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 Cerebellum

The cerebellum contains more neurons than the neocortex, yet historically has been relegated to a purely motor role, perhaps due in part to its homogeneous cellular architecture arguing against a complex functional role in limbic or cognitive processing (Schmahmann, 2019). Nonetheless, recent research has reenergized interest in this structure and illuminated its contributions to diverse processes, including those arising from connections with the BG (discussed in the following section). Here, the intrinsic organization of the cerebellum and its numerous connections are described in relation to our growing understanding of its functional role in emotion processing.

The cerebellum consists of the vermis, paravermis, hemispheric lobules I–X and the DCN (consisting of the dentate, emboliform/globose (interpositus) and fastigial nuclei). It receives input from the inferior olivary complex and other brainstem areas, as well as from pontine nuclei that transmit signals from the neocortex (Kelly and Strick, 2003; Granziera et al., 2009). The output of the cerebellum occurs via inhibitory Purkinje cells, which project to the DCN and then to the thalamus and ultimately feedback to the same regions of the cortex from which the cerebellum receives input. The multisynaptic nature of these connections has made them difficult to identify until recently, but it is recognized now that nearly all of cortex, not merely motor areas, projects to and receives projections from the cerebellum (Middleton and Strick, 1994; Kelly and Strick, 2003; Bostan et al., 2013; Buckner, 2013).

The cerebellum also has functional subdivisions, similar to those identified in the BG: motor, association and limbic zones with broadly topographic organization (Leggio and Olivito, 2018; Schmahmann, 2019). The anterior lobules are connected primarily with sensorimotor cortical and brainstem regions, the posterior lobules are connected heavily with cortical association regions, and parts of the vermis and flocculonodular lobe are connected via the fastigial nucleus to limbic cortical and subcortical regions (Figure 1; Anand et al., 1959; Heath and Harper, 1974; Olivito et al., 2017a; Schmahmann, 2019). The anterior lobe mainly performs the traditional motor coordination role attributed to the cerebellum, yet the association regions in the posterior lobe constitute the greatest proportion of cerebellar volume in humans, reflecting an evolutionary expansion in attention and executive functions in frontal and parietal cortices (Schmahmann, 2019). Furthermore, these functional domains may be maintained in the DCN, with studies identifying both motor and non-motor projections of the dentate nucleus in particular (Dum and Strick, 2003; Kuper et al., 2011; Bostan et al., 2013).

In the limbic cerebellum, the vermis has been associated with basic emotions such as fear, while regions of the posterior cerebellar hemispheres have been associated with complex emotions and social interactions, reflecting the former's anatomical connections with brainstem nuclei controlling autonomic functions and the latter's connections with associative prefrontal cortex controlling theory of mind and higher cognitive functions (Stoodley and Schmahmann, 2009; Watson et al., 2013; Van Overwalle et al., 2014; Strata, 2015; Leggio and Olivito, 2018). Rodent studies have demonstrated that the limbic cerebellum and its connections with the amygdala contribute to fear-related learning (Supple Jr. et al., 1987; Sacchetti et al., 2002; Zhu et al., 2011; Strata, 2015), while human studies (described below) have indicated activity in the vermis in response to both negative and positive emotions (Baumann and Mattingley, 2012; Schraa-Tam et al., 2012).

Neuroimaging Studies on the Affective Functions of the Cerebellum

The use of neuroimaging and sensitive neurological assessments in recent years has vastly expanded our understanding of the human cerebellum's role in a wide range of non-motor functions (Koziol et al., 2014). Early studies showed cerebellar activation during a word generation task (Petersen et al., 1989) and a problem-solving task (Kim et al., 1994), while more recent reviews and meta-analyses have highlighted the cerebellum's functional involvement in diverse tasks related to emotion, attention, working memory and language (Buckner, 2013; Adamaszek et al., 2017; Guell et al., 2018; Pleger and Timmann, 2018; Stoodley and Schmahmann, 2018; Schmahmann, 2019). Additionally, resting-state neuroimaging studies have reported cerebellar co-activation with common cortical functional networks, and noted an expanded cerebellar representation of frontal-parietal association areas (Buckner et al., 2011; Marek et al., 2018), as well as co-activation with limbic networks that included the amygdala, insula and BG (Sang et al., 2012; Habas, 2018).

