IU Indianapolis ScholarWorks :: Browsing by Author "Bolbecker, Amanda R."

Browsing by Author "Bolbecker, Amanda R."

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Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats
(Karger, 2017) Martin, Ashley M. Schnakenberg; O'Donnell, Brian F.; Millward, James B.; Vohs, Jenifer L.; Leishman, Emma; Bolbecker, Amanda R.; Rass, Olga; Morzorati, Sandra L.; Psychiatry, School of Medicine
BACKGROUND/AIMS: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. METHODS: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. RESULTS: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. CONCLUSIONS: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.
Auditory feature perception and auditory hallucinatory experiences in schizophrenia spectrum disorder
(Springer, 2017-09-21) Schnakenberg Martin, Ashley M.; Bartolomeo, Lisa; Howell, Josselyn; Hetrick, William P.; Bolbecker, Amanda R.; Breier, Alan; Kidd, Gary; O’Donnell, Brian F.; Psychiatry, School of Medicine
Schizophrenia spectrum disorder (SZ) is associated with deficits in auditory perception as well as auditory verbal hallucinations (AVH). However, the relationship between auditory feature perception and auditory verbal hallucinations (AVH), one of the most commonly occurring symptoms in psychosis, has not been well characterized. This study evaluated perception of a broad range of auditory features in SZ and to determine whether current AVHs relate to auditory feature perception. Auditory perception, including frequency, intensity, duration, pulse-train and temporal order discrimination, as well as an embedded tone task, was assessed in both AVH (n = 20) and non-AVH (n = 24) SZ individuals and in healthy controls (n = 29) with the Test of Basic Auditory Capabilities (TBAC). The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) was used to assess the experience of auditory hallucinations in patients with SZ. Findings suggest that compared to controls, the SZ group had greater deficits on an array of auditory features, with non-AVH SZ individuals showing the most severe degree of abnormality. IQ and measures of cognitive processing were positively associated with performance on the TBAC for all SZ individuals, but not with the HPSVQ scores. These findings indicate that persons with SZ demonstrate impaired auditory perception for a broad range of features. It does not appear that impaired auditory perception is associated with recent auditory verbal hallucinations, but instead associated with the degree of intellectual impairment in SZ.
Bifactor Structure of the Schizotypal Personality Questionnaire Across the Schizotypy Spectrum
(Guilford Press, 2021-08) Moussa-Tooks, Alexandra B.; Bailey, Allen J.; Bolbecker, Amanda R.; Viken, Richard J.; O’Donnell, Brian F.; Hetrick, William P.; Psychiatry, School of Medicine
Despite widespread use in schizophrenia-spectrum research, uncertainty remains around an empirically supported and theoretically meaningful factor structure of the Schizotypal Personality Questionnaire (SPQ). Current identified structures are limited by reliance on exclusively nonclinical samples. The current study compared factor structures of the SPQ in a sample of 335 nonpsychiatric individuals, 292 schizotypy-spectrum individuals (schizophrenia, schizoaffective disorder, or schizotypal personality disorder), and the combined group (N = 627). Unidimensional, correlated, and hierarchical models were assessed in addition to a bifactor model, wherein subscales load simultaneously onto a general factor and a specific factor. The best-fitting model across samples was a two-specific factor bifactor model, consistent with the nine symptom dimensions of schizotypy as primarily a direct manifestation of a unitary construct. Such findings, for the first time demonstrated in a clinical sample, have broad implications for transdiagnostic approaches, including reifying schizotypy as a construct underlying diverse manifestations of phenomenology across a wide range of severity.
Cerebellar Activation Deficits in Schizophrenia During an Eyeblink Conditioning Task
(Oxford University Press, 2021-08-28) Lundin, Nancy B.; Kim, Dae-Jin; Tullar, Rachel L.; Moussa-Tooks, Alexandra B.; Kent, Jerillyn S.; Newman, Sharlene D.; Purcell, John R.; Bolbecker, Amanda R.; O’Donnell, Brian F.; Hetrick, William P.; Psychiatry, School of Medicine
The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders (n = 31) and healthy controls (n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were "early" and "late" stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework.
Cerebellar Structure and Function in Autism Spectrum Disorder
(Hapres, 2022) Bloomer, Bess F.; Morales, Jaime J.; Bolbecker, Amanda R.; Kim, Dae-Jin; Hetrick, William P.; Psychiatry, School of Medicine
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by early-onset repetitive behaviors, restricted interests, sensory and motor difficulties, and impaired social interactions. Converging evidence from neuroimaging, lesion and postmortem studies, and rodent models suggests cerebellar involvement in ASD and points to promising targets for therapeutic interventions for the disorder. This review elucidates understanding of cerebellar mechanisms in ASD by integrating and contextualizing recent structural and functional cerebellar research.
