Decreased Conflict- and Error-Related Activity in the Anterior Cingulate Cortex in Subjects With Schizophrenia

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
American Journal of Psychiatry (Impact Factor: 13.56). 11/2005; 162(10):1833-9. DOI: 10.1176/appi.ajp.162.10.1833
Source: PubMed

ABSTRACT People with schizophrenia have exhibited reduced functional activity in the anterior cingulate cortex during the performance of many types of cognitive tasks and during the commission of errors. According to conflict theory, the anterior cingulate cortex is involved in the monitoring of response conflict, acting as a signal for a need for greater cognitive control. This study examined whether impaired conflict monitoring in people with schizophrenia could underlie reduced anterior cingulate activity during both correct task performance and error-related activity.
Functional activity in the anterior cingulate of 13 schizophrenia patients and 13 healthy comparison subjects was investigated by using event-related fMRI and a Stroop task that allowed simultaneous examination of activity during both conflict (incongruent trials) and error (commission of error trials).
In the presence of comparable reaction time measures for conflict as well as comparable error rates, the schizophrenia subjects showed both decreased conflict- and error-related activity in the same region of the anterior cingulate cortex. Moreover, those with schizophrenia did not exhibit significant post-conflict or post-error behavioral adjustments.
Concurrently reduced conflict- and error-related activity in the anterior cingulate cortex along with reduced trial-to-trial adjustments in performance has not previously been reported in schizophrenia. The current results suggest that impaired conflict monitoring by the anterior cingulate cortex might play an important role in contributing to cognitive control deficits in patients with schizophrenia.

Download full-text


Available from: Angus W MacDonald, Aug 29, 2015
1 Follower
  • Source
    • "Structural magnetic resonance imaging (MRI) and neuropathological findings demonstrate gray matter reductions of the ACC in patients with psychosis, occurring already prior to its onset and, eventually, progressing with illness duration (Fornito et al., 2009). In functional MRI (fMRI) studies, patients with schizophrenia showed reduced conflict-(Snitz et al., 2005) as well as errorrelated activity in the ACC (see Melcher et al., 2008, for a review; Carter et al., 2001; Alain et al., 2002; Kerns et al., 2005), which may normalize upon administration of antipsychotic medications (Snitz et al., 2005; Adams and David, 2007). Studies reported hypo-activation in patients only for the rostral division of the ACC during Stroop (Carter et al., 1997), Go/NoGo (Laurens et al., 2003), oddball (Liddle et al., 2006), or emotion recognition tasks (Habel et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF) seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC), a central hub for cognitive processing, is one of the brain regions known to be dysfunctional in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI) in patients with schizophrenia to enable them to control their ACC activity. Training was performed over 3 days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI). Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. In a stepwise regression analysis, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, patients with schizophrenia can learn to regulate localized brain activity. However, cognitive strategies and neural network location differ from healthy controls. These data emphasize that for therapeutic interventions in patients with schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social NF based on fMRI may be one method to accomplish precise learning targets.
    Frontiers in Behavioral Neuroscience 06/2015; 9:169. DOI:10.3389/fnbeh.2015.00169 · 4.16 Impact Factor
  • Source
    • "Additionally, they are again consistent with the relationship between schizotypy in healthy subjects and the schizophrenia continuum. Consistently, previous studies have indicated that patients with schizophrenia have abnormal prefrontal activity and worse behavioral performance during attentional processing (Weiss et al., 2003; Honey et al., 2005; Kerns et al., 2005; Laurens et al., 2005; MacDonald et al., 2005; Gur et al., 2007). Furthermore, evidence of abnormal prefrontal activity has been reported during cognitive processing in patients with schizophrenia carrying the rs1076560 T allele (Bertolino et al., 2009a,b, 2010; Blasi et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: "Schizotypy" is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum.
    Frontiers in Behavioral Neuroscience 07/2014; 8(235):eCollection2014. DOI:10.3389/fnbeh.2014.00235 · 4.16 Impact Factor
  • Source
    • "Post-mortem studies in brains of schizophrenic patients show that specific markers for populations of inhibitory and excitatory neurons are diminished in auditory-related ACC and mid-dorsolateral prefrontal areas, disrupting the excitatory and inhibitory balance necessary for normal cognitive functions (reviewed in Benes, 2000; Beasley et al., 2002; Volk and Lewis, 2002; Vogels and Abbott, 2007; Fornito et al., 2009; Eisenberg and Berman, 2010). For instance, the ACC shows a decrease in pyramidal neuron density in the deep layers (Benes et al., 2001) and reduced overall activity in schizophrenia (Fletcher et al., 1999; Kerns et al., 2005; Snitz et al., 2005; Allen et al., 2007; Leicht et al., 2010). The deep layers of ACC give rise to projections to lateral prefrontal cortices in monkeys, in a pattern expected to hold for humans based on the predictions of the structural model for connections (Barbas and Rempel-Clower, 1997). "
    [Show abstract] [Hide abstract]
    ABSTRACT: No other modality is more frequently represented in the prefrontal cortex than the auditory, but the role of auditory information in prefrontal functions is not well understood. Pathways from auditory association cortices reach distinct sites in the lateral, orbital, and medial surfaces of the prefrontal cortex in rhesus monkeys. Among prefrontal areas, frontopolar area 10 has the densest interconnections with auditory association areas, spanning a large antero-posterior extent of the superior temporal gyrus from the temporal pole to auditory parabelt and belt regions. Moreover, auditory pathways make up the largest component of the extrinsic connections of area 10, suggesting a special relationship with the auditory modality. Here we review anatomic evidence showing that frontopolar area 10 is indeed the main frontal "auditory field" as the major recipient of auditory input in the frontal lobe and chief source of output to auditory cortices. Area 10 is thought to be the functional node for the most complex cognitive tasks of multitasking and keeping track of information for future decisions. These patterns suggest that the auditory association links of area 10 are critical for complex cognition. The first part of this review focuses on the organization of prefrontal-auditory pathways at the level of the system and the synapse, with a particular emphasis on area 10. Then we explore ideas on how the elusive role of area 10 in complex cognition may be related to the specialized relationship with auditory association cortices.
    Frontiers in Neuroscience 04/2014; 8:77. DOI:10.3389/fnins.2014.00077 · 3.70 Impact Factor
Show more