Functional brain changes underlying irritability in premanifest <scp>H</scp>untington's disease

Stock, Jan Van den; Winter, François‐Laurent De; Ahmad, Rawaha; Sunaert, Stefan; Laere, Koen Van; Vandenberghe, Wim; Vandenbulcke, Mathieu

doi:10.1002/hbm.22799

Cited by 32 publications

(25 citation statements)

References 47 publications

(94 reference statements)

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“…It is possible that the pattern of hostility exhibited by HD monkeys is due to alterations in amygdala activity. Recent studies in HD patients have shown decreased amygdala activity during emotional tasks lending support for this hypothesis (Mason et al, 2015; Van den Stock, et al, 2015). Additionally, HD patients have also been shown to exhibit lower fear and higher anger ratings of fearful pictures as compared to healthy controls (Eddy, et al, 2011).…”

Section: Discussionmentioning

confidence: 79%

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Increased irritability, anxiety, and immune reactivity in transgenic Huntington’s disease monkeys

Raper

Bosinger²,

Johnson³

et al. 2016

Brain, Behavior, and Immunity

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Although the most notable clinical symptoms of Huntington’s disease (HD) are motor disturbances and brain atrophy, other symptoms include cognitive dysfunction, emotional and hormonal dysregulation. Emotional dysregulation (irritability, anger/aggression, and anxiety) and increased inflammation are early emerging symptoms which can be detected decades before the onset of motor symptoms in HD patients. Despite the advances in understanding the genetic causes of HD there is still no cure or preventative treatment. Thus, to better understand the pathogenesis of HD and develop effective treatments, a holistic understanding of HD is needed, as well as animal models that replicate the full spectrum of HD symptoms. The current study examined the emotional, hormonal, and gene expression responses to an acute stressor of adult male transgenic HD rhesus monkeys (HD, n=2) as compared to wild-type controls (n=2). Results revealed that HD monkeys expressed increased anxiety and irritability/aggression as compared to controls. Reactive cortisol response to the stressor was similar between groups. However, HD monkeys exhibited increased pro-inflammatory cytokines and higher induction of immune pathway genes as compared to controls. Overall, results reveal that HD monkeys exhibit these early emerging symptoms of HD and may be an effective animal model to facilitate the development of new therapeutics for HD patients.

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Section: Discussionmentioning

confidence: 79%

“…Similar to anxiety, irritability has been seen prior to motor symptom onset in humans (Bouwens, et al, 2015; Van den Stock, et al, 2015). The current study used the Human Intruder task to examine the ability of HD monkeys to modulate their emotional response based on the salience of the threat present.…”

Section: Discussionmentioning

confidence: 98%

Increased irritability, anxiety, and immune reactivity in transgenic Huntington’s disease monkeys

Raper

Bosinger²,

Johnson³

et al. 2016

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

show abstract

“…Likewise, PCC and PCUN respond strongly when people are asked to imagine emotionally hurtful events that may induce anger69. Finally, increased anger-selective activation has been found in the PCC and PCUN of participants with preclinical Huntington’s disease, of which irritability in an important manifestation70. In this context, the anger-specific functional integration of amygdala and brain stem, particularly with the pons, is a quite novel finding, though coherent with human and animal models or aggression.…”

Section: Discussionmentioning

confidence: 95%

Dynamic Changes in Amygdala Psychophysiological Connectivity Reveal Distinct Neural Networks for Facial Expressions of Basic Emotions

Diano

Tamietto

Celeghin

et al. 2017

Sci Rep

134

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The quest to characterize the neural signature distinctive of different basic emotions has recently come under renewed scrutiny. Here we investigated whether facial expressions of different basic emotions modulate the functional connectivity of the amygdala with the rest of the brain. To this end, we presented seventeen healthy participants (8 females) with facial expressions of anger, disgust, fear, happiness, sadness and emotional neutrality and analyzed amygdala’s psychophysiological interaction (PPI). In fact, PPI can reveal how inter-regional amygdala communications change dynamically depending on perception of various emotional expressions to recruit different brain networks, compared to the functional interactions it entertains during perception of neutral expressions. We found that for each emotion the amygdala recruited a distinctive and spatially distributed set of structures to interact with. These changes in amygdala connectional patters characterize the dynamic signature prototypical of individual emotion processing, and seemingly represent a neural mechanism that serves to implement the distinctive influence that each emotion exerts on perceptual, cognitive, and motor responses. Besides these differences, all emotions enhanced amygdala functional integration with premotor cortices compared to neutral faces. The present findings thus concur to reconceptualise the structure-function relation between brain-emotion from the traditional one-to-one mapping toward a network-based and dynamic perspective.

