Frequency-dependent neural activity, CBF, and BOLD fMRI to somatosensory stimuli in isoflurane-anesthetized rats

Abstract

Inhalation anesthetics (e.g. isoflurane) are preferable for longitudinal fMRI experiments in the same animals. We previously implemented isoflurane anesthesia for rodent forepaw stimulation studies, and optimized the stimulus parameters with short stimuli (1-3 s long stimulation with ten electric pulses). These parameters, however, may not be applicable for long periods of stimulation because repetitive stimuli induce neural adaptation. Here we evaluated frequency-dependent responses (pulse width of 1.0 ms and current of 1.5 mA) for 30-s long stimulation under 1.3-1.5% isoflurane anesthesia. The cerebral blood flow (CBF) response (using laser Doppler flowmetry: CBF LDF ) and field potential (FP) changes were simultaneously measured for nine stimulus frequencies (1-24 Hz). CBF (using arterial spin labeling: CBF ASL ) and blood oxygenation level dependent (BOLD) fMRI responses were measured at 9.4 T for four stimulus frequencies (1.5-12 Hz). Higher stimulus frequencies (12-24 Hz) produced a larger FP per unit time initially, but decreased more rapidly later due to neural adaptation effects. On the other hand, lower stimulus frequencies (1-3 Hz) induced smaller, but sustained FP activities over the entire stimulus period. Similar frequency-dependencies were observed in CBF LDF , CBF ASL and BOLD responses. A linear relationship between FP and CBF LDF was observed for all stimulus frequencies. Stimulation frequency for the maximal cumulative neural and hemodynamic changes is dependent on stimulus duration; 8-12 Hz for short stimulus durations (< 10 s) and 6-8 Hz for 30-s stimulation. Our findings suggest that neural adaptation should be considered in determining the somatosensory stimulation frequency and duration under isoflurane anesthesia.

Water diffusion in brain cortex closely tracks underlying neuronal activity

“…2). However, within blocks, the LFPs showed a sharp decrease after the stimulation onset, a neuronal adaptation effect (21,26), which the DfMRI signal was precisely able to pick up. On the contrary, the hemodynamic response did not show this neural adaptation effect as clearly, the response lagging after its onset, in agreement with previous studies (26,27).…”

“…Next we investigated the frequency dependence of BOLD and DfMRI responses to electrical stimulation under 1.5% isoflurane anesthesia as the neural adaptation is known to depend upon the stimulation frequency (21). Four frequencies (3, 7, 10, and 13 Hz) were used, whereas the other parameters of the electrical stimulation were fixed.…”

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

“…These human and animal studies suggest that the mismatch ratio and general glucose metabolism may depend on many criteria such as: age of the subject (Kalpouzos et al, 2009;Nelhig, 1997), brain regions, methodology, stimulus frequency (Vafaee and Gjedde, 2000;Vafaee et al, 1999) and duration (Herman et al, 2009;Mintun et al, 2002), basal metabolic status (Shen et al, 2008;Sicard and Duong, 2005) and the use of anesthesia (Austin et al, 2005;Dienel, 2012;Kim et al, 2010). Finally, (Dienel, 2012) reviewed that different stimulus paradigm increase CMR Glc with different rates.…”

Imaging Neurovascular Function and Functional Recovery after Stroke in the Rat Striatum Using Forepaw Stimulation

“…Robust and repeatable fMRI responses have been shown in the primary somatosensory cortex (S1) in well-ventilated rats under isoflurane anesthesia. [13][14][15] Whether the aforementioned negative striatal fMRI response can be observed under isoflurane anesthesia remain unknown. The ability to do so could have long-term applications to assess striatal function during disease progression as well as monitor treatment effects in vivo.…”