Faculty Bibliography
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55
Response to letter to the editor: Safety of transcranial direct current stimulation: Evidence based update 2016 [Letter]
PMCID:5975364
PMID: 28734680
ISSN: 1876-4754
CID: 2644722
Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation [Meeting Abstract]
Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. Here we measure electric potentials intracranially in ten epilepsy patients and estimate electric fields across the entire brain by leveraging calibrated current- flow models. Electric field magnitudes at the cortical surface reach values of 0.4 V/m, which is at the lower limit of effectiveness in animal studies. When individual anatomy is taken into account, the predicted electric field magnitudes correlate with the recorded values (r=0.89 and r=0.84 in cortical and depth electrodes, respectively). Modeling white matter anisotropy and different skull compartments does not improve accuracy, but correct magnitude estimates require an adjustment of conductivity values used in the literature. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation for targeting of stimulation and interpretation of clinical trials
EMBASE:617344087
ISSN: 1876-4754
CID: 2645502
Parahippocampal and Entorhinal Resection Extent Predicts Verbal Memory Decline in an Epilepsy Surgery Cohort
The differential contribution of medial-temporal lobe regions to verbal declarative memory is debated within the neuroscience, neuropsychology, and cognitive psychology communities. We evaluate whether the extent of surgical resection within medial-temporal regions predicts longitudinal verbal learning and memory outcomes. This single-center retrospective observational study involved patients with refractory temporal lobe epilepsy undergoing unilateral anterior temporal lobe resection from 2007 to 2015. Thirty-two participants with Engel Classes 1 and 2 outcomes were included (14 left, 18 right) and followed for a mean of 2.3 years after surgery (+/-1.5 years). Participants had baseline and postsurgical neuropsychological testing and high-resolution T1-weighted MRI scans. Postsurgical lesions were manually traced and coregistered to presurgical scans to precisely quantify resection extent of medial-temporal regions. Verbal learning and memory change scores were regressed on hippocampal, entorhinal, and parahippocampal resection volume after accounting for baseline performance. Overall, there were no significant differences in learning and memory change between patients who received left and right anterior temporal lobe resection. After controlling for baseline performance, the extent of left parahippocampal resection accounted for 27% (p = .021) of the variance in verbal short delay free recall. The extent of left entorhinal resection accounted for 37% (p = .004) of the variance in verbal short delay free recall. Our findings highlight the critical role that the left parahippocampal and entorhinal regions play in recall for verbal material.
PMID: 27991184
ISSN: 1530-8898
CID: 2465052
Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation
Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimate electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.4 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (r=0.89) and depth (r=0.84) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials.
PMCID:5370189
PMID: 28169833
ISSN: 2050-084x
CID: 2437392
Direct experimental validation of computational current flowmodels with intra-cranial recordings in human and non-human primates [Meeting Abstract]
Computational models of Transcranial Electric Stimulation (TES) have been used extensively to predict the precise intensity and distribution of electric fields across the brain. The goal of such modeling is to guide the targeting of particular brain areas for clinical trials and research studies. While computational models have increased in sophistication and detail, to date there has been limited empirical evaluation of their precision. Previous efforts have been limited to comparing model predictions with voltage recordings on the scalp surface. To address the uncertainty of model accuracy inside the head, we recorded intra-cranial electric fields generated by TES in patients undergoing invasive monitoring for epilepsy surgery. Highresolution finite element models were constructed from patient's MRIs at 1 mm3 resolution, and voltage distribution inside the head were simulated for 1 mA currents. Preliminary analysis shows a general correspondence of model predictions and trans-cranial recordings (in over 150 cortical and subcortical electrodes for each of two patients). To determine specific conductivity values in-vivo for different tissues we are in the process of recording from depth electrodes also in rhesus macaque monkey leveraging ongoing neurophysiology experiments with TES. We have already segmented the macaque head anatomy for one subject at 1mm3 resolution and completed current flow modeling. These combined human and nonhuman primate recordings should provide strong constraints for future modeling efforts and will establish a firm empirical foundation for future clinical studies with TES that aim to target specific cortical and sub-cortical brain regions
EMBASE:614511219
ISSN: 1876-4754
CID: 2480042
Are we missing non-motor seizures in Parkinson's disease? Two case reports
BACKGROUND: Parkinson's disease (PD) is predominantly recognized for its motor symptoms, but patients struggle from a morbid and heterogeneous collection of non-motor symptoms (NMS-PD) that can affect their quality of life even more. NMS-PD is a rather generalized term and the heterogeneity and non-specific nature of many symptoms poses a clinical challenge when a PD patient presents with non-motor complaints that may not be NMS-PD. CASE PRESENTATION: We report two patients with idiopathic PD who presented with acute episodes of cognitive changes. Structural brain images, cardiovascular and laboratory assessment were unremarkable. Both patients experienced a considerable delay before receiving an epilepsy-evaluation, at which point electroencephalogram abnormalities supported the diagnosis of focal non-motor seizures with alteration of awareness. Antiepileptic therapy was implemented and was effective in both cases. CONCLUSIONS: Diagnosing non-motor seizures can be challenging. However, PD patients pose an even greater challenge given their eclectic non-motor clinical manifestations and other disease-related complications that could confound and mislead adequate clinical interpretation. Our two cases provide examples of non-motor seizures that may mimic non-motor symptoms of PD. Treating physicians should always consider other possible causes of non-motor symptoms that may coexist in PD patients. Epilepsy work-up should be contemplated in the differential of acute changes in cognition, behavior, or alertness.