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“…Unseen facial and bodily expressions have yielded similar findings when presented in the blind fields of patients with affective blindsight. This indicates that a functional subcortical route to the Amg is invovled in emotion perception during sensory unawareness (Morris et al, 2001; de Gelder et al, 2005, 2011; Pegna et al, 2005; Tamietto and de Gelder, 2010; Van den Stock et al, 2011a,b, 2013, 2015a; Georgy et al, 2016). The involvement of the superior colliculus and pulvinar is in keeping with their connectional pattern and physiological properties.…”

Section: Pathways To the Amg Relevant For Non-conscious Emotion Percementioning

confidence: 94%

“…On the one hand, Amg activity contingent upon sensory and attentional awareness in healthy as well as brain damaged patients has emerged from the use of non-facial stimuli, thereby extending evidence of non-conscious emotion processing to other stimulus categories. Bodily expressions of emotions, both static and dynamic, have been the most extensively studied non-facial stimuli (de Gelder and Hadjikhani, 2006; de Gelder et al, 2006, 2010; Tamietto et al, 2009; Van den Stock et al, 2011a,b, 2013, 2015a,b; Tamietto et al, 2015). Visual stimuli associated to danger in our evolutionary past, such as snakes and spiders, have also been studied during attentional and sensory unawareness.…”

Section: Stimulus Categories and Properties Triggering Amygdala Respomentioning

confidence: 99%

Amygdala Response to Emotional Stimuli without Awareness: Facts and Interpretations

et al. 2017

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Over the past two decades, evidence has accumulated that the human amygdala exerts some of its functions also when the observer is not aware of the content, or even presence, of the triggering emotional stimulus. Nevertheless, there is as of yet no consensus on the limits and conditions that affect the extent of amygdala’s response without focused attention or awareness. Here we review past and recent studies on this subject, examining neuroimaging literature on healthy participants as well as brain-damaged patients, and we comment on their strengths and limits. We propose a theoretical distinction between processes involved in attentional unawareness, wherein the stimulus is potentially accessible to enter visual awareness but fails to do so because attention is diverted, and in sensory unawareness, wherein the stimulus fails to enter awareness because its normal processing in the visual cortex is suppressed. We argue this distinction, along with data sampling amygdala responses with high temporal resolution, helps to appreciate the multiplicity of functional and anatomical mechanisms centered on the amygdala and supporting its role in non-conscious emotion processing. Separate, but interacting, networks relay visual information to the amygdala exploiting different computational properties of subcortical and cortical routes, thereby supporting amygdala functions at different stages of emotion processing. This view reconciles some apparent contradictions in the literature, as well as seemingly contrasting proposals, such as the dual stage and the dual route model. We conclude that evidence in favor of the amygdala response without awareness is solid, albeit this response originates from different functional mechanisms and is driven by more complex neural networks than commonly assumed. Acknowledging the complexity of such mechanisms can foster new insights on the varieties of amygdala functions without awareness and their impact on human behavior.

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Functional brain changes underlying irritability in premanifest Huntington's disease

Cited by 32 publications

References 47 publications

Increased irritability, anxiety, and immune reactivity in transgenic Huntington’s disease monkeys

Increased irritability, anxiety, and immune reactivity in transgenic Huntington’s disease monkeys

Dynamic Changes in Amygdala Psychophysiological Connectivity Reveal Distinct Neural Networks for Facial Expressions of Basic Emotions

Amygdala Response to Emotional Stimuli without Awareness: Facts and Interpretations

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