Advancing clinical response characterization to frontotemporal transcranial direct current stimulation with electric field distribution in patients with schizophrenia and auditory hallucinations: a pilot study.
- 作者列表："Mondino M","Fonteneau C","Simon L","Dondé C","Haesebaert F","Poulet E","Brunelin J
:Transcranial direct current stimulation (tDCS) has been proposed as a therapeutic option for treatment-resistant auditory verbal hallucinations (AVH) in schizophrenia. In such cases, repeated sessions of tDCS are delivered with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. Despite promising findings, the clinical response to tDCS is highly heterogeneous among patients. Here, we explored baseline differences between responders and nonresponders to frontotemporal tDCS using electric field modeling. We hypothesized that responders would display different tDCS-induced electric field strength in the brain areas involved in AVH compared to nonresponders.Using baseline structural MRI scans of 17 patients with schizophrenia and daily AVH who received 10 sessions of active frontotemporal tDCS, we constructed individual realistic whole brain models estimating electric field strength. Electric field maps were compared between responders (n = 6) and nonresponders to tDCS (n = 11) using an independent two-sample t test. Clinical response was defined as at least a 50% decrease of AVH 1 month after the last tDCS session.Results from the electric field map comparison showed that responders to tDCS displayed higher electric field strength in the left transverse temporal gyrus at baseline compared to nonresponders (T = 2.37; p = 0.016; 32 voxels).These preliminary findings suggested that the strength of the tDCS-induced electric field reaching the left transverse temporal gyrus could play an important role in the response to frontotemporal tDCS. In addition, this work suggests the interest of using electric field modeling to individualize tDCS and increase response rate.
: 经颅直流电刺激 (tDCS) 已被提议作为精神分裂症治疗抵抗性听觉言语幻觉 (AVH) 的治疗选择。在这种情况下，tDCS 的重复会话与左侧前额叶皮层的阳极和左侧颞顶交界的阴极一起递送。尽管有可喜的发现，但 tDCS 的临床反应在患者中高度异质性。在此，我们利用电场建模探讨了额颞 tDCS 应答者和非应答者之间的基线差异。我们假设与无应答者相比，应答者在参与 AVH 的脑区显示不同的 tDCS 诱导的电场强度。使用 17 例接受 10 次活动额颞 tDCS 的精神分裂症和每日 AVH 患者的基线结构 MRI 扫描，我们构建了个体真实的估计电场强度的全脑模型。采用独立双样本 t 检验比较 tDCS 应答者 (n = 6) 和非应答者 (n = 11) 的电场图。临床反应定义为最后一次 tDCS 治疗后 1 个月 AVH 至少下降 50%。电场图比较结果表明，tDCS 应答者在基线时左侧颞横回的电场强度高于无应答者 (t = 2.37; P = 0.016;32 体素)。这些初步发现表明，到达左侧颞横回的 tDCS 感应电场强度在对额颞 tDCS 的反应中起重要作用。此外，这项工作表明了使用电场建模来个性化 tDCS 和提高响应率的兴趣。
METHODS::In recent years, transcranial electrical stimulation (tES) has been used to improve cognitive and perceptual abilities and to boost learning. In the visual domain, transcranial random noise stimulation (tRNS), a type of tES in which electric current is randomly alternating in between two electrodes at high frequency, has shown potential in inducing long lasting perceptual improvements when coupled with tasks such as contrast detection. However, its cortical mechanisms and online effects have not been fully understood yet, and it is still unclear whether these long-term improvements are due to early-stage perceptual enhancements of contrast sensitivity or later stage mechanisms such as learning consolidation. Here we tested tRNS effects on multiple spatial frequencies and orientation, showing that tRNS enhances detection of a low contrast Gabor, but only for oblique orientation and high spatial frequency (12 cycles per degree of visual angle). No improvement was observed for low contrast and vertical stimuli. These results indicate that tRNS can enhance contrast sensitivity already after one training session, however this early onset is dependent on characteristics of the stimulus such as spatial frequency and orientation. In particular, the shallow depth of tRNS is likely to affect superficial layers of the visual cortex where neurons have higher preferred spatial frequencies than cells in further layers, while the lack of effect on vertical stimuli might reflect the optimization of the visual system to see cardinally oriented low contrast stimuli, leaving little room for short-term improvement. Taken together, these results suggest that online tRNS effects on visual perception are the result of a complex interaction between stimulus intensity and cortical anatomy, consistent with previous literature on brain stimulation.
