Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli.

Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodynamic parameters but still allows enhanced neural responses to be reflected in enhanced haemodynamic responses. The current study investigated the possibility that for more intense stimuli, the raised background may produce a protracted attenuation of the haemodynamic response. Three experiments were performed to measure effects of i.v. cocaine administration (0.5 mg/kg) or saline on responses in rat barrel cortex to electrical stimulation of the whisker pad. The first experiment used optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) to measure haemodynamic changes. Cocaine caused an increase in baseline blood flow (peak approximately 90%), which lasted for the duration of the test period (25 min). Haemodynamic responses to whisker stimulation were substantially reduced throughout. The second experiment used a 16-channel multi-electrode to measure evoked potentials at 100 mum intervals through the barrel cortex. Summed neural responses (collapsed across the spatial dimension) after cocaine administration were similar to those after saline. The third experiment extended experiment 1 by examining the effects of cocaine on whisker sensory responses using functional magnetic resonance imaging (and concurrent OIS or LDF). Cocaine caused a similar increase in baseline and reduction in the evoked response to that seen in experiment 1. Together, the results of these three experiments show that cocaine produces a protracted decoupling of neural activity and haemodynamic responses to intense sensory stimulation, which suggests that imaging techniques based on changes in haemodynamic parameters may be unsuitable for studying the effects of cocaine on sensory processing in humans.

Design and initial evaluation of a low-cost 3-Tesla research system for combined optical and functional MR imaging with interventional capability.

A 3-Tesla research system has been developed for functional and interventional magnetic resonance imaging (MRI) procedures on animal models based on a low field niche spectrometer. Use of two stages of fourth harmonic frequency multiplication has allowed us to produce a high-frequency spectrometer with good frequency stability based on a low-frequency direct digital synthesizer. The system has been designed with the ability to introduce interventional tools such as biopsy needles, radiofrequency (RF) electrodes, and fiber optics for optical spectroscopy and thermal ablation as well as drug infusions to allow function to be studied in the presence of external challenges. Full MR-compatible physiologic support capability allows animals to be maintained in a stable condition over extended periods of study. Functional MR images have been acquired by using gradient echoes (TR/TE = 40/12 msec) from the rat whisker barrel cortex using electrical stimulation (5-V, 1.5-mA, 1-msec pulses at 5 Hz via two needle electrodes inserted into the rat whisker pad). Initial results using respiratory gas challenges of 100% N(2), 100% O(2), and 10% CO(2) have shown excellent agreement between single wavelength (633 nm) optical and functional MR time series with subsecond time resolution. The 1-mm copper electrodes for interventional radiofrequency ablation procedures were easily visualized in the superior colliculus by using gradient echo sequences. This novel, low-cost, high field system appears to be a useful research tool for functional and interventional studies of rat brain and allows concurrent optical spectroscopy. J. Magn. Reson. Imaging 2001;13:87-92.