My research area is examining how disruptions in brain connectivity may influence the pathophysiology, prognosis and treatment of neuropsychiatric disorders. To this end, my group has been focussing on the examination of white matter, whose axons form the anatomical basis of brain connectivity. Much of my work has focussed on the use of a novel magnetic resonance neuroimaging method, diffusion tensor imaging (DTI) to quantitatively assess white matter microstructural status. Our group was one of the first to apply this methodology to the study of schizophrenia (Lim et al., 1999).
My research focus has been two-fold. The first has been to determine the specificity of white matter abnormalities in various neuropsychiatric disorders with known or suspected white matter involvement. To this end we have demonstrated that DTI changes are observed in schizophrenia, normal aging, HIV-1 infection and cocaine dependence. The second focus has been determining the functional consequences of altered white matter diffusion parameters. We have demonstrated significant correlations between white matter DTI measures and functional measures. For example in schizophrenia we have observed significant correlations on measures of impulsivity and aggression (Hoptman et al. 2002) and negative symptoms with orbitofrontal white matter. With regards to treatment response, we found that frontal white matter integrity predicted response to anti-depressant treatment in geriatric depression (Alexopoulos et al., in press).
Future directions are to elucidate the neurobiological underpinnings of the in vivo imaging findings. One strategy is the simultaneous study of fixed tissue (using DTI) and frozen tissue (using Western blot of myelin basic protein, neurofilaments) to uncover potential biochemical correlates of DTI measures. Other avenues we are exploring are the use of mutant (e.g. Shiverer) and transgenic mouse models with known biochemical deficits to tease apart the biochemical contributions to the DTI signal. Recent postmortem gene expression studies in schizophrenia have found reductions in myelination related genes, providing potential genomic targets which may be relevant to the observed white matter imaging findings. For future human in vivo studies, we plan to supplement our imaging data with genomic information starting with the examination of single nucleotide polymorphisms of myelination related genes identified from post-mortem gene expression studies or from convergent loci and convergent functional genomics approaches. Additional magnetic resonance imaging methods are also being developed to provide more specific information about myelin status and neuroaxonal tissue.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Klimes-Dougan B, Chong LS, Samikoglu A, Thai M, Amatya P, Cullen KR, Lim KO. Transcendental meditation and hypothalamic-pituitary-adrenal axis functioning: a pilot, randomized controlled trial with young adults. Stress. 2019 Sep 11:1-11. doi: 10.1080/10253890.2019.1656714.
- Westlund Schreiner M, Klimes-Dougan B, Mueller BA, Nelson KJ, Lim KO, Cullen KR. Neurocircuitry associated with symptom dimensions at baseline and with change in borderline personality disorder. Psychiatry Res Neuroimaging. 2019 Aug 30;290:58-65.
- Lee EHM, Camchong J, Skouras S, Hui CLM, Chan PY, Law EYL, Chong CSY, Chang WC, Chan SKW, Lo WTL, Chen EYH, Lim KO. Differential cortical thinning of auditory cortex in first episode schizophrenia: Association with auditory verbal hallucinations. Schizophr Res. 2018 Dec 1. pii: S0920-9964(18)30665-0.
- Moghimi P, Lim KO, Netoff TI. Data driven classification using fMRI network measures: Application to schizophrenia. Front Neuroinform. 2018 Oct 30;12:71.
- Bishop JR, Lee AM, Mills LJ, Thuras PD, Eum S, Clancy D, Erbes CR, Polusny MA, Lamberty GJ, Lim KO. Methylation of FKBP5 and SLC6A4 in relation to treatment response to mindfulness based stress reduction for posttraumatic stress disorder. Front Psychiatry. 2018 Sep 18;9:418.