Cognitive manipulation of brain electric microstates
(Elsevier, 2017-02-01) Seitzman, Benjamin A.; Abell, Malene; Bartley, Samuel C.; Erickson, Molly A.; Bolbecker, Amanda R.; Hetrick, William P.; Psychiatry, School of Medicine
EEG studies of wakeful rest have shown that there are brief periods in which global electrical brain activity on the scalp remains semi-stable (so-called microstates). Topographical analyses of this activity have revealed that much of the variance is explained by four distinct microstates that occur in a repetitive sequence. A recent fMRI study showed that these four microstates correlated with four known functional systems, each of which is activated by specific cognitive functions and sensory inputs. The present study used high density EEG to examine the degree to which spatial and temporal properties of microstates may be altered by manipulating cognitive task (a serial subtraction task vs. wakeful rest) and the availability of visual information (eyes open vs. eyes closed conditions). The hypothesis was that parameters of microstate D would be altered during the serial subtraction task because it is correlated with regions that are part of the dorsal attention functional system. It was also expected that the sequence of microstates would preferentially transition from all other microstates to microstate D during the task as compared to rest. Finally, it was hypothesized that the eyes open condition would significantly increase one or more microstate parameters associated with microstate B, which is associated with the visual system. Topographical analyses indicated that the duration, coverage, and occurrence of microstate D were significantly higher during the cognitive task compared to wakeful rest; in addition, microstate C, which is associated with regions that are part of the default mode and cognitive control systems, was very sensitive to the task manipulation, showing significantly decreased duration, coverage, and occurrence during the task condition compared to rest. Moreover, microstate B was altered by manipulations of visual input, with increased occurrence and coverage in the eyes open condition. In addition, during the eyes open condition microstates A and D had significantly shorter durations, while C had increased occurrence. Microstate D had decreased coverage in the eyes open condition. Finally, at least 15 microstates (identified via k-means clustering) were required to explain a similar amount of variance of EEG activity as previously published values. These results support important aspects of our hypotheses and demonstrate that cognitive manipulation of microstates is possible, but the relationships between microstates and their corresponding functional systems are complex. Moreover, there may be more than four primary microstates.
Disturbances of postural sway components in cannabis users
(Elsevier, 2018-09) Bolbecker, Amanda R.; Apthorp, Deborah; Martin, Ashley Schanakenberg; Tahayori, Behdad; Moravec, Leah; Gomez, Karen L.; O'Donnell, Brian F.; Newman, Sharlene D.; Hetrick, William P.; Psychiatry, School of Medicine
Introduction A prominent effect of acute cannabis use is impaired motor coordination and driving performance. However, few studies have evaluated balance in chronic cannabis users, even though density of the CB1 receptor, which mediates the psychoactive effects of cannabis, is extremely high in brain regions critically involved in this fundamental behavior. The present study measured postural sway in regular cannabis users and used rambling and trembling analysis to quantify the integrity of central and peripheral nervous system contributions to the sway signal. Methods Postural sway was measured in 42 regular cannabis users (CB group) and 36 non-cannabis users (N-CB group) by asking participants to stand as still as possible on a force platform in the presence and absence of motor and sensory challenges. Center of pressure (COP) path length was measured, and the COP signal was decomposed into rambling and trembling components. Exploratory correlational analyses were conducted between sway variables, cannabis use history, and neurocognitive function. Results The CB group had significantly increased path length and increased trembling in the anterior-posterior (AP) direction. Exploratory correlational analyses suggested that AP rambling was significantly inversely associated with visuo-motor processing speed. Discussion Regular cannabis use is associated with increased postural sway, and this appears to be predominantly due to the trembling component, which is believed to reflect the peripheral nervous system’s contribution to the sway signal.
