Results from this case study indicate that the patient showed significant improvement in both symptomatic domains (i.e., OCD and autism) following DBS to the left outer shell of the nucleus accumbens (NAc) and the internal capsule. Shared neurocircuitry abnormalities and anatomic substrates between the conditions is the most probable basis of the unanticipated benefit in autism symptoms with VC/VS stimulation.
Neural circuits implicated in OCD include the limbic system, the basolateral circuit, and the cortico-striato-thalamo-cortical loop (Göttlich et al., 2014; Göttlich et al., 2015; Ahmari and Dougherty, 2015). Among the key anatomic substrates in OCD pathophysiology are the orbitofrontal cortex, anterior cingulate cortex, basal ganglia, and thalamus. Structural neuroimaging studies using voxel-based morphometry analysis have shown significantly smaller volumes of frontal gray and white matter bilaterally in OCD patients compared to controls, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula (de Wit et al., 2014). Additionally, compared to healthy controls, patients with OCD show significantly increased gray matter volume in the left caudate, left thalamus, and posterior cingulate cortex (Hou et al., 2013). Tractography studies have demonstrated altered topography and structural connectivity of fibers between the orbitofrontal cortex and the striatum (Nakamae et al., 2014). Functional imaging studies have shown a hyperactivity of frontal cortex and subcortical structures in OCD that improves after successful treatment (Micallef and Blin, 2001; Nakao, 2011).
Neural circuits implicated in autism include the frontostriatal circuitry with key structures within the frontal cortex (anterior cingulate cortex, middle frontal gyrus, paracingulate gurys, orbitofrontal cortex) and the striatum (nucleus accumbens, caudate). Increased functional connectivity within these regions is associated with the core characteristics of the condition (i.e., lack of social interest and communication, restricted interests, behavioral repetitions)(Delmonte et al., 2013; Turner et al., 2006). Autism pathophysiology includes the following key anatomic substrates: anterior cingulate cortex, medial prefrontal gyrus, orbitofrontal cortex, posterior cingulate gyrus. A few structural imaging studies using diffusion tensor MRI (DTI) showed no structural corticostriatal connectivity differences compared to healthy matched controls in young adolescents and high-functioning adults with autism (Hou et al., 2013; Kirkovski et al., 2015). Other studies have reported reductions in the size of the corpus callosum in children and adults with Autism (Frazier and Hardan, 2009) and also reduced volume and increased diffusion in the corpus callosum (Alexander et al., 2007). Several DTI studies report microstructural differences in white matter organization and potentially myelination in ASD with the altered structure within long-range white matter tracts linking socio-emotional processing regions (Ameis and Catani, 2015). Functional connectivity in children with autism compared to neurotypical children show patterns of increased connectivity in striatal circuits as well as increased functional connectivity between nearly all striatal subregions, associative, and limbic cortex previously implicated in the pathophysiology of autism (e.g., insular and right superior temporal gyrus)(Di Martino et al., 2010). Additionally, PET and functional MRI studies have shown both short-range local network cortico-cortical over-connectivity in areas associated with social behavior (amygdala, fusiform gyrus, posterior superior temporal sulcus and prefrontal cortex) and long-range functional under-connectivity (Wass, 2011; Turner et al., 2006). There are functional abnormalities of language lateralization, mesolimbic social reward and long-range functional resting connectivity between anterior and posterior brain regions. EEG studies also have demonstrated reduced short-distance and reduced, as well as increased, long-distance coherences for the ASD-groups, when compared to the controls (Duffy and Als, 2012).
Therefore, there is clear evidence in the literature for cortico-basal ganglia circuit dysfunction in both OCD and ASD (Graybiel and Rauch, 2000; Delmonte et al., 2013), as well as additional abnormal activity of limbic circuitry. Acute DBS at the VC/VS target has been shown to activate the implicated frontal–basal ganglia–thalamic circuit in OCD (Rauch et al., 2006). DBS of the NAc also seems to normalize it’s activity and reduce excessive connectivity between the NAc and prefrontal cortex (Figee et al., 2013). The effect of DBS at the VC/VS target in the shared neurocircuitry nodes for both OCD and Autism is the most plausible factor behind the observed changes in this case.
OCD and restricted and repetitive patterns of behavior, interests, and activities inherent to ASD share a series of characteristics that can make their differential diagnosis extremely difficult. In ASD, the restricted and repetitive patterns of behavior or activities represent a pleasurable affective experience, intrinsically motivating and reinforcing. In patients with ASD, these patterns of behavior are egosyntonic; that is, individuals feel good about themselves when they perform the behavior, without the behavior generating any conflict or negative judgment about themselves, and the behavior even becomes a source of pleasure and satisfaction, intrinsically motivating and reinforcing. In OCD, obsessions and compulsions are egodystonic. That is, they are perceived as intrusive, unwanted, and unpleasant. DSM-V-TR clarifies that obsessions and compulsions “provoke significant clinical discomfort” in individuals who suffer from them. Therefore, it is important to determine the amount of anxiety associated with these symptoms, as in OCD, they will cause severe anxiety to resist them or put them away. (Doshi et al. 2019).
