Neuroimaging. The ability to perform brain imaging studies on acute stroke patients is vital for physicians to make a fast, accurate diagnosis of stroke patients. Brain imaging studies include CT scans. A Primary Stroke Center must be capable of performing an imaging study within twenty-five (25) minutes of a physician's order. The image shall be evaluated by a physician within twenty (20) minutes of completion.
Neuroimaging. Functional magnetic resonance imaging (fMRI) has been used since 1991 to measure hemodynamic responses in the brain (Xxxxx et al., 1992). Blood-oxygen-level-dependant (BOLD) contrast is used to visualize blood flow throughout the brain. An increase in neural activity causes a change in the ratio of deoxygenated hemoglobin to oxygenated hemoglobin, which is detected by the fMRI scanner. This process produces a T2* weighted image, which has poor spatial resolution. The T1-weighted image is collected by measuring the rate at which protons align and spin after being exposed to a magnetic pulse at a specific radio frequency (Damadian, Goldsmith, & Minkoff, 1977). This MRI image shows the detailed, anatomical structure of the brain, but does not show any functional activation. The two images are then superimposed and co-registered to better identify the locations of changes in BOLD signal from the T2* images using the anatomically detailed T1 image (further discussion in Methods section). Although BOLD signal should not be confused with the actual firing of neurons, several studies have shown similarities in function between areas implicated by fMRI and lesion studies (Gaillard et al., 2006; Menon & Xxxxxxx, 0000; Saygin, 2007). Voxel-based morphometry (VBM) is a method to measure grey matter volume using the T1 weighted MRI image. A voxel is a volumetric pixel that represents a value in 3D space. The images are first registered to a standard brain and smoothed to allow for comparison between subjects (Ashburner & Friston, 2000). Grey matter density is then compared across subjects (Ashburner & Friston, 2000). Neuroanatomical features are highly heritable, as demonstrated in twin studies (Xxxxxx, Sham, Murray, Weinberger, & Bullmore, 2002). Cooperative behavior could be motivated by the rewarding feeling of doing good for others or the negative feeling from non-cooperative behavior. How either of these motivations are processed in the brain is of interest to this study and can be illuminated when one considers the neural response to other rewarding or negative stimuli. Using fMRI and VBM, several brain structures have been implicated in reward processing. These structures include the medial orbitofrontal cortex (mOFC), amygdala, and nucleus accumbens (NAc), which are activated by rewards such as sexual activity and food (XxXxxxx, York, & Montague, 2004). Social rewards, such as beautiful faces (Aharon et al., 2001) and cooperation (Xxxxxxx et al., 2002), have be...
Neuroimaging. Two assessments will be needed for each animal: the first just prior to implantation of the Microbot device to determine the extent of ventriculomegaly and the second just prior to termination of the experiment to determine the effectiveness of the device. As described under “Animals”, fewer studies may be conducted if the objectives have been met. Furthermore, if ultrasonography can be shown to accurately determine the extent of ventriculomegaly then the CT scans will not be needed. However, if CT scans are needed, then transportation and veterinary care expenses will be incurred as required by the IACUC protocol.
Neuroimaging. Neuroimaging techniques have added to our knowledge of which brain structures are active during the experience of nocebo effects. Again studies in the pain field have tended to show that nocebo effects are mediated by the hippocampus and regions involved in anticipatory anxiety processing. Xxxx et al. (2008) compared functional magnetic resonance imaging responses following thermal stimuli of equal intensity delivered at control sites or at nocebo sites (where participants were conditioned or told to expect pain) on participants’ right forearms. Increased pain reports for the nocebo sites were associated with increased activity in the medial pain matrix, which included the bilateral dorsal anterior cingulate cortex, insula, left frontal and parietal operculum, orbitofrontal cortex, and hippocampus. In a subsequent study that investigated the influence of expectancy on the analgesic effect of remifentanil, Xxxxxx et al. (2011) found that positive expectancy effects were associated with activity in the endogenous pain modulatory system, and negative expectancy effects with activity in the hippocampus, suggesting different mechanisms underlying placebo and nocebo effects. However Xxxxx et al. (2008) found an overlapping network. In this study, placebo responding to a 20 minute pain challenge was associated with enhanced opioid neurotransmission in the anterior cingulate, orbitofrontal and insular cortex, nucleus accumbens, amygdala, and periaqueductal gray, as well as DA in the ventral basal ganglia, including the nucleus accumbens. Nocebo responding was associated with the opposite changes in brain activity: a decrease of DA, and decreased opioid release in those brain regions. Endogenous opioids and DA have also been identified as neurochemical systems involved in nocebo responses (Xxxxxx, Xxxxxxx, & Xxxxxxxx, 2016), as highlighted previously. Studies that directly compare the placebo and nocebo effects using the same cohort of subjects may help provide a general model of how different expectancies can modulate brain responses. Xxxxxxx et al. (2015) manipulated subjects' treatment expectation of the effectiveness of different inert creams administered before noxious stimuli and found that the expectation of an increase in pain induced significant activity in the insula, orbitofrontal cortex, and periaqueductal gray, whereas the expectation of pain relief evoked significant activity in the striatum. There were no brain regions which were common to both posit...