Neuroimaging studies of healthy individuals recently have demonstrated the relevance of the cerebellum (particularly the vermis, hemispheric Crus I and II and the fastigial nucleus) to emotion perception and recognition (Lee et al., 2004; Bermpohl et al., 2006; Stoodley and Schmahmann, 2009; Baumann and Mattingley, 2012; Schraa-Tam et al., 2012; Adamaszek et al., 2017; Ferrari et al., 2018). Baumann and Mattingley (2012) proposed that the vermis, as part of the limbic cerebellum, assesses emotional relevance (threat) and regulates emotional responses, supported by connections with the medial prefrontal cortex and the amygdala. Additionally, they reported partially distinct cerebellar activation patterns for individual emotion categories with significant activation for both negative and positive emotions (Baumann and Mattingley, 2012), although others have reported activation primarily for negative emotions (Beauregard et al., 1998; Schraa-Tam et al., 2012; Adamaszek et al., 2017). These results are complemented by functional connectivity studies and meta-analyses of task data that have identified co-activation of widespread emotion networks with portions of the cerebellum (Habas et al., 2009; Stoodley and Schmahmann, 2009; Schienle and Scharmuller, 2013; Guell et al., 2018; Habas, 2018).

Interestingly, some findings demonstrated a lateralization of cerebellum function with greater language activation in the right cerebellum and greater spatial attention activation in the left cerebellum (Petersen et al., 1989; Habas et al., 2009; Lesage et al., 2012; Wang et al., 2013; Schmahmann, 2019). This cerebellar lateralization mirrors neocortical lateralization, reflecting the contralateral anatomical connectivity between, e.g. left frontal cortex language centers and right cerebellar cortex (Connor et al., 2006; Frings et al., 2006; Kelly and Strick, 2003; D. Wang et al., 2013; Xiao et al., 2018).

While neuroimaging studies describe functional activation correlated with task performance, neuromodulatory studies seek to assess the causal impact of the cerebellum on emotion processing by directly affecting neural activity. In a study by Schutter and van Honk, repetitive transcranial magnetic stimulation (TMS) was applied to the cerebellar vermis and occipital cortex of healthy subjects prior to an emotion regulation task (Schutter and van Honk, 2009). Following inhibition of only the cerebellum, an increase in negative mood was reported after viewing aversive scenes, suggesting a disruption of the limbic network's ability to regulate or suppress negative affect. In another study, high-frequency, excitatory TMS of the medial cerebellum resulted in increased reaction times for an implicit processing of masked happy faces, suggesting enhanced attention to these emotional stimuli (Schutter et al., 2009). Further work utilizing transcranial direct current stimulation of the cerebellum also reported improved processing of negative (but not positive) facial expressions (Ferrucci et al., 2012). The differences in positive vs negative emotion effects remain to be clarified, although the specific region of the cerebellum that is targeted, the task design and the modulation strength may all contribute to the pattern of results in these stimulation studies.

Many human studies on the cerebellum have focused on basic emotion recognition, yet the cerebellum also has been shown to be involved in reward processing in relation to prediction error. Studies in mice have demonstrated that climbing fibers and granule cells signal reward occurrence, omission or predictability to functional microzones of Purkinje cells (Wagner et al., 2017; Kostadinov et al., 2019), while reward-related activations also have been reported in human neuroimaging studies (Ramnani et al., 2004; Tanaka et al., 2004; Shigemune et al., 2013), likely in relation to updating of internal models (Peterburs et al., 2018). Furthermore, the cerebellum has been shown to have direct connections with the dopaminergic ventral tegmental area and BG nuclei (Ikai et al., 1992; Herrera-Meza et al., 2014; Carta et al., 2019), providing a further link with the reward system and affective valuation.

