The neuroimaging studies of psychopathy can be divided into “structural” studies, which assess brain morphology, and “functional” studies, which assess brain activity (Table 28.1). Structural neuroimaging studies associate psychopathy with a host of morphological brain abnormalities: reduced volumes of the amygdala, (Boccardi et al. 2011; Ermer et al. 2012; Yang et al. 2009, 2010); reduced volume of the basolateral nucleus of the amygdala and increased volumes of the central and lateral nuclei of the amygdala (Boccardi et al. 2011); reduced gray matter volumes in frontal cortex, especially the orbitofrontal cortex, the frontopolar cortex, the anterior rostral prefrontal cortex, and right inferior frontal gyrus (Boccardi et al. 2011; de Oliveira-Souza et al. 2008; Ermer et al. 2012; Gregory et al. 2012; Ly et al. 2012; Muller et al. 2008a; Yang et al. 2005b, 2010, 2011); reduced volume of the dorsal anterior cingulate cortex and bilateral precentral gyri (Ly et al. 2012); reduced volumes in temporal cortex, especially right superior temporal gyrus, anterior temporal cortices, superior temporal sulcus, and bilateral temporal pole (de Oliveira-Souza et al. 2008; Ermer et al. 2012; Gregory et al. 2012; Ly et al. 2012; Muller et al. 2008a; Yang et al. 2011); reduced volume of midline cortical structures (Boccardi et al. 2011); reduced volume of the posterior cingulate cortex (Ermer et al. 2012); increased volume of the striatum (Glenn et al. 2010a); increased volume of the left nucleus accumbens (Pujara et al. 2013); increased volume of the corpus callosum (Raine et al. 2003); reduced volume of posterior hippocampus (Laakso et al. 2001); normal volume but abnormal shape of the hippocampus (Boccardi et al. 2010); reduced volume in parahippocampal regions (Ermer et al. 2012); reduced volume of the insula (de Oliveira-Souza et al. 2008; Gregory et al. 2012; Ly et al. 2012); presence of cavum septum pellucidum (Raine et al. 2010); and reduced structural integrity of the uncinate fasciculus (Craig et al. 2009; Motzkin et al. 2011). Overall these studies link psychopathy with a variety of structural abnormalities within frontal and temporal areas, involving cortical and subcortical gray matter structures as well as white matter pathways. The identified structures play important roles in emotion and social cognition (amygdala, superior temporal cortex, uncinate fasciculus) as well as learning and memory (striatum, hippocampus). But within this broad functional/anatomical grouping of the study results, the available structural imaging data have not yet demonstrated reliable, replicated structural abnormalities in many of the identified brain regions.

