The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible. Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field “hot spots” in the cortex. However, these maxima were not substantially stronger than those seen in a healthy control. The electric field pattern induced by TMS was not substantially changed by the lesions. However, the average field strength generated by TDCS was substantially decreased. This effect occurred for both head models and even when both electrodes were distant to the lesion, caused by increased current shunting through the lesion and enlarged ventricles. Judging from the similar peak field strengths compared to the healthy control, both TBS methods are safe in patients with large brain lesions (in practice, however, additional factors such as potentially lowered thresholds for seizure-induction have to be considered). Focused stimulation by TMS seems to be possible, but standard tDCS protocols appear to be less efficient than they are in healthy subjects, strongly suggesting that tDCS studies in this population might benefit from individualized treatment planning based on realistic field calculations. Keywords: Transcranial magnetic stimulation, Transcranial direct current stimulation, Chronic stroke, Brain lesions, Field simulations, Finite element metho

A principled approach to conductivity uncertainty analysis in electric field calculations

Uncertainty surrounding ohmic tissue conductivity impedes accurate calculation of the electric fields generated by non-invasive brain stimulation. We present an efficient and generic technique for uncertainty and sensitivity analyses, which quantifies the reliability of field estimates and identifies the most influential parameters. For this purpose, we employ a non-intrusive generalized polynomial chaos expansion to compactly approximate the multidimensional dependency of the field on the conductivities. We demonstrate that the proposed pipeline yields detailed insight into the uncertainty of field estimates for transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), identifies the most relevant tissue conductivities, and highlights characteristic differences between stimulation methods. Specifically, we test the influence of conductivity variations on (i) the magnitude of the electric field generated at each gray matter location, (ii) its normal component relative to the cortical sheet, (iii) its overall magnitude (indexed by the 98th percentile), and (iv) its overall spatial distribution. We show that TMS fields are generally less affected by conductivity variations than tDCS fields. For both TMS and tDCS, conductivity uncertainty causes much higher uncertainty in the magnitude as compared to the direction and overall spatial distribution of the electric field. Whereas the TMS fields were predominantly influenced by gray and white matter conductivity, the tDCS fields were additionally dependent on skull and scalp conductivities. Comprehensive uncertainty analyses of complex systems achieved by the proposed technique are not possible with classical methods, such as Monte Carlo sampling, without extreme computational effort. In addition, our method has the advantages of directly yielding interpretable and intuitive output metrics and of being easily adaptable to new problems

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Optimizing the electric field strength in multiple targets for multichannel transcranial electric stimulation:Note

OBJECTIVE: Most approaches to optimize the electric field pattern generated by multichannel Transcranial Electric Stimulation (TES) require the definition of a preferred direction of the electric field in the target region(s). However, this requires knowledge about how the neural effects depend on the field direction, which is not always available. Thus, it can be preferential to optimize the field strength in the target(s), irrespective of the field direction. However, this results in a more complex optimization problem. APPROACH: We introduce and validate a novel optimization algorithm that maximizes focality while controlling the electric field strength in the target to maintain a defined value. It obeys the safety constraints, allows limiting the number of active electrodes and allows also for multi-target optimization. MAIN RESULTS: The optimization algorithm outperformed naïve search approaches in both quality of the solution and computational efficiency. Using the amygdala as test case, we show that it allows for reaching a reasonable trade-off between focality and field strength in the target. In contrast, simply maximizing the field strength in the target results in far more extended fields. In addition, by maintaining the pre-defined field strengths in the targets, the new algorithm allows for a balanced stimulation of two or more regions. SIGNIFICANCE: The novel algorithm can be used to automatically obtain individualized, optimal montages for targeting regions without the need to define preferential directions. It will automatically select the field direction that achieves the desired field strength in the target(s) with the most focal stimulation pattern