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Browsing by Author "Hetrick, William P."
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Item 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 MedicineBackground: 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.Item 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 MedicineSchizophrenia 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.Item The auditory steady-state response (ASSR): a translational biomarker for schizophrenia(Elsevier, 2013) O'Donnell, Brian F.; Vohs, Jenifer L.; Krishnan, Giri P.; Rass, Olga; Hetrick, William P.; Morzorati, Sandra L.; Department of Psychiatry, IU School of MedicineElectrophysiological methods have demonstrated disturbances of neural synchrony and oscillations in schizophrenia which affect a broad range of sensory and cognitive processes. These disturbances may account for a loss of neural integration and effective connectivity in the disorder. The mechanisms responsible for alterations in synchrony are not well delineated, but may reflect disturbed interactions within GABAergic and glutamatergic circuits, particularly in the gamma range. Auditory steady-state responses (ASSRs) provide a non-invasive technique used to assess neural synchrony in schizophrenia and in animal models at specific response frequencies. ASSRs are electrophysiological responses entrained to the frequency and phase of a periodic auditory stimulus generated by auditory pathway and auditory cortex activity. Patients with schizophrenia show reduced ASSR power and phase locking to gamma range stimulation. We review alterations of ASSRs in schizophrenia, schizotypal personality disorder, and first-degree relatives of patients with schizophrenia. In vitro and in vivo approaches have been used to test cellular mechanisms for this pattern of findings. This translational, cross-species approach provides support for the role of N-methyl-D-aspartate and GABAergic dysregulation in the genesis of perturbed ASSRs in schizophrenia and persons at risk.Item 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 MedicineDespite 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.Item 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 MedicineThe 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.Item 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 MedicineAutism 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.Item Cerebellar tDCS consistency and metabolite changes: A recommendation to decrease barriers to replicability(Elsevier, 2020-11) Moussa-Tooks, Alexandra B.; Burroughs, Leah P.; Rejimon, Abinand C.; Cheng, Hu; Hetrick, William P.; Psychiatry, School of MedicineItem 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 MedicineEEG 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.Item Correction to: Psychometric evaluation of the Pinocchio Illusion Questionnaire(SpringerLink, 2020-07) Purcell, John R.; Chen, John; Moussa-Tooks, Alexandra B.; Hetrick, William P.; Psychiatry, School of MedicineThe authors would like to correct the following. Erratum for: Psychometric evaluation of the Pinocchio Illusion Questionnaire. Purcell JR, Chen J, Moussa-Tooks AB, Hetrick WP. Atten Percept Psychophys. 2020 Jul;82(5):2728-2737. doi: 10.3758/s13414-020-02011-4. PMID: 32185641 Free PMC article.Item 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 MedicineObjectives: 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.
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