Niranjan Khadka1, Marom Bikson2. 1. Department of Psychiatry, Laboratory for Neuropsychiatry and Neuromodulation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 2. Department of Biomedical Engineering, The City College of New York, CUNY, New York, NY, USA.
Abstract
OBJECTIVES: We consider two consequences of brain capillary ultrastructure in neuromodulation. First, blood-brain barrier (BBB) polarization as a consequence of current crossing between interstitial space and the blood. Second, interstitial current flow distortion around capillaries impacting neuronal stimulation. MATERIALS AND METHODS: We developed computational models of BBB ultrastructure morphologies to first assess electric field amplification at the BBB (principle 1) and neuron polarization amplification by the presence of capillaries (principle 2). We adapt neuron cable theory to develop an analytical solution for maximum BBB polarization sensitivity. RESULTS: Electrical current crosses between the brain parenchyma (interstitial space) and capillaries, producing BBB electric fields (EBBB ) that are >400x of the average parenchyma electric field (ĒBRAIN ), which in turn modulates transport across the BBB. Specifically, for a BBB space constant (λBBB ) and wall thickness (dth-BBB ), the analytical solution for maximal BBB electric field (EA BBB ) is given as: (ĒBRAIN × λBBB )/dth-BBB . Electrical current in the brain parenchyma is distorted around brain capillaries, amplifying neuronal polarization. Specifically, capillary ultrastructure produces ~50% modulation of the ĒBRAIN over the ~40 μm inter-capillary distance. The divergence of EBRAIN (Activating function) is thus ~100 kV/m2 per unit ĒBRAIN . CONCLUSIONS: BBB stimulation by principle 1 suggests novel therapeutic strategies such as boosting metabolic capacity or interstitial fluid clearance. Whereas the spatial profile of EBRAIN is traditionally assumed to depend only on macroscopic anatomy, principle 2 suggest a central role for local capillary ultrastructure-which impact forms of neuromodulation including deep brain stimulation (DBS), spinal cord stimulation (SCS), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and transcranial electrical stimulation (tES)/transcranial direct current stimulation (tDCS).
OBJECTIVES: We consider two consequences of brain capillary ultrastructure in neuromodulation. First, blood-brain barrier (BBB) polarization as a consequence of current crossing between interstitial space and the blood. Second, interstitial current flow distortion around capillaries impacting neuronal stimulation. MATERIALS AND METHODS: We developed computational models of BBB ultrastructure morphologies to first assess electric field amplification at the BBB (principle 1) and neuron polarization amplification by the presence of capillaries (principle 2). We adapt neuron cable theory to develop an analytical solution for maximum BBB polarization sensitivity. RESULTS: Electrical current crosses between the brain parenchyma (interstitial space) and capillaries, producing BBB electric fields (EBBB ) that are >400x of the average parenchyma electric field (ĒBRAIN ), which in turn modulates transport across the BBB. Specifically, for a BBB space constant (λBBB ) and wall thickness (dth-BBB ), the analytical solution for maximal BBB electric field (EA BBB ) is given as: (ĒBRAIN × λBBB )/dth-BBB . Electrical current in the brain parenchyma is distorted around brain capillaries, amplifying neuronal polarization. Specifically, capillary ultrastructure produces ~50% modulation of the ĒBRAIN over the ~40 μm inter-capillary distance. The divergence of EBRAIN (Activating function) is thus ~100 kV/m2 per unit ĒBRAIN . CONCLUSIONS: BBB stimulation by principle 1 suggests novel therapeutic strategies such as boosting metabolic capacity or interstitial fluid clearance. Whereas the spatial profile of EBRAIN is traditionally assumed to depend only on macroscopic anatomy, principle 2 suggest a central role for local capillary ultrastructure-which impact forms of neuromodulation including deep brain stimulation (DBS), spinal cord stimulation (SCS), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and transcranial electrical stimulation (tES)/transcranial direct current stimulation (tDCS).
Authors: Darin D Dougherty; Tina Chou; Andrew K Corse; Amanda R Arulpragasam; Alik S Widge; Cristina Cusin; Karleyton C Evans; Benjamin D Greenberg; Suzanne N Haber; Thilo Deckersbach Journal: J Neurosurg Date: 2016-02-19 Impact factor: 5.115
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Authors: Suellen Marinho Andrade; Maria Cecília de Araújo Silvestre; Eduardo Ériko Tenório de França; Maria Heloísa Bezerra Sales Queiroz; Kelly de Jesus Santana; Marcela Lais Lima Holmes Madruga; Cristina Katya Torres Teixeira Mendes; Eliane Araújo de Oliveira; João Felipe Bezerra; Renata Gomes Barreto; Silmara Maria Alves Fernandes da Silva; Thais Alves de Sousa; Wendy Chrystyan Medeiros de Sousa; Mariana Patrícia da Silva; Vanessa Meira Cintra Ribeiro; Paulo Lucena; Daniel Beltrammi; Rodrigo Ramos Catharino; Egas Caparelli-Dáquer; Benjamin M Hampstead; Abhishek Datta; Antonio Lucio Teixeira; Bernardino Fernández-Calvo; João Ricardo Sato; Marom Bikson Journal: Brain Stimul Date: 2022-05-11 Impact factor: 9.184