Dopamine Medication Research Articles

Effect of dopamine on limbic network connectivity at rest in Parkinson's disease patients with freezing of gait.

Freezing of gait (FOG) in Parkinson's disease (PD) has a poorly understood pathophysiology, which hinders treatment development. Recent work showed a dysfunctional fronto-striato-limbic circuitry at rest in PD freezers compared to non-freezers in the dopamine "OFF" state. While other studies found that dopaminergic replacement therapy alters functional brain organization in PD, the specific effect of dopamine medication on fronto-striato-limbic functional connectivity in freezers remains unclear. To evaluate how dopamine therapy alters resting state functional connectivity (rsFC) of the fronto-striato-limbic circuitry in PD freezers, and whether the degree of connectivity change is related to freezing severity and anxiety. Twenty-three PD FOG patients underwent MRI at rest (rsfMRI) in their clinically defined "OFF" and "ON" dopaminergic medication states. A seed-to-seed based analysis was performed between a priori defined limbic circuitry ROIs. Functional connectivity was compared between OFF and ON states. A secondary correlation analyses evaluated the relationship between Hospital Anxiety and Depression Scale (HADS)-Anxiety) and FOG Questionnaire with changes in rsFC from OFF to ON. PD freezers' OFF compared to ON showed increased functional coupling between the right hippocampus and right caudate nucleus, and between the left putamen and left posterior parietal cortex (PPC). A negative association was found between HADS-Anxiety and the rsFC change from OFF to ON between the left amygdala and left prefrontal cortex, and left putamen and left PPC. These findings suggest that dopaminergic medication partially modulates the frontoparietal-limbic-striatal circuitry in PD freezers, and that the influence of medication on the amygdala, may be related to clinical anxiety in freezer.

Cortico-cortical connectivity is influenced by levodopa in tremor-dominant Parkinson's disease

Resting tremor is the most common presenting motor symptom in Parkinson's disease (PD). The supplementary motor area (SMA) is a main target of the basal-ganglia-thalamo-cortical circuit and has direct, facilitatory connections with the primary motor cortex (M1), which is important for the execution of voluntary movement. Dopamine potentially modulates SMA and M1 activity, and both regions have been implicated in resting tremor. This study investigated SMA-M1 connectivity in individuals with PD ON and OFF dopamine medication, and whether SMA-M1 connectivity is implicated in resting tremor. Dual-site transcranial magnetic stimulation was used to measure SMA-M1 connectivity in PD participants ON and OFF levodopa. Resting tremor was measured using electromyography and accelerometry. Stimulating SMA inhibited M1 excitability OFF levodopa, and facilitated M1 excitability ON levodopa. ON medication, SMA-M1 facilitation was significantly associated with smaller tremor than SMA-M1 inhibition. The current findings contribute to our understanding of the neural networks involved in PD which are altered by levodopa medication and provide a neurophysiological basis for the development of interventions to treat resting tremor.

A framework for quantifying the coupling between brain connectivity and heartbeat dynamics: Insights into the disrupted network physiology in Parkinson's disease.

Parkinson's disease (PD) often shows disrupted brain connectivity and autonomic dysfunctions, progressing alongside with motor and cognitive decline. Recently, PD has been linked to a reduced sensitivity to cardiac inputs, that is, cardiac interoception. Altogether, those signs suggest that PD causes an altered brain-heart connection whose mechanisms remain unclear. Our study aimed to explore the large-scale network disruptions and the neurophysiology of disrupted interoceptive mechanisms in PD. We focused on examining the alterations in brain-heart coupling in PD and their potential connection to motor symptoms. We developed a proof-of-concept method to quantify relationships between the co-fluctuations of brain connectivity and cardiac sympathetic and parasympathetic activities. We quantified the brain-heart couplings from electroencephalogram and electrocardiogram recordings from PD patients on and off dopaminergic medication, as well as in healthy individuals at rest. Our results show that the couplings of fluctuating alpha and gamma connectivity with cardiac sympathetic dynamics are reduced in PD patients, as compared to healthy individuals. Furthermore, we show that PD patients under dopamine medication recover part of the brain-heart coupling, in proportion with the reduced motor symptoms. Our proposal offers a promising approach to unveil the physiopathology of PD and promoting the development of new evaluation methods for the early stages of the disease.

