Research Interns are needed to work alongside an Assistant Professor for University of Maryland School of Medicine at the MD Psychiatric Research Center on Schizophrenia studies.
IF INTERESTED, Apply to Intern Listing 9247017 via UMBCworks TODAY!
Below are the two research Abstracts the research assistants with focus on for the fall semester.
Abstract 1:
Schizophrenia is one of several disorders where attentional problems are a hallmark and may be linked to an abnormal regulation of the so-called default network of resting brain functions. The default network maintains internally directed thought when the mind is free to wander, but it also maintains a level
of broad watchfulness toward the external environment, presumably as a safety mode when attention is not directed to specific external stimuli. People with schizophrenia display deficits in such broad, diffuse watchfulness. For example, they perform much worse in visuospatial attention tasks than healthy participants when there is no advance information about where a target signal will occur, i.e. when attention should not be directed to any particular location. The aim of the present project is to test whether these
problems may be based on a disruption of this broad monitoring, so-called “sentinel” function of the default network. To test this neural circuit explanation, 12 participants with schizophrenia and 12 matched healthy
participants will perform a visuospatial attention paradigm that manipulates the spatial predictability of a target signal. When the target is completely unpredictable and attention has to be kept broad and undirected, performance of this task has previously been shown to be related to activity in central regions of the default network. Using a functional Magnetic Resonance Imaging method that can measure brain responses to individual task events, the present experiment will measure the trial-by-trial association of
reaction time with activity in the default network. The prediction is that, when target signals are spatially unpredictable, activity of these regions will be related to task performance in healthy participants but not in people with schizophrenia. In other words, broad spatial monitoring in healthy people is expected to be aided by the sentinel function of the default network, as shown previously, but in people with schizophrenia, this mechanism is expected to be absent. Results will be corroborated by comparing average brain responses, independent of performance, to task trials that enable advance orienting of attention to trials that require broad spatial monitoring. The significance of pinpointing brain mechanisms underlying this specific
attentional abnormality in schizophrenia is twofold: (1) Linking specific attention deficits to specific neural systems helps reduce the complexity of cognitive deficits in schizophrenia to a small number of underlying
problems, which may be more amenable to treatment and may more easily be linked to specific gene variants. (2) Although in the early stages of investigation, activity of the default network is sensitive to manipulation by nicotine, and these effects are related to performance benefits. Thus, the sentinel function of the default network may be aided by drugs similar to nicotine and may evolve to be a robust biomarker of treatment development designed to enhance cognitive function.
Abstract 2:
Neuroimaging studies indicate that a functionally interconnected set of brain structures, the so-called “default network” of resting brain function, maintains mental processes during passive rest such as mindwandering. Several chronic disease states characterized by cognitive dysfunction, such as Alzheimer’s disease and schizophrenia, are reported to display deficient down-regulation of default network activity when engaging into attention-demanding tasks. Failure to deactivate default activity is known to lead to
acute performance errors and attentional lapses. The potential of manipulating default activity pharmacologically would thus open up a novel approach to improving cognition in these disease populations. A recent experiment in minimally deprived smokers suggests that enhanced attention by largedose
nicotine may be mediated by enhanced task-induced deactivation of the default network. The currently proposed project is designed to determine whether default network activity is modulated by nicotinic tone.
Demonstrating such modulation and associated performance effects by nicotinic ligands would open up a novel mechanism to improving attention, and would lay the groundwork for investigations on clinical benefits
of this mechanism. Functional Magnetic Resonance Imaging will be employed to measure effects of transdermal nicotine and the nicotinic antagonist mecamylamine on default network activity during cognitive task performance. Both drugs will be tested in the same group of subjects, who will be scanned three times, once after receiving either drug and once after placebo. All participants will be non-smokers; default network modulation by nicotine in nicotine-naïve individuals would demonstrate that the effect does not reflect
reversal of a withdrawal state and provide the proof of concept needed for a clinical application. Nicotine is expected to aid task-induced deactivation of default activity, particularly under conditions that invited taskindependent
thought and attentional lapses. This effect is expected to be associated with enhanced performance. Mecamylamine, in contrast, is expected to weaken task-induced default deactivation, and this effect is expected to be associated with performance impairment and greater performance variability as
seen in AD and schizophrenia. A state of low nicotinic receptor tone would thus model default dysregulation and specific performance deficits seen in these patient populations and suggest that it may be causal to these problems. Finally, nicotinic modulation of functional connectivity of default regions will be examined. Such connectivity has been shown to influence cognitive performance, and a strengthening by nicotine and
weakening by mecamylamine may be another mechanism of performance modulation. Demonstration of robust effects of nicotinic receptor ligands on default network activity would not only motivate a broad range
of future investigations on clinical applications of this mechanism but also provide an important neuroimaging test model in the search for novel nicotinic agonists with cognitive-enhancing potential.
