TY - JOUR
T1 - Hypo-metabolism of the rostral anterior cingulate cortex associated with working memory impairment in 18 cases of schizophrenia
AU - Mazgaj, Robert
AU - Tal, Assaf
AU - Goetz, Raymond
AU - Lazar, Mariana
AU - Rothman, Karen
AU - Messinger, Julie Walsh
AU - Malaspina, Dolores
AU - Gonen, Oded
N1 - Funding Information:
This work was supported by NIH Grants NS050520, EB01015, RC1MH088843, and MH01699.
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Working memory (Work-Mem), the capacity to hold and manipulate information, activates the anterior cingulate cortex (ACC), especially its caudal subregion. Impaired Work-Mem and structural and functional abnormalities of the ACC are reported in schizophrenia. This study aims to elucidate the pathogenesis of Work-Mem dysfunction in schizophrenia by comparing metabolite concentrations across ACC subregions. This retrospective study of 18 schizophrenia cases and 10 matched controls used proton magnetic resonance spectroscopic imaging (1H-MRSI, TR/TE = 1800/35 ms, 0.5 cm3 spatial resolution) to test whether the Work-Mem Index of the Wechsler Adult Intelligence Scale, third edition is associated with differences in the rostral to caudal ACC ratios of N-acetylaspartate (NAA) and creatine (Cr). Higher caudal:rostral ACC Cr (but not NAA) concentrations were associated with decreased Work-Mem Index in cases (r = -0.6, p = 0.02), with a similar trend in controls (r = -0.56, p = 0.10), although caudal:rostral ACC Cr correlated with NAA in cases and controls (r = 0.67 and 0.62, p < 0.05 for both). NAA and Cr ratios did not correlate with myo-inositol, excluding gliosis as the underlying process. Subjects’ sex and age had no effects on these relationships. The findings suggest that rostral ACC energy hypo-metabolism, possibly arising from neurodevelopmental processes, is associated with working memory impairment in schizophrenia. Changes in the rostral (not the expected caudal) subregion underscore the interconnections between the ACC subregions and may offer laboratory markers for treatment trials, etiology studies, and perhaps even enhanced identification of prodromal “at risk” subjects.
AB - Working memory (Work-Mem), the capacity to hold and manipulate information, activates the anterior cingulate cortex (ACC), especially its caudal subregion. Impaired Work-Mem and structural and functional abnormalities of the ACC are reported in schizophrenia. This study aims to elucidate the pathogenesis of Work-Mem dysfunction in schizophrenia by comparing metabolite concentrations across ACC subregions. This retrospective study of 18 schizophrenia cases and 10 matched controls used proton magnetic resonance spectroscopic imaging (1H-MRSI, TR/TE = 1800/35 ms, 0.5 cm3 spatial resolution) to test whether the Work-Mem Index of the Wechsler Adult Intelligence Scale, third edition is associated with differences in the rostral to caudal ACC ratios of N-acetylaspartate (NAA) and creatine (Cr). Higher caudal:rostral ACC Cr (but not NAA) concentrations were associated with decreased Work-Mem Index in cases (r = -0.6, p = 0.02), with a similar trend in controls (r = -0.56, p = 0.10), although caudal:rostral ACC Cr correlated with NAA in cases and controls (r = 0.67 and 0.62, p < 0.05 for both). NAA and Cr ratios did not correlate with myo-inositol, excluding gliosis as the underlying process. Subjects’ sex and age had no effects on these relationships. The findings suggest that rostral ACC energy hypo-metabolism, possibly arising from neurodevelopmental processes, is associated with working memory impairment in schizophrenia. Changes in the rostral (not the expected caudal) subregion underscore the interconnections between the ACC subregions and may offer laboratory markers for treatment trials, etiology studies, and perhaps even enhanced identification of prodromal “at risk” subjects.
KW - Anterior cingulate cortex
KW - Creatine
KW - Energy metabolism
KW - Proton magnetic resonance spectroscopic imaging
KW - Schizophrenia
KW - Working memory
UR - http://www.scopus.com/inward/record.url?scp=84959931737&partnerID=8YFLogxK
U2 - 10.1007/s11682-015-9372-x
DO - 10.1007/s11682-015-9372-x
M3 - Article
C2 - 25804309
AN - SCOPUS:84959931737
SN - 1931-7557
VL - 10
SP - 115
EP - 123
JO - Brain Imaging and Behavior
JF - Brain Imaging and Behavior
IS - 1
ER -