Resting-state electroencephalographic functional network alterations in major depressive disorder following magnetic seizure therapy.

Magnetic seizure therapy (MST) is emerging as a safe and well-tolerated experimental intervention for major depressive disorder (MDD), with very minimal cognitive side-effects. However, the underlying mechanism of action of MST remains uncertain. Here, we used resting-state electroencephalography (RS-EEG) to characterise the physiological effects of MST for treatment resistant MDD. We recorded RS-EEG in 21 patients before and after an open label trial of MST applied over the prefrontal cortex using a bilateral twin coil. RS-EEG was analysed for changes in functional connectivity, network topology, and spectral power. We also ran further baseline comparisons between the MDD patients and a cohort of healthy controls (n = 22). Network-based connectivity analysis revealed a functional subnetwork of significantly increased theta connectivity spanning frontal and parieto-occipital channels following MST. The change in theta connectivity was further found to predict clinical response to treatment. An additional widespread subnetwork of reduced beta connectivity was also elucidated. Graph-based topological analyses showed an increase in functional network segregation and reduction in integration in the theta band, with a decline in segregation in the beta band. Finally, delta and theta power were significantly elevated following treatment, while gamma power declined. No baseline differences between MDD patients and healthy subjects were observed. These results highlight widespread changes in resting-state brain dynamics following a course of MST in MDD patients, with changes in theta connectivity providing a potential physiological marker of treatment response. Future prospective studies are required to confirm these initial findings.

Extent of Dorsolateral Prefrontal Cortex Plasticity and Its Association With Working Memory in Patients With Alzheimer Disease.

Importance: The extent of dorsolateral prefrontal cortex (DLPFC) plasticity in Alzheimer disease (AD) and its association with working memory are not known. Objectives: To determine whether participants with AD had impaired DLPFC plasticity compared with healthy control participants, to compare working memory between participants with AD and controls, and to determine whether DLPFC plasticity was associated with working memory. Design, Setting, and Participants: This cross-sectional study included 32 participants with AD who were 65 years or older and met diagnostic criteria for dementia due to probable AD with a score of at least 17 on the Mini-Mental State Examination and 16 age-matched control participants. Participants were recruited from a university teaching hospital from May 2013 to October 2016. Main Outcomes and Measures: Plasticity of the DLPFC measured as potentiation of cortical-evoked activity using paired associative stimulation (a combination of peripheral nerve electrical stimulation and transcranial magnetic stimulation) combined with electroencephalography. Working memory was assessed with the n-back task (1- and 2-back) and measured using the A' statistic. Results: Among the 32 participants with AD, 17 were women and 15 were men (mean [SD] age, 76.3 [6.3] years); among the 16 controls, 8 were men and 8 were women (mean [SD] age, 76.4 [5.1] years). Participants with AD had impaired DLPFC plasticity (mean [SD] potentiation, 1.18 [0.25]) compared with controls (mean [SD] potentiation, 1.40 [0.35]; F1,44 = 5.90; P = .02; between-group comparison, Cohen d = 0.77; P = .01). Participants with AD also had impaired performances on the 1-back condition (mean [SD] A' = 0.47 [0.30]) compared with controls (mean [SD] A' = 0.96 [0.01]; Cohen d = 1.86; P < .001), with similar findings for participants with AD on the 2-back condition (mean [SD] A' = 0.29 [0.2]) compared with controls (mean [SD], A' = 0.85 [0.18]; Cohen d = 2.83; P < .001). Plasticity of DLPFC was positively associated with working memory performance on the 1-back A' (parameter estimate B [SE] = 0.32 [0.13]; standardized ß = 0.29; P = .02) and 2-back A' (B [SE] = 0.43 [0.15]; ß = 0.39; P = .006) across both groups after controlling for age, education, and attention. Conclusions and Relevance: This study demonstrated impaired in vivo DLPFC plasticity in patients with AD. The findings support the use of DLPFC plasticity as a measure of DLPFC function and a potential treatment target to enhance DLPFC function and working memory in patients with AD.

Characterization of Glutamatergic and GABAA-Mediated Neurotransmission in Motor and Dorsolateral Prefrontal Cortex Using Paired-Pulse TMS-EEG.

Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are noninvasive transcranial magnetic stimulation (TMS) measures of GABAA receptor-mediated inhibition and glutamatergic excitatory transmission, respectively. Conventionally these measures have been restricted to the motor cortex. We investigated whether SICI and ICF could be recorded from the dorsolateral prefrontal cortex (DLPFC) using combined TMS and electroencephalography (TMS-EEG). We first characterized the neural signature of SICI and ICF in M1 in terms of TMS-evoked potentials (TEPs) and spectral power modulation. Subsequently, these paradigms were applied in the DLPFC to determine whether similar neural signatures were evident. With TMS at M1, SICI and ICF led to bidirectional modulation (inhibition and facilitation, respectively) of P30 and P60 TEP amplitude, which correlated with MEP amplitude changes. With DLPFC stimulation, P60 was bidirectionally modulated by SICI and ICF in the same manner as for M1 stimulation, whereas P30 was absent. The sole modulation of early TEP components is in contradistinction to other measures such as long-interval intracortical inhibition and may reflect modulation of short latency excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs). Overall, the data suggest that SICI and ICF can be recorded using TMS-EEG in DLPFC providing noninvasive measures of glutamatergic and GABAA receptor-mediated neurotransmission. This may facilitate future research attempting to ascertain the role of these neurotransmitters in the pathophysiology and treatment of neurological and psychiatric disorders.

Analysis of morphological features of thalamocortical neurons from the ventroposterolateral nucleus of the cat.

Morphological features of the dendritic arborization can affect neuronal responses and thus the input-output function of a particular neuron. In this study, morphological data of eight fully reconstructed thalamocortical (TC) neurons from the ventroposterolateral (VPL) nucleus of adult cats have been analyzed. We examined several geometrical and topological parameters, which have been previously shown to have a high impact on the neuron firing pattern and propagation of signals in the dendritic tree. In addition to well-known morphological parameters such as number of dendritic trees (8.3 +/- 1.5) and number of branching points (80-120), we investigated the distribution of dendritic membrane area, branching points, geometrical ratio, asymmetry index, and mean path length for all subtrees of the TC neurons. We demonstrate that due to extensive branching in proximal and middle dendritic sections, the maximum value of the dendritic area distribution is reached at 120-160 mum from the soma. Our analysis reveals that TC neurons are highly branched cells and their dendritic branching pattern does not follow Rall's 3/2 power rule; average values at proximal vs. distal dendritic sections were different. We also found that the dendritic branching pattern of each subtree of the cell had a wide range in symmetry index, whereas the mean path length did not show a large variation through the dendritic arborizations.