Synaptically activated burst-generating conductances may underlie a group-pacemaker mechanism for respiratory rhythm generation in mammals

Breathing, chewing, and walking are critical life-sustaining behaviors in mammals that consist essentially of simple rhythmic movements. Breathing movements in particular involve the diaphragm, thorax, and airways but emanate from a network in the lower brain stem. This network can be studied in reduced preparations in vitro and using simplified mathematical models that make testable predictions. An iterative approach that employs both in vitro and in silico models argues against canonical mechanisms for respiratory rhythm in neonatal rodents that involve reciprocal inhibition and pacemaker properties. We present an alternative model in which emergent network properties play a rhythmogenic role. Specifically, we show evidence that synaptically activated burst-generating conductances-which are only available in the context of network activity-engender robust periodic bursts in respiratory neurons. Because the cellular burst-generating mechanism is linked to network synaptic drive we dub this type of system a group pacemaker. © 2010 Elsevier B.V

The control of frequency of a conditional oscillator simultaneously subjected to multiple oscillatory inputs

A conditional oscillator is one that requires input to oscillate. An example of such is the gastric mill network of the stomatogastric ganglion of the crab Cancer borealis which requires modulatory input from outside the stomatogastric ganglion and fast input from the pyloric network of the animal in order to become active. This dissertation studies how the frequency of the gastric mill network is determined when it is simultaneously subjected to two different rhythmic inputs whose timing may be mismatched. We derive a mathematical model of the gastric mill network and deduce that the difference in timing between the pyloric and modulatory inputs is crucial in determining what effect it will have on the frequency of the gastric mill network. Over a certain range of the time mismatch, the pyloric input plays no role in determining the network frequency, while in another range of the time mismatch, both inputs work together to determine the frequency. The existence and stability of periodic solutions to the modeling set of equations are obtained analytically using geometric singular perturbation theory and an analytic approximation of the frequency is obtained. The results are validated through numerical simulations of the model and are shown to extend to a detailed Hodgkin-Huxley type compartmental model of the gastric mill network. Comparisons to experiments are also presented

Math Modeling of Interlimb Coordination in Cat Locomotion

Locomotion is an evolutionary adaptation that allows animals to move in 3-D space. The way that mammalian locomotion is controlled has been studied for generations. It remains unclear how the neuronal network that controls locomotion is structured and how the mammalian locomotor network keeps balance in the face of a changing environment. In this body of research, we build mathematical models of locomotion and fit our models to experimental data of walking cats to gain understanding of network connectivity and of balance control. Specifically, we test the biological plausibility of a particular connectivity of the mammalian locomotor network by matching network activity to phases of walking in different experimental conditions. We gain understanding of balance control with an inverted pendulum model that fits the center of mass oscillations during walking in different experimental conditions

Investigating profiles of attention and arousal in Autism Spectrum Condition (ASC)

The present doctoral project aimed to investigate profiles of arousal and attention in autistic individuals and identify how atypicalities in these relate with specific clinical symptoms of autism. I recruited children and young people between the ages of 7 and 15 years who were either neurotypical (n= 31) or had autism (n= 18). I included a clinical control group of children and young people with ADHD (n= 24) as well as those who had comorbid autism and ADHD (n= 33). I collected indices of arousal and attention by measuring heart rate, brain activity (using electrophysiology) and eye movements in response to experimental tasks requiring involuntary orienting of attention to auditory and visual stimuli, and also systematically manipulated characteristics of the stimuli used. I found that there were no group-level differences in arousal profiles related to autism; but rather, that participants with ADHD (with or without autism) exhibited profiles of sympathetic underarousal. Given the heterogeneity in arousal profiles due to presence of ADHD in autistic participants, and due to heterogeneity apparent in the arousal literature in autism, I investigated the presence of subgroups with different arousal profiles in the autistic sample. This revealed that autistic participants could be stratified into distinct subgroups who showed tonic hyper- and hypo-arousal. These subgroups presented with different clinical profiles, such that the hyper-aroused subgroup showed worse autism symptom severity and higher rates of anxiety and sensory avoidance behaviours; while the hypo-aroused subgroup showed higher rates of hyperactive and impulsive behaviours as well as more sensory-seeking behaviours. I also found that autistic participants demonstrated intact abilities to orient to and habituate to simple auditory and visual stimuli. However, autistic participants (without ADHD) showed atypicalities in their profile of orienting to stimuli with higher complexity. These atypicalities in attention were related with social interaction symptoms of autism. Further, these atypicalities appeared to relate with presence of tonic hyperarousal. I verified the atypicalities observed in orienting to more complex visual stimuli in an independent sample of neurotypical children (n= 64) and found that neurotypical children with higher levels of subclinical autistic traits showed similar atypicalities in orienting attention to more complex stimuli. The implications of these findings within the context of the literature on arousal and attention and recommendations for future research are discussed

Investigating profiles of attention and arousal in Autism Spectrum Condition (ASC)

The present doctoral project aimed to investigate profiles of arousal and attention in autistic individuals and identify how atypicalities in these relate with specific clinical symptoms of autism. I recruited children and young people between the ages of 7 and 15 years who were either neurotypical (n= 31) or had autism (n= 18). I included a clinical control group of children and young people with ADHD (n= 24) as well as those who had comorbid autism and ADHD (n= 33). I collected indices of arousal and attention by measuring heart rate, brain activity (using electrophysiology) and eye movements in response to experimental tasks requiring involuntary orienting of attention to auditory and visual stimuli, and also systematically manipulated characteristics of the stimuli used. I found that there were no group-level differences in arousal profiles related to autism; but rather, that participants with ADHD (with or without autism) exhibited profiles of sympathetic underarousal. Given the heterogeneity in arousal profiles due to presence of ADHD in autistic participants, and due to heterogeneity apparent in the arousal literature in autism, I investigated the presence of subgroups with different arousal profiles in the autistic sample. This revealed that autistic participants could be stratified into distinct subgroups who showed tonic hyper- and hypo-arousal. These subgroups presented with different clinical profiles, such that the hyper-aroused subgroup showed worse autism symptom severity and higher rates of anxiety and sensory avoidance behaviours; while the hypo-aroused subgroup showed higher rates of hyperactive and impulsive behaviours as well as more sensory-seeking behaviours. I also found that autistic participants demonstrated intact abilities to orient to and habituate to simple auditory and visual stimuli. However, autistic participants (without ADHD) showed atypicalities in their profile of orienting to stimuli with higher complexity. These atypicalities in attention were related with social interaction symptoms of autism. Further, these atypicalities appeared to relate with presence of tonic hyperarousal. I verified the atypicalities observed in orienting to more complex visual stimuli in an independent sample of neurotypical children (n= 64) and found that neurotypical children with higher levels of subclinical autistic traits showed similar atypicalities in orienting attention to more complex stimuli. The implications of these findings within the context of the literature on arousal and attention and recommendations for future research are discussed