Many studies of ‘executive control’ have focused on the prefrontal cortex (PFC), which contains the neuronal functional properties, modulatory neurotransmitters, and network connections with sensory and motor regions to make this large brain area a candidate region to provide all the necessary elements to voluntarily control behavior. However, like the motor and premotor cortex, the PFC is integrated with the basal ganglia (BG) in such a similar fashion, that it is impossible not to consider that the PFC might depend on the BG to implement executive control effectively. This thesis draws on knowledge of PFC and BG function, and combines studies that require the instantaneous top-down control over motor behavior with a neurological patient group with primarily BG dysfunction (Parkinson’s disease), to provide for a new understanding of prefrontal-BG networks sub-serving executive control. The tasks performed by subjects consist of antisaccades (generate a voluntary eye-movement away from a visual stimulus) and those dealing with task switching (change behavior after an alternate was previously required). Numerous neural and functional imaging studies have identified key areas of the prefrontal cortex and BG that are critical to antisaccade generation, and studies in task switching have implicated similar neural mechanisms that are involved in overriding one behavior with another. By combining task switching with antisaccades, this thesis specifically examines the neural mechanisms related to suddenly changing behavior, under conditions where one behavior is easier to perform than the other. The methods utilize on-line eye-tracking in healthy young adults and older adults with, and without, Parkinson’s disease, to develop theories of a role of the BG in executive control, and to search for specific neural correlates of executive control signals in the PFC, premotor cortex and BG using functional magnetic resonance imaging (fMRI). Together, the conclusions drawn from this thesis point to an important role of the BG in overriding more automatic behavior with behavior that is more difficult to perform. This thesis also suggests that this overriding mechanism occurs through the boosting of cortical executive control signals via net excitatory feedback from the BG. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2010-09-09 12:17:46.904

Parkinson’s disease (PD) is a movement disorder that is of basal ganglia origin. It is characterized by a severe loss of dopaminergic input to the striatum and symptoms such as bradykinesia, rigidity and tremor. There is growing evidence that PD is associated with pathological synchronous oscillatory activity in the basal ganglia, which primarily occurs in the 11-30 Hz range, the so-called beta band. The aim of this project was to better understand the oscillatory activity recorded from the basal ganglia of PD patients and to elucidate the significance of this activity in PD. To do this, neuronal firing and local field potentials (LFPs) were recorded from the subthalamic nucleus (STN) and globus pallidus internus (GPi) of PD patients undergoing stereotactic neurosurgery for implantation of therapeutic deep brain stimulation electrodes. Beta oscillatory LFP activity in the STN and GPi was found to be coherent with, and reflect to a certain degree, rhythmic activity in a population of local neurons. I have demonstrated for the first time that the degree of beta oscillatory firing in the STN, which is maximal in the motor portion, correlates with the patients’ benefit from dopaminergic medications, but not with baseline motor deficits. My study has also established that beta oscillatory firing in the STN does not positively correlate with the patients’ tremor scores and that during periods of tremor patients tend to have less beta oscillatory firing and increased neuronal oscillatory firing at the tremor frequency. Temporal examination of the LFPs recorded during periods of intermittent resting tremor revealed that stronger tremor is associated with increased LFP power in the low gamma range (35-55 Hz) and there is a decrease in the ratio of beta to gamma coherence. Similarly, a change in balance between oscillatory activities was observed during levodopa-induced dyskinesias. Finally, when the oscillatory activity in the GPi of PD patients was compared to that in dystonia I found that in dystonia, oscillatory LFP activity is less likely to reflect the neuronal firing. These findings indicate that beta oscillatory activity in the basal ganglia might reflect the degree of dopamine deficiency in the striatum and that the relative strength of oscillatory rhythms may play an important role in mediating the pathological features in PD.