Evidence of familial confounding of the association between cannabis use and cerebellar-cortical functional connectivity using a twin study
(Elsevier, 2022) Sepe-Forrest, Linnea; Kim, Dae-Jin; Quinn, Patrick D.; Bolbecker, Amanda R.; Wisner, Krista M.; Hetrick, William P.; O'Donnell, Brian F.; Psychiatry, School of Medicine
Cerebellar-cortical resting-state functional connectivity (rsFC) has been reported to be altered in cannabis users. However, this association may be due to genetic and environmental confounding rather than a causal relationship between cannabis use and changes in rsFC. In this co-twin control study, linear mixed models were used to assess relationships between the number of lifetime cannabis uses (NLCU) and age of cannabis onset (ACO) with cerebellar-cortical rsFC. The rsFC with seven functional networks was evaluated in 147 monozygotic and 82 dizygotic twin pairs. Importantly, the use of genetically informed models in this twin sample facilitated examining whether shared genetic or environmental effects underlie crude associations between cannabis measures and connectivity. Individual-level phenotypic analyses (i.e., accounting for twin-pair non-independence) showed that individuals in the full sample with earlier ACO and higher NLCU had lower cerebellar rsFC within the VA, DA, and FP networks. Yet, there were no significant differences in cerebellar-cortical rsFC between monozygotic twins who were discordant for cannabis measures. These findings suggest shared genetic or environmental confounds contribute to associations between cannabis use and altered cerebellar-cortical rsFC, rather than unique causal impacts of cannabis use on cerebellar-cortical rsFC.
Eyeblink Conditioning in Schizophrenia: A Critical Review
(Frotiers, 2015) Kent, Jerillyn S.; Bolbecker, Amanda R.; O'Donnell, Brian F.; Hetrick, William P.; Department of Psychiatry, IU School of Medicine
There is accruing evidence of cerebellar abnormalities in schizophrenia. The theory of cognitive dysmetria considers cerebellar dysfunction a key component of schizophrenia. Delay eyeblink conditioning (EBC), a cerebellar-dependent translational probe, is a behavioral index of cerebellar integrity. The circuitry underlying EBC has been well characterized by non-human animal research, revealing the cerebellum as the essential circuitry for the associative learning instantiated by this task. However, there have been persistent inconsistencies in EBC findings in schizophrenia. This article thoroughly reviews published studies investigating EBC in schizophrenia, with an emphasis on possible effects of antipsychotic medication and stimulus and analysis parameters on reports of EBC performance in schizophrenia. Results indicate a consistent finding of impaired EBC performance in schizophrenia, as measured by decreased rates of conditioning, and that medication or study design confounds do not account for this impairment. Results are discussed within the context of theoretical and neurochemical models of schizophrenia.
Impaired Cerebellar-Dependent Eyeblink Conditioning in First-Degree Relatives of Individuals With Schizophrenia
(Oxford University Press, 2014-09) Bolbecker, Amanda R.; Kent, Jerillyn S.; Petersen, Isaac T.; Klaunig, Mallory J.; Forsyth, Jennifer K.; Howell, Josselyn M.; Westfall, Daniel R.; O’Donnell, Brian F.; Hetrick, William P.; Department of Psychiatry, IU School of Medicine
Consistent with reports of cerebellar structural, functional, and neurochemical anomalies in schizophrenia, robust cerebellar-dependent delay eyeblink conditioning (dEBC) deficits have been observed in the disorder. Impaired dEBC is also present in schizotypal personality disorder, an intermediate phenotype of schizophrenia. The present work sought to determine whether dEBC deficits exist in nonpsychotic first-degree relatives of individuals with schizophrenia. A single-cue tone dEBC paradigm consisting of 10 blocks with 10 trials each (9 paired and 1 unpaired trials) was used to examine the functional integrity of cerebellar circuitry in schizophrenia participants, individuals with a first-degree relative diagnosed with schizophrenia, and healthy controls with no first-degree relatives diagnosed with schizophrenia. The conditioned stimulus (a 400ms tone) coterminated with the unconditioned stimulus (a 50ms air puff to the left eye) on paired trials. One relative and 2 healthy controls were removed from further analysis due to declining conditioned response rates, leaving 18 schizophrenia participants, 17 first-degree relatives, and 16 healthy controls. Electromyographic data were subsequently analyzed using growth curve models in hierarchical linear regression. Acquisition of dEBC conditioned responses was significantly impaired in schizophrenia and first-degree relative groups compared with controls. This finding that cerebellar-mediated associative learning deficits are present in first-degree relatives of individuals with schizophrenia provides evidence that dEBC abnormalities in schizophrenia may not be due to medication or course of illness effects. Instead, the present results are consistent with models of schizophrenia positing cerebellar-cortical circuit abnormalities and suggest that cerebellar abnormalities represent a risk marker for the disorder.

Browsing by Author "Bolbecker, Amanda R."

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