Alik Widge, MD, Ph.D.
My lab focuses on turning basic neuroscience insights into new treatments, particularly for depression, obsessive-compulsive, trauma-related, and substance-related disorders. In all of these areas, an explosion of new tools lets us dissect circuit function in experimental animals as never before. More than ever, we know that mental disorders arise from problems of information flow in distributed brain circuits, and we know specific patterns of neural activity that are necessary for healthy function. The challenge is finding ways to restore those healthy circuit patterns within the limits of clinical technology: no head fixation, no bulky plugs sticking out of the head, keeping the skull mostly intact, and minimizing (or eliminating!) genetic manipulations. We build the technologies and do the science to make that translation possible. Our work includes basic animal neuroscience, human neuroscience, and applied/clinical studies in humans. Examples of recent projects include:
- Technologies that lock electrical stimulation to the peaks and troughs of brain oscillations, allowing us to control how those oscillations synchronize (or fall out of sync) between brain regions. This oscillatory coherence is believed to be the basic of brain network communication, and controlling it may be a path to restoring circuit function.
- Measuring and modeling how existing clinical stimulation changes ongoing neural firing. From those models, we hope to design rational and theory-informed algorithms that will (A) let us drive brain networks to any desired state and (B) ensure that we are creating the specific patterns that matter most for clinical symptom relief.
- Testing novel neurostimulation designs in human populations, including research with psychiatric patients in formal clinical trials, in epilepsy patients with large-scale brain monitoring montages, movement disorders patients undergoing deep brain stimulation, and healthy volunteers.
- Neuroethics. 2023;16(2):14. doi: 10.1007/s12152-023-09520-7. The role of family members in psychiatric deep brain stimulation trials: More than psychosocial support.
- Harv Rev Psychiatry. 2023 May-Jun 01;31(3):162-171. Closed-loop deep brain stimulation for psychiatric disorders.
- J Neural Eng. 2023 Apr 27. doi: 10.1088/1741-2552/acd0d5. In silico development and validation of Bayesian methods for optimizing deep brain stimulation to enhance cognitive control.
- Am J Psychiatry. 2023 Apr 19:appiajp20220685. Structural racism in psychiatric research careers: Eradicating barriers to a more diverse workforce.
- J Addict Med. 2023 Mar 3. doi: 10.1097/ADM.0000000000001150. Deep brain stimulation for substance use disorders? An exploratory qualitative study of perspectives of people currently in treatment.
- Neurosci Biobehav Rev. 2023 Jan;144:105005. Causally mapping human threat extinction relevant circuits with depolarizing brain stimulation methods.
- J Neurosci Methods. 2022 Dec 1;382:109725. Quantifying defensive behavior and threat response through integrated headstage accelerometry.
- Wendt K, Denison T, Foster G, Krinke L, Thomson A, Wilson S, Widge AS. Physiologically informed neuromodulation. J Neurol Sci. 2021 Dec 28;434:120121.
- Schatza MJ, Blackwood EB, Nagrale SS, Widge AS.Toolkit for oscillatory real-time tracking and estimation (TORTE). J Neurosci Methods. 2021 Nov 14:109409.
- Basu I, Yousefi A, Crocker B, Zelmann R, Paulk AC, Peled N, Ellard KK, Weisholtz DS, Cosgrove GR, Deckersbach T, Eden UT, Eskandar EN, Dougherty DD, Cash SS, Widge AS. Closed-loop enhancement and neural decoding of cognitive control in humans. Nat Biomed Eng. 2023 Apr;7(4):576-588.
- Front Psychiatry. 2022 Oct 18;13:938694. Toward biophysical markers of depression vulnerability.
- de Oliveira AR, Reimer AE, Simandl GJ, Nagrale SS, Widge AS. Lost in translation: no effect of repeated optogenetic cortico-striatal stimulation on compulsivity in rats. Transl Psychiatry. 2021 May 24;11(1):315.
- Wodeyar A, Schatza M, Widge AS, Eden UT, Kramer MA. A state space modeling approach to real-time phase estimation. Elife. 2021 Sep 27;10:e68803.
- Kraguljac NV, McDonald WM, Widge AS, Rodriguez CI, Tohen M, Nemeroff CB. Neuroimaging biomarkers in schizophrenia. Am J Psychiatry. 2021 Aug 1;178(8):715-729.
- Pathoulas JT, Olson SJ, Idnani A, Farah RS, Hordinsky MK, Widge AS. Cross-sectional survey examining skin picking and hair pulling disorders during the COVID-19 pandemic. J Am Acad Dermatol. 2021;84(3):771-773.
- Sullivan CRP, Olsen S, Widge AS. Deep brain stimulation for psychiatric disorders: From focal brain targets to cognitive networks. Neuroimage. 2021 Jan 15;225:117515.
- Grzenda A, Widge AS. Electroencephalographic biomarkers for predicting antidepressant response: New methods, old questions. JAMA Psychiatry. 2020;77(4):347-348.
- Widge AS, Heilbronner SR, Hayden BY. Prefrontal cortex and cognitive control: new insights from human electrophysiology. F1000Res. 2019 Sep 27;8. pii: F1000 Faculty Rev-1696.
- Widge AS, Zorowitz S, Basu I, Paulk AC, Cash SS, Eskandar EN, Deckersbach T, Miller EK, Dougherty DD. Deep brain stimulation of the internal capsule enhances human cognitive control and prefrontal cortex function. Nat Commun. 2019;10:1536.
- Widge AS, Miller EK. Targeting cognition and networks through neural oscillations: Next-generation clinical brain stimulation. JAMA Psychiatry. 2019;76(7):671-672.
- Widge AS, Bilge MT, Montana R, Chang W, Rodriguez CI, Deckersbach T, Carpenter LL, Kalin NH, Nemeroff CB. Electroencephalographic biomarkers for treatment response prediction in major depressive illness: A meta-analysis. Am J Psychiatry. 2019;176(1):44-56.
- Provenza NR, Paulk AC, Peled N, Restrepo MI, Cash SS, Dougherty DD, Eskandar EN, Borton DA, Widge AS. Decoding task engagement from distributed network electrophysiology in humans. J Neural Eng. 2019 Aug 16;16(5):056015.
- Widge AS, Malone DAJ, Dougherty DD. Closing the loop on deep brain stimulation for treatment-resistant depression. Front Neurosci. 2018;12:175.
- Herman AB, Widge AS. Dynamic network targeting for closed loop deep brain stimulation. Neuropsychopharmacology. 2019;44(1):219-220.
- Bilge MT, Gosai A, Widge AS. Deep brain stimulation in psychiatry: mechanisms, models, and next-generation therapies. Psychiatric Clinics of North America. 2018;41(3):373–83.
- Widge AS, Ellard KK, Paulk AC, Basu I, Yousefi A, Zorowitz S, Gilmour A, Afzal A, Deckersbach T, Cash SS, Kramer MA, Eden UT, Dougherty DD, Eskandar EN. Treating refractory mental illness with closed-loop brain stimulation: progress towards a patient-specific transdiagnostic approach. Experimental Neurology. 2017;287(4):361–472.
- Lo M-C, Widge AS. Closed-loop neuromodulation systems: next-generation treatments for psychiatric illness. International Review of Psychiatry. 2017;29(2):191–204.
Current Graduate Students
Ellie Sachse (Neuroscience, University of Minnesota)