No description available.

Inhibitory control, described as the ability to suppress one response in favor of a goal-directed response, is thought to play an important role in the development of emotional regulation as well as various forms of psychopathology, including ADHD. Up until very recently, inhibitory control has been researched within two completely separate fields of study: temperament and neuropsychology. In the temperament/personality literature, inhibitory control is a major component of the overarching temperament/personality factor of Effortful Control/Conscientiousness. In the field of neuropsychology, inhibitory control is considered one aspect of executive function. Further complicating the current understanding of inhibitory control is the complexity of the underlying neural networks implicated in inhibitory control. This study examined inhibitory control in temperament and executive function in children with and without ADHD, and it explored the relationship between inhibitory control and the superior frontal cortex (SFC) and orbital frontal cortex (OFC) volumes. In order to assess subareas of the OFC and SFC, an innovative parcellation method was used. Results suggested that the temperament and executive function measures of inhibitory control did form a single factor as long as they were measured within the same modality, parent-report. In contrast, the performance-based measure of inhibitory control was not correlated with any of the parent-report measures of inhibitory control and was, therefore, analyzed separately in relation to OFC and SFC volumes. Parent-rated inhibitory control was predicted by ADHD status only, but exploratory analyses suggested that left anterior SFC, right and left anterior medial OFC, and gender were related to parent-rated inhibitory control. In contrast, performance-based inhibitory control was predicted by gender and left SFC, specifically posterior left SFC. Taken together, these findings suggest a conceptual overlap between temperament and executive function that brings together two areas of the literature and has implications for the understanding of various forms of psychopathology characterized by deficits in inhibitory control. This study provides evidence for the role of the SFC and the OFC in inhibitory control, depending upon the measurement method, and contributes to the broader understanding of the neural mechanisms of inhibitory control in children.

In a multi‐agent environment, animals must often adopt a stochastic mixed‐strategy approach to maximize reward and minimize costs; otherwise, competitive opponents can exploit predictable choice patterns. This thesis tested the hypothesis that the frontal eye field (FEF) are involved in selecting mixed‐strategy saccades. To this end, I recorded preparatory activity of single FEF neurons and manipulated the preparatory activity of neuronal ensembles within the FEF while a monkey played an oculomotor version of the mixed­‐strategy game ‘matching­‐pennies’. Each trial began with fixation on a central visual stimulus which was extinguished for a predetermined warning period before two targets were presented; one in the center and the other opposite the neuron’s response field. If both the monkey and the adaptive computer opponent chose the same target, the monkey received a liquid reward; otherwise the monkey received no reward for that trial. Like humans, monkeys chose each target in equal proportions but showed a ‘win‐stay’ bias in their choice patterns. Signal detection theory was used to analyze how accurately FEF preparatory activity predicted upcoming saccade choices. My data demonstrates that the accuracy by which FEF preparatory activity predicted upcoming strategic choices gradually increased as the time of saccade execution approached. This pattern of preparatory activity is consistent with an accumulation of evidence for each potential option towards a decision threshold. Subthreshold micro­‐stimulation biased mixed‐strategy saccadic choices, further suggesting a role for the FEF in choosing mixed­‐strategy saccades, albeit unexpectedly, in favor of saccades opposite the stimulation sites. Lastly, a particular advantage of my experiment is that the same monkey performed this task using neurophysiological experimentation in the FEF and intermediate layers of the superior colliculus (SCi). This allowed me to compare the timing and magnitude of neuronal selectivity and effects of subthreshold microstimulation across these two structures, during strategic decision‐making. My results indicate that the selection of mixed­‐strategy saccades occurred earlier and was greater in magnitude in the FEF compared to the SC, indicative of a decision process that occurs earlier in the frontal cortex before being relayed on to premotor regions in the midbrain. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2012-03-28 10:57:30.638