The NAc is considered to be a key structure related to social reward response in ASD. Scott-Van Zeeland et al. 2019 found that the activity within the VS was decreased in autistic patients, and this may be the reason for impaired social reciprocity. These observations make NAc a potential target to modulate in ASD. NAc shell high-frequency stimulation (HFS) also increased concentrations of NAc dopamine and serotonin, which are shown to be responsible for reducing the symptoms of OCD. The widespread and specific alterations in synchronous local field potential activity produced by HF NAc DBS provide further evidence that the therapeutic actions of DBS depend not only on the activity in the stimulated nucleus but also are due to widespread changes along the thalamocortical circuit (Traub et al. 2004). The therapeutic proof of the role of NAc is further obtained from a number of case reports that have documented benefit of stimulation of VS, including NAc in patients with OCD. Hence, NAc forms one of the important targets for the control of OCD symptoms and Autism.
At present, most interventions targeting social-communicative skill defects and other behavioral problems in ASD rely on the principles of applied behavior analysis (ABA), especially operant techniques, where desired behaviors are reinforced using a variety of rewards (for example, verbal praise, candy, or stickers) (Kohls, Chevallier, Troiani, Schultz, 2012).. Accumulating evidence from over 40 years of research indicates that these reinforcement-based interventions significantly increase both cognitive and social outcomes, and successfully reduce aberrant behaviors (Virués-Ortega et al. 2010). It is not yet understood how and why behavioral approaches work well for some people with ASD but not for others.
One hypothesis is that the core deficits found in autism can be explained by the fact that people with autism are not able to recognize that other persons have minds. To recognize that another person has a mind is to recognize that person as someone who has a mental life independent of your own, with beliefs, preferences, desires, and the whole range of intentional attitudes. There are two accounts of the failure of theory of mind. One account is that persons who lack a functioning theory of mind have difficulty ascribing intentional states to others at all. Thus, they are unable to take the intentional stance toward others. On another account, the failure of theory of mind could result in a mistaken attribution of the autistic person’s intentional states to all other intentional agents. The state of affairs that would result would be akin to “unified consciousness” view on the part of persons with autism - the mistaken belief that everyone shares the same intentional states as he does. In summary, the theory of mind in autism seeks to explain the diagnostic criteria of autism by postulating that persons with autism fail to recognize the mental lives of others. Such a failure would explain difficulties in social interaction and impairments in communication, as both of these are strongly tied to an understanding of other people.
Dopamine is the neurotransmitter predominantly associated with reward processing (Schultz et al. 200). Although dopamine had long been thought to mediate ‘liking recent evidence indicates that dopamine is neither necessary nor sufficient for generating ‘liking’ responses, but plays a more important role in the motivational component (‘wanting’) of reward (Berridge KC et al. 2003). Most dopaminergic neurons within the core reward circuitry, particularly in the VS, show short bursts of phasic activation in
Rewarding situations are characterized by an anticipation phase or the ‘wanting’ of a reward, which often results in a phase of reward consumption or ‘liking’, with some rewards causing a peak level of subjective pleasantness (for example, a lottery win, job promotion, encounter with an old friend, favorite meal or music, sexual orgasm, drug high). Many rewarding episodes are followed by a period of satiation for the specific reward experienced. To our knowledge, there are currently no data available to suggest that the ‘wanting’/’liking’ model would apply differently to social and non-social types of reward. However, some rewards lack satiation effects or result in only short periods of satiation (for example, money).
In general, physiological or drive states (for example, satiation, deprivation, stress, anxiety) strongly modulate an individual’s responsiveness to reward. Both reward ‘wanting’ and reward ‘liking’ have been associated with discrete (and to a specific extent with some overlapping) neural correlates. Whereas ‘wanting’ is mainly driven by phasic dopaminergic neural firing in the ventral striatum (including the nucleus accumbens), ‘liking’ is largely influenced by the opioid system, and recruits the ventromedial prefrontal cortex (vmPFC).
This summary of reward processing suggests there is good evidence that reward ‘wanting’ is disrupted in ASD, particularly in the social domain, whereas the available data for reward ‘liking’ are inconclusive. (Kohls et al). response to reward and, after learning, in response to conditioned cues that signal a potential reward (Schultz W et al.)