IU Indianapolis ScholarWorks :: Browsing by Author "O’Donnell, Brian F."

Browsing by Author "O’Donnell, Brian F."

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A magnetic resonance imaging-safe method for the study of human eyeblink conditioning
(Elsevier, 2013) Kent, Jerillyn S.; Bailey, D. Michael; Vollmer, Jennifer M.; Newman, Sharlene D.; Bolbecker, Amanda R.; O’Donnell, Brian F.; Hetrick, William P.; Psychiatry, School of Medicine
Eyeblink conditioning (EBC) is a widely used translational probe of cerebellar function in both humans and non-human animals. Decades of animal research have identified the cerebellum as critical for EBC. While there is evidence for the involvement of the cerebellum in human EBC, the neural circuitry of EBC in healthy humans has yet to be fully elucidated. The purpose of this study was to design and validate a highly customisable system for EBC stimulus presentation and response recording using infrared (IR) reflectance suitable for use in magnetic resonance imaging (MRI) environments; in this way, the neural activity of EBC could be investigated using fMRI in humans. Four participants underwent delay EBC and simultaneous fMRI. The results indicate (1) a high signal-to-noise ratio in the IR reflectance data that effectively quantifies the eyeblink morphology and timing and (2) evidence of conditioning in the fMRI environment. The quality of the data, the feasibility of conducting EBC experiments in the fMRI environment, and the customisability of the current system to fit a variety of EBC experimental design parameters are discussed.
Altered cerebellar-cortical resting-state functional connectivity in cannabis users
(Sage, 2021) Schnakenberg Martin, Ashley M.; Kim, Dae-Jin; Newman, Sharlene D.; Cheng, Hu; Hetrick, William P.; Mackie, Ken; O’Donnell, Brian F.; Psychiatry, School of Medicine
Background: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. Aims: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. Methods: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). Results: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. Conclusions: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.
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.
Auditory Steady State Response in the Schizophrenia, First-Degree Relatives, and Schizotypal Personality Disorder
(Elsevier, 2012) Rass, Olga; Forsyth, Jennifer; Krishnan, Giri; Hetrick, William P.; Klaunig, Mallory; Breier, Alan; O’Donnell, Brian F.; Brenner, Colleen A.; Psychiatry, School of Medicine
The power and phase synchronization of the auditory steady state response (ASSR) at 40 Hz stimulation is usually reduced in schizophrenia (SZ). The sensitivity of the 40 Hz ASSR to schizophrenia spectrum phenotypes, such as schizotypal personality disorder (SPD), or to familial risk has been less well characterized. We compared the ASSR of patients with SZ, persons with schizotypal personality disorder, first degree relatives of patients with SZ, and healthy control participants. ASSRs were obtained to 20, 30, 40 and 50 Hz click trains, and assessed using measures of power (mean trial power or MTP) and phase consistency (phase locking factor or PLF). The MTP to 40 Hz stimulation was reduced in relatives, and there was a trend for MTP reduction in SZ. The 40 Hz ASSR was not reduced in SPD participants. PLF did not differ among groups. These data suggest the 40 Hz ASSR is sensitive to familial risk factors associated with schizophrenia.
Auditory steady state responses in a schizophrenia rat model probed by excitatory/inhibitory receptor manipulation
(Elsevier, 2012) Vohs, Jenifer L.; Chambers, R. Andrew; O’Donnell, Brian F.; Krishnan, Giri P.; Morzorati, Sandra L.; Psychiatry, School of Medicine
Alterations in neural synchrony and oscillations may contribute to the pathophysiology of schizophrenia and reflect aberrations in cortical glutamatergic and GABAergic neurotransmission. We tested the effects of a GABA agonist and a NMDA antagonist on auditory steady state responses (ASSRs) in awake rats with neonatal ventral hippocampal lesions (NVHLs) as a neurodevelopmental model of schizophrenia. NVHL vs. SHAM lesioned rats were injected with saline then either ketamine (NMDA antagonist) or muscimol (GABAA agonist). Time-frequency analyses examined alterations in phase locking (consistency) across trials and changes in total power (magnitude). ASSRs were compared at 5 stimulation frequencies (10, 20, 30, 40, and 50 Hz). In