Randy Summers

Motor Area Activity During Mental Rotation Studied by Time-Resolved Single-Trial fMRI

The functional equivalence of overt movements and dynamic imagery is of fundamental importance in neuroscience. Here, we investigated the participation of the neocortical motor areas in a classic task of dynamic imagery, Shepard and Metzlers mental rotation task, by time-resolved single-trial functional Magnetic Resonance Imaging (fMRI). The subjects performed the mental-rotation task 16 times, each time with different object pairs. Functional images were acquired for each pair separately, and the onset times and widths of the activation peaks in each area of interest were compared to the response times. We found a bilateral involvement of the superior parietal lobule, lateral premotor area, and supplementary motor area in all subjects; we found, furthermore, that those areas likely participate in the very act of mental rotation. We also found an activation in the left primary motor cortex, which seemed to be associated with the right-hand button press at the end of the task period.

Neuronal damage after hypothermic circulatory arrest and retrograde cerebral perfusion in the pig.

BACKGROUND Antegrade and retrograde cerebral perfusion during hypothermic circulatory arrest (HCA) has been reported to provide better brain protection during operation than hypothermic circulatory arrest alone. However, the efficacy of these techniques remains to be fully determined, especially when used for prolonged periods. We used a pig model to evaluate the histopathologic consequences of HCA and the potential benefit of cerebral perfusion during HCA. METHODS Twenty-two pigs were divided into four groups and exposed to either anesthesia alone, 120 minutes of HCA (15 degrees C), 120 minutes of retrograde cerebral perfusion at 15 degrees C during HCA, or 120 minutes of antegrade cerebral perfusion at 15 degrees C during HCA, and then reperfused for 60 minutes under cardiopulmonary bypass at 37 degrees C. The brains were perfusion fixed at the end of the experiments and examined by light microscopy. RESULTS There were no morphologic changes in any areas of the brains in the anesthesia group, and very minor changes in some areas of the brains in the antegrade cerebral perfusion. group. Varying severity of neuronal damage was found in the brains of all the pigs in the HCA and retrograde cerebral perfusion groups. The severity of ischemic damage in the brain showed the following descending order: hippocampus (CA4), caudate nucleus, cerebral cortex, putamen, thalamus, Purkinje cells of the cerebellum, pons, and mesencephalic gray matter. In the hippocampus the order of damage was CA4, CA3, polymorphous layer of the dentate gyrus, prosubiculum, CA2, CA1, and granule cell layer of the dentate gyrus. The damage in the retrograde cerebral perfusion group was less severe relative to the HCA group in many areas (no significance except mesencephalic gray matter). CONCLUSIONS These results demonstrate that the pattern of neuronal damage in pigs subjected to HCA and retrograde cerebral perfusion differs from the traditional pattern in that the caudate nucleus and hippocampal CA4 region are the most vulnerable to ischemia-hypoxia. Our results also suggest that antegrade cerebral perfusion prevented ischemic damage to the brain and retrograde cerebral perfusion provided some protection but moderately severe damage occurred.

A Vaccination Model for Transmission Dynamics of Influenza

Despite the availability of preventive vaccines and public health vaccination programs, influenza inflicts substantial morbidity, mortality, and socio-economic costs and remains a major public heal...

A 31P-magnetic resonance study of antegrade and retrograde cerebral perfusion during aortic arch surgery in pigs

To evaluate the effect of hypothermic circulatory arrest on brain metabolism, we used 31P-magnetic resonance spectroscopy to monitor brain metabolites in pigs during 2 hours of ischemia and 1 hour of reperfusion. Twenty-eight pigs were divided into five groups. Anesthesia (n = 5) and hypothermic cardiopulmonary bypass groups (n = 5) served as controls. In the circulatory arrest (n = 6), antegrade perfusion (n = 6), and retrograde (n = 6) brain perfusion groups, the bypass flow rate was 60 to 100 ml.kg-1.min-1. In the antegrade group, the brain was perfused via the carotid arteries at a blood flow rate of 180 to 200 ml.min-1 during circulatory arrest at 15 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml.min-1 during circulatory arrest at 15 degrees C. The intracellular pH was 7.1 +/- 0.1 and 7.3 +/- 0.1 in the anesthesia and hypothermic cardiopulmonary bypass groups, respectively. In the circulatory arrest group, the intracellular pH decreased to 6.2 +/- 0.1 and did not recover to its initial value (7.0 +/- 0.1) during reperfusion (p < 0.05 compared with the value obtained from the control groups at the corresponding time). Inorganic phosphate did not return to its initial level during reperfusion. In three animals in this group, levels of high-energy phosphates, adenosine triphosphate and phosphocreatine, recovered partially but did not reach the levels observed before arrest. In the group receiving antegrade perfusion, cerebral metabolites and intracellular pH were unchanged throughout the protocol. During circulatory arrest in the retrograde perfusion group the intracellular pH decreased to 6.4 +/- 0.1 and recovered fully during reperfusion (7.1 +/- 0.1). High-energy phosphates also returned to their initial levels during reperfusion. These studies show that deep hypothermic circulatory arrest with antegrade brain perfusion provides the best brain protection of the options investigated.

