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Callosal Interhemispheric Communication in Mild Traumatic Brain Injury: A Mediation Analysis on WM Microstructure Effects

Chung, Sohae; Bacon, Tamar; Rath, Joseph F; Alivar, Alaleh; Coelho, Santiago; Amorapanth, Prin; Fieremans, Els; Novikov, Dmitry S; Flanagan, Steven R; Bacon, Joshua H; Lui, Yvonne W
BACKGROUND AND PURPOSE/OBJECTIVE:Because the corpus callosum connects the left and right hemispheres and a variety of WM bundles across the brain in complex ways, damage to the neighboring WM microstructure may specifically disrupt interhemispheric communication through the corpus callosum following mild traumatic brain injury. Here we use a mediation framework to investigate how callosal interhemispheric communication is affected by WM microstructure in mild traumatic brain injury. MATERIALS AND METHODS/METHODS:Multishell diffusion MR imaging was performed on 23 patients with mild traumatic brain injury within 1 month of injury and 17 healthy controls, deriving 11 diffusion metrics, including DTI, diffusional kurtosis imaging, and compartment-specific standard model parameters. Interhemispheric processing speed was assessed using the interhemispheric speed of processing task (IHSPT) by measuring the latency between word presentation to the 2 hemivisual fields and oral word articulation. Mediation analysis was performed to assess the indirect effect of neighboring WM microstructures on the relationship between the corpus callosum and IHSPT performance. In addition, we conducted a univariate correlation analysis to investigate the direct association between callosal microstructures and IHSPT performance as well as a multivariate regression analysis to jointly evaluate both callosal and neighboring WM microstructures in association with IHSPT scores for each group. RESULTS:Several significant mediators in the relationships between callosal microstructure and IHSPT performance were found in healthy controls. However, patients with mild traumatic brain injury appeared to lose such normal associations when microstructural changes occurred compared with healthy controls. CONCLUSIONS:This study investigates the effects of neighboring WM microstructure on callosal interhemispheric communication in healthy controls and patients with mild traumatic brain injury, highlighting that neighboring noncallosal WM microstructures are involved in callosal interhemispheric communication and information transfer. Further longitudinal studies may provide insight into the temporal dynamics of interhemispheric recovery following mild traumatic brain injury.
PMID: 38637026
ISSN: 1936-959x
CID: 5650822

Veteran Beliefs About the Causes of Gulf War Illness and Expectations for Improvement

Kane, Naomi S; Hassabelnaby, Raghad; Sullivan, Nicole L; Graff, Fiona; Litke, David R; Quigley, Karen S; Pigeon, Wilfred R; Rath, Joseph F; Helmer, Drew A; McAndrew, Lisa M
BACKGROUND:Individuals' beliefs about the etiology of persistent physical symptoms (PPS) are linked to differences in coping style. However, it is unclear which attributions are related to greater expectations for improvement. METHOD AND RESULTS/RESULTS:A cross-sectional regression analysis (N = 262) indicated that Veterans with Gulf War Illness (GWI) who attributed their GWI to behavior, (e.g., diet and exercise), had greater expectations for improvement (p = .001) than those who attributed their GWI to deployment, physical, or psychological causes (p values > .05). CONCLUSIONS:Findings support the possible clinical utility of exploring perceived contributing factors of PPS, which may increase perceptions that improvement of PPS is possible. TRIAL REGISTRATION/ Identifier: NCT02161133.
PMID: 36973578
ISSN: 1532-7558
CID: 5624242

Microstructural and Microvascular Alterations in Psychotic Spectrum Disorders: A Three-Compartment Intravoxel Incoherent Imaging and Free Water Model