SHAM rats, phase locking and power generally increased with stimulation frequency. Both ketamine and muscimol also increased phase locking and power in SHAM rats, but mostly in the 20 to 40 Hz range. NVHL and ketamine altered the frequency dependence of phase locking, while only ketamine changed power frequency dependence. Muscimol affected power, but not phase locking, in the NVHL rats. NVHL and ketamine models of schizophrenia produce similar independent effects on ASSR, potentially representing similar forms of cortical network/glutamatergic dysfunction, albeit the effects of ketamine were more robust. Muscimol produced NVHL-dependent reductions in ASSR measures, suggesting that cortical networks in this model are intolerant to post-synaptic GABAergic stimulation. These findings suggest the utility of combining lesion, pharmacological, and ASSR approaches in understanding neural mechanisms underlying disturbed synchrony in schizophrenia.
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.
Computer-Assisted Cognitive Remediation for Schizophrenia: A Randomized Single-Blind Pilot Study
(Elsevier, 2012) Rass, Olga; Forsyth, Jennifer K.; Bolbecker, Amanda R.; Hetrick, William P.; Breier, Alan; Lysaker, Paul H.; O’Donnell, Brian F.; Psychiatry, School of Medicine
Cognitive impairment is a core symptom in schizophrenia that has a significant impact on psychosocial function, but shows a weak response to pharmacological treatment. Consequently, a variety of cognitive remediation strategies have been evaluated to improve cognitive function in schizophrenia. The efficacy of computer-based cognitive remediation as a stand-alone intervention on general measures of neuropsychological function remains unclear. We tested the effectiveness of biweekly training using computerized cognitive remediation programs on neuropsychological and event-related potential outcome measures. Schizophrenia patients were randomly assigned to cognitive remediation training (N=17), active control (TV-watching; N=17), or treatment-as-usual (N=10) groups for ten weeks and run in parallel. Cognitive and ERP measures revealed no differential improvement over time in the cognitive remediation group. Practice effects might explain change over time on several cognitive measures for all groups, consistent with studies indicating task-specific improvement. Computer-assisted cognitive remediation alone may not be sufficient for robust or generalized effects on cognitive and electrophysiological measures in schizophrenia patients.
Differential Cognitive Performance in Females and Males with Regular Cannabis Use
(Cambridge University Press, 2021) Schnakenberg Martin, Ashley M.; D’Souza, Deepak Cyril; Newman, Sharlene D.; Hetrick, William P.; O’Donnell, Brian F.; Psychiatry, School of Medicine
Objectives: Preclinical and clinical studies suggest that males and females may be differentially affected by cannabis use. This study evaluated the interaction of cannabis use and biological sex on cognition, and the association between observed cognitive deficits and features of cannabis use. Methods: Cognitive measures were assessed in those with regular, ongoing, cannabis use (N = 40; 22 female) and non-using peers (N = 40; 23 female). Intelligence, psychomotor speed, and verbal working memory were measured with the Wechsler Abbreviated Scale of Intelligence, Digit Symbol Test, and Digit Span and Hopkins Verbal Learning Test, respectively. Associations between cognitive measures and cannabis use features (e.g., lifetime cannabis use, age of initiation, time since last use of cannabis, recent high-concentration tetrahydrocannabinoid exposure) were also evaluated. Results: No main effects of group were observed across measures. Significant interactions between group and biological sex were observed on measures of intelligence, psychomotor speed, and verbal learning, with greatest group differences observed between males with and without regular cannabis use. Psychomotor performance was negatively correlated with lifetime cannabis exposure. Female and male cannabis use groups did not differ in features of cannabis use. Conclusions: Findings suggest that biological sex influences the relationship between cannabis and cognition, with males potentially being more vulnerable to the neurocognitive deficits related to cannabis use.
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 "O’Donnell, Brian F."

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