The American College of Sports Medicine (ACSM) currently recommends 1 set of 8 - 12 repetitions as the minimal dose of resistance training (RT) required to achieve the health and fitness benefits gained from RT. Yet, certain benefits derived from resistance training are not mentioned by the ACSM. An increase in basal metabolic rate (BMR) is a possible health benefit derived from RT. However, no previous studies have examined the effect of the ACSM's current resistance training recommendations on BMR. Therefore, the purpose of this study was to determine if this low level of RT could increase BMR in currently active older men. Sixteen subjects were assigned to either a training group or control group for 10 weeks of training. The training group continued their current aerobic activity while adding 1 set of RT 2x/week as recommended by the ACSM. The control group continued their aerobic activity with no modifications. Measurements of strength, fat free mass (FFM), and BMR were made pre- and posttraining. The training group showed an increase in strength (P<0.05) while the control group did not change. The training and control groups showed no change in FFM or BMR (P<0.05). The strength increases reported in the current study were of expected values while FFM and BMR have not been previously examined with this protocol. It was concluded that 10 weeks of RT using 1 set of 8 - 12 repetitions does not increase BMR in currently active older men. / School of Physical Education

The purpose of this thesis was to monitor body composition and energy expenditure changes during weight loss in subjects encouraged to maintain a diet equal to 90% of resting energy expenditure (REE). Over six months, 69 female subjects had REE measured at baseline and weeks 13 and 25 with fortnightly body composition measurements. Subjects lost significant total body mass (17.2 lb) and fat mass (16.7 lb) (p≤.000). Fat-free mass remained stable during the six month period. REE was significantly higher at baseline (1701.1 kcal) than weeks 13 (1576.3 kcal) and 25 (1579.4) (p≤.000); REE at weeks 13 and 25 were similar (p≥.05). Predicted REE at weeks 13 (1671.3 ± 254.7 kcal) and 25 (1658.5 ± 252.4 kcal), compared to measured REE, was significantly lower, 1576.3 kcal and 1579.4 kcal, respectively (p≤.000). Results of this study illustrate that individuals can lose significant amounts of total body mass while preserving fat-free mass and that during active weight loss, there is a metabolic adaptation to reduced caloric intake. / Department of Family and Consumer Sciences

Parkinson’s disease (PD) is characterized by the loss of dopamine in the basal ganglia and leads to paucity of movements, rigidity of the limbs, and rest tremor. Synaptic plasticity was characterized in the substantia nigra pars reticulata (SNr), a basal ganglia output structure, in 18 PD patients undergoing implantation of deep brain stimulating electrodes. Field evoked potentials (fEPs) in SNr were measured with one microelectrode using single pulses from a second microelectrode ~ 1 mm away. High frequency stimulation (HFS – 4 trains of 2s at 100Hz) in the SNr failed to induce a lasting change in test fEPs amplitudes in patients OFF medication. Following L-Dopa, HFS induced a potentiation of the fEPs that lasted more than 150s. Our findings suggest that extrastriatal dopamine modulates activity dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of PD.

Parkinson’s disease (PD) is accompanied by a significant amount of beta β-band (11Hz-30Hz) neuronal and local field potential (LFP) oscillatory activity in the subthalamic nucleus (STN). The aim of this study was to measure the spatial extent of β coherent activity in the STN and coherence between STN-SNr in PD patients OFF levodopa by systematically varying the vertical distance between two microelectrodes. We found significant β-LFP coherence across the dorsoventral extent of STN. Spatially extended beta LFP was positively correlated with the mUPDRS scores of the PD patients in the OFF state. Additionally, a significant coherence was found between β-LFPs in dorsal STN and dorsal SNr. These data suggest that the whole STN may be entrained within the β band in PD patients OFF meds. The finding of coherence between STN and SNr suggests that β oscillations synchronize both the input and output nuclei of the basal ganglia.

Parkinson’s disease (PD) is characterized by the loss of dopamine in the basal ganglia and leads to paucity of movements, rigidity of the limbs, and rest tremor. Synaptic plasticity was characterized in the substantia nigra pars reticulata (SNr), a basal ganglia output structure, in 18 PD patients undergoing implantation of deep brain stimulating electrodes. Field evoked potentials (fEPs) in SNr were measured with one microelectrode using single pulses from a second microelectrode ~ 1 mm away. High frequency stimulation (HFS – 4 trains of 2s at 100Hz) in the SNr failed to induce a lasting change in test fEPs amplitudes in patients OFF medication. Following L-Dopa, HFS induced a potentiation of the fEPs that lasted more than 150s. Our findings suggest that extrastriatal dopamine modulates activity dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of PD.

