may abolish the acute effects of theta-burst stimulation on synaptic facilitation or inhibition. As many patients presenting for repetitive transcranial magnetic stimulation are taking antipsychotic medications as augmentation for treatment-resistant depression, this finding is potentially concerning for the implementation of theta-burst stimulation in clinical settings. Here, we examined whether treatment-resistant depression patients taking antipsychotics have worse outcomes after a course of intermittent theta-burst stimulation. A chart review identified 105 treatment-resistant depression patients who underwent dorsomedial prefrontal-intermittent theta-burst stimulation; clinical outcomes on Hamilton Depression Rating Scale and Beck Depression Inventory were compared for those taking and not taking antipsychotics. The 29 of 105 patients who were taking antipsychotics showed non-significantly better response and remission rates, and non-significantly larger percentage improvements on both scales, with a positive but non-significant correlation between higher antipsychotic dose and larger percentage improvement. Contrary to expectations, outcomes were not significantly worse, and in some analyses trended towards being better, in patients taking antipsychotics. Future randomized controlled studies of repetitive transcranial magnetic stimulation combined with standardized dopaminergic manipulations may be justified and warranted. [ABSTRACT FROM AUTHOR]

• Interhemispheric signal propagation was elevated in schizophrenia and depression patients relative to healthy controls. • Interhemispheric signal propagation did not differ between patient groups. • There were no medication effects on interhemispheric signaling from inter-individual comparisons and no significant correlation with symptom severity. Altered interhemispheric connectivity is implicated in the pathophysiology of schizophrenia (SCZ) and major depressive disorder (MDD) and may account for deficits in lateralized cognitive processes. We measured transcranial magnetic stimulation evoked interhemispheric signal propagation (ISP), a non-invasive measure of transcallosal connectivity, and hypothesized that the SCZ and MDD groups will have increased ISP compared to healthy controls. We evaluated ISP over the dorsolateral prefrontal cortex in 34 patients with SCZ and 34 patients with MDD compared to 32 age and sex-matched healthy controls. ISP was significantly increased in patients with SCZ and patients with MDD compared to healthy controls but did not differ between patient groups. There were no effects of antidepressant, antipsychotic, and benzodiazepine medications on ISP and our results remained unchanged after re-analysis with a region of interest method. Altered ISP was found in both SCZ and MDD patient groups. This indicates that disruptions of interhemispheric signaling processes can be indexed with ISP across psychiatric populations. These findings enhance our knowledge of the physiological mechanisms of interhemispheric imbalances in SCZ and MDD, which may serve as potential treatment targets in future patients. [ABSTRACT FROM AUTHOR]

• Baseline resting EEG theta connectivity and alpha power predicted response to rTMS for depression in our previous research. • These measures did not differentiate responders and non-responders in a larger independent dataset. • Theta connectivity and alpha power are unlikely to be clinically useful predictors of response to rTMS for depression. Our previous research showed high predictive accuracy at differentiating responders from non-responders to repetitive transcranial magnetic stimulation (rTMS) for depression using resting electroencephalography (EEG) and clinical data from baseline and one-week following treatment onset using a machine learning algorithm. In particular, theta (4–8 Hz) connectivity and alpha power (8–13 Hz) significantly differed between responders and non-responders. Independent replication is a necessary step before the application of potential predictors in clinical practice. This study attempted to replicate the results in an independent dataset. We submitted baseline resting EEG data from an independent sample of participants who underwent rTMS treatment for depression (N = 193, 128 responders) (Krepel et al., 2018) to the same between group comparisons as our previous research (Bailey et al., 2019). Our previous results were not replicated, with no difference between responders and non-responders in theta connectivity (p = 0.250, Cohen's d = 0.1786) nor alpha power (p = 0.357, η p 2 = 0.005). These results suggest that baseline resting EEG theta connectivity or alpha power are unlikely to be generalisable predictors of response to rTMS treatment for depression. These results highlight the importance of independent replication, data sharing and using large datasets in the prediction of response research. [ABSTRACT FROM AUTHOR]

Objective We aimed to investigate neuromodulatory effects of high-frequency left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) on resting-state electroencephalography (EEG) and their clinical and cognitive correlates in patients with depression. Methods Thirty-one patients diagnosed with depression included in the present study. Resting-state gamma power and theta–gamma coupling (TGC) were calculated before and after a course of rTMS. We explored the relationship among gamma power, TGC, and clinical/cognitive outcomes as measured with the Hamilton Rating Scale for Depression (HAM-D 17 ), Beck Depression Inventory (BDI), and Wisconsin Card Sorting Test (WCST). Results Following rTMS, depressed patients demonstrated significant increases of resting gamma power at the F3 and F4 electrode sites and resting TGC at the C3 and T3 electrode sites. Furthermore, the increased gamma power at the F3 electrode site was significantly correlated with improved score on the HAM-D 17 and BDI, while the increased TGC at the C3 electrode site was significantly correlated with reduced number of errors on the WCST. Conclusion Thus, resting-state gamma power and TGC may represent potential biomarkers of depression associated with therapeutic effects of rTMS. Significance Resting-state EEG may provide potential biomarkers related to therapeutic effects of rTMS. [ABSTRACT FROM AUTHOR]