The Neural Underpinnings of Associative Learning in Health and Psychosis: How Can Performance Be Preserved When Brain Responses Are Abnormal?

Brain Mapping Unit, University of Cambridge, Box 189, Cambridge CB2 0QQ, UK.
Schizophrenia Bulletin (Impact Factor: 8.45). 02/2010; 36(3):465-71. DOI: 10.1093/schbul/sbq005
Source: PubMed


Associative learning experiments in schizophrenia and other psychoses reveal subtle abnormalities in patients' brain responses. These are sometimes accompanied by intact task performance. An important question arises: How can learning occur if the brain system is not functioning normally? Here, we examine a series of possible explanations for this apparent discrepancy: (1) standard brain activation patterns may be present in psychosis but partially obscured by greater noise, (2) brain signals may be more sensitive to real group differences than behavioral measures, and (3) patients may achieve comparable levels of performance to control subjects by employing alternative or compensatory neural strategies. We consider these explanations in relation to data from causal- and reward-learning imaging experiments in first-episode psychosis patients. The findings suggest that a combination of these factors may resolve the question of why performance is sometimes preserved when brain patterns are disrupted.

Download full-text


Available from: Philip Corlett, Dec 27, 2013
  • Source
    • "This type of discrepancy has been frequently reported in the fMRI literature. Possible explanations include: higher sensitivity of brain signals than behavioural measures to detect group differences; or alternative neural strategies employed by patients to achieve comparable levels of performance (Murray et al., 2010). We were unable to differentiate which explanation best accounted for our data, nevertheless, the importance of aberrant brain activation cannot be overlooked. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. Methods: Eighty-two Depressed and 24 healthy female adolescents, aged 12-17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. Results: At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalised after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35-13.27) were related at trend-level to activation changes in orbitofrontal cortex. Limitations: In the follow-up section, a limited number of post-CBT patients were recruited. Conclusions: To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration.
    Journal of Affective Disorders 09/2015; 189:54-61. DOI:10.1016/j.jad.2015.09.008 · 3.38 Impact Factor
  • Source
    • "Problems in emotion processing may cause impaired associative emotional learning in schizophrenia (Exner et al., 2004; Dieleman and Roder, 2013). Some studies have shown deficits in associative emotional learning in patients (Exner et al., 2004) though other studies showed normal associative learning (for review: Murray et al., 2010). Impairments in associative emotional learning might also be associated with difficulties in describing one's feelings with words, which is referred to as emotional verbalizing (Vorst and Bermond, 2001; Aleman, 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Emotional deficits are among the core features of schizophrenia and both associative emotional learning and the related ability to verbalize emotions can be reduced. We investigated whether schizophrenia patients demonstrated impaired function of limbic and prefrontal areas during associative emotional learning. Patients and controls filled out an alexithymia questionnaire and performed an associative emotional learning task with positive, negative and neutral picture-word pairs during fMRI scanning. After scanning, they indicated for each pair whether they remembered it. We conducted standard GLM analysis and Independent Component Analysis (ICA). Both the GLM results and task-related ICA components were compared between groups. The alexithymia questionnaire indicated more cognitive-emotional processing difficulties in patients than controls, but equal experienced intensity of affective states. Patients remembered less picture-word pairs, irrespective of valence. GLM analysis showed significant visual, temporal, amygdalar/hippocampal, and prefrontal activation in all subjects. ICA identified a network of brain areas similar to GLM, mainly in response to negative stimuli. Neither analysis showed differences between patients and controls during learning. Although in previous studies schizophrenia patients showed abnormalities in both memory and emotion processing, neural circuits involved in cross-modal associative emotional learning may remain intact to a certain degree, which may have potential consequences for treatment.
    10/2013; 214(3). DOI:10.1016/j.pscychresns.2013.08.008
  • Source
    • "Second, the neuroanatomical separation of positive and negative saliences in the ARMS-specific brain–cognition patterns, which was particularly expressed by the conversion group, suggests a differential neurocognitive involvement of neural structures. In the light of the considerable neural plasticity observed in early adulthood [Pantelis et al., 2005; Rapoport and Gogtay, 2008; Shaw et al., 2008], one speculative interpretation may be that positive brain–cognition correlations reflect the biological processes associated with the risk for conversion to psychosis, while negative associations result from continuous compensatory processes, which lead to an augmentation of GMV and WMV in the associated brain structures, e.g., through an increase in synaptic density [Murray et al., 2010; Ragland et al., 2004; Rü sch et al., 2007]. This interpretation may be further supported by findings of volumetric increments within paralimbic, inferior temporal, parietal and occipital brain regions of converters vs. nonconverters [Borgwardt et al., 2007] and first-episode patients vs. HC [Cocchi et al., 2009], as well as by reports of ''counterintuitive'' negative brain–cognition correlations in schizophrenic patients vs. HC [Cocchi et al., 2009; Rü sch et al., 2007; Sanfilipo et al., 2002]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Neuropsychological deficits are a core feature of established psychosis and have been previously linked to fronto-temporo-limbic brain alterations. Both neurocognitive and neuroanatomical abnormalities characterize clinical at-risk mental states (ARMS) for psychosis. However, structure-cognition relationships in the ARMS have not been directly explored using multivariate neuroimaging techniques. Methods: Voxel-based morphometry and partial least squares were employed to study system-level covariance patterns between whole-brain morphological data and processing speed, working memory, verbal learning/IQ, and executive functions in 40 ARMS subjects and 30 healthy controls (HC). The detected structure-cognition covariance patterns were tested for significance and reliability using non-parametric permutation and bootstrap resampling. Results: We identified ARMS-specific covariance patterns that described a generalized association of neurocognitive measures with predominantly prefronto-temporo-limbic and subcortical structures as well as the interconnecting white matter. In the conversion group, this generalized profile particularly involved working memory and verbal IQ and was positively correlated with limbic, insular and subcortical volumes as well as negatively related to prefrontal, temporal, parietal, and occipital cortices. Conversely, the neurocognitive profiles in the HC group were confined to working memory, learning and IQ, which were diffusely associated with cortical and subcortical brain regions. Conclusions: These findings suggest that the ARMS and prodromal phase of psychosis are characterized by a convergent mapping from multi-domain neurocognitive measures to a set of prefronto-temporo-limbic and subcortical structures. Furthermore, a neuroanatomical separation between positive and negative brain-cognition correlations may not only point to a biological process determining the clinical risk for disease transition, but also to possible compensatory or dysmaturational neural processes.
    Human Brain Mapping 09/2012; 33(9). DOI:10.1002/hbm.21342 · 5.97 Impact Factor
Show more