Parkinson’s disease (PD) is accompanied by a significant amount of beta β-band (11Hz-30Hz) neuronal and local field potential (LFP) oscillatory activity in the subthalamic nucleus (STN). The aim of this study was to measure the spatial extent of β coherent activity in the STN and coherence between STN-SNr in PD patients OFF levodopa by systematically varying the vertical distance between two microelectrodes. We found significant β-LFP coherence across the dorsoventral extent of STN. Spatially extended beta LFP was positively correlated with the mUPDRS scores of the PD patients in the OFF state. Additionally, a significant coherence was found between β-LFPs in dorsal STN and dorsal SNr. These data suggest that the whole STN may be entrained within the β band in PD patients OFF meds. The finding of coherence between STN and SNr suggests that β oscillations synchronize both the input and output nuclei of the basal ganglia.

No description available.

Cholinergic interneurons are relatively rare neurons in the rat striatum. These sparsely distributed neurons display a synchronous pause in their tonic firing pattern during reward-related learning. It has been hypothesised that a specialised fast-conducting crossed-corticostriatal pathway is involved in synchronising the pause in tonic firing of these interneurons. This study aimed to detail the innervation of cholinergic interneurons by mapping their proximal and distal inputs and to describe the innervation of the crossed-corticostriatal pathway in male Wistar rats. In vivo electrophysiological recording methods were used to label single crossed-corticostriatal neurons but inadequately labeled their axons. Thus, an anterograde neuronal tracing study was conducted. Biotinylated dextran amine (BDA; 1.2 [mu]l) was pressure-injected into the left cerebral hemisphere. Six days later, the rat was perfused-fixed and the brain sectioned. BDA-labelled axons were traced to both the ipsilateral and contralateral striata. Cholinergic interneurons in the right striatum were double-immunolabelled using an optimised protocol including a polyclonal rabbit anti-m2-muscarinic receptor antibody and a monoclonal goat anti-choline acetyltransferase antibody. All sections were processed for transmission electron microscopy. Serial ultrathin sections were montaged and distal (from non BDA-labelled tissue) and proximal synapses were each mapped separately. A reconstructed distal dendrite from a cholinergic interneuron, located 225 [mu]m from the soma, was analysed. It had an average width of 1 .25[mu]m and 0.726 synapses per [mu]m. This was compared to dendrites in the same tissue and from BDA-labelled tissue. Two dendrites were presumed to be distal profiles of either cholinergic or somatostatin interneurons, while the third was thought to belong to another interneuronal cell type. In terms of surface area, there were less somal synapses compared to those made onto the distal dendrite of the cholinergic interneuron. Somal synapse counts were similar to those reported previously from our laboratory, where symmetric synapses were most common. Crossed-corticostriatal BDA-labelled axons were found to course across proximal dendrites and somas of immunolabelled cholinergic interneurons. Varicosities from these axons were found in close proximity to proximal dendrites and somas of cholinergic interneurons. Of all cholinergic interneurons in an adjacent section, 77% showed closely associated proximal varicosities. Of these, 76% of varicosities were associated with the soma, 11% to proximal dendrites and 13% to both locations. Twenty-nine BDA-labeled axons were analysed using transmission electron microscopy. Most were observed making asymmetric synaptic contact with unlabelled spines. In two cases spines were traced to medium spiny projection neurons. Two axon segments were seen touching the proximal regions of separate cholinergic interneurons. At these contact sites interrupted membrane thickenings were observed. It is proposed here that synapses may form at these sites during reward-related learning. However labelling of the contact sites with a postsynaptic marker would be necessary to confirm their synaptic nature. The current study has gathered information about the distal and proximal innervation patterns of these neurons and described the termination pattern of the crossed-corticostriatal pathway in relation to these neurons for the first time. These findings support the crossed-corticostriatal pathway as one possible anatomical substrate for synchronising the pause response on both sides of the brain.