- Hare SM, Law AS, Ford JM, Mathalon DH, Ahmadi A, Damaraju E, Bustillo J, Belger A, Lee HJ, Mueller BA, Lim KO, Brown GG, Preda A, van Erp TGM, Potkin SG, Calhoun VD, Turner JA. Disrupted network cross talk, hippocampal dysfunction and hallucinations in schizophrenia. Schizophr Res. 2018 Mar 20;. PMID: 29571753
- Hendrickson TJ, Mueller BA, Sowell ER, Mattson SN, Coles CD, Kable JA, Jones KL, Boys CJ, Lee S, Lim KO, Riley EP, Wozniak JR. Two-year cortical trajectories are abnormal in children and adolescents with prenatal alcohol exposure. Dev Cogn Neurosci. 2018 Feb 21;30:123-133. PMID: 29486453
- Bikson M, Brunoni AR, Charvet LE, Clark VP, Cohen LG, Deng ZD, Dmochowski J, Edwards DJ, Frohlich F, Kappenman ES, Lim KO, Loo C, Mantovani A, McMullen DP, Parra LC, Pearson M, Richardson JD, Rumsey JM, Sehatpour P, Sommers D, Unal G, Wassermann EM, Woods AJ, Lisanby SH. Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop. Brain Stimul. 2017 Dec 29;. PMID: 29398575
- Chong LS, Thai M, Cullen KR, Lim KO, Klimes-Dougan B. Cortisol awakening response, internalizing symptoms, and life satisfaction in emerging adults. Int J Mol Sci. 2017 Nov 27;18(12). pii: E2501.
- Gilmore CS, Dickmann PJ, Nelson BG, Lamberty GJ, Lim KO. Transcranial direct current stimulation (tDCS) paired with a decision-making task reduces risk-taking in a clinically impulsive sample. Brain Stimul. 2017 Nov 21. pii: S1935-861X(17)30967-1.
- Nelson BG, Bassett DS, Camchong J, Bullmore ET, Lim KO. Comparison of large-scale human brain functional and anatomical networks in schizophrenia. Neuroimage Clin. 2017;15:439-448.
- Atkinson DM, Rodman JL, Thuras PD, Shiroma PR, Lim KO. Examining burnout, depression, and self-compassion in Veterans Affairs mental health staff. J Altern Complement Med. 2017;23(7):551-557.
- Albott CS, Shiroma PR, Cullen KR, Johns B, Thuras P, Wels J, Lim KO. The antidepressant effect of repeat dose intravenous ketamine Is delayed by concurrent benzodiazepine use. J Clin Psychiatry. 2017 Mar;78(3):e308-e309.
- Shiroma PR, Thuras P, Johns B, Lim KO. Facial recognition of happiness among older adults with active and remitted major depression. Psychiatry Res. 2016 Sep 30;243:287-291.
- Camchong J, Lim KO, Kumra S. Adverse effects of cannabis on adolescent brain development: A longitudinal study. Cereb Cortex. 2017 1;27:1922-1930.
- Xu T, Cullen KR, Mueller B, Schreiner MW, Lim KO, Schulz SC, Parhi KK. Related Articles Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI. Neuroimage Clin. 2016;11:302-15.
- White LR, Edland SD, Hemmy LS, Montine KS, Zarow C, Sonnen JA, Uyehara-Lock JH, Gelber RP, Ross GW, Petrovitch H, Masaki KH, Lim KO, Launer LJ, Montine TJ. Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia aging studies. Neurology. 2016;86:1000-1008.
- Geisler D, Walton E, Naylor M, Roessner V, Lim KO, Charles Schulz S, Gollub RL, Calhoun VD, Sponheim SR, Ehrlich S. Brain structure and function correlates of cognitive subtypes in schizophrenia. Psychiatry Res. 2015;234:74-83.
- Mueller BA, Lim KO, Hemmy L, Camchong diffusion MRI and its role in neuropsychology. J. Neuropsychol Rev. 2015;25(3):250-271.
- Polusny MA, Erbes CR, Thuras P, Moran A, Lamberty GJ, Collins RC, Rodman JL, Lim KO. Mindfulness-based stress reduction for posttraumatic stress disorder among veterans: A randomized clinical trial. JAMA. 2015;314(5):456-465.
- Shapiro EG, Nestrasil I, Rudser K, Delaney K, Kovac V, Ahmed A, Yund B, Orchard PJ, Eisengart J, Niklason GR, Raiman J, Mamak E, Cowan MJ, Bailey-Olson M, Harmatz P, Shankar SP, Cagle S, Ali N, Steiner RD, Wozniak J, Lim KO, Whitley CB. Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment. Mol Genet Metab. 2015;116:61-68.
- Musgrove D, Eberly L, Klimes-Dougan B, Basgoze Z, Thomas KM, Mueller BA, Houri A, Lim KO, Cullen KR. Impaired bottom-up effective connectivity between amygdala and subgenual anterior cingulate cortex in unmedicated adolescents with major depression: Results from a dynamic causal modeling analysis. Brain Connect. 2015;5(10):608-619.
- Cullen KR, LaRiviere LL, Vizueta N, Thomas KM, Hunt RH, Miller MJ, Lim KO, Schulz SC. Brain activation in response to overt and covert fear and happy faces in women with borderline personality disorder. Brain Imaging Behav. 2016;10:319-331.
- Fryer SL, Roach BJ, Ford JM, Turner JA, van Erp TG, Voyvodic J, Preda A, Belger A, Bustillo J, O'Leary D, Mueller BA, Lim KO, McEwen SC, Calhoun VD, Diaz M, Glover G, Greve D, Wible CG, Vaidya J, Potkin SG, Mathalon DH. Relating Intrinsic Low-Frequency BOLD cortical oscillations to cognition in schizophrenia. Neuropsychopharmacology. 2015;40:2705-2714.
- Launer LJ, Lewis CE, Schreiner PJ, Sidney S, Battapady H, Jacobs DR, Lim KO, D'Esposito M, Zhang Q, Reis J, Davatzikos C, Bryan RN.Vascular factors and multiple measures of early brain health: CARDIA brain MRI study. PLoS One. 2015 Mar 26;10(3):e0122138.
- Bond DJ, Lim KO. (13)C magnetic resonance spectroscopy and glutamate metabolism in mood disorders: current challenges, potential opportunities. Am J Psychiatry. 2014;171:1240-1242.
- Klimes-Dougan B, Eberly LE, Westlund Schreiner M, Kurkiewicz P, Houri A, Schlesinger A, Thomas KM, Mueller BA, Lim KO, Cullen KR. Multilevel assessment of the neurobiological threat system in depressed adolescents: Interplay between the limbic system and hypothalamic-pituitary-adrenal axis. Dev Psychopathol. 2014;26(4 Pt 2):1321-35.
- Camchong J, Macdonald AW 3rd, Mueller BA, Nelson B, Specker S, Slaymaker V, Lim KO. Changes in resting functional connectivity during abstinence in stimulant use disorder: a preliminary comparison of relapsers and abstainers. Drug Alcohol Depend. 2014;139:145-51.
- Wozniak JR, Mueller BA, Lim KO, Hemmy LS, Day JW. Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1. J Neurol Sci. 2014;341(1-2):73-78.
- van Erp TG, Preda A, Nguyen D, Faziola L, Turner J, Bustillo J, Belger A, Lim KO, McEwen S, Voyvodic J, Mathalon DH, Ford J, Potkin SG, Fbirn. Converting positive and negative symptom scores between PANSS and SAPS/SANS. Schizophr Res. 2014;152:289-294.
Current Graduate Students:
Elias Boroda (Neuroscience, University of Minnesota)
Former Graduate Students:
Craig Moodie (Ph. D. 2014, Neuroscience, University of Minnesota).
Dan Franc (Ph.D. 2008, Neuroscience, University of Minnesota).