BACKGROUND: Mild Traumatic Brain Injury (mTBI) is increasingly recognized as an adverse health consequence for athletes who participate in contact sports, such as football or boxing, as well as military personnel who are exposed to concussive blasts during training and combat operations. A consequence of this repetitive brain injury can be the development of a number of neurodegenerative diseases, particularly chronic traumatic encephalopathy (CTE), a disease involving the buildup of toxic phosphorylated tau (p-tau) in the pre-frontal cortical tissue. Additionally, it has been found that military personnel suffering repeated mTBI from primary blast concussions are prone to development of post traumatic stress disorder (PTSD), a disease that is becoming increasingly common among returning service members. Because mTBI is a common cause for both PTSD and CTE, it is possible for the two diseases to manifest comorbidly in an individual. Though much is known about PTSD psychologically and CTE neuropathologically, little is known about the overlapping effect of the two diseases together as well as PTSD neuropathologically. What is known, however, is that aquaporin-4; a channel involved in the movement of water through the blood brain barrier, is often affected by CTE and may play a role in PTSD as well. OBJECTIVE: The objective of this study was to primarily to analyze the disruption of aquaporin-4 around cerebral blood vessels due to chronic traumatic encephalopathy. A secondary objective of this project was to determine if any unique physiopathological biomarkers exist in PTSD and if the effects of CTE are exacerbated when present comorbidly with PTSD. METHODS: This study involved the analysis of multiple cohorts that had suffered from CTE, PTSD and CTE comorbidly, or neither disease as a control. In order to assess the primary objective, two cohorts, a CTE-only and a control, were analyzed to determine the effect of p-tau on aquaporin-4 directly around cerebral vessels in the pre-frontal cortex. The samples were cut from blocks and stained for the desired markers. Following staining, images were taken using a confocal microscope and the images were analyzed using Amaris and FIJI. For the secondary objective, samples were prepared in a similar way with three cohorts: CTE-only, CTE+PTSD comorbid, and a control. Images were obtained and processed in the same way. RESULTS: It was found that aquaporin-4 density is significantly reduced around both arterial and venous lesional vessels. Additionally, it was found that p-tau was more readily deposited in the depths of the sulci of the pre-frontal cortex due to the unique forces caused by repeated mTBI. However, PTSD was not found to significantly compound the disease when comorbidly present with CTE nor to have a unique biomarkers present. CONCLUSION: P-tau present in CTE causes a significant reduction in aquaporin-4 around cerebral vessels in the pre-frontal cortex, thereby potentially inhibiting the movement of fluids and clearance of metabolites into and out of the brain. Additionally, p-tau is more readily deposited in the depths of the sulci of the pre-frontal cortex. However, PTSD does not compound the CTE disease process when comorbidly present. / 2018-07-13T00:00:00Z

No description available.

Temporal context memory is memory for the timing of events. People can make temporal judgments based on strategies such as assessing the relative familiarity of events or inferring temporal order from the semantic associations among events. The purpose of present study is to investigate the brain regions that support temporal context retrieval in the absence of such non-temporal strategies (i.e. pure temporal context memory). We used three word familiar phrases (triplets) as stimuli. In study phase, three words were presented quickly one after another in either familiar or scrambled order. Participants were instructed to read aloud each word and try to remember the order of the words. Then they were tested on their memory for the order of the words in each triplet. We propose that memory for the scrambled triplets reflects primarily temporal retrieval for two reasons. First, participants were prevented from using semantic strategies during encoding. Second, the relative familiarity of the words in each triplet was similar and not diagnostic of the order of the words during encoding. Neuroimaging results indicate that temporal context retrieval, memory for the order of words in scrambled triplets, was associated with the hippocampus, parahippocampal cortex, ventromedial prefrontal cortex, retrosplenial cortex, and posterior cingulate, which are consistent with the retrieval of non-temporal context in episodic memory. The results also suggest that temporal context retrieval could rely on familiarity, which was demonstrated by the higher accuracy and greater activation of PRc in familiar phrases and scrambled triplets presented in studied order in the test phase. / Master of Science

No description available.

No / Acute administration of the psychotomimetic phencyclidine (PCP) can mimic some features of schizophrenia, while a repeated treatment regimen of PCP may provide a more effective way to model in animals the enduring cognitive dysfunction observed in many schizophrenic patients. The present study aims to investigate behavioural and neuropathological effects of sub-chronic PCP administration. The cognitive deficit induced by sub-chronic PCP was examined using a previously established operant reversal-learning paradigm. Subsequently, the effect of sub-chronic PCP on parvalbumin-immunoreactive (parvalbumin-IR) neurons was assessed using immunohistochemical techniques. Rats were trained to respond for food in an operant reversal-learning paradigm for approximately 6 weeks, followed by sub-chronic administration of PCP (2mg/kg) or vehicle twice daily for 7 days followed 7 days later by behavioural testing. Six weeks post PCP, brains were analysed using immunohistochemical techniques to determine the size and density of parvalbumin-IR in the frontal cortex and hippocampus. Sub-chronic PCP significantly reduced (p <0.001) percentage correct responding in the reversal phase relative to the initial phase, an effect that persisted throughout the experimental period (4 weeks). The density of parvalbumin-IR neurons was reduced in the hippocampus, with significant reductions in the dentate gyrus and CA2/3 regions (p <0.001). There were significant changes in the frontal cortex, with a reduction (p <0.01) in the M1 (motor area 1) region and increases in the M2 (motor area 2) region and cingulate cortex (p <0.01-p <0.001). These results parallel findings of profound hippocampal and more subtle cortical deficits of parvalbumin-IR neurons in schizophrenia, and provide evidence to suggest that sub-chronic PCP can induce a lasting cognitive deficit, an effect that may be related to the observed neuronal deficits.