Retrograde cerebral perfusion provides limited distribution of blood to the brain: A study in pigs

OBJECTIVE The objective of this study was to investigate flow distribution during retrograde and antegrade cerebral perfusion with India ink as a marker. METHODS Ten pigs received cerebral perfusion with a solution containing 50% filtered India ink for 5 minutes either antegradely through both internal carotid arteries at a flow of 180 to 200 ml/min (n = 5) or retrogradely via the superior vena cava at a flow of 300 to 500 ml/min (n = 5). The brains were then fixed for quantitative measurement of the density of ink-filled capillaries (reported as a percentage of the total selected area). The assessment was done with the use of an in-house software program. RESULTS In the antegrade cerebral perfusion group, the intracranial arterial and venous systems were completely filled with ink. The gray matter was colored uniformly black, and light coloring was observed in the white matter. During retrograde cerebral perfusion, the majority of ink was returned to the inferior vena cava, and only a small amount of ink was found in the innominate artery draining from the brain. Massive ink filling was observed in the sagittal sinus and other venous sinuses in all the pigs. Vessels on the surface of the brain and large vessels in the brain were also well filled with ink. However, only 10% of capillaries were filled with ink during retrograde cerebral perfusion relative to the number observed with antegrade cerebral perfusion. CONCLUSIONS Retrograde cerebral perfusion supplies a limited amount of blood to brain tissue, which flows mainly through superficial and large deep cerebral vessels.

Functional MRI involving painful stimulation of the ankle and the effect of physiotherapy joint mobilization

We examined whether cerebral activation due to secondary hyperalgesia resulting from intrajoint capsaicin injection could be detected using functional magnetic resonance imaging (fMRI) in alpha-chloralose anesthetized rats. We also examined whether we could detect analgesic changes in the central nervous system response to pain as a result of physiotherapy joint manipulation. Robust activation of areas of the brain known to be associated with the processing of pain, namely the anterior cingulate (bilateral), frontal cortex (bilateral) and sensory motor cortex (contralateral), was found in all animals following injection of 25 microl of capsaicin (128 microg/ml in 7.5% DMSO) into the plantar surface of the rat hindpaw (n = 7) and 75 microL into the ankle joint (n = 13). Significantly greater activation was observed when capsaicin was injected into the plantar surface of the hindpaw compared to the ankle joint. Mechanical allodynia and secondary hyperalgesia following capsaicin injection into the ankle joint also resulted in activation of the same brain regions. Trends toward decreased areas of activation in brain regions associated with pain in animals following physiotherapy joint mobilization were observed.

ASSESSMENT OF CLUSTER HOMOGENEITY IN fMRI DATA USING KENDALL'S COEFFICIENT OF CONCORDANCE

In fMRI both model-led and exploratory data-driven methods are used to identify groups of voxels according to their correlation either with an external reference or with some similarity measure. Here we present a technique to assess intragroup homogeneity using Kendalls coefficient of concordance W once groups have been identified. We show that the time-courses belonging to the group may be ranked according to their contribution to the overall concordance and describe an algorithm for group purification. We suggest the use of W as a cluster validation index in exploratory data analysis approaches, such as fuzzy or hard clustering, principal component analysis, independent component analysis and Kohonen maps.

Cerebral protection during moderate hypothermic circulatory arrest: Histopathology and magnetic resonance spectroscopy of brain energetics and intracellular pH in pigs☆☆☆★★★♢

