The Basal Ganglia and the Cerebellum in Human Emotion

Jordan E. Pierce; Julie Péron

Disclosures

Soc Cogn Affect Neurosci. 2020;15(5):599-613. 

In This Article

Basic Anatomy and Function of the BG

The BG are a set of subcortical nuclei including the striatum (caudate/putamen/nucleus accumbens), globus pallidus (internal/external segments), substantia nigra and subthalamic nucleus (STN). The primary input nucleus in the BG is the striatum, which receives excitatory input from most of the cortex (Mink, 1996), the thalamus (Nambu et al., 2002) and the deep cerebellar nuclei (DCN) (as discussed below; Hoshi et al., 2005; Chen et al., 2014; Xiao et al., 2018). Cortical input to the striatum is organized according to functional domains, in broadly topographic stripes, with sensorimotor, associative and limbic subdivisions (Parent and Hazrati, 1995a; Mink, 1996; Arsalidou et al., 2013). The striatum then sends inhibitory projections to other BG nuclei via the direct and indirect pathways, which largely maintain these functional subdivisions, ultimately shaping the appropriate behavioral response in cortical output regions via decreased or increased inhibition of thalamocortical pathways, respectively (Parent and Hazrati, 1995a; Lanciego et al., 2012; Simonyan, 2019).

Affective Functions of the Striatum and STN

Cortical input to the striatum is supplemented by motivation- and reward-sensitive dopamine release from the substantia nigra pars compacta and the ventral tegmental area in the midbrain (Jin et al., 2014; Keeler et al., 2014; Ikemoto et al., 2015; Bostan and Strick, 2018). These reward signals support reinforcement learning (Box 1) in the BG, with positive or negative feedback to a behavior or internal state shaping its affective value and how the individual will respond to future occurrences of a given condition (Schultz et al., 1997; Caligiore et al., 2019). Dopaminergic neurons encode the reward signal as a prediction error, representing the difference between the expected reward and the actual reward received, meaning that unexpected rewards result in the largest responses because they are the most informative for updating values associated with a stimulus or condition (Schultz et al., 1997; Daniel and Pollmann, 2014).

Furthermore, the size of the reward drives the neural response within the ventral portion of the striatum, with the nucleus accumbens showing a greater response to large rewards of various types (e.g. food, money (Knutson et al., 2005; Haber and Knutson, 2010), as well as to punishments (Shigemune et al., 2013). The dorsal striatum, on the other hand, may be more sensitive to motivation (Miller et al., 2014) and instrumental learning of action–outcome contingencies (Delgado, 2007; Yin et al., 2008). This reward valuation process is related closely to the appraisal of the emotional valence of the stimulus with relevant rewarding stimuli tending to elicit positive emotions and motivate approach behaviors (Brosch et al., 2010; Barbaro et al., 2017; Sander et al., 2018), although the causality and timing of these factors are complex and context-dependent (Grandjean and Scherer, 2008; Paul et al., 2020). Overall, the stimulation of dopamine-sensitive neurons across the striatum results in increased activity in the direct pathway and decreased activity in the indirect pathway, further strengthening a selected behavior following a positive outcome (Kravitz et al., 2012; Calabresi et al., 2014).

Another important region of the BG in affective processing is the STN, which receives input from other BG nuclei as well as (frontal) cortex, the posterior thalamus (distinct from projections to the striatum) and the amygdala (Parent and Hazrati, 1995b; Nambu et al., 2002; Lambert et al., 2012; Péron et al., 2016). These broad connections and findings of limbic and associative functional subdivisions within the STN indicate a critical role in emotional processing (Kuhn et al., 2005; Temel et al., 2005; Brunenberg et al., 2012; Haynes and Haber, 2013; Péron et al., 2013; Rossi et al., 2015; Sieger et al., 2015; Péron et al., 2016). It has been proposed that the STN is responsible for integrating input across functional domains to modulate neural oscillations in cortical output regions, affecting multiple facets of emotion processing from autonomic arousal to emotional motor expression to subjective feeling (Péron et al., 2013). Additionally, the hyperdirect pathway from the cortex through the STN may have a supervisory role in decision-making, establishing a threshold for action and inhibiting irrelevant activity based on salient contextual information provided by the prefrontal cortex (Cavanagh et al., 2011; Haynes and Haber, 2013; Eisinger et al., 2018).

Insight From Patient Studies

While healthy functioning of the BG leads to behavioral optimization based on a history of rewarding outcomes, dysfunction of the dopamine-sensitive neurons in the ventral striatum (Robbins and Everitt, 1996; Schultz et al., 2000; Haber and Knutson, 2010; Ikemoto et al., 2015; Wang et al., 2016) factors strongly into the occurrence of addiction disorders and substance abuse (Belin et al., 2009; Calabresi et al., 2014; Cox et al., 2009; Makris et al., 2008). The influence of dopamine on the BG results in the reinforcement of the initial behavior or internal state, but when these striatal reward processes are imbalanced, it can lead to repetitive pleasure-seeking behaviors that are dissociated from positive emotional feelings, as in cocaine dependency or gambling addiction (Belin and Everitt, 2008; Contreras-Rodriguez et al., 2015; Luijten et al., 2017). Furthermore, connections with the ventromedial prefrontal cortex, the anterior cingulate cortex, the hypothalamus and the amygdala allow the striatum to influence limbic processing in diverse contexts associated with reward valuation (Friedman et al., 2002; Heimer and Van Hoesen, 2006; Haber, 2008; Ahmad et al., 2017; Luijten et al., 2017) and in psychiatric disorders such as depression and anxiety (Denys et al., 2010; Robinson et al., 2012; Ubl et al., 2015; Gunaydin and Kreitzer, 2016).