Functional imaging studies measure brain activity, either at “rest” or during a particular cognitive task. In psychopathy research, functional imaging studies have typically featured tasks involving social and/or emotional processing, such as fear conditioning (Birbaumer et al. 2005), viewing facial expressions of emotion (Carré et al. 2013; Deeley et al. 2006; Gordon et al. 2004), emotion attribution (Sommer et al. 2010), moral decision-making (Glenn et al. 2009; Harenski et al. 2009, 2010; Pujol et al. 2012), identification of emotionally salient words (Intrator et al. 1997), memory for emotionally salient words (Kiehl et al. 2001), selective attention and emotional processing during an emotion-word Stroop task (Sadeh et al. 2013), viewing emotionally salient scenes (Muller et al. 2003, 2008b), social cooperation (Rilling et al. 2007), anticipation and/or receipt of reward (Bjork et al. 2012; Buckholtz et al. 2010; Carré et al. 2013; Pujara et al. 2013), and punishment administration (Veit et al. 2010). Accordingly, many of these studies focus their analyses on emotion-related regions of interest, such as the amygdala (Birbaumer et al. 2005; Carré et al. 2013; Glenn et al. 2009; Gordon et al. 2004; Kiehl et al. 2001; Rilling et al. 2007). However, the imaging results indicate that psychopathy is associated with abnormal activity in widespread areas of the brain, not just those associated with emotional processing. Reduced activity has been observed in limbic and paralimbic areas, including amygdala (Birbaumer et al. 2005; Carré et al. 2013; Glenn et al. 2009; Kiehl et al. 2001; Rilling et al. 2007), hippocampus and parahippocampal gyri (Kiehl et al. 2001; Muller et al. 2003), anterior and posterior cingulate cortex (Birbaumer et al. 2005; Kiehl et al. 2001; Muller et al. 2003; Rilling et al. 2007), ventral striatum (Kiehl et al. 2001), and insula (Birbaumer et al. 2005). On the other hand, reduced activity has also been observed in association areas within frontal and temporal cortices (Birbaumer et al. 2005; Gordon et al. 2004; Muller et al. 2003, 2008b; Rilling et al. 2007) as well as sensory areas, such as posterior visual cortices (Deeley et al. 2006; Muller et al. 2003) and parietal somatosensory cortex (Birbaumer et al. 2005; Deeley et al. 2006), and motor structures such as cerebellum (Deeley et al. 2006) and primary motor cortex (Deeley et al. 2006). Increased activity has been observed in frontal and temporal cortices (Intrator et al. 1997; Kiehl et al. 2001; Muller et al. 2003), nucleus accumbens (Bjork et al. 2012; Buckholtz et al. 2010), as well as areas of parietal lobe, occipital lobe, cerebellum, cingulate cortex, and amygdala (Muller et al. 2003). Functional imaging studies may also assess the correlated activity, or “functional connectivity,” between various brain regions at rest or during a task. Psychopathy was associated with connectivity among brain regions known as the “default mode network,” which includes the medial prefrontal cortex, posterior cingulate, and the inferior parietal lobule; frontoparietal connectivity; and a visual/posterior cingulate connectivity during an auditory “oddball” task (Juárez et al. 2013). Further, amygdala dysfunction in psychopaths during a task of moral decision-making was associated with reduced functional connectivity between the amygdala and the striatum (Osumi et al. 2012). At rest, psychopaths exhibit a reduction in functional connectivity between the left insula and dorsal ACC, the vmPFC and the amygdala, the vmPFC and medial parietal cortex, and the posterior cingulate cortex and anterior frontal cortical areas (Ly et al. 2012; Motzkin et al. 2011; Pujol et al. 2012). Taken together, these functional imaging data associate psychopathy with abnormal activity in limbic, subcortical, and cortical structures. As such, it is difficult to group the findings in any particular functional domain.

An intriguing observation is that, depending on the experimental context, the same brain area could be reported as either hypo- or hyperactive. For example, amygdala activity was abnormally low during fear conditioning (Birbaumer et al. 2005), moral decision-making (Glenn et al. 2009), social cooperation (Rilling et al. 2007), viewing facial expressions of fear (Carré et al. 2013; Dolan and Fullam 2009), and memory for emotionally salient words (Kiehl et al. 2001) but abnormally high during the viewing of certain emotionally salient scenes (Muller et al. 2003) and facial expressions of anger (Carré et al. 2013). Similarly, ventral striatum activity was abnormally low during memory for emotionally salient words (Kiehl et al. 2001) but abnormally high during reward anticipation (Bjork et al. 2012; Buckholtz et al. 2010). These results suggest that neural processing abnormalities in psychopathy may be significantly context dependent. In other words, there is not yet clear evidence for a particular area being persistently hypo- or hyperactive; the functional activation data associated with psychopathy seem to depend critically on the experimenters’ selection of task and stimuli.

In sum, the structural and functional abnormalities associated with psychopathy are widespread and rather variable, although regions within frontal and temporal lobe appear to be the most commonly identified in both types of study. Given the broad array of imaging results, it is reasonable to ask whether differences in methodology could account for some of the variability in the findings. In the following sections we highlight three methodological issues that could potentially limit the consistency and generalizability of results across the imaging studies.