Combining optogenetic stimulation and fMRI to validate a multivariate dynamical systems model for estimating causal brain interactions.

State-space multivariate dynamical systems (MDS) (Ryali et al. 2011) and other causal estimation models are being increasingly used to identify directed functional interactions between brain regions. However, the validity and accuracy of such methods are poorly understood. Performance evaluation based on computer simulations of small artificial causal networks can address this problem to some extent, but they often involve simplifying assumptions that reduce biological validity of the resulting data. Here, we use a novel approach taking advantage of recently developed optogenetic fMRI (ofMRI) techniques to selectively stimulate brain regions while simultaneously recording high-resolution whole-brain fMRI data. ofMRI allows for a more direct investigation of causal influences from the stimulated site to brain regions activated downstream and is therefore ideal for evaluating causal estimation methods in vivo. We used ofMRI to investigate whether MDS models for fMRI can accurately estimate causal functional interactions between brain regions. Two cohorts of ofMRI data were acquired, one at Stanford University and the University of California Los Angeles (Cohort 1) and the other at the University of North Carolina Chapel Hill (Cohort 2). In each cohort, optical stimulation was delivered to the right primary motor cortex (M1). General linear model analysis revealed prominent downstream thalamic activation in Cohort 1, and caudate-putamen (CPu) activation in Cohort 2. MDS accurately estimated causal interactions from M1 to thalamus and from M1 to CPu in Cohort 1 and Cohort 2, respectively. As predicted, no causal influences were found in the reverse direction. Additional control analyses demonstrated the specificity of causal interactions between stimulated and target sites. Our findings suggest that MDS state-space models can accurately and reliably estimate causal interactions in ofMRI data and further validate their use for estimating causal interactions in fMRI. More generally, our study demonstrates that the combined use of optogenetics and fMRI provides a powerful new tool for evaluating computational methods designed to estimate causal interactions between distributed brain regions.

Rescue of cortical neurovascular functions during the hyperacute phase of ischemia by peripheral sensory stimulation.

To investigate the potential therapeutic effects of peripheral sensory stimulation during the hyperacute phase of stroke, the present study utilized electrophysiology and photoacoustic imaging techniques to evaluate neural and vascular responses of the rat cortex following ischemic insult. We employed a rat model of photothrombotic ischemia (PTI), which targeted the forelimb region of the primary somatosensory cortex (S1FL), due to its high reproducibility in creating localized ischemic injury. We also established a hybrid, dual-modality system, including six-channel electrocorticography (ECoG) and functional photoacoustic microscopy (fPAM), termed ECoG-fPAM, to image brain functional responses to peripheral sensory stimulation during the hyperacute phase of PTI. Our results showed that the evoked cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) recovered to 84±7.4% and 79±6.2% of the baseline, respectively, when stimulation was delivered within 2.5 h following PTI induction. Moreover, neural activity significantly recovered, with 77±8.6%, 76±5.3% and 89±8.2% recovery for the resting-state inter-hemispheric coherence, alpha-to-delta ratio (ADR) and somatosensory evoked potential (SSEP), respectively. Additionally, we integrated the CBV or SO2 with ADR values as a recovery indicator (RI) to assess functional recovery after PTI. The RI indicated that 80±4.2% of neurovascular function was preserved when stimulation was delivered within 2.5h. Additionally, stimulation treatment within this optimal time window resulted in a minimal infarct volume in the ischemic hemisphere (4.6±2.1%). In contrast, the infarct volume comprised 13.7±1.7% of the ischemic hemisphere when no stimulation treatment was applied.

FMRI of deep brain stimulation at the rat ventral posteromedial thalamus.

BACKGROUND: Functional magnetic resonance imaging (fMRI) of deep brain stimulation (DBS) has potentials to reveal neuroanatomical connectivity of a specific brain region in vivo. OBJECTIVE: This study aimed to demonstrate frequency and amplitude tunings of the thalamocortical tract using DBS fMRI at the rat ventral posteromedial thalamus. METHODS: Blood oxygenation level dependent (BOLD) fMRI data were acquired in a total of twelve rats at a high-field 11.7 T MRI scanner with modulation of nine stimulus frequencies (1-40 Hz) and seven stimulus amplitudes (0.2-3.6 mA). RESULTS: BOLD response in the barrel cortex peaked at 25 Hz. The response increased with stimulus amplitude and reached a plateau at 1 mA. Cortical spreading depolarization (CSD) was observed occasionally after DBS that carries >10% BOLD waves spanning the entire ipsilateral cortex. CONCLUSION: fMRI is sensitive to the frequency effect of DBS and has potential to investigate the function of a particular neuroanatomical pathway.