McKenna, Faye; Gupta, Pradeep Kumar; Sui, Yu Veronica; Bertisch, Hilary; Gonen, Oded; Goff, Donald C; Lazar, Mariana
BACKGROUND AND HYPOTHESIS:Microvascular and inflammatory mechanisms have been hypothesized to be involved in the pathophysiology of psychotic spectrum disorders (PSDs). However, data evaluating these hypotheses remain limited. STUDY DESIGN:We applied a three-compartment intravoxel incoherent motion free water imaging (IVIM-FWI) technique that estimates the perfusion fraction (PF), free water fraction (FW), and anisotropic diffusion of tissue (FAt) to examine microvascular and microstructural changes in gray and white matter in 55 young adults with a PSD compared to 37 healthy controls (HCs). STUDY RESULTS:We found significantly increased PF, FW, and FAt in gray matter regions, and significantly increased PF, FW, and decreased FAt in white matter regions in the PSD group versus HC. Furthermore, in patients, but not in the HC group, increased PF, FW, and FAt in gray matter and increased PF in white matter were significantly associated with poor performance on several cognitive tests assessing memory and processing speed. We additionally report significant associations between IVIM-FWI metrics and myo-inositol, choline, and N-acetylaspartic acid magnetic resonance spectroscopy imaging metabolites in the posterior cingulate cortex, which further supports the validity of PF, FW, and FAt as microvascular and microstructural biomarkers of PSD. Finally, we found significant relationships between IVIM-FWI metrics and the duration of psychosis in gray and white matter regions. CONCLUSIONS:The three-compartment IVIM-FWI model provides metrics that are associated with cognitive deficits and may reflect disease progression.
PMID: 36921060
ISSN: 1745-1701
CID: 5590612

Comparison of Informational and Educational Resource Provision for Individuals Living With Traumatic Brain Injury Based on Language, Nativity, and Neighborhood

Wilson, Judith; McGiffin, Jed N; Smith, Michelle; Garduño-Ortega, Olga; Talis, Elina; Zarate, Alejandro; Jenkins, Natalie; Rath, Joseph F; Bushnik, Tamara
OBJECTIVE:To examine a resource provision program for individuals living with moderate-to-severe traumatic brain injury (TBI), using a comparison of the resources provided across social differences of language, nativity, and neighborhood. SETTING/METHODS:The Rusk Rehabilitation TBI Model System (RRTBIMS) collects data longitudinally on individuals from their associated private and public hospitals, located in New York City. PARTICIPANTS/METHODS:A total of 143 individuals with TBI or their family members. DESIGN/METHODS:An observational study of relative frequency of resource provision across variables of language, nativity, and neighborhood, using related-samples nonparametric analyses via Cochran's Q test. MAIN MEASURES/METHODS:Variables examined were language, place of birth, residence classification as medically underserved area/population (MUA), and resource categories. RESULTS:Results indicate that US-born persons with TBI and those living in medically underserved communities are provided more resources than those who are born outside the United States or reside in communities identified as adequately medically served. Language was not found to be a factor. CONCLUSION/CONCLUSIONS:Lessons learned from this research support the development of this resource provision program, as well as guide future programs addressing the gaps in health information resources for groups negatively impacted by social determinants of health (SDoH). An approach with immigrant participants should take steps to elicit questions and requests, or offer resources explicitly. We recommend research looking at what interpreter strategies are most effective and research on SDoH in relation to the dynamic interaction of variables in the neighborhood setting.
PMID: 36730859
ISSN: 1550-509x
CID: 5420432

Effect of Problem-solving Treatment on Self-reported Disability Among Veterans With Gulf War Illness: A Randomized Clinical Trial

McAndrew, Lisa M; Quigley, Karen S; Lu, Shou-En; Litke, David; Rath, Joseph F; Lange, Gudrun; Santos, Susan L; Anastasides, Nicole; Petrakis, Beth Ann; Greenberg, Lauren; Helmer, Drew A; Pigeon, Wilfred R
IMPORTANCE/UNASSIGNED:Few evidence-based treatments are available for Gulf War illness (GWI). Behavioral treatments that target factors known to maintain the disability from GWI, such as problem-solving impairment, may be beneficial. Problem-solving treatment (PST) targets problem-solving impairment and is an evidence-based treatment for other conditions. OBJECTIVE/UNASSIGNED:To examine the efficacy of PST to reduce disability, problem-solving impairment, and physical symptoms in GWI. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This multicenter randomized clinical trial conducted in the US Department of Veterans Affairs compared PST with health education in a volunteer sample of 511 Gulf War veterans with GWI and disability (January 1, 2015, to September 1, 2019); outcomes were assessed at 12 weeks and 6 months. Statistical analysis was conducted between January 1, 2019, and December 31, 2020. INTERVENTIONS/UNASSIGNED:Problem-solving treatment taught skills to improve problem-solving. Health education provided didactic health information. Both were delivered by telephone weekly for 12 weeks. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was reduction from baseline to 12 weeks in self-report of disability (World Health Organization Disability Assessment Schedule). Secondary outcomes were reductions in self-report of problem-solving impairment and objective problem-solving. Exploratory outcomes were reductions in pain, pain disability, and fatigue. RESULTS/UNASSIGNED:A total of 268 veterans (mean [SD] age, 52.9 [7.3] years; 88.4% male; 66.8% White) were randomized to PST (n = 135) or health education (n = 133). Most participants completed all 12 sessions of PST (114 of 135 [84.4%]) and health education (120 of 133 [90.2%]). No difference was found between groups in reductions in disability at the end of treatment. Results suggested that PST reduced problem-solving impairment (moderate effect, 0.42; P = .01) and disability at 6 months (moderate effect, 0.39; P = .06) compared with health education. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial of the efficacy of PST for GWI, no difference was found between groups in reduction in disability at 12 weeks. Problem-solving treatment had high adherence and reduced problem-solving impairment and potentially reduced disability at 6 months compared with health education. These findings should be confirmed in future studies. TRIAL REGISTRATION/ Identifier: NCT02161133.
PMID: 36472870
ISSN: 2574-3805
CID: 5374962

