Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis
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Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n = 35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness.
KeywordsEpisodic memory Encoding Recognition Early phase psychosis fMRI Cognition
The authors thank Megan Gaunnac, Teresa Kulig, Emmalee Metzler, Heidi Hedrick, John West, Yang Wang, Kelsey Benson, Kami Walters, Katie White, Joan Showalter, and David Spradley for their technical support and recruitment efforts. The authors would also like to thank the Eskenazi Health Midtown Community Mental Health Center for its continued research support.
The authors would like to thank the Stanley Medical Research Institute, grant #10T-002, for providing funding for this study. Additional support was obtained from grant #UH3TR000955, supported by the National Center For Advancing Translational Sciences of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Stanley Medical Research Institute or the National Institutes of Health.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.
Drs. Francis, Hummer, Vohs, Liffick, Radnovich, McDonald, Saykin, and Breier and Ms. Mehdiyoun and Mr. Yung declare that they have no conflict of interest.
- Allen, P., Seal, M. L., Valli, I., Fusar-Poli, P., Perlini, C., Day, F., & McGuire, P. K. (2011). Altered prefrontal and hippocampal function during verbal encoding and recognition in people with prodromal symptoms of psychosis. Schizophrenia Bulletin, 37(4), 746–756. doi: 10.1093/schbul/sbp113.PubMedPubMedCentralCrossRefGoogle Scholar
- Cohen, N. J., Ryan, J., Hunt, C., Romine, L., Wszalek, T., & Nash, C. (1999). Hippocampal system and declarative (relational) memory: summarizing the data from functional neuroimaging studies. Hippocampus, 9(1), 83–98. doi: 10.1002/(SICI)1098-1063(1999)9:1<83::AID-HIPO9>3.0.CO;2-7.PubMedCrossRefGoogle Scholar
- Davidson, M., Galderisi, S., Weiser, M., Werbeloff, N., Fleischhacker, W. W., Keefe, R. S., & Kahn, R. S. (2009). Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). The American Journal of Psychiatry, 166(6), 675–682. doi: 10.1176/appi.ajp.2008.08060806.PubMedCrossRefGoogle Scholar
- First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2002). Structured clinical Interview for DSM-IV-TR Axis I disorders, research version, patient edition. New York: Biometrics Research, New York State Psychiatric Institute.Google Scholar
- Friedman, J. I., Harvey, P. D., Coleman, T., Moriarty, P. J., Bowie, C., Parrella, M., & Davis, K. L. (2001). Six-year follow-up study of cognitive and functional status across the lifespan in schizophrenia: a comparison with Alzheimer’s disease and normal aging. The American Journal of Psychiatry, 158(9), 1441–1448.PubMedCrossRefGoogle Scholar
- Harvey, P. D., & McGurk, S. R. (2000). Cost of schizophrenia: focus on vocational impairment. The Economics of Neuroscience, 2, 42–48.Google Scholar
- Hofer, A., Weiss, E. M., Golaszewski, S. M., Siedentopf, C. M., Brinkhoff, C., Kremser, C., & Fleischhacker, W. W. (2003). Neural correlates of episodic encoding and recognition of words in unmedicated patients during an acute episode of schizophrenia: a functional MRI study. The American Journal of Psychiatry, 160(10), 1802–1808.PubMedCrossRefGoogle Scholar
- Keefe, R. S., Harvey, P. D., Goldberg, T. E., Gold, J. M., Walker, T. M., Kennel, C., & Hawkins, K. (2008). Norms and standardization of the Brief Assessment of Cognition in Schizophrenia (BACS). Schizophrenia Research, 102(1–3), 108–115. doi: 10.1016/j.schres.2008.03.024.PubMedCrossRefGoogle Scholar
- Pantelis, C., Velakoulis, D., McGorry, P. D., Wood, S. J., Suckling, J., Phillips, L. J., & McGuire, P. K. (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet, 361(9354), 281–288. doi: 10.1016/S0140-6736(03)12323-9.PubMedCrossRefGoogle Scholar
- Ragland, J. D., Gur, R. C., Raz, J., Schroeder, L., Kohler, C. G., Smith, R. J., & Gur, R. E. (2001). Effect of schizophrenia on frontotemporal activity during word encoding and recognition: a PET cerebral blood flow study. The American Journal of Psychiatry, 158(7), 1114–1125.PubMedPubMedCentralCrossRefGoogle Scholar
- Ragland, J. D., Laird, A. R., Ranganath, C., Blumenfeld, R. S., Gonzales, S. M., & Glahn, D. C. (2009). Prefrontal activation deficits during episodic memory in schizophrenia. The American Journal of Psychiatry, 166(8), 863–874. doi: 10.1176/appi.ajp.2009.08091307.PubMedPubMedCentralCrossRefGoogle Scholar
- Snitz, B. E., Macdonald, A. W., 3rd, & Carter, C. S. (2006). Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophrenia Bulletin, 32(1), 179–194. doi: 10.1093/schbul/sbi048.PubMedPubMedCentralCrossRefGoogle Scholar
- Spaniol, J., Davidson, P. S., Kim, A. S., Han, H., Moscovitch, M., & Grady, C. L. (2009). Event-related fMRI studies of episodic encoding and retrieval: meta-analyses using activation likelihood estimation. Neuropsychologia, 47(8–9), 1765–1779. doi: 10.1016/j.neuropsychologia.2009.02.028.PubMedCrossRefGoogle Scholar
- Sponheim, S. R., Jung, R. E., Seidman, L. J., Mesholam-Gately, R. I., Manoach, D. S., O’Leary, D. S., & Schulz, S. C. (2010). Cognitive deficits in recent-onset and chronic schizophrenia. Journal of Psychiatric Research, 44(7), 421–428. doi: 10.1016/j.jpsychires.2009.09.010.PubMedPubMedCentralCrossRefGoogle Scholar
- Stolz, E., Pancholi, K. M., Goradia, D. D., Paul, S., Keshavan, M. S., Nimgaonkar, V. L., & Prasad, K. M. (2012). Brain activation patterns during visual episodic memory processing among first-degree relatives of schizophrenia subjects. NeuroImage, 63(3), 1154–1161. doi: 10.1016/j.neuroimage.2012.08.030.PubMedPubMedCentralCrossRefGoogle Scholar
- Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain. 3-Dimensional proportional system: an approach to cerebral imaging.Google Scholar
- Tulving, E. (1972). Episodic and semantic memory. New York: Academic Press, Inc.Google Scholar
- Tulving, E., Kapur, S., Markowitsch, H. J., Craik, F. I., Habib, R., & Houle, S. (1994). Neuroanatomical correlates of retrieval in episodic memory: auditory sentence recognition. Proceedings of the National Academy of Sciences of the United States of America, 91(6), 2012–2015.PubMedPubMedCentralCrossRefGoogle Scholar
- Wiser, A. K., Andreasen, N. C., O’Leary, D. S., Watkins, G. L., Boles Ponto, L. L., & Hichwa, R. D. (1998). Dysfunctional cortico-cerebellar circuits cause ‘cognitive dysmetria’ in schizophrenia. Neuroreport, 9(8), 1895–1899.Google Scholar