IU Indianapolis ScholarWorks :: Browsing by Author "Francis, Michael M."

Browsing by Author "Francis, Michael M."

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Brain Activation Patterns during Visual Scene Encoding and Recognition fMRI Tasks in Early Phase Psychosis
(Office of the Vice Chancellor for Research, 2015-04-17) Ayoubi, Nawead Z.; Mehdiyoun, Nicole F.; Yung, Matthew G.; Hummer, Tom; Francis, Michael M.; Breier, Alan
Schizophrenia is a chronic and disabling illness that is associated with significant impairments in areas such as independent living, social functioning, and vocational functioning. Cognitive dysfunction is a core facet of schizophrenia with deficits occurring in areas of abstraction, attention, language, and memory. Episodic memory (EM) is a cognitive domain that has been shown to be impaired in schizophrenia. EM combines event-specific autobiographical experiences and information regarding the context in which events took place. Patients with schizophrenia may exhibit broad impairments in EM, with deficits occurring during encoding and retrieval with both visual and verbal tasks. There are a number of inconsistencies in the EM fMRI literature and indicating a need for first episode psychosis (FEP) versus chronic phase schizophrenia research. FEP have fewer and less severe medical comorbidities, shorter durations of antipsychotic treatment exposure, and lower severity of illness, all of which can impact data interpretation. In this study, brain activation patterns were assessed during performance of visual scene encoding and recognition fMRI tasks in FEP patients and healthy control subjects. It is hypothesized that FEP patients would demonstrate decreased activation during encoding and recognition in the main areas that mediate EM function, namely the hippocampus, prefrontal, and parietal cortices. Within the FEP group correlations can be determined by comparing brain activation patterns with cognition (Brief Assessment of Cognition in Schizophrenia [BACS]) and symptom (Positive and Negative Syndrome Scale [PANSS]) outcome measures. Results indicate that during the encoding task FEP exhibited significantly lower activation in the hippocampus and fusiform gyrus when compared to controls. During the recognition task FEP showed a significantly weaker cortical response in the posterior cingulate cortex, the precuneus, and the left middle temporal cortex when compared to controls. These results demonstrate a pattern of alteration in hippocampal, parietal, and temporal activity during EM processes in FEP. Altered hippocampal response in FEP may reflect dysfunctional binding mechanisms and less efficient encoding.
Characterization of white matter abnormalities in early-stage schizophrenia
(Wiley, 2016) Hummer, Tom A.; Francis, Michael M.; Vohs, Jenifer L.; Liffick, Emily; Mehdiyoun, Nicole F.; Breier, Alan; Department of Psychiatry, IU School of Medicine
Aim White matter abnormalities have been reported in schizophrenia and may indicate altered cortical network integrity and structural connectivity, which have been hypothesized as key pathophysiological components of this illness. In this study, we aimed to further characterize the nature and progression of white matter alterations during the early stages of the disorder. Methods We employed diffusion tensor imaging (DTI) approaches to investigate fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) in 40 patients with schizophrenia and related psychotic disorders (aged 18–30 years) who were within 5 years of illness, along with an age-, sex- and race-matched sample of 21 healthy controls. Relationships with illness duration, lifetime antipsychotic medication exposure and symptom levels were examined. Results Patients had lower FA and higher RD than controls in numerous white matter tracts, including the corpus callosum (CC) and the superior longitudinal fasciculus. Illness duration was associated with lower FA and higher RD, most prominently in the CC. No group differences or relationships to illness duration were detected with AD, and no relationships between any DTI measurements and lifetime antipsychotic medication use were found. Conclusions This investigation provides evidence of widespread disruptions to structural connectivity in the early stages of schizophrenia. The relationship to illness duration, coupled with an absence of relationships to AD or antipsychotic drug exposure, provides evidence of a progressive disease process, although prospective assessments with repeated DTI measurements are needed to fully characterize the trajectory of white matter abnormalities in this illness.
Functional network connectivity in early-stage schizophrenia
(Elsevier, 2020-04) Hummer, Tom A.; Yung, Matthew G.; Goñi, Joaquín; Conroy, Susan K.; Francis, Michael M.; Mehdiyoun, Nicole F.; Breier, M. A. Alan; Psychiatry, School of Medicine
Schizophrenia is a disorder of altered neural connections resulting in impaired information integration. Whole brain assessment of within- and between-network connections may determine how information processing is disrupted in schizophrenia. Patients with early-stage schizophrenia (n = 56) and a matched control sample (n = 32) underwent resting-state fMRI scans. Gray matter regions were organized into nine distinct functional networks. Functional connectivity was calculated between 278 gray matter regions for each subject. Network connectivity properties were defined by the mean and variance of correlations of all regions. Whole-brain network measures of global efficiency (reflecting overall interconnectedness) and locations of hubs (key regions for communication) were also determined. The control sample had greater connectivity between the following network pairs: somatomotor-limbic, somatomotor-default mode, dorsal attention-default mode, ventral attention-limbic, and ventral attention-default mode. The patient sample had greater variance in interactions between ventral attention network and other functional networks. Illness duration was associated with overall increases in the variability of network connections. The control group had higher global efficiency and more hubs in the cerebellum network, while patient group hubs were more common in visual, frontoparietal, or subcortical networks. Thus, reduced functional connectivity in patients was largely present between distinct networks, rather than within-networks. The implications of these findings for the pathophysiology of schizophrenia are discussed.
Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates
(MDPI AG (Basel, Switzerland), 2015-06-29) Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H; Breier, Alan; Department of Psychiatry, IU School of Medicine
Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis.
PSYCHOSIS IN HINDSIGHT: A COLLECTIVE RECOLLECTION OF THE ONSET OF PSYCHOSIS
(Office of the Vice Chancellor for Research, 2012-04-13) Francis, Michael M.; Liffick, Emily C.; Mehdiyoun, Nicole F.; Radnovich, Alexander; Breier, Alan
Psychotic disorders cause marked cognitive, perceptual, and social impairments and may lead to significant disability. Those affected with these illnesses may have great difficulty in educational, occupational, and social functioning; especially troubling is the fact that these illness often strike when those afflicted should be entering into some of the most productive years of their lives. The primary purpose of this study is to ascertain the perspective of subjects with psychotic disorders on the mental health system and treatment, stigmatization, social functioning, and symptom experience. This information will be of use in improving treatment engagement, compliance, and education of providers. Fifty subjects with nonaffective psychoses in each of two arms (new onset psychosis and chronic psychosis) will be enrolled and asked to complete a self-administered questionnaire. After subjects complete the questionnaire, investigators will review medical records to confirm subject age and diagnosis, compare subject report with symptomatology, and look for trends or topics of interest in comparing patient survey reports with medical records which may provide for useful insight upon further investigation.
Relationship Between Cognitive Deficits and Duration of Illness in Early-Phase Schizophrenia
(Office of the Vice Chancellor for Research, 2016-04-08) Ayoubi, Nawead Z.; Mehdiyoun, Nicole F.; Francis, Michael M.
Schizophrenia is a chronic and disabling illness in which the etiology is unknown and there is no cure; approximately 1% of people have this disorder that costs an estimated $60 billion annually. The cognitive deficits associated with schizophrenia are a major facet of the disease and attribute to dysfunction in areas of attention, memory, and language. The inconsistencies and scarcity of literature examining the relationship between these cognitive deficits and duration of illness indicate need for this type of research. The primary aim of this study is to determine the correlation between cognitive deficits and duration of illness in early-phase schizophrenia. It is hypothesized that cognition and duration are indirectly related; this hypothesis will be tested using baseline cognitive data from A Double-Blind Trial of Adjunctive Valacyclovir to Improve Cognition in Early Phase Schizophrenia. These correlations can ultimately lead to the next step in discovering the cure for schizophrenia.
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.
Repetitive Transcranial Magnetic Stimulation as a Therapeutic and Probe in Schizophrenia: Examining the Role of Neuroimaging and Future Directions
(Elsevier, 2021) Brandt, Stephen J.; Oral, Halimah Y.; Arellano‑Bravo, Carla; Plawecki, Martin H.; Hummer, Tom A.; Francis, Michael M.; Psychiatry, School of Medicine
Schizophrenia is a complex condition associated with perceptual disturbances, decreased motivation and affect, and disrupted cognition. Individuals living with schizophrenia may experience myriad poor outcomes, including impairment in independent living and function as well as decreased life expectancy. Though existing treatments may offer benefit, many individuals still experience treatment resistant and disabling symptoms. In light of the negative outcomes associated with schizophrenia and the limitations in currently available treatments, there is a significant need for novel therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can modulate the activity of discrete cortical regions, allowing direct manipulation of local brain activation and indirect manipulation of the target's associated neural networks. rTMS has been studied in schizophrenia for the treatment of auditory hallucinations, negative symptoms, and cognitive deficits, with mixed results. The field's inability to arrive at a consensus on the use rTMS in schizophrenia has stemmed from a variety of issues, perhaps most notably the significant heterogeneity amongst existing trials. In addition, it is likely that factors specific to schizophrenia, rather than the rTMS itself, have presented barriers to the interpretation of existing results. However, advances in approaches to rTMS as a biologic probe and therapeutic, many of which include the integration of neuroimaging with rTMS, offer hope that this technology may still play a role in improving the understanding and treatment of schizophrenia.

Browsing by Author "Francis, Michael M."

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