PMCID:5583992
PMID: 28879018
ISSN: 2054-7072
CID: 2687612
Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016
This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (
PMCID:5007190
PMID: 27372845
ISSN: 1876-4754
CID: 2225122
Exploring the efficacy of a 5-day course of transcranial direct current stimulation (TDCS) on depression and memory function in patients with well-controlled temporal lobe epilepsy
INTRODUCTION: Depression and memory dysfunction significantly impact the quality of life of patients with epilepsy. Current therapies for these cognitive and psychiatric comorbidities are limited. We explored the efficacy and safety of transcranial direct current stimulation (TDCS) for treating depression and memory dysfunction in patients with temporal lobe epilepsy (TLE). METHODS: Thirty-seven (37) adults with well-controlled TLE were enrolled in a double-blinded, sham-controlled, randomized, parallel-group study of 5days of fixed-dose (2mA, 20min) TDCS. Subjects were randomized to receive either real or sham TDCS, both delivered over the left dorsolateral prefrontal cortex. Patients received neuropsychological testing and a 20-minute scalp EEG at baseline immediately after the TDCS course and at 2- and 4-week follow-up. RESULTS: There was improvement in depression scores immediately after real TDCS, but not sham TDCS, as measured by changes in the Beck Depression Inventory (BDI change: -1.68 vs. 1.27, p<0.05) and NDDI-E (-0.83 vs. 0.9091, p=0.05). There was no difference between the groups at the 2- or 4-week follow-up. There was no effect on delayed or working memory performance. Transcranial direct current stimulation was well-tolerated and did not increase seizure frequency or interictal discharge frequency. Transcranial direct current stimulation induced an increase in delta frequency band power over the frontal region and delta, alpha, and theta band power in the occipital region after real stimulation compared to sham stimulation, although the difference did not reach statistical significance. DISCUSSION: This study provides evidence for the use of TDCS as a safe and well-tolerated nonpharmacologic approach to improving depressive symptoms in patients with well-controlled TLE. However, there were no changes in memory function immediately following or persisting after a stimulation course. Further studies may determine optimal stimulation parameters for maximal mood benefit.
PMID: 26720704
ISSN: 1525-5069
CID: 1927302
Experience with a healthy subject population at a sleep research center undergoing cognitive neuroscience research [Meeting Abstract]
Introduction: The role of sleep in learning and memory has gained significant attention in cognitive neuroscience. We report our experience with a healthy subject population at a sleep research center. Methods: We recruited subjects for a daytime nap and overnight sleep study by advertising at an urban university over one year. Subjects were eligible if aged 18 to 35, English-speaking, and scored above 26 on the Montreal Cognitive Assessment (MOCA). They were excluded for any diagnosis of a neurologic or psychiatric disorder, including a sleep disorder (as identified by the insomnia symptom questionnaire, STOP-BANG, and Morningness-Eveningness scale); used psychoactive medications, alcohol or recreational drugs; or recent travel across time zones. Subjects participated in cognitive tasks and slept with simultaneous EEG-PSG, which was scored by a board-certified sleep neurologist. Results: We obtained 40 nap studies and 20 nighttime studies. Screening questionnaires identified eligible subjects with a low risk of insomnia (0.22 +/- 0.52), low r isk of sleep apnea (0.82 +/- 0.75), and inter mediate ci rcadian preferences (47.15 +/- 0.75). There was a wide var iance in sleep efficiency (0.68 +/- 0.29) and total sleep time (TST, 69.86 +/- 33.78 min) during naps; with less variance seen during nocturnal studies (SD 0.84 +/- 0.08; TST 454.13 +/- 45.0 min). Three (15%) nap subjects demonstrated excessive daytime REM. Two nap subjects (5%) and three (15%) nighttime subjects were diagnosed with OSA. One nap subject (2.5%) and two nighttime subjects (10%) were diagnosed with periodic limb movements of sleep (PLMS). Conclusion: Our experience with a healthy subject population suggests a wide variance in daytime sleep behavior and a notable prevalence of sleep disorders such as OSA, PLMS, and excessive daytime REM. These variables should be considered in planning and analysis of sleep and cognition studies
EMBASE:72303238
ISSN: 1550-9109
CID: 2152932
Transcranial Magnetic Stimulation in the Treatment of Neurological Disease
Transcranial magnetic stimulation (TMS) holds great potential in the treatment of a host of neurological conditions due to its ability to focally modulate-suppress or enhance-activity in targeted cortical brain regions and modify activity across specific brain networks. Results from early trials in a number of neurological indications are presented, including stroke rehabilitation, Parkinson's disease, tinnitus, chronic pain, migraine, and epilepsy. We emphasize both the challenges, such as the limited efficacy to date in tinnitus, as well as the opportunities, such as the use of TMS in epilepsy caused by focal/cortical lesions. However, to establish TMS as a clinically valuable neurological therapeutic intervention, a number of hurdles must be overcome, including accurate targeting of the treatment, characterization of its therapeutic benefit for specific patients/symptoms, proof of efficacy in multicenter trials that are adequately blinded and powered, proof of the durability of the effects, and assessment of potential adverse effects of cumulative dose and repeated application.
ISI:000338827700008
ISSN: 1938-2456
CID: 1102792