Schizophrenia remains an enigmatic disorder with unclear neuropathology. Recent advances in neuroimaging and genetic research suggest alterations in glutamate-dopamine interactions adversely affecting synaptic plasticity both intracortically and subcortically. Relating these changes to the manifestation of symptoms presents a great challenge, requiring a constrained framework to capture the most salient elements. Here, a biologically-grounded computational model of basal ganglia-mediated action selection was used to explore two pathological processes that hypothetically underpin schizophrenia. These were a drop in the efficiency of cortical transmission, reducing both the signal-to-noise ratio (SNR) and overall activity levels; and an excessive compensatory upregulation of subcortical dopamine release. It was proposed that reduced cortical efficiency was the primary process, which led to a secondary disinhibition of subcortical dopamine release within the striatum. This compensation was believed to partly recover lost function, but could then induce disorganised-type symptoms - summarised as selection ”Instability” - if it became too pronounced. This overcompensation was argued to be countered by antipsychotic medication. The model’s validity was tested during an fMRI (functional magnetic resonance imaging) study of 16 healthy volunteers, using a novel perceptual decision-making task, and was found to provide a good account for pallidal activation. Its account for striatum was developed and improved with a small number of principled model modifications: the inclusion of fast spiking interneurons within striatum, and their inhibition by the basal ganglia’s key regulatory nucleus, external globus pallidus. A key final addition was the explicit modelling of dopaminergic midbrain, which is dynamically regulated by both cortex and the basal ganglia. This enabled hypotheses concerning the effects of cortical inefficiency, compensatory dopamine release and medication to be directly tested. The new model was verified with a second set of 12 healthy controls. Its pathological predictions were compared to data from 12 patients with schizophrenia. Model simulations suggested that Instability went hand-in-hand with cortical inefficiency and secondary dopamine upregulation. Patients with high Instability scores showed a loss of SNR within decision-related cortex (consistent with cortical inefficiency); an exaggerated response to task demands within substantia nigra (consistent with dopaminergic upregulation); and had an improved fit to simulated data derived from increasingly cortically-inefficient models. Simulations representing the healthy state provided a good account for patients’ motor putamen, but only cortically-inefficient simulations representing the ill state provided a fit for ventral-anterior striatum. This fit improved as the simulated model became more medicated (increased D2 receptor blockade). The relative improvement of this account correlated with patients’ medication dosage. In summary, by distilling the hypothetical neuropathology of schizophrenia into two simplified umbrella processes, and using a computational model to consider their effects within action selection, this work has successfully related patients’ fMRI activation to particular symptomatology and antipsychotic medication. This approach has the potential to improve patient care by enabling a neurobiological appreciation of their current illness state, and tailoring their medication level appropriately.