METHODS:OBJECTIVE:There is growing interest in treating diseases by electrical stimulation and block of peripheral autonomic nerves, but a paucity of studies on excitation and block of small diameter autonomic axons. We conducted in vivo quantification of the strength-duration properties, activity-dependent slowing (ADS), and responses to kilohertz frequency (KHF) signals for the rat vagus nerve (VN). APPROACH:We conducted acute in vivo experiments in urethane-anesthetised rats. We placed two cuff electrodes on the left cervical VN and one cuff electrode on the anterior subdiaphragmatic VN. The rostral cervical cuff was used to deliver pulses to quantify recruitment and ADS. The caudal cervical cuff was used to deliver KHF signals. The subdiaphragmatic cuff was used to record compound action potentials (CAPs). MAIN RESULTS:We quantified the input-output recruitment and strength-duration curves. Fits to the data using standard strength-duration equations were qualitatively similar, but the resulting chronaxie and rheobase estimates varied substantially. We measured larger thresholds for the slowest fibres (0.5 to 1 m/s), especially at shorter pulse widths. Using a novel cross-correlation CAP-based analysis, we measured ADS of ~2.3% after 3 min of 2 Hz stimulation, which is comparable to ADS reported for sympathetic efferents in somatic nerves, but much smaller than ADS in cutaneous nociceptors. We found greater ADS with higher stimulation frequency and non-monotonic changes in CV in select cases. We found monotonically increasing block thresholds across frequencies from 10 to 80 kHz for both fast and slow fibres. Further, following 25 s of KHF signal, neural conduction could require tens of seconds to recover. SIGNIFICANCE:The quantification of mammalian autonomic nerve responses to conventional and KHF signals provides essential information for development of peripheral nerve stimulation therapies and for understanding their mechanisms of action.
METHODS:BACKGROUND:Early accounts of forced thought were reported at the onset of a focal seizure, and characterized as vague, repetitive, and involuntary intellectual auras distinct from perceptual or psychic hallucinations or illusions. Here, we examine the neural underpinnings involved in conceptual thought by presenting a series of 3 patients with epilepsy reporting intrusive thoughts during electrical stimulation of the left lateral prefrontal cortex (PFC) during invasive surgical evaluation. We illustrate the widespread networks involved through two independent brain imaging modalities: resting state functional magnetic resonance imaging (fMRI) (rs-fMRI) and task-based meta-analytic connectivity modeling (MACM). METHODS:We report the clinical and stimulation characteristics of three patients with left hemispheric language dominance who demonstrate forced thought with functional mapping. To examine the brain networks underlying this phenomenon, we used the regions of interest (ROI) centered at the active electrode pairs. We modeled functional networks using two approaches: (1) rs-fMRI functional connectivity analysis, representing 81 healthy controls and (2) meta-analytic connectivity modeling (MACM), representing 8260 healthy subjects. We also determined the overlapping regions between these three subjects' rs-fMRI and MACM networks through a conjunction analysis. RESULTS:We identified that left PFC was associated with a large-scale functional network including frontal, temporal, and parietal regions, a network that has been associated with multiple cognitive functions including semantics, speech, attention, working memory, and explicit memory. CONCLUSIONS:We illustrate the neural networks involved in conceptual thought through a unique patient population and argue that PFC supports this function through activation of a widespread network.