[Show abstract][Hide abstract] ABSTRACT: Background
Obsessive–compulsive disorder (OCD) is characterized by maladaptive repetitive behaviors that persist despite feedback. Using multimodal neuroimaging, we tested the hypothesis that this behavioral rigidity reflects impaired use of behavioral outcomes (here, errors) to adaptively adjust responses. We measured both neural responses to errors and adjustments in the subsequent trial to determine whether abnormalities correlate with symptom severity. Since error processing depends on communication between the anterior and the posterior cingulate cortex, we also examined the integrity of the cingulum bundle with diffusion tensor imaging.
Participants performed the same antisaccade task during functional MRI and electroencephalography sessions. We measured error-related activation of the anterior cingulate cortex (ACC) and the error-related negativity (ERN). We also examined post-error adjustments, indexed by changes in activation of the default network in trials surrounding errors.
OCD patients showed intact error-related ACC activation and ERN, but abnormal adjustments in the post- vs. pre-error trial. Relative to controls, who responded to errors by deactivating the default network, OCD patients showed increased default network activation including in the rostral ACC (rACC). Greater rACC activation in the post-error trial correlated with more severe compulsions. Patients also showed increased fractional anisotropy (FA) in the white matter underlying rACC.
Impaired use of behavioral outcomes to adaptively adjust neural responses may contribute to symptoms in OCD. The rACC locus of abnormal adjustment and relations with symptoms suggests difficulty suppressing emotional responses to aversive, unexpected events (e.g., errors). Increased structural connectivity of this paralimbic default network region may contribute to this impairment.
[Show abstract][Hide abstract] ABSTRACT: Recognizing errors and adjusting responses are fundamental to adaptive behavior. The error-related negativity (ERN) and error-related functional MRI (fMRI) activation of the dorsal anterior cingulate cortex (dACC) index these processes and are thought to reflect the same neural mechanism. In the present study, we evaluated this hypothesis. Although errors elicited robust dACC activation using fMRI, combined electroencephalography and magnetoencephalography data localized the ERN to the posterior cingulate cortex (PCC). ERN amplitude correlated with fMRI activation in both the PCC and dACC, and these two regions showed coordinated activity based on functional connectivity MRI. Finally, increased microstructural integrity of the posterior cingulum bundle, as measured by diffusion tensor imaging, predicted faster error correction. These findings suggest that the PCC generates the ERN and communicates with the dACC to subserve error processing. They challenge current models that view fMRI activation of the dACC as the hemodynamic reflection of the ERN.
Proceedings of the National Academy of Sciences 10/2011; 108(42):17556-61. DOI:10.1073/pnas.1103475108 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.
Using an antisaccade paradigm, we found that the 677T allele induces a dose-dependent blunting of dorsal anterior cingulate cortex (dACC) activation in response to errors, a pattern that was identical in healthy individuals and patients with schizophrenia. Further, the normal relationship between dACC activation and error rate was disrupted among carriers of the 677T allele.
These findings implicate an epigenetic mechanism in the neural response to errors, and provide insight into normal cognitive variation through a schizophrenia risk gene.
PLoS ONE 09/2011; 6(9):e25253. DOI:10.1371/journal.pone.0025253 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While existing evidence suggests that older adults have compromised spatial navigation abilities, the effects of age on specific aspects of navigational skill are less well specified. The current study examined age effects on spatial navigation abilities considering the multiple cognitive and neural factors that contribute to successful navigation. Young and older adults completed wayfinding and route learning tasks in a virtual environment and aspects of environmental knowledge were assessed. Prefrontal, caudate and hippocampal volumes were obtained in a subset of older adults. Age differences were observed in both wayfinding and route learning. For wayfinding, there were age effects in recalling landmarks, and recognizing environmental scenes. In the route learning condition, older adults evidenced difficulty with the location, temporal order and directional information of landmarks. In both conditions, there was evidence of age-related differences in the acquisition of configural knowledge. Wayfinding was associated with the hippocampus whereas route learning was associated with the caudate nucleus. These results provide indications of specific aspects of navigational learning that may contribute to age-related declines and potential neural substrates.
Behavioural brain research 05/2010; 209(1):49-58. DOI:10.1016/j.bbr.2010.01.012 · 3.03 Impact Factor