Insight From Patient Studies

Beyond neuroimaging studies of healthy cerebellar function, studies of cerebellar lesion patients have elucidated the role of this structure in affective processes by identifying specific behavioral difficulties that occur in patients (Schmahmann, 2019). Reports have described problems with emotion recognition and expression in patients, as well as alterations in mood control and the experience of emotional states, with cerebellar patients exhibiting a variety of behavioral and mood disturbances (Schmahmann et al., 2007; Lupo et al., 2015; Clausi et al., 2019a). Problems with social cognition and understanding of others' emotions have been reported in patients with cerebellar degeneration, including spinocerebellar ataxia, potentially related to disrupted formation of internal models that predict others' behavior using theory of mind processes (Sokolovsky et al., 2010; Leggio and Olivito, 2018; Clausi et al., 2019b). More generally, damage to or reduced volume of the cerebellum is associated with high rates of depression, anxiety, psychosis and autism spectrum disorders, and patients may experience blunted affect, uncontrollable laughter or crying or increased aggression (Escalona et al., 1993; Leroi et al., 2002; Schmahmann et al., 2007; Schutter et al., 2012; Lupo et al., 2018).

Considering autism spectrum disorders in more detail, difficulties with social interaction and emotion recognition are common, as are cerebellar (and BG) structural abnormalities including a reduction in the number of Purkinje cells in the cerebellar hemispheres (Whitney et al., 2008; Fatemi et al., 2012; Subramanian et al., 2017; Bruchhage et al., 2018). Reduced volume of the posterior vermis also is associated with autism spectrum disorders, although a variety of malformations, both within and beyond the cerebellum, have been reported (Scott et al., 2009; Bruchhage et al., 2018). The exact role of cerebellar dysfunction in autism and other disorders remains to be defined fully, as even a focal lesion may lead to network level changes in structure or function over time (Hernandez-Castillo et al., 2015; Olivito et al., 2017a; Olivito et al., 2017b), but it is clear that some association exists between cerebellar abnormalities and social, emotional and cognitive dysfunctions in several conditions (Bruchhage et al., 2018; Olivito et al., 2018; Schmahmann, 2019). Finally, such clinical symptoms may depend upon the functional connections of the cerebellum with the BG and limbic circuitry as it has been suggested that hyperactivation of the cerebellum in Parkinson's disease results from the decreased activity of BG dopaminergic nuclei (T. Wu and Hallett, 2005; Yu et al., 2007).

Beyond these assessments of distinct clinical disorders, other studies have addressed more subtle alterations in affective performance in patients with cerebellar damage. One study found that cerebellar patients experienced weaker positive emotion than controls when viewing pleasant images and that they differentially recruited an emotion network (greater prefrontal/BG activation and weaker amygdala activation) when viewing unpleasant images (Turner et al., 2007). Another study showed that cerebellar patients had impaired awareness of their own negative affect when it occurred as a result of their own actions (i.e. regret) in a gambling task (Clausi et al., 2015). Finally, a recent study reported that cerebellar patients ranked fear stimuli higher on a surprise index than did control subjects and that this misattribution was associated with right-sided lesions in cerebellar hemisphere lobules VII, VIII and IX (Thomasson et al., 2019; see also Biseul et al., 2005 for a similar misattribution in STN DBS patients).

The Cerebellum Minimizes Prediction Error Across Domains

Based on the variety of tasks that activate the cerebellum and its largely uniform neuronal architecture, Schmahmann has proposed that the function of the cerebellum is comparable across motor, cognitive and limbic domains, performing an automatic modulation of processing based on the widespread inputs it receives about ongoing behaviors or thoughts compared to the desired or predicted outcome (Schmahmann, 1991, 2019). Subsequently, the cerebellum provides feedback to the cortex for fine-tuning not only motor output but also processes such as decision-making or emotion recognition (Bostan and Strick, 2018; Schmahmann, 2019). Similar theories emphasize the cerebellum's role in detecting and minimizing prediction error based on differences in current sensorimotor and cognitive information and the intended goal state (referred to as supervised learning; see Box 1; Jueptner and Weiller, 1998; Sokolov et al., 2017; Caligiore et al., 2019; Popa and Ebner, 2019).

Such a broad function in monitoring the current state relative to a desired or expected state in order to adjust behavior is consistent with the cerebellum's closed loop connectivity with the cortex (Kelly and Strick, 2003; Bostan and Strick, 2018) and with the difficulty in pinpointing a single cognitive dysfunction across patients with cerebellar lesions (Schmahmann and Sherman, 1997; Schmahmann et al., 2007; Lupo et al., 2018; Schmahmann, 2019). Combining this understanding of cerebellar anatomy and function with that of the BG, the next sections will examine evidence of the structural connectivity between these subcortical regions and how this allows for a coordinated influence on affective processing.

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