PMC8322436_01
Baseline MRI brain images and HD-tDCS montage. Selected axial T2-weighted/FLAIR images that depict encephalomalacia involving the right frontal and temporal lobes and several foci of signal hyperintensity within the right frontal centrum semiovale (A). HD-tDCS is applied using a 4 x 1 montage, including the anodal electrode at Fz (1 mA) paired with four cathodal electrodes at FPz, Cz, F7, F8 (0.25 mA each) as shown after reconstruction of the subject's gray matter surface (B) and scalp (C). Normalized electric field is then simulated to represent its intensity and distribution based on the subject's own T1 and T2 weighted images presented over the gray matter surface (D), saggital section (E), and coronal section (F). Even though the distribution of electric field is slightly asymmetric due to chronic right temporal lobe volume loss and right lateral ventricular enlargement, the focus of HD-tDCS is located to the medial superior part of the pre-Supplementary area and the dorsal anterior cingulate cortex. Normalized electric field is in the unit of Volt per meter. All analyses were performed using SimNIBS 3.2.1.
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Brain MRI acquired within a few months of treatment initiation showed encephalomalacia involving the right frontal and temporal lobes (Figure 1A). Behavioral performance improved significantly as well, with Go reaction time reduced from 635 ms at baseline to 447 and 327 ms immediately and at 6 weeks post intervention, respectively, in the more perceptually driven task (Figure 3, Task 1), and improved from 662 ms at baseline to 559 and 494 ms immediately and 6 weeks post intervention, respectively, in the more semantically driven task (Figure 3, Task 2).
Study protocol and performance change in response to HD-tDCS after each session and at longitudinal follow ups after completion of intervention. Study protocol is demonstrated (A). Verbal fluency demonstrated significant improvements after each single HD-tDCS session, which wore off prior to the next session, but the post-session performance had a steady improvement as the number of sessions increased, with some expected fluctuations (B). Phonemic fluency (P-FL) was scored with the summed number of items from COWAT (letters F, A, and S) and category fluency (C-FL) was scored with the total item using animal category (B). At baseline, category fluency was more than 1 standard deviation (SD) below average. Performance on most of these tests improved to closer to or within 1 standard deviation from average after the HD-tDCS intervention, except for D-KEFS inhibition. These positive effects persisted over 6 and 14 weeks (C). References for these neuropsychological measures are cited in Table 1.
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The overall study protocol is demonstrated in Figure 2A. She also demonstrated impaired executive functions (Trails Making B, color-word interference), speed of processing (Trails Making A) and facial recognition (the Benton face test) on neuropsychological measures (Figure 2C). Improvement in performance was found in tasks at which the patient was most impaired, most evident in verbal retrieval and executive function tests, including trails B, confrontational naming, phonemic and category fluency (Table 1, Figure 2C). Behavioral performance improved significantly as well, with Go reaction time reduced from 635 ms at baseline to 447 and 327 ms immediately and at 6 weeks post intervention, respectively, in the more perceptually driven task (Figure 3, Task 1), and improved from 662 ms at baseline to 559 and 494 ms immediately and 6 weeks post intervention, respectively, in the more semantically driven task (Figure 3, Task 2).
ERP effects in response to HD-tDCS. ERPs at the midline fronto-central electrode (FCz) were examined for the two response inhibition tasks (Go/NoGo), each contingent upon a different level of complexity [Task 1 is more perceptually based, requiring distinguishing between single exemplars of a car and a dog; Task 2 is more semantically based, requiring distinguishing between multiple exemplars of animals from non-animal objects. Refer to for more detailed description of the tasks]. N2 (a negative deflection of evoked potentials peaking around 200 ms post-stimulus) and P3 (a positive deflection of evoked potentials peaking 300-500 ms post-stimulus) components are classically reported in this type of task, with NoGo trials eliciting more prominent N2/P3 amplitude than do Go trials. There was no evident N2/P3 prior to HD-tDCS. Both N2 and P3 components appeared after 10 sessions of HD-tDCS, which persisted after 6 weeks. In Task 1, comparing immediate post to 6 weeks post data, N2 peak amplitude/latency changed from -4.1 muV/293 ms to -4.4 muV/255 ms, while P3 peak amplitude/latency changed from 5.2 muV/448 ms to 7.7 muV/382 ms. In Task 2, N2 peak amplitude/latency changed from -3.8 muV/267 ms to -6.1 muV/298 ms, while P3 peak amplitude/latency changed from 4.6 muV/527 ms to 8.6 muV with a latency at 525 ms.
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While we recorded absent and markedly diminished N2/P3 components prior to HD-tDCS, we found restoration and normalization of the typical N2/P3 ERP components after completion of treatment (Figure 3), which persisted until 6 weeks after intervention, with overall increased amplitude and decreased latency in both N2 and P3 components. Behavioral performance improved significantly as well, with Go reaction time reduced from 635 ms at baseline to 447 and 327 ms immediately and at 6 weeks post intervention, respectively, in the more perceptually driven task (Figure 3, Task 1), and improved from 662 ms at baseline to 559 and 494 ms immediately and 6 weeks post intervention, respectively, in the more semantically driven task (Figure 3, Task 2).