OBJECTIVE We evaluated the effect of antegrade and retrograde brain perfusion during moderate hypothermic circulatory arrest at 28 degrees C. METHODS Phosphorus 31-magnetic resonance spectroscopy was used to follow brain energy metabolites and intracellular pH in pigs during 2 hours of ischemia and 1 hour of reperfusion. Histopathologic analysis of brain tissue fixed at the end of the experimental protocol was performed. Fourteen pigs were divided into two experimental groups subjected to antegrade (n = 6) or retrograde (n = 8) brain perfusion. Anesthesia (n = 8) and hypothermic cardiopulmonary bypass groups (15 degrees C, n = 8) served as control subjects. In the antegrade and retrograde brain perfusion groups, the initial bypass flow rate was 60 to 100 ml x kg(-1) x min(-1). In the antegrade group, the brain was perfused through the carotid arteries at a flow rate of 180 to 210 ml x min(-1) during circulatory arrest at 28 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml x min(-1) during circulatory arrest at 28 degrees C. RESULTS The intracellular pH was 7.1 +/- 0.1 and 7.2 +/- 0.1 in the anesthesia and hypothermic bypass groups, respectively. Brain intracellular pH and high-energy metabolites (adenosine triphosphate, phosphocreatine) did not change during the course of the 3.5-hour study. In the antegrade group, adenosine triphosphate and intracellular pH were unchanged throughout the protocol. In the retrograde perfusion group, the intracellular pH level decreased to 6.4 +/- 0.1, and adenosine triphosphate and phosphocreatine levels decreased within the first 30 minutes of circulatory arrest and remained at low levels until the end of reperfusion. High-energy phosphates did not return to their initial levels during reperfusion. Histopathologic analysis of nine regions of the brain showed good preservation of cell structure in the anesthesia, hypothermic bypass, and antegrade perfusion groups. The retrograde perfusion group showed changes in all the regions examined. CONCLUSIONS The study shows that moderate hypothermic circulatory arrest at 28 degrees C with antegrade brain perfusion during circulatory arrest protects the brain but that retrograde cerebral perfusion at 28 degrees C does not protect the brain.

Increased pressure during retrograde cerebral perfusion in an acute porcine model improves brain tissue perfusion without increase in tissue edema.

BACKGROUND There is a significant lack of scientific data to support the clinically accepted view that 25 to 30 mm Hg is the maximum safe perfusion pressure during retrograde cerebral perfusion (RCP). This study was designed to investigate whether perfusion pressure greater than 30 mm Hg during RCP is beneficial to the brain during prolonged HCA in an acute porcine model. METHODS Sixteen pigs underwent 120 minutes of circulatory arrest in conjunction with RCP at a perfusion pressure of either 23 to 29 mm Hg (group L, n = 8) or 34 to 40 mm Hg (group H, n = 8) at 15 degrees C, followed by 60 minutes of normothermic cardiopulmonary bypass. Cortical blood flow and oxygenation were measured continuously with a laser flowmeter and near-infrared spectroscopy, respectively. Tissue water content was measured at the end of the experiments. RESULTS Brain tissue blood flow was significantly higher in group H than in group L (16.8% +/- 4.1% vs 4.8% +/- 0.9% of baseline, p < 0.01) during RCP. Brain oxygen extraction in group L reached a maximum (approximately 70%) immediately after starting RCP, whereas in group H it increased gradually and reached a maximum at 120 minutes of RCP, indicating a greater supply of oxygen to tissue in group H than in group L. After RCP, the ability of brain tissue to use oxygen was better preserved in group H than in group L, as indicated by tissue oxygen saturation and the deoxyhemoglobin level. There was no significant increase in tissue water content in either group (group H 79.2% +/- 0.3%, group L 79.1% +/- 0.4%) relative to normal control pigs (78.7% +/- 0.1%). CONCLUSIONS In this acute porcine model, increasing perfusion pressure from 23-29 to 34-40 mm Hg during RCP increases tissue blood flow and provides better tissue oxygenation, without increasing tissue edema. The optimal perfusion pressure for RCP needs to be further investigated.

A new technique of coronary artery ligation: Experimental myocardial infarction in rats in vivo with reduced mortality

In vivo models of myocardial infarction following coronary artery ligation in the rat still suffer from high early mortality and a low rate of success of myocardial infarction. This study investigated the possibility of reducing early mortality and increasing the rate of myocardial infarction by modifications of surgical techniques. Eighteen rats were divided into two groups: normal control (3 rats) and ligation (15 rats). The major modifications of surgical techniques used in this study include: (1) no exteriorization of the heart, (2) ligation of the origins of the branches rather than the main trunk of the left coronary artery, (3) removal of air from the chest after closure, (4) supplying oxygen immediately after extubation. Following surgery, the rats recovered uneventfully and 11 rats were alive after 16 weeks. One rat, with a large myocardial infarction, died 2 h after surgery. Early mortality (during surgery and 1 week after surgery) was 6.7% with a success rate of myocardial infarction of 85%. The left ventricle in the ligation group showed significant dilation relative to normal and sham-operated control hearts (317% of control hearts, p < 0.001). However, myocardial mass did not increase. The average infarct size was 33%. These results demonstrate that a reduction in early mortality and an increased success rate of myocardial infarction can be achieved by modifications of surgical techniques. (Mol Cell Biochem 176: 227-233, 1997)