Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele

Department of Neurology, University of Lübeck, Ratzeburger Alle 160, 23538 Lübeck, Germany.
Brain (Impact Factor: 9.2). 03/2012; 135(Pt 4):1128-40. DOI: 10.1093/brain/aws040
Source: PubMed


Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia-cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia-cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons ('mirror neurons') in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia-cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in the right ventrolateral premotor cortex during execution and perception of affective facial gestures than healthy controls. Furthermore, Parkin mutation carriers showed a slightly reduced ability to recognize facial emotions that was least severe in individuals who showed the strongest increase of ventrolateral premotor activity. In addition, Parkin mutation carriers showed a significantly weaker than normal increase of activity in the left lateral orbitofrontal cortex (inferior frontal gyrus pars orbitalis, Brodmann area 47), which was unrelated to facial emotion recognition ability. These findings are consistent with the hypothesis that compensatory activity in the ventrolateral premotor cortex during processing of affective facial gestures can reduce impairments in facial emotion recognition in subclinical Parkin mutation carriers. A breakdown of this compensatory mechanism might lead to the impairment of facial expressivity and facial emotion recognition observed in manifest Parkinson's disease.

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Available from: Peter P Pramstaller, Feb 17, 2015
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    • "One further explanation for unimpaired facial emotion recognition in PD could be due to compensatory mechanisms as long as the disease is less advanced. Findings by Anders et al. [50] who investigated positive facial expressions in Parkin mutation carriers revealed that compensatory (increased) activity in the ventrolateral premotor cortex during emotion processing can diminish recognition impairments . Furthermore, Wieser et al. [16] reported that early visual discrimination of facial expressions was diminished on electrocortical level in PD, whereas patients showed no impairments in emotion recognition as measured by affective ratings. "
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    ABSTRACT: A specific non-motor impairment in Parkinson's disease (PD) concerns difficulties to accurately identify facial emotions. Findings are numerous but very inconsistent, ranging from general discrimination deficits to problems for specific emotions up to no impairment at all. By contrast, only a few studies exist about emotion experience, altered affective traits and states in PD.
    Preview · Article · Dec 2015
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    • "This effect was present in the hypodopaminergic state and could partially be restored by dopamine repletion . In a more recent fMRI study by Anders et al. (2012) asymptomatic Parkin mutation carriers were presented with affective facial expressions (happiness, fear, disgust, anger, sadness, and surprise) [13]. Relative to healthy controls, the mutation carriers showed a comparable recognition accuracy for 'clear-cut' affective expressions, but their recognition performance was decreased for 'fuzzy' emotional faces. "
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    ABSTRACT: Background: Findings of behavioral studies on facial emotion recognition in Parkinson's disease (PD) are very heterogeneous. Therefore, the present investigation additionally used functional magnetic resonance imaging (fMRI) in order to compare brain activation during emotion perception between PD patients and healthy controls. Methods and findings: We included 17 nonmedicated, nondemented PD patients suffering from mild to moderate symptoms and 22 healthy controls. The participants were shown pictures of facial expressions depicting disgust, fear, sadness, and anger and they answered scales for the assessment of affective traits. The patients did not report lowered intensities for the displayed target emotions, and showed a comparable rating accuracy as the control participants. The questionnaire scores did not differ between patients and controls. The fMRI data showed similar activation in both groups except for a generally stronger recruitment of somatosensory regions in the patients. Conclusions: Since somatosensory cortices are involved in the simulation of an observed emotion, which constitutes an important mechanism for emotion recognition, future studies should focus on activation changes within this region during the course of disease.
    Full-text · Article · Aug 2015 · PLoS ONE
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    • "During this period, it is assumed that effective neural plasticity and functional reserve, allows people to cope surprisingly well with progressive neural dysfunction (Palop et al., 2006). Neuroimaging studies of nonmanifesting carriers of known genetic risk factors for PD such as mutations in the Parkin and PINK1 genes have shed light on cerebral changes in population at risk (Buhmann et al., 2005; van Nuenen et al., 2009; Anders et al., 2012). The G2019S mutation causes disease that is similar to idiopathic PD in most regards and hence can be seen as a model for idiopathic PD (Thaler et al., 2009). "
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    ABSTRACT: Introduction: The G2019S mutation in the leucine rich repeat kinase 2 (LRRK2) gene is prevalent among Ashkenazi Jewish patients with Parkinson's disease (PD). Cognitive deficits are common in early stage PD. We aimed to characterize the effect of the G2019S mutation on neural mechanisms of executive function processing by testing whether healthy mutation carriers who are an "at risk" population for the future development of PD differed from non-carriers on an functional magnetic resonance imaging (fMRI) Stroop interference task. Methods: Cognitive performance and task related cerebral activity were measured in 40 healthy first-degree relatives of Ashkenazi PD patients (19 carriers and 21 non-carriers of the G2019S mutation). Both regional differences in neural activity and seed region driven functional connectivity methods were performed using fMRI. Results: Compared to non-carriers, mutation carriers had greater baseline deactivation and increased task related activity in the right inferior parietal lobe, right precuneus and right fusiform gyrus. Whole brain functional connectivity analysis revealed stronger coupling between these regions and both basal ganglia structures as well as cortical regions in the carrier group. Non-manifesting G2019S mutation carriers and non-carriers performed similarly on the task and on all other assessed measures, so behavioral differences in task performance and baseline cognitive functions cannot explain the observed imaging differences. Conclusions: G2019S carriers, at risk for developing PD, had similar behavioral performance as non-carriers during the Stroop task, but increased activity in brain regions that have previously been found to be part of the ventral attention system together with stronger coupling between task related areas and structures that make up the ventral and dorsal attention system as well as the basal ganglia-thalamocortical network. This suggests a neural compensatory mechanism that enables intact cognitive performance in asymptomatic mutation carriers.
    Full-text · Article · Jan 2013 · Cortex
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