Browsing by Subject "Neurophysiology"

Now showing 1 - 3 of 3
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    Decision making gone awry: Dorsal striatum, decision-making, and addiction
    (2015-02) Regier, Paul
    Millions of people use addictive substances, such as alcohol and cocaine, however only a subset of individuals become dependent on these types of substances. Addiction can be thought of as a maladaptive decision-making process, driven by distinct neural regions. As behavior shifts from goal-directed to habit-based behavior, control of this behavior by corticostriatal circuits shifts from the associative circuit, which includes the dorsomedial striatum, to the sensorimotor circuit, which includes dorsolateral striatum. Once behavior becomes more habit-based, and control shifts to the sensorimotor corticostriatal circuit, actions become difficult to devalue. Thus, behavior becomes difficult to change. In this dissertation, I explore a behavioral shift to habit-based behavior as one potential way addiction can occur. I focus on the dorsomedial and the dorsolateral striatum and the role of these two regions in goal-directed and habit-based behavior, respectively, and the role of these two regions in drug-seeking behavior. In addition, I discuss the dorsomedial and dorsolateral striatum in relation to animal models of drug addiction that differentially seek drugs, and I discuss these two regions as potential biomarkers of addiction treatment. Finally, I relate previous research as well as my own research, presented throughout the dissertation, to human drug use and consider how analogues of dorsal striatum in the human brain might play a role in human addiction and addiction treatment. In all, consideration of addiction as a maladaptive decision-making process as well as understanding the neural correlates of this process may help to generate new ways of perceiving, studying, and treating addiction.
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    Neural basis of context processing dysfunction in schizophrenia: a monkey model
    (2013-08) Blackman, Rachael Keir
    Ranking among the top ten causes of years lost due to disability worldwide, schizophrenia is a psychiatric disease whose pathophysiology has not been fully characterized to-date. The objective of my dissertation is to characterize the change in neuronal information processing that leads to cognitive dysfunction in the disease. To this end, I trained monkeys to perform a translational cognitive task that measures context processing deficits in schizophrenia patients. Context processing is the ability to use prior contextual information maintained in working memory to conditionally respond to subsequent stimuli. I then recorded neural activity from the prefrontal (PFC) and posterior parietal (PAR) cortex after administering N-methyl-D-aspartate (NMDA) receptor antagonists that 1) are known to mimic symptoms of schizophrenia in human control subjects, and 2) block the NMDA receptor which is thought to be dysfunctional in the disease. I found that after drug administration, monkeys produced essentially the same pattern of behavioral errors on this task that schizophrenia patients commit. Further, by recording neural activity in PFC and PAR during the period of cognitive impairment, I was able to determine that the maintenance of contextual information in PFC was selectively diminished. In addition, I was able to use trial-by-trial changes in neural activity in both cortical areas to predict errors on the task, linking neuronal activity to behavioral performance. Overall, I have been able to characterize for the first time the change in cortical information processing at a cellular level that could account for context processing dysfunction in schizophrenia.
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    Neurophysiology and Neuromodulation: Incorporating Task Training to Harness Cerebellar Neuroplasticity in Rehabilitation
    (2018-12) Summers, Rebekah
    Dystonia is a neurologic movement disorder characterized by involuntary muscular contractions that may be sustained or intermittent, resulting in abnormal movement and postures. The burden associated with dystonia is considerable as there is no cure or known pathophysiology. Despite the immediate need for innovative treatments, alternative interventions are barred by a lack of understanding of the pathology and mechanism of dystonia. To develop and refine effective rehabilitative interventions for patients with focal dystonia, the pathology must be better understood and methods to assess corticospinal excitability refined. There are emerging lines of evidence that suggest there is an altered balance of inhibition and excitation contributing to the cause of dystonia. This may be due to dysfunctional interplays between the cerebellum, basal ganglia and motor cortex that generate network dysfunction. One strategy to study the affected brain regions in people with dystonia is via the use of non-invasive brain stimulation to measure and modulate motor cortical excitability. The overall goal of this dissertation is to evaluate the use of non-invasive brain stimulation, using both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), to assess and modulate aspects of neurophysiology and neuroplasticity in people with cervical dystonia (CD) and healthy controls. Four studies were designed to achieve this research goal. 1) The first study evaluated the validity of using fine-wire electrodes to record motor evoked responses. Fine-wire electrodes were found to be a valid means to record muscle responses, allowing the investigation of motor cortical excitability in small or intrinsic muscles that can be affected by dystonia. 2) The second study evaluated the use of cerebellar neuromodulation with simultaneous task training in healthy adults. This investigation revealed that cerebellar neuromodulation interfered with practice-related changes in corticospinal excitability. 3) The third study evaluated ipsilateral and contralateral motor evoked responses in the upper trapezius between people with CD and controls and provided evidence that inhibitory responses are asymmetrically regulated in people with CD. 4) The fourth study explored the use of cerebellar tDCS to modulate eye-blink classical conditioning and measures of motor cortical excitability. The results suggest poor conditioning responses in all participants, limiting the interpretation of the study; however, no differences between groups were detected in outcomes of motor cortical excitability. These studies add to our understanding of how non-invasive brain stimulation may be used to assess measures of excitation and inhibition in-vivo to probe aspects of neuroplasticity and the effects of neuromodulation.