A Pilot Trial of Dopamine Replacement for Dynamic Facial Expressions in Parkinson's Disease.

Current conflict exists regarding the potential beneficial effects of dopamine medications on facial expressivity in Parkinson's disease. Via digital video analysis software, we previously found reduced facial movement (entropy) and slower time to reach peak entropy in individuals with Parkinson's disease compared to controls. We aimed to determine whether levodopa medications improved parameters of dynamic facial expressions (amplitude, speed). A total of 34 individuals with idiopathic Parkinson's disease were videotaped making voluntary facial expressions (happy, fear, anger, disgust) when "on" and "off" levodopa. Participants were 52 to 80 years old, early to mid-stage disease, non-demented, and included more men (65%). Expressions were digitized and analyzed using software that extracted three variables: two indices of movement change (total entropy, percent entropy change) and time to reach peak expression. Indices of facial movement (total entropy, peak entropy) and timing were significantly improved when patients were "on" vs "off" medication (all F's ≥ 3.00, P < 0.05). For total movement and time to reach peak entropy, levodopa-related improvements were emotion nonspecific. Levodopa-related improvement for peak entropy was driven primarily by happy expressions. There was no relationship between quantitative indices and clinical measures of mood (depression, anxiety) and motor disease severity. The effects of levodopa on Parkinson's disease voluntary facial movement and on timing were robust and consistent with those of levodopa on other intentional movements in Parkinson's disease. This improvement possibly occurred because of levodopa enhanced activation of face representation areas in fronto-cortical regions or because of less movement-based suppression.

‘Anxious fluctuators’ a subgroup of Parkinson's disease with high anxiety and problematic on-off fluctuations

Anxiety that occurs in association with on-off dopamine medication fluctuations is a major cause of distress, dysfunction, and lower quality of life in people with Parkinson's disease (PD). However, the association between anxiety and on-off fluctuations is poorly understood and it is difficult to predict which patients will suffer from this atypical form of anxiety. To understand whether fluctuating anxiety in PD exists as part of an endophenotype that is associated with other signs or symptoms, we prospectively assessed the change in anxiety and a battery of clinical variables when transitioning from the off-dopamine medication state to the on state in 200 people with PD. We performed latent profile analysis with observed variables as latent profile indicators measuring the on-off-state difference in anxiety, depression, motor function, daily functioning, and the wearing off questionnaire 19 item scale (WOQ-19) in order to model unobserved (i.e., latent) profiles. A two-class model produced the best fit. The majority of participants, 69%, were categorized as having a ‘typical on-off response’ compared to a second profile constituting 31% of the sample who experienced a worsening in anxiety in the off state that was three times that of other participants. This profile referred to as “anxious fluctuators” had a Hamilton Anxiety Rating Scale change between the off and on medication state of 10.22(32.85) compared to 3.27 (7.62), higher depression scores, greater disability and was less likely to improve on select WOQ-19 items when in the on-state. Anxious fluctuators were more likely to be male and have a family history of anxiety disorder. Given the adverse impact of this profile we believe it may be important to distinguish patients with a typical on-off response from those with this more problematic course of fluctuations.

Corticospinal Suppression Underlying Intact Movement Preparation Fades in Parkinson's Disease.

In Parkinson's disease (PD), neurophysiological abnormalities within the primary motor cortex (M1) have been shown to contribute to bradykinesia, but exact modalities are still uncertain. We propose that such motor slowness could involve alterations in mechanisms underlying movement preparation, especially the suppression of corticospinal excitability-called "preparatory suppression"-which is considered to propel movement execution by increasing motor neural gain in healthy individuals. On two consecutive days, 29 PD patients (on and off medication) and 29 matched healthy controls (HCs) underwent transcranial magnetic stimulation over M1, eliciting motor-evoked potentials (MEPs) in targeted hand muscles, while they were either at rest or preparing a left- or right-hand response in an instructed-delay choice reaction time task. Preparatory suppression was assessed by expressing MEP amplitudes during movement preparation relative to rest. Contrary to HCs, PD patients showed a lack of preparatory suppression when the side of the responding hand was analyzed, especially when the latter was the most affected one. This deficit, which did not depend on dopamine medication, increased with disease duration and also tended to correlate with motor impairment, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (both total and bradykinesia scores). Our novel findings indicate that preparatory suppression fades in PD, in parallel with worsening motor symptoms, including bradykinesia. Such results suggest that an alteration in this marker of intact movement preparation could indeed cause motor slowness and support its use in future studies on the relation between M1 alterations and motor impairment in PD. © 2022 International Parkinson and Movement Disorder Society.

Sleep Disorders in Older People with Special Focus on Parkinson’s Disease

This paper examines sleep disorders in older people, focusing on Parkinson’s disease (PD). It defines PD and explores those conditions associated with sleep disorders and their relationship to PD. It identifies specific conditions which cause sleep disoders in patients with PD, namely: REM sleep behaviour disorder (RDB) which may be a precursor to PD; obstructive sleep apnoea (OSA) which is very prevalent amongst people with PD; depression and mood disorders which both increase with age and are more common in people with PD; nocturia which increases with age and has a negative impact on those with PD; restless leg syndrome (RLS) which some argue is an accompaniment but others argue against this, due to the relationship to iron metabolism, although both respond to dopamine medications; and excessive daytime sleepiness (EDS) which completes the picture. The paper offers suggestions to the approach to these conditions and offers suggestions for therapeutic intervention.

Hormonal Imbalances Association to Persistent Genital Arousal Disorder in Females

ABSTRACT Introduction The etiology of the uncommon presentation of persistent genital arousal disorder (PGAD) can provide an insight into the hormonal imbalances that effect sexual function and dysfunction in females. We examine, review, and analyze the correlation of the known cases of PGAD that involved hormonal imbalances with a focus on hormone imbalances (HI) from a urological perspective. Objective To review the literature regarding hormonal imbalances in females with PGAD with a focus on HI. Methods A literature review of articles and clinical studies was performed to define the diagnosis, etiology, and treatment outcomes of PGAD. Search terms included hormone imbalances and/or, persistent genital arousal disorder, diagnosis of persistent genital arousal disorder, defining persistent genital arousal disorder, as well as treatment of persistent genital arousal disorder. Results We found the of onset of PGAD on average was 49.2± 13.1 years with the average length of symptoms 4.7± 11.2 years. The common etiology of cases presented as hormonal imbalances with most individuals experiencing this as their only etiology. Overall, individuals who underwent treatment had a 72.2% rate of symptoms being resolved. The treatments administered involved pharmacological, clinical intervention, diet modification, and hypnotherapy. Clinical intervention was used the less than pharmacological treatment but was more successful. Conclusions There was a high frequency of PGAD presentation and treatment involving dopamine medications such as selective serotonin receptor inhibitors (SSRI). When evaluating for this rare disease it is important to keep in consideration the effect of hormone imbalances. Further studies are needed to get a more thorough understanding of the effects of dopamine may have on sexual dysfunction disorders such as PGAD. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast and Boston Scientific

Disrupted reward processing in Parkinson’s disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis

BackgroundNeuropsychiatric symptoms are common in Parkinson’s disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control...

Decision making in Parkinson's disease: An analysis of the studies using the Iowa Gambling Task.

In Parkinson's disease (PD) impairments in decision making can occur, in particular because of the tendency toward risky and rewarding options. The Iowa Gambling Task has been widely used to investigate decision processes involving these options. The task assesses the ability to manage risk and to learn from feedback. The present paper aims at critically examining those studies in which this task has been administered to PD patients, in order to understand possible anomalies in patients' decision processes and which variables are responsible for that. A meta‐analysis has been conducted as well. Features of the task, sociodemographic and clinical aspects (including daily drugs intake), cognitive conditions and emotional disorders of the patients have been taken into account. Neural correlates of decision‐making competences were considered. It emerged that PD patients show a trend of preference toward risky choices, probably due to an impairment in anticipating the unrewarding consequences or to an insensitiveness to punishment. The possible role played by dopamine medications in decision making under uncertain conditions, affecting basal ganglia and structures involved in the limbic loop, was discussed. Attention has been focused on some aspects that need to be investigated in further research, in order to delve into this issue and promote patients' quality of life.

Anxiety in Parkinson’s Disease: A Systematic Review of Neuroimaging Studies

The mechanisms and neuronal networks associated with anxiety in Parkinson's disease (PD) are incompletely understood. One of the best tools for investigating both component function and neuronal networks associated with psychiatric symptoms is functional MRI (fMRI). Unlike structural scans, functional scans, whether task-based or resting-state, are more likely to be clinically relevant and sensitive to changes related to treatment. The investigators provide a comprehensive review of and present results for imaging studies of anxiety in PD. A systematic review of the literature on fMRI and anxiety in PD was conducted, and the quality of all included studies was simultaneously assessed. Eighteen studies were included: 15 studies assessed anxiety directly, and three evaluated emotional processing. Imaging methodology and behavioral assessments varied across studies, preventing direct comparison of results in most cases. There was a convergence in findings across methods, implicating involvement of the amygdala, caudate, and putamen in association with anxiety in PD. For both task-based activation and resting-state connectivity, dopamine medication status was associated with differences in activation and behavioral function. Although there is little consensus in the current fMRI literature studying anxiety in PD, these results suggest an overlap between structures classically involved in the brain's fear circuit (particularly the amygdala) and the alterations in the nigro-striatal system (e.g., the caudate and putamen and on-off dopamine findings) related to PD and its dopaminergic treatments.

Dopamine and reward hypersensitivity in Parkinson's disease with impulse control disorder.

Impulse control disorders in Parkinson's disease are common neuropsychiatric complications associated with dopamine replacement therapy. Some patients treated with dopamine agonists develop pathological behaviours, such as gambling, compulsive eating, shopping, or disinhibited sexual behaviours, which can have a severe impact on their lives and that of their families. In this study we investigated whether hypersensitivity to reward might contribute to these pathological behaviours and how this is influenced by dopaminergic medication. We asked participants to shift their gaze to a visual target as quickly as possible, in order to obtain reward. Critically, the reward incentive on offer varied over trials. Motivational effects were indexed by pupillometry and saccadic velocity, and patients were tested ON and OFF dopaminergic medication, allowing us to measure the effect of dopaminergic medication changes on reward sensitivity. Twenty-three Parkinson's disease patients with a history of impulse control disorders were compared to 26 patients without such behaviours, and 31 elderly healthy controls. Intriguingly, behavioural apathy was reported alongside impulsivity in the majority of patients with impulse control disorders. Individuals with impulse control disorders also exhibited heightened sensitivity to exogenous monetary rewards cues both ON and OFF (overnight withdrawal) dopamine medication, as indexed by pupillary dilation in anticipation of reward. Being OFF dopaminergic medication overnight did not modulate pupillary reward sensitivity in impulse control disorder patients, whereas in control patients reward sensitivity was significantly reduced when OFF dopamine. These effects were independent of cognitive impairment or total levodopa equivalent dose. Although dopamine agonist dose did modulate pupillary responses to reward, the pattern of results was replicated even when patients with impulse control disorders on dopamine agonists were excluded from the analysis. The findings suggest that hypersensitivity to rewards might be a contributing factor to the development of impulse control disorders in Parkinson's disease. However, there was no difference in reward sensitivity between patient groups when ON dopamine medication, suggesting that impulse control disorders may not emerge simply because of a direct effect of dopaminergic drug level on reward sensitivity. The pupillary reward sensitivity measure described here provides a means to differentiate, using a physiological measure, Parkinson's disease patients with impulse control disorder from those who do not experience such symptoms. Moreover, follow-up of control patients indicated that increased pupillary modulation by reward can be predictive of the risk of future emergence of impulse control disorders and may thereby provide the potential for early identification of patients who are more likely to develop these symptoms.

Arterial spin labeling detects perfusion patterns related to motor symptoms in Parkinson's disease

IntroductionImaging neurovascular disturbances in Parkinson's disease (PD) is an excellent measure of disease severity. Indeed, a disease-specific regional pattern of abnormal metabolism has been identified using positron emission tomography. Only a handful of studies, however, have applied perfusion MRI to detect this disease pattern. Our goal was to replicate the evaluation of a PD-related perfusion pattern using scaled subprofile modeling/principal component analysis (SSM-PCA). Methods. We applied arterial spin labeling (ASL) MRI for this purpose. Uniquely, we assessed this pattern separately in PD individuals ON and OFF dopamine medications. We further compared the existence of these patterns and their strength in each individual with their Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor (MDS-UPDRS) scores, cholinergic tone as indexed by short-term afferent inhibition (SAI), and other neuropsychiatric tests. Results. We observed a PD-related perfusion pattern that was similar to previous studies. The patterns were observed in both ON and OFF states but only the pattern in the OFF condition could significantly (AUC=0.72) differentiate between PD and healthy subjects. In the ON condition, PD subjects were similar to controls from a CBF standpoint (AUC=0.45). The OFF pattern prominently included the posterior cingulate, precentral region, precuneus, and the subcallosal cortex. Individual principal components from the ON and OFF states were strongly associated with MDS-UPDRS scores, SAI amplitude and latency. Conclusion. Using ASL, our study identified patterns of abnormal perfusion in PD and were associated with disease symptoms.

Two Cases of Parkinson’s Disease for Which Dental Treatment Was Effective

The purpose of this study is to document the improvement observed in two cases of Parkinson’s disease (PD) after dental treatment. The first subject is a man in his 60s with severe Parkinson’s disease; medication has not been very effective in this case. Prior to treatment, he was unable to stand without support due to rigidity. Just after removing as much of the dental infection as possible, he was able to walk, albeit slowly, and as a result of continuing treatment, one month later, the symptoms had significantly improved. The second subject is a woman in her 40s, who became aware of joint stiffness seven years ago, and was later diagnosed with PD independently at three hospitals. Her main symptoms were rigidity, knee pain, and speech disorder. The dopamine medication worked well against rigidity, but the symptoms reappeared after the medication stopped working. Her condition was significantly improved just after one tooth with an apical lesion was extracted. Although the underlying mechanism has not been clarified, I hypothesize that, at least in these cases, negative signals that passed through the trigeminal nerve to the midbrain affected predominantly the dopaminergic neurons in the substantia nigra of the midbrain. Removal of the harmful signals from the oral area resulted in normalization of the substantia nigra. Further research should be promoted with dental and medical cooperation.

Dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson's disease.

Reduced levels of dopamine in Parkinson's disease contribute to changes in learning, resulting from the loss of midbrain neurons that transmit a dopaminergic teaching signal to the striatum. Dopamine medication used by patients with Parkinson's disease has previously been linked to behavioural changes during learning as well as to adjustments in value-based decision-making after learning. To date, however, little is known about the specific relationship between dopaminergic medication-driven differences during learning and subsequent changes in approach/avoidance tendencies in individual patients. Twenty-four Parkinson's disease patients ON and OFF dopaminergic medication and 24 healthy controls subjects underwent functional MRI while performing a probabilistic reinforcement learning experiment. During learning, dopaminergic medication reduced an overemphasis on negative outcomes. Medication reduced negative (but not positive) outcome learning rates, while concurrent striatal blood oxygen level-dependent responses showed reduced prediction error sensitivity. Medication-induced shifts in negative learning rates were predictive of changes in approach/avoidance choice patterns after learning, and these changes were accompanied by systematic striatal blood oxygen level-dependent response alterations. These findings elucidate the role of dopamine-driven