IF INTERESTED, Apply to Intern Listing 9247017 via UMBCworks TODAY!
Below are the two research Abstracts the research assistants with focus on for the fall semester.
Abstract 1:
Schizophrenia is one of several disorders where attentional problems are a hallmark and may be linked to an abnormal regulation of the so-called default network of resting brain functions. The default network maintains internally directed thought when the mind is free to wander, but it also maintains a level
of broad watchfulness toward the external environment, presumably as a safety mode when attention is not directed to specific external stimuli. People with schizophrenia display deficits in such broad, diffuse watchfulness. For example, they perform much worse in visuospatial attention tasks than healthy participants when there is no advance information about where a target signal will occur, i.e. when attention should not be directed to any particular location. The aim of the present project is to test whether these
problems may be based on a disruption of this broad monitoring, so-called “sentinel” function of the default network. To test this neural circuit explanation, 12 participants with schizophrenia and 12 matched healthy
participants will perform a visuospatial attention paradigm that manipulates the spatial predictability of a target signal. When the target is completely unpredictable and attention has to be kept broad and undirected, performance of this task has previously been shown to be related to activity in central regions of the default network. Using a functional Magnetic Resonance Imaging method that can measure brain responses to individual task events, the present experiment will measure the trial-by-trial association of
reaction time with activity in the default network. The prediction is that, when target signals are spatially unpredictable, activity of these regions will be related to task performance in healthy participants but not in people with schizophrenia. In other words, broad spatial monitoring in healthy people is expected to be aided by the sentinel function of the default network, as shown previously, but in people with schizophrenia, this mechanism is expected to be absent. Results will be corroborated by comparing average brain responses, independent of performance, to task trials that enable advance orienting of attention to trials that require broad spatial monitoring. The significance of pinpointing brain mechanisms underlying this specific
attentional abnormality in schizophrenia is twofold: (1) Linking specific attention deficits to specific neural systems helps reduce the complexity of cognitive deficits in schizophrenia to a small number of underlying
problems, which may be more amenable to treatment and may more easily be linked to specific gene variants. (2) Although in the early stages of investigation, activity of the default network is sensitive to manipulation by nicotine, and these effects are related to performance benefits. Thus, the sentinel function of the default network may be aided by drugs similar to nicotine and may evolve to be a robust biomarker of treatment development designed to enhance cognitive function.
Abstract 2:
Neuroimaging studies indicate that a functionally interconnected set of brain structures, the so-called “default network” of resting brain function, maintains mental processes during passive rest such as mindwandering. Several chronic disease states characterized by cognitive dysfunction, such as Alzheimer’s disease and schizophrenia, are reported to display deficient down-regulation of default network activity when engaging into attention-demanding tasks. Failure to deactivate default activity is known to lead to
acute performance errors and attentional lapses. The potential of manipulating default activity pharmacologically would thus open up a novel approach to improving cognition in these disease populations. A recent experiment in minimally deprived smokers suggests that enhanced attention by largedose
nicotine may be mediated by enhanced task-induced deactivation of the default network. The currently proposed project is designed to determine whether default network activity is modulated by nicotinic tone.
Demonstrating such modulation and associated performance effects by nicotinic ligands would open up a novel mechanism to improving attention, and would lay the groundwork for investigations on clinical benefits
of this mechanism. Functional Magnetic Resonance Imaging will be employed to measure effects of transdermal nicotine and the nicotinic antagonist mecamylamine on default network activity during cognitive task performance. Both drugs will be tested in the same group of subjects, who will be scanned three times, once after receiving either drug and once after placebo. All participants will be non-smokers; default network modulation by nicotine in nicotine-naïve individuals would demonstrate that the effect does not reflect
reversal of a withdrawal state and provide the proof of concept needed for a clinical application. Nicotine is expected to aid task-induced deactivation of default activity, particularly under conditions that invited taskindependent
thought and attentional lapses. This effect is expected to be associated with enhanced performance. Mecamylamine, in contrast, is expected to weaken task-induced default deactivation, and this effect is expected to be associated with performance impairment and greater performance variability as
seen in AD and schizophrenia. A state of low nicotinic receptor tone would thus model default dysregulation and specific performance deficits seen in these patient populations and suggest that it may be causal to these problems. Finally, nicotinic modulation of functional connectivity of default regions will be examined. Such connectivity has been shown to influence cognitive performance, and a strengthening by nicotine and
weakening by mecamylamine may be another mechanism of performance modulation. Demonstration of robust effects of nicotinic receptor ligands on default network activity would not only motivate a broad range
of future investigations on clinical applications of this mechanism but also provide an important neuroimaging test model in the search for novel nicotinic agonists with cognitive-enhancing potential.
