Functional Magnetic Resonance Imaging (fMRI) has the potential of fulfilling a long held dream of the neuroscience community and of the public at large to view the human brain in action. However, the detailed relation between the neurovascular parameters mapped in fMRI, and the underlying neural activity, are poorly understood at present. In our previous work we demonstrated a nonlinear relationship between hemoglobin concentration and oxygenation, and neuronal spiking and synaptic electrical activity in rat somatosensory (Barrel) cortex. In this proposal we will extend our study to the cerebellar cortex in order to investigate whether the same general rules can be applied to neurovascular coupling in both structures. While the main focus of this proposal is on the cerebellum, we will in parallel continue and expand our previous work in Barrel cortex to facilitate the comparison between the two (2). We will perform simultaneous optical measurements of hemodynamic signals (blood flow, volume, oxygenation) and electrophysiological measurements of neuronal activity, and will use an empirically developed relationship to construct a """"""""transfer function"""""""" of neurovascular coupling. Despite fundamental differences in neuronal and vascular organization between cerebral and cerebellar cortices we hypothesize a conservation of the main principles of coupling when taking into account the sum activity of Purkinje and granule cells, and differentiating the contribution of simple and complex spikes. The combination of optical imaging techniques and """"""""gold standard"""""""" electrophysiology not only provides a tool for correlation of hemodynamic and neuronal signals, but also enables better spatio-temporal estimation of brain activity. Thus, in addition to addressing the question of neurovascular coupling, we will study key questions of cerebellar physiology centered around the influence of parallel fibers on spatial extend of cerebellar cortical activation. Investigations proposed here will provide essential information to bridge the gap between the growing body of fMRI data and generations of detailed electrophysiological studies in cerebrum and cerebellum. Ultimately, accurate interpretation of imaging data in terms of neuronal activity will play an important role in the early detection, diagnosis and treatment of human disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Golanov, Eugene V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Sridhar, Vishnu B; Tian, Peifang; Dale, Anders M et al. (2014) Neurovascular Network Explorer 1.0: a database of 2-photon single-vessel diameter measurements with MATLAB(®) graphical user interface. Front Neuroinform 8:56
Gratiy, Sergey L; Pettersen, Klas H; Einevoll, Gaute T et al. (2013) Pitfalls in the interpretation of multielectrode data: on the infeasibility of the neuronal current-source monopoles. J Neurophysiol 109:1681-2
Nizar, Krystal; Uhlirova, Hana; Tian, Peifang et al. (2013) In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase. J Neurosci 33:8411-22
Reznichenko, Lidia; Cheng, Qun; Nizar, Krystal et al. (2012) In vivo alterations in calcium buffering capacity in transgenic mouse model of synucleinopathy. J Neurosci 32:9992-8
Devor, Anna; Sakadzic, Sava; Srinivasan, Vivek J et al. (2012) Frontiers in optical imaging of cerebral blood flow and metabolism. J Cereb Blood Flow Metab 32:1259-76
Tian, Peifang; Devor, Anna; Sakadzi?, Sava et al. (2011) Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain. J Biomed Opt 16:016006
Devor, Anna; Sakadzic, Sava; Saisan, Payam A et al. (2011) ""Overshoot"" of O? is required to maintain baseline tissue oxygenation at locations distal to blood vessels. J Neurosci 31:13676-81
Tian, Peifang; Teng, Ivan C; May, Larry D et al. (2010) Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal. Proc Natl Acad Sci U S A 107:15246-51
Sakadzi?, Sava; Roussakis, Emmanuel; Yaseen, Mohammad A et al. (2010) Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue. Nat Methods 7:755-9
Yucel, Meryem A; Devor, Anna; Akin, Ata et al. (2009) The Possible Role of CO(2) in Producing A Post-Stimulus CBF and BOLD Undershoot. Front Neuroenergetics 1:7

Showing the most recent 10 out of 23 publications