How Does STN-DBS Influence Emotional Conflict Decision in Parkinson's Disease: a EEG Study
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      A large body of evidence points to impairment in the decoding of emotional stimuli in
      Parkinson's disease (PD). These changes seem to be related to dysfunction of the
      mesocorticolimbic projections leading to dysfunction of the limbic cortico-subcortical loop
      that, throughout the basal ganglia, projects to limbic cortical regions such as the anterior
      cingulate cortex and the orbitofrontal cortex, which are known to be involved in emotional
      processing. Thus, presumably the occurrence of non-motor psychic symptoms and fluctuations in
      PD would also rely on the degeneration of this circuitry. Dopamine modulation of emotions has
      been frequently reported both in healthy subjects or PD patients, but the effect of
      subthalamic nucleus deep brain stimulation (STN-DBS) over mood symptoms is more controversial
      and there is still a paucity of data demonstrating its role in emotional processing. The
      objective of our study is to assess and compare the behavioral and electrophysiological
      effects of both dopamine and STN-DBS in PD during emotional processing. To do so, the
      Emotional Stroop task, a version of the classical Stroop test developed to investigate
      inhibition of emotional interference, will be performed by STN-DBS PD patients in four
      different treatment conditions while high resolution electroencephalographic cortical mapping
      is conducted. Using this approach, the investigators expect to better separate the mechanisms
      of psychic features related to either disease, dopaminergic treatment, subthalamic
      stimulation or the association of both, with the final aim of optimizing the clinical
      management of PD.
    

Detailed description: 
      Non-motor symptoms of Parkinson's disease (PD) and particularly mood manifestations such as
      apathy, depression and anxiety have gained attention in the last few decades due to its high
      frequency and impact in patient's quality of life. In addition, these psychic non-motor
      features have been shown to fluctuate alike motor symptoms do, concurring to non-motor
      fluctuations (NMF) that can be more disabling than motor symptoms. The physiopathological
      basis of psychic NMF is unclear but mesolimbic dopaminergic denervation has been suggested to
      underlie mood manifestations during off-periods . At the same time, it has been demonstrated
      that PD patients suffer from abnormal emotional processing deficits in facial expression
      recognition and emotional prosody especially concerning negative valanced emotions, and that
      these impairments could also be linked to mesolimbic dopaminergic mechanisms. The mesolimbic
      pathway is one of the functional cortico-subcortical loops in which basal ganglia are
      segregated. It lies in the ventral subportion of each nucleus (ventromedial in the case of
      the subthalamic nucleus) and through the mediodorsal thalamus projects to the orbito-frontal
      cortex and the anterior cingulate cortex (ACC), limbic cortical areas that robust evidence
      has involved in the pathophysiology of mood disturbances and emotional processes like facial
      expression recognition or emotional conflict resolution. In summary, in the same way that
      dopamine depletion of the nigrostriatal pathway is at the origin of the parkinsonian motor
      triad, the lack of dopamine in the mesolimbic loop would account for non-motor psychic
      manifestations including apathy, anxiety, depression and disturbances in emotional decoding.
      A proper way to explore these phenomena is through tasks that involve exposure to affective
      stimuli.

      The Stroop Test is a tool that allows exploring selective attention, cognitive conflict
      resolution (inhibition of irrelevant reading automatism) and processing speed, and is usually
      applied to evaluate executive functions. A modified version, the facial Emotional Stroop
      (ES), was developed in order to address the interference of irrelevant affective distractors.
      With this task, the authors demonstrated in healthy volunteers, that dorsolateral prefrontal
      cortex and the amygdala are the areas implicated in emotional conflict monitoring whereas
      rostral anterior cingulate cortex (rACC) activation associates with emotional conflict
      resolution through a top-down inhibition of the amygdala in order to avoid the interference
      of new irrelevant emotional distracters. The same group designed a variant of the task by
      adding non-emotional cognitive trials in which subjects had to identify the gender of the
      faces instead of the affect. Through this paradigm, they were able to dissociate neural nets
      involved in cognitive conflict resolution from those specifically involved in emotional
      conflict resolution. Hence, while lateral prefrontal cortex (LPFC) was shown to resolve
      non-emotional conflict, the pregenual part of the anterior cingulate cortex, that is, the
      rACC is involved in emotional conflict resolution. On the contrary, the detection of both
      types of conflict share activation of a common region of the dorsal anterior cingulate
      cortex.

      By using the ES task, our group has recently demonstrated in a functional MRI study with PD
      patients that dopamine modulates emotional conflict resolution by "normalizing" the activity
      of rACC, which was hypoactivate in the off-drug state compared to the on-drug state and to
      healthy controls. The rACC receives massive dopamine projections from the ventral tegmental
      area (VTA), and thus is part of the cortico-subcortical limbic loop. Therefore, these
      findings would support the implication of this circuitry in emotional decoding disturbances
      in PD and match with the hypothesis proposed that dopaminergic mesolimbic degeneration would
      underlie mood manifestations and psychic NMF of the disorder. It is well demonstrated that
      STN-DBS improves levodopa-sensitive motor symptoms of PD. STN-DBS does not change overall
      cognitive function, except for some impairment in executive functions like verbal fluency
      but, in an experimental scenario, it has been proved to increase impulsivity during cognitive
      tasks in PD patients. However, its clinical effect in the affective domain of PD is highly
      controversial and there is only very limited data regarding emotional processing. A few
      available studies comparing patients before and after surgery point to a worsening in facial
      emotion and prosody recognition. These findings could not be replicated in a more recent
      work. Such studies however do not take into account the desensitization of the dopaminergic
      system related to marked decrease in medication after STN DBS. Because of the major changes
      in dopaminergic treatment and chronic desensitization all studies which do not compare
      stimulation conditions should be interpreted very cautiously. In our opinion, due to the
      large available clinical data that demonstrate behavioral changes after STN-DBS, and
      considering the anatomic overlapping of STN functional subdivisions, it is likely that
      stimulation would exert some effect over the limbic basal ganglia loop even with electrodes
      that are well implanted in the sensorimotor territory and thus, induce changes in both motor
      and affective domains, even though with some dissociation.

      With this rationale, the investigators aim to reproduce in an electrophysiological
      perspective the functional magnetic resonance imaging (fMRI) evidences of limbic cortical
      regions involvement in emotional decoding processes and to differentiate them from those
      involved in cognitive conflict. In addition, the investigators want to confirm dopamine
      modulation when dealing with emotional conflict, and elucidate STN-DBS effect in behavioral
      and cortical electrophysiological terms.
    

Intervention name(s): stroop test in condition DBS off; stroop test in condition DBS on
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Patients were evaluated in DBS Off; Patients were evaluated in DBS On
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science