Decreased basal ganglia and thalamic iron in early psychotic spectrum disorders are associated with increased psychotic and schizotypal symptoms

Sui, Yu Veronica; McKenna, Faye; Bertisch, Hilary; Storey, Pippa; Anthopolos, Rebecca; Goff, Donald C; Samsonov, Alexey; Lazar, Mariana
Iron deficits have been reported as a risk factor for psychotic spectrum disorders (PSD). However, examinations of brain iron in PSD remain limited. The current study employed quantitative MRI to examine iron content in several iron-rich subcortical structures in 49 young adult individuals with PSD (15 schizophrenia, 17 schizoaffective disorder, and 17 bipolar disorder with psychotic features) compared with 35 age-matched healthy controls (HC). A parametric approach based on a two-pool magnetization transfer model was applied to estimate longitudinal relaxation rate (R1), which reflects both iron and myelin, and macromolecular proton fraction (MPF), which is specific to myelin. To describe iron content, a synthetic effective transverse relaxation rate (R2*) was modeled using a linear fitting of R1 and MPF. PSD patients compared to HC showed significantly reduced R1 and synthetic R2* across examined regions including the pallidum, ventral diencephalon, thalamus, and putamen areas. This finding was primarily driven by decreases in the subgroup with schizophrenia, followed by schizoaffective disorder. No significant group differences were noted for MPF between PSD and HC while for regional volume, significant reductions in patients were only observed in bilateral caudate, suggesting that R1 and synthetic R2* reductions in schizophrenia and schizoaffective patients likely reflect iron deficits that either occur independently or precede structural and myelin changes. Subcortical R1 and synthetic R2* were also found to be inversely related to positive symptoms within the PSD group and to schizotypal traits across the whole sample. These findings that decreased iron in subcortical regions are associated with PSD risk and symptomatology suggest that brain iron deficiencies may play a role in PSD pathology and warrant further study.
PMID: 36071113
ISSN: 1476-5578
CID: 5332512

Development of an MMPI reference group for outpatients with persisting symptoms following mild TBI

Childs, Amanda; Bertisch, Hilary; Talis, Elina; Ricker, Joseph H; Rath, Joseph F
OBJECTIVE/UNASSIGNED:To develop an MMPI-2-RF reference group for persistently symptomatic patients with mTBI in order to aid interpretation and better evaluate atypical scale elevations. METHOD/UNASSIGNED:Using the Q Local MMPI-2-RF Comparison Group Generator (CGG), 200 valid MMPI-2-RF profiles were aggregated for mTBI outpatients with persisting symptoms 2-24 months post injury. RESULTS/UNASSIGNED:scores > 60 and standard deviations > 10 were observed for the F-r (Infrequent Responses), Fs (Infrequent Somatic Responses), FBS-r (Symptom Validity), RBS (Response Bias Scale), RC1 (Somatic Complaints), MLS (Malaise), HPC (Head Pain Complaints), NUC (Neurological Complaints), and COG (Cognitive Complaints) scales. All other scales were consistent with established norms for the general population. CONCLUSION/UNASSIGNED:This study is the first to establish an empirically derived MMPI reference group for individuals with persisting symptoms following mTBI. By comparing MMPI profiles of patients with mTBI against this reference group, clinicians may be better able to identify abnormal symptomatology. Evaluating profiles within this context may allow for more accurate case conceptualization and targeted treatment recommendations for those patients who demonstrate disproportionate symptomatology outside the range of the mTBI reference group.
PMID: 36324279
ISSN: 1362-301x
CID: 5358662

