I lead a multidisciplinary group of researchers in the use of engineering and quantitative principles to better understand and treat children's brains. Through my Neurodynamics Laboratory, I study the biophysics and biology underlying epilepsy and hydrocephalus as well as the use of advanced imaging and radiological tools, mathematical analyses and robotics.
Our lab applies these progressive tools to hydrocephalus and epilepsy research, specifically integrating strides in biology, imaging, mathematics and engineering to provide a much needed framework to these important fields. Recent efforts in our engineering approach have generated new concepts in the fundamental understanding of these conditions, and development of devices to improve care.
In epilepsy, our work has correlated the frequency and phase of specifically recorded intracranial signals with cognitive events, particularly memory and perception. Our current efforts focus on utilizing these methods to improve surgical patient selection and operative resection planning, as well as to understand the mechanisms of nonresective surgical strategies such as vagal nerve stimulation.
In patients evaluated for resective surgery, we assume that there may actually exist an optimal neurosurgical intervention tailored to the individual patient. Techniques of applied mathematics, such as Granger causality calculations on large datasets of intracranial EEG, might allow the most objective practical determination of this intervention.
In hydrocephalus, we have proposed that failure of a mechanism to absorb the kinetic energy of cardiac pulsations may underlie headache and clinical symptoms of hydrocephalus. We have recently published the world’s largest experience with noninvasive thermal measurement of shunt flow, and we now correlate these findings with an MRI-based technique to quantify shunt flow.
Building on a project initiated with Dr. Judah Folkman, we are investigating the levels of VEGF in cerebrospinal fluid, and pursuing a pharmacological strategy resulting from the interplay of these investigations. The impact on diagnosis of shunt problems has led to improved therapy in individual patients and we anticipate therapeutic advances with measurable impact on outcomes for the large population of children with hydrocephalus.
My research has resulted in publications that have advanced the field and provided new options to patients, including:
Sederberg PB, Schulze-Bonhage A, Madsen JR, Bromfield EB, Litt B, Brandt A, Kahana MJ. Gamma oscillations distinguish true from false memories. Psychol Sci. 2007;18:927-932.
Zou R, Park EH, Kelly EM, Egnor M, Wagshul ME, Madsen JR. Intracranial pressure waves: characterization of a pulsation absorber with notch filter properties using systems analysis: laboratory investigation. J Neurosurg Pediatrics. 2008; 2: 83-94.
Liu H, Buckner RL, Talukdar T, Tanaka N, Madsen JR, Stufflebeam SM. Task-free presurgical mapping using functional magnetic resonance imaging intrinsic activity. J Neurosurg. 2009; 111: 746-754.
Liu H, Agam Y, Madsen JR, Kreiman G. Timing, timing, timing: fast decoding of object information from intracranial field potentials in human visual cortex. Neuron. 2009;62:281-290.
Grinberg L, Anor T, Cheever E, Madsen JR, Karniadakis GE. Simulation of the human intracranial arterial tree. Philos Transact A Math Phys Eng Sci. 2009; 367: 2371-2386.
Cash SS, Halgren E, Dehghani N, Rossetti AO, Thesen T, Wang C, Devinsky O, Kuzniecky R, Doyle W, Madsen JR, Bromfield E, Eross L, Halász P, Karmos G, Csercsa R, Wittner L, Ulbert I. The human K-complex represents an isolated cortical down-state. Science. 2009; 324: 1084-1087.
Eide PK, Rapoport BI, Gormley WB, Madsen JR. A dynamic nonlinear relationship between the static and pulsatile components of intracranial pressure in patients with subarachnoid hemorrhage. J Neurosurg. 2010; 112: 616-625.
Park EH, Dombrowski S, Luciano M, Zurakowski D, Madsen JR. Alterations of pulsation absorber characteristics in experimental hydrocephalus. J Neurosurg Pediatr. 2010; 6:159-170.
Stufflebeam SM, Liu H, Sepulcre J, Tanaka N, Buckner RL, Madsen JR. Localization of focal epileptic discharges using functional connectivity magnetic resonance imaging. J Neurosurg. 2011; 114: 1693-1697.
Truccolo W, Donoghue JA, Hochberg LR, Eskandar EN, Madsen JR, Anderson WS, Brown EN, Halgren E, Cash SS. Single-neuron dynamics in human focal epilepsy. Nat Neurosci. 2011; 14: 635-641.
Poh MZ, Loddenkemper T, Reinsberger C, Swenson NC, Goyal S, Madsen JR, Picard RW. Autonomic changes with seizures correlate with postictal EEG suppression. Neurology. 2012; 78:1868-1876.
Park EH, Eide PK, Zurakowski D, Madsen JR. Impaired pulsation absorber mechanism in idiopathic normal pressure hydrocephalus. J Neurosurg. 2012; 117:1189-1196.
Jha RM, Liu X, Chrenek R, Madsen JR, Cardozo DL. The postnatal human filum terminale is a source of autologous multipotent neurospheres capable of generating motor neurons. Neurosurgery. 2013; 72: 118-129.
Duffy FH, Eksioglu YZ, Rotenberg A, Madsen JR, Shankardass A, Als H. The frequency modulated auditory evoked response (FMAER), a technical advance for study of childhood language disorders: cortical source localization and selected case studies. BMC Neurology. 2013; 13: 12.
Tanaka N, Peters JM, Prohl AK, Takaya S, Madsen JR, Bourgeois BF, Dworetzky BA, Hämäläinen MS, Stufflebeam SM. Clinical value of magnetoencephalographic spike propagation represented by spatiotemporal source analysis: correlation with surgical outcome. Epilepsy Res. 2014; 108: 280-288.
Shim JW, Sandlund J, Han CH, Hameed MQ, Connors S, Klagsbrun M, Madsen JR, Irwin N. VEGF, which is elevated in the CSF of patients with hydrocephalus, causes ventriculomegaly and ependymal changes in rats. Exp Neurol. 2013; 247:703-709.
Singer JM, Madsen JR, Anderson WS, Kreiman G. Sensitivity to timing and order in human visual cortex. J Neurophysiol. 2015; 113: 1656-1669.