Another condition caused by dysfunction of the BG is Parkinson's disease, where a loss of dopaminergic neurons in the substantia nigra leads to motor deficits such as tremor. Importantly, however, the increasing use of deep brain stimulation (DBS) of the STN as a treatment for Parkinson's disease has revealed the non-motor role of this structure as well, based on observations of cognitive and emotional side effects in some patients (Temel et al., 2006; Halpern et al., 2009; Zangaglia et al., 2009; Rossi et al., 2015; Mehanna et al., 2017). Although the target of the stimulation is the STN motor domain, side effects include disruptions of verbal fluency (Anzak et al., 2011; Eisinger et al., 2018; B. Wu et al., 2014), emotional facial recognition (Drapier et al., 2008; Le Jeune et al., 2008), auditory emotion recognition (Péron et al., 2010), emotional conflict control (Irmen et al., 2017) and subjective emotion experience (Vicente et al., 2009).

For example, Drapier et al. (2008) tested Parkinson's disease patients on measures of apathy and recognition of basic facial emotions 3 months before and after STN DBS surgery. They found that patients were significantly worse at recognizing fearful and sad faces and exhibited greater apathy following DBS treatment, although the two effects were not correlated. These results supported previous findings on the role of the STN in limbic facial recognition, potentially mediated by connections with the amygdala, orbitofrontal cortex and anterior cingulate cortex (Schroeder et al., 2004; Biseul et al., 2005; Drapier et al., 2008; Le Jeune et al., 2008; for a recent review, see Wagenbreth et al., 2019). Similar impairments with negative emotions were described by Vicente et al. (2009) when asking STN DBS patients to report their subjective feelings in response to emotional film clips: the post-operative patients experienced diminished emotional responses to fearful and sad clips compared to the pre-operative and control groups. These effects may reflect a disruption of the STN's ability to bias an appropriate response pattern, introducing noise into limbic processing and creating ambiguity between negative affective states that may share some underlying (e.g. physiological) features.

Other findings additionally suggest that STN stimulation in Parkinson's disease can lead to impulsivity disorders or depressive symptoms (Volkmann et al., 2001; Volkmann et al., 2010; Moum et al., 2012; Rossi et al., 2015). In one study, 25% of Parkinson's patients experienced depressive symptoms following STN DBS surgery (Berney et al., 2002), although reports of mood changes vary widely and may depend on electrode placement or dopamine levels (Volkmann et al., 2010). Interestingly, the impact of STN DBS on emotion or mood may depend upon the laterality of the substantia nigra degeneration in Parkinson's disease: patients with predominantly left-sided motor impairments (right BG dysfunction) showed worse vocal emotion recognition for happy stimuli than patients with right-sided impairments (left BG dysfunction) or controls (Stirnimann et al., 2018). These results imply that the right BG play a greater role in affective processes (Péron et al., 2017), but further research is needed to confirm these findings and understand how interactions with both the cortex and cerebellum impact this laterality.

In addition to deficits in emotional behavior performance, Parkinson's disease patients also have exhibited changes in glucose metabolism in emotion networks throughout the brain, including the orbitofrontal cortex (Le Jeune et al., 2008; Péron et al., 2013; Ory et al., 2017) and the cerebellum. An increased cerebellar metabolism was associated with worse facial emotion recognition (Le Jeune et al., 2008) and a decreased subjective feeling of disgust after viewing emotional film clips (Ory et al., 2017). Such widespread changes support the functional link between the BG and cerebellum (see Section 5) and imply broad effects on emotion processing when STN function is disrupted. It is important to note, however, that these results partially may reflect pathological brain function, dopaminergic medication effects or other non-specific effects of the DBS procedure.

The BG Select and Coordinate Cortical Response Patterns

The studies described above demonstrate that the BG support not only motor functions (Graybiel, 1998; Yin et al., 2004; Keeler et al., 2014; Pidoux et al., 2018) but also limbic functions such as reward valuation and motivation (Yin et al., 2008; Miller et al., 2014) that contribute to the assessment of affective valence and formation of emotional states. Clinical reports highlight the key function of the striatum in reward processing in addiction and psychiatric disorders and the contribution of the STN to emotion recognition. Overall, the dense connections and functional organizations of the BG position them perfectly to exert a broad coordinating influence on emotion processing, a function that is supported further by their interactions with the cerebellum.

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