Introdução: A anemia aguda tem sido associada com distúrbios neurofisiológicos e cognitivos em pacientes saudáveis. Evidências experimentais sugerem que a hemodiluição pode aumentar lesões cerebrais, limitando o suprimento de oxigênio ao tecido cerebral. No entanto, o mecanismo exato pelo qual as lesões cerebrais ocorrem em pacientes anêmicos ainda não está claramente definido. O objetivo desse estudo foi avaliar os precursores da apoptose neuronal Bax, Bcl-x no córtex frontal, atividade das caspases 3 e 9 na fração citosólica do hipocampo e na fração mitocondrial do córtex frontal, assim como a fragmentação do DNA na fração nuclear e mitocondrial do córtex frontal, após hemodiluição normovolêmica aguda. Métodos: Vinte e quatro porcos foram anestesiados e randomizados em 4 grupos de 6 animais: Controle, hemodiluição normovolêmica aguda (HNA) com hematócrito alvo de 15% (Ht 15%), HNA com hematócrito alvo de 10% (Ht 10%) e hipóxia-hipóxica (HH). A HNA foi realizada com 1ml de hidroxetil amido (130/0,4) por ml de sangue retirado, até o hematócrito alvo desejado (10 ou 15%). O HH consistiu de ventilação com baixa fração expirada de O2 (FiO2), sendo de 6% por 60 minutos, servindo como grupo controle positivo. Os animais do grupo controle não sofreram nenhuma dessas intervenções. As proteínas pró-apoptótica Bax e anti-apoptótica Bcl-x foram avaliadas por Western blotting nas frações nucleares e mitocondriais do córtex frontal. A atividade das caspases 3 e 9 foi avaliada nas frações mitocondrial e citosólica do hipocampo por espectrofluorometria. A fragmentação do DNA foi avaliada por eletroforese nas frações nuclear e mitocondrial do córtex frontal. Os dados foram comparados por análise de variância (ANOVA) seguida por teste de Tukey (p<0,05). Resultados: Não foi observada diferença significativa entre os grupos controle, Ht 15% e Ht 10% em relação à proteína pró-apoptótica Bax nas frações nuclear e mitocondrial. Entretanto, o grupo HH foi significativamente diferente dos grupos controle e Ht 15% na fração nuclear e de todos os grupos na fração mitocondrial. Não foi encontrada diferença significativa em relação à Bcl-x. A atividade das caspases 3 e 9 nas frações mitocondrial e nuclear foi diferente no grupo HH quando comparado com os demais grupos. Não foi observada diferença significativa em relação à fragmentação do DNA entre os grupos controle, Ht 15% e Ht 10%. Conclusão: A avaliação dos precursores da apoptose demonstrou que a hemodiluição normovolêmica aguda com hematócrito alvo de 15% e 10% não induziu apoptose, sugerindo que a oxigenação cerebral foi preservada / Background: Acute anemia has been associated with neurophysiologic and cognitive dysfunctions in healthy patients. Experimental evidences suggest that hemodilution may increase cerebral lesions, limiting oxygen supply to the brain tissue. Nevertheless, the exact mechanisms through which cerebral lesions occur in anemic patients havent been clearly defined. Therefore, the objective of the present study was to evaluate neuronal apoptosis precursors Bax, Bcl-x in the frontal cortex, caspase 3 and 9 activity in the mitochondrial and cytosolic fractions of the hippocampus, even as DNA fragmentation in the mitochondrial and nuclear fractions of the frontal cortex after acute normovolemic hemodilution. Methods: Twenty four pigs were anesthetized and randomized into 4 groups of 6 animals: sham, acute normovolemic hemodilution (ANH) to reach a hematocrit of 15% (Ht 15%), ANH to reach a hematocrit of 10% (Ht 10%) and hypoxic-hipoxia (HH). ANH was performed with 1ml hydroxyethyl starch 130/0.4 (HES) per ml of blood withdrawn to the desired target hematocrit (10 or 15%). HH consisted of ventilation with low fraction of inspired oxygen (FiO2) of 6% for 60 minutes, serving as a positive control group. Sham animals were not involved in any of these interventions. Pro-apoptotic Bax and anti-apoptotic Bcl-x proteins were evaluated by Western blotting in nuclear and mitochondrial fractions of the frontal cortex and activities of caspases-3 and-9 were evaluated in the mitochondrial and cytosolic fractions of the hippocampus by spectrofluorometry. DNA fragmentation was evaluated by electrophoresis in the mitochondrial and nuclear fraction. Data were compared by analysis of variance (ANOVA) followed by Tukeys test (p<0.05). Results: No statistical significance was found among sham, Ht 15% or Ht 10% groups regarding pro-apoptotic protein Bax, in nuclear or mitochondrial fractions. However, group HH presented significant difference from sham and Ht 15% groups in the nuclear fraction and from all groups in the mitochondrial fraction. No statistical significance was found with Bcl-x. The activities of caspases-3 and-9 in cytosolic and mitochondrial fractions were statisticaly different in group HH when compared with all other groups. No statistical significance was found in relation to DNA fragmentation among sham, Ht 15% or Ht 10%. Conclusion: The evaluation of apoptosis precursors demonstrated that ANH with target hematocrit 15% and 10% did not induce neuronal lesion, suggesting that cerebral oxygenation was preserved