Intracardiac pathways mediating the parasympathetic control of various cardiac functions are incompletely understood. Several intracardiac ganglia have been demonstrated to potently influence cardiac rate [the sinoatrial (SA) ganglion], atrioventricular (AV) conduction (the AV ganglion), or left ventricular contractility (the cranioventricular ganglion). However, there are numerous ganglia found throughout the heart whose functions are poorly characterized. One such ganglion, the posterior atrial (PA) ganglion, is found in a fat pad on the rostral dorsal surface of the right atrium. We have investigated the potential impact of this ganglion on cardiac rate and AV conduction. We report that microinjections of a ganglionic blocker into the PA ganglion significantly attenuates the negative chronotropic effects of vagal stimulation without significantly influencing negative dromotropic effects. Because prior evidence indicates that the PA ganglion does not project to the SA node, we neuroanatomically tested the hypothesis that the PA ganglion mediates its effect on cardiac rate through an interganglionic projection to the SA ganglion. Subsequent to micro-injections of the retrograde tracer fast blue into the SA ganglion, >70% of the retrogradely labeled neurons found within five intracardiac ganglia throughout the heart were observed in the PA ganglion. The neuroanatomic data further indicate that intraganglionic neuronal circuits are found within the SA ganglion. The present data support the hypothesis that two interacting cardiac centers, i.e., the SA and PA ganglia, mediate the peripheral parasympathetic control of cardiac rate. These data further support the emerging concept of an intrinsic cardiac nervous system.

Path integration is a navigational process that humans and animals use to track changes in their position and orientation. Animal and computational studies suggest that a spatially-tuned navigation system supports path integration, yet this system is not well understood in humans. Here, the prediction was tested that path integration mechanisms and goal-directed navigation in humans would recruit the same key brain regions within the parietal cortex and medial temporal lobes as predicted by animal and computational models. The three experiments described in this dissertation used behavioral and functional magnetic resonance imaging methods in 131 adults (18-35 years) to examine behavioral and brain correlates of navigation. In a landmark-free environment, path integration mechanisms are utilized to update position and orientation to a goal. Experiment 1 examined neural correlates of these mechanisms in the human brain. The results demonstrated that successful first and third person perspective navigation recruited the anterior hippocampus. The posterior hippocampus was found to track distance and temporal proximity to a goal location. The retrosplenial and posterior parietal cortices were additionally recruited for successful goal-directed navigation. In a landmark-rich environment, humans utilize route-based strategies to triangulate between their position, landmarks, and navigational goal. Experiment 2 contrasted path integration and landmark-based strategies by adding a solitary landmark to a sparse environment. The results demonstrated that successful navigation with and without an orienting landmark recruited the anterior hippocampus. Activity in the bilateral posterior hippocampus was modulated by larger triangulation between current position, landmark, and goal location during first person perspective navigation. The caudate nucleus was additionally recruited for landmark-based navigation. Experiment 3 used functional connectivity methods coupled with two fMRI tasks to determine whether areas responsive to optic flow, specifically V3A, V6, and the human motion complex (hMT+), are functionally connected to brain regions recruited during first person perspective navigation. The results demonstrated a functional relationship between optic flow areas and navigationally responsive regions, including the hippocampus, retrosplenial, posterior parietal, and medial prefrontal cortices. These studies demonstrate that goal-directed navigation is reliant upon a navigational system supported by hippocampal position computations and orientation calculations from the retrosplenial and posterior parietal cortices.

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It is well documented that adolescent substance use is associated with deficits in brain function and behavior. However, possible deficits that predate substance use initiation remain poorly characterized in preadolescents at-risk for developing substance use disorder (SUD). To characterize potential brain and behavioral differences that predate substance use, substance naïve preadolescents, ages 11–12, were recruited into three groups to complete functional magnetic resonance imaging delay discounting: (1) High-risk youth (n=35) with a family history of SUD and externalizing psychiatric disorders, (2) psychiatric controls (n=35) with no family history of SUD, but equivalent externalizing psychiatric disorders as high-risk youth, and (3) healthy controls (n=29) with no family history of SUD and minimal psychopathology. While no behavioral differences between groups were identified, there were group differences in posterior cingulate cortex (PCC) function during decision making. Specifically, the high-risk group showed stronger deactivation of the PCC than healthy controls. These results suggest that high-risk preadolescents may need to suppress activity of key nodes of the default mode network (a task negative network) to a greater extent to properly allocate attention to the task.

Indiana University-Purdue University Indianapolis (IUPUI) / It is well documented that adolescent substance use is associated with deficits in brain function and behavior. However, possible deficits that predate substance use initiation remain poorly characterized in preadolescents at-risk for developing substance use disorder (SUD). To characterize potential brain and behavioral differences that predate substance use, substance naïve preadolescents, ages 11–12, were recruited into three groups to complete functional magnetic resonance imaging delay discounting: (1) High-risk youth (n=35) with a family history of SUD and externalizing psychiatric disorders, (2) psychiatric controls (n=35) with no family history of SUD, but equivalent externalizing psychiatric disorders as high-risk youth, and (3) healthy controls (n=29) with no family history of SUD and minimal psychopathology. While no behavioral differences between groups were identified, there were group differences in posterior cingulate cortex (PCC) function during decision making. Specifically, the high-risk group showed stronger deactivation of the PCC than healthy controls. These results suggest that high-risk preadolescents may need to suppress activity of key nodes of the default mode network (a task negative network) to a greater extent to properly allocate attention to the task.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12817号 / 論医博第2079号 / 新制||医||1004(附属図書館) / 31304 / 京都大学大学院医学研究科脳統御医科学系専攻 / (主査)教授 河野 憲二, 教授 金子 武嗣, 教授 大森 治紀 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18854号 / 医博第3965号 / 新制||医||1007(附属図書館) / 31805 / 京都大学大学院医学研究科医学専攻 / (主査)教授 古川 壽亮, 教授 髙橋 良輔, 教授 富樫 かおり / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Final publication is available at http://dx.doi.org/10.1111/ejn.12882 / 京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13040号 / 論医博第2115号 / 新制||医||1017(附属図書館) / 33032 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 影山 龍一郎, 教授 髙橋 良輔 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第21042号 / 人健博第58号 / 新制||人健||4(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 坪山 直生, 教授 黒木 裕士, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21674号 / 医博第4480号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 安達 泰治, 教授 黒田 知宏, 教授 戸口田 淳也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM