Browsing by Author "Bartolomeo, Lisa A."

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    Impaired Effective Connectivity During a Cerebellar-Mediated Sensorimotor Synchronization Task in Schizophrenia
    (Oxford University Press, 2019-04) Moussa-Tooks, Alexandra B.; Kim, Dae-Jin; Bartolomeo, Lisa A.; Purcell, John R.; Bolbecker, Amanda R.; Newman, Sharlene D.; O’Donnell, Brian F.; Hetrick, William P.; Psychiatry, School of Medicine
    Prominent conceptual models characterize schizophrenia as a dysconnectivity syndrome, with recent research focusing on the contributions of the cerebellum in this framework. The present study examined the role of the cerebellum and its effective connectivity to the cerebrum during sensorimotor synchronization in schizophrenia. Specifically, the role of the cerebellum in temporally coordinating cerebral motor activity was examined through path analysis. Thirty-one individuals diagnosed with schizophrenia and 40 healthy controls completed a finger-tapping fMRI task including tone-paced synchronization and self-paced continuation tapping at a 500 ms intertap interval (ITI). Behavioral data revealed shorter and more variable ITIs during self-paced continuation, greater clock (vs motor) variance, and greater force of tapping in the schizophrenia group. In a whole-brain analysis, groups showed robust activation of the cerebellum during self-paced continuation but not during tone-paced synchronization. However, effective connectivity analysis revealed decreased connectivity in individuals with schizophrenia between the cerebellum and primary motor cortex but increased connectivity between cerebellum and thalamus during self-paced continuation compared with healthy controls. These findings in schizophrenia indicate diminished temporal coordination of cerebral motor activity by cerebellum during the continuation tapping portion of sensorimotor synchronization. Taken together with the behavioral finding of greater temporal variability in schizophrenia, these effective connectivity results are consistent with structural and temporal models of dysconnectivity in the disorder.
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    Long-Term Aberrations To Cerebellar Endocannabinoids Induced By Early-Life Stress
    (Nature Research, 2020-04-29) Moussa-Tooks, Alexandra B.; Larson, Eric R.; Gimeno, Alex F.; Leishman, Emma; Bartolomeo, Lisa A.; Bradshaw, Heather B.; Green, John T.; O’Donnell, Brian F.; Mackie, Ken; Hetrick, William P.; Psychiatry, School of Medicine
    Emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling with studies on stress-induced endocannabinoid dysregulation focusing on cerebral changes that are temporally proximal to stressors. Little is known about temporally distal and sex-specific effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Following limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids, related lipids, and mRNA were assessed, and behavioral performance evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar interpositus nucleus in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Cerebellar interpositus transcriptomics revealed substantial sex effects, with minimal stress effects. Stress did impair novel object recognition in both sexes and social preference in females. Accordingly, the cerebellar endocannabinoid system exhibits robust sex-specific differences, malleable through early-life stress, suggesting the role of endocannabinoids and stress to sexual differentiation of the brain and cerebellar-related dysfunctions.
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    Prism Adaptation Deficits in Schizophrenia
    (Oxford University Press, 2020-03-17) Bartolomeo, Lisa A.; Shin, Yong-Wook; Block, Hannah J.; Bolbecker, Amanda R.; Breier, Alan F.; O’Donnell, Brian; Hetrick, William P.; Psychiatry, School of Medicine
    Recent clinical and neurobehavioral evidence suggests cerebellar dysfunction in schizophrenia (SZ). We used the prism adaptation motor task (PAT) to probe specific cerebellar circuits in the disorder. PAT requires cerebellum-dependent motor adaptation, perceptual remapping, and strategic control. A failure to engage in early corrective processes may indicate impairment within either the cerebellum or regions contributing to strategic components, such as the parietal lobe, while an inability to develop and retain a visuomotor shift with time strongly suggests cerebellar impairment. Thirty-one individuals with SZ and 31 individuals without a history of psychological disorders completed PAT. Subjects reached to a target before, during, and following prism exposure, while their movements were recorded using motion-sensing technology. The SZ group performed worse on conditions consisting of adaptation, post-adaptation, aftereffects, and reorientation, thereby demonstrating a failure to adapt to the same degree as healthy controls. SZ performance remained impaired even with visual feedback and did not differ from controls at baseline, suggesting the observed deficit is specific to adaptation. Results indicate that sensorimotor adaptation is impaired in SZ and implicate disturbances in cerebellar circuits.
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    Relationship of Auditory Electrophysiological Responses to Magnetic Resonance Spectroscopy Metabolites in Early Phase Psychosis
    (Elsevier, 2019) Bartolomeo, Lisa A.; Wright, Andrew M.; Ma, Ruoyun E.; Hummer, Tom A.; Francis, Michael M.; Visco, Andrew C.; Mehdiyoun, Nicole F.; Bolbecker, Amanda R.; Hetrick, William P.; Dydak, Ulrike; Barnard, John; O'Donnell, Brian F.; Breier, Alan; Psychiatry, School of Medicine
    Both auditory evoked responses and metabolites measured by magnetic resonance spectroscopy (MRS) are altered in schizophrenia and other psychotic disorders, but the relationship between electrophysiological and metabolic changes are not well characterized. We examined the relation of MRS metabolites to cognitive and electrophysiological measures in individuals during the early phase of psychosis (EPP) and in healthy control subjects. The mismatch negativity (MMN) of the auditory event-related potential to duration deviant tones and the auditory steady response (ASSR) to 40 Hz stimulation were assessed. MRS was used to quantify glutamate+glutamine (Glx), N-Acetylasparate (NAA), creatine (Cre), myo-inositol (Ins) and choline (Cho) at a voxel placed medially in the frontal cortex. MMN amplitude and ASSR power did not differ between groups. The MRS metabolites Glx, Cre and Cho were elevated in the psychosis group. Partial least squares analysis in the patient group indicated that elevated levels of MRS metabolites were associated with reduced MMN amplitude and increased 40 Hz ASSR power. There were no correlations between the neurobiological measures and clinical measures. These data suggest that elevated neurometabolites early in psychosis are accompanied by altered auditory neurotransmission, possibly indicative of a neuroinflammatory or excitotoxic disturbance which disrupts a wide range of metabolic processes in the cortex.