Brief Report: Cognitive Dependence in Physically Independent Patients at Discharge from Acute Traumatic Brain Injury Rehabilitation

Rath, Joseph F; McGiffin, Jed N; Glubo, Heather; McDermott, Hannah W; Beattie, Aaron; Arutiunov, Caitlyn; Schaefer, Lynn A; Im, Brian; Bushnik, Tamara
OBJECTIVE:To determine the incidence of cognitive dependence in adults who are physically independent at discharge from acute traumatic brain injury (TBI) rehabilitation. DESIGN/METHODS:Analysis of historical clinical and demographic data obtained from inpatient stay. SETTING/METHODS:Inpatient rehabilitation unit in a large, metropolitan university hospital. PARTICIPANTS/METHODS:Adult inpatients with moderate-to-severe TBI (N = 226) who were physically independent at discharge from acute rehabilitation. INTERVENTIONS/METHODS:Not applicable MAIN OUTCOME MEASURES: FIM Motor and Cognitive subscales, discharge destination, and care plan. RESULTS:Approximately 69% (n = 155) of the physically independent inpatients were cognitively dependent at discharge from acute rehabilitation, with the highest proportions of dependence found in the domains of problem solving and memory. Most (82.6%; n =128) of these physically independent, yet cognitively dependent, patients were discharged home. Of those discharged to home, 82% (n = 105) were discharged to the care of family members, and 11% (n = 15) were discharged home alone. Patients from racial-ethnic minority backgrounds were significantly more likely than White patients to be discharged while cognitively dependent. CONCLUSIONS:The majority of physically independent TBI patients were cognitively dependent at the time of discharge from acute inpatient rehabilitation. Further research is needed to understand the impact of cognitive dependence on caregiver stress and strain and the disproportionate burden on racial-ethnic minority patients and families. Given the potential functional and safety limitations imposed by cognitive deficits, healthcare policy and practice should facilitate delivery of cognitive rehabilitation services in acute TBI rehabilitation.
PMID: 35196504
ISSN: 1532-821x
CID: 5163132

Multi-shell diffusion MR imaging and brain microstructure after mild traumatic brain injury: A focus on working memory

Chapter by: Chung, Sohae; Fieremans, Els; Rath, Joseph F.; Lui, Yvonne W.
in: Cellular, Molecular, Physiological, and Behavioral Aspects of Traumatic Brain Injury by
[S.l.] : Elsevier, 2022
pp. 393-403
ISBN: 9780128230602
CID: 5349102

The effects of plasticity-based cognitive rehabilitation on resting-state functional connectivity in chronic traumatic brain injury: A pilot study

Lindsey, Hannah M; Lazar, Mariana; Mercuri, Giulia; Rath, Joseph F; Bushnik, Tamara; Flanagan, Steven; Voelbel, Gerald T
BACKGROUND:Traumatic brain injury (TBI) often results in chronic impairments to cognitive function, and these may be related to disrupted functional connectivity (FC) of the brain at rest. OBJECTIVE:To investigate changes in default mode network (DMN) FC in adults with chronic TBI following 40 hours of auditory processing speed training. METHODS:Eleven adults with chronic TBI underwent 40-hours of auditory processing speed training over 13-weeks and seven adults with chronic TBI were assigned to a non-intervention control group. For all participants, resting-state FC and cognitive and self-reported function were measured at baseline and at a follow-up visit 13-weeks later. RESULTS:No significant group differences in cognitive function or resting-state FC were observed at baseline. Following training, the intervention group demonstrated objective and subjective improvements on cognitive measures with moderate-to-large effect sizes. Repeated measures ANCOVAs revealed significant (p <  0.001) group×time interactions, suggesting training-related changes in DMN FC, and semipartial correlations demonstrated that these were associated with changes in cognitive functioning. CONCLUSIONS:Changes in the FC between the DMN and other resting-state networks involved in the maintenance and manipulation of internal information, attention, and sensorimotor functioning may be facilitated through consistent participation in plasticity-based auditory processing speed training in adults with chronic TBI.
PMID: 35404295
ISSN: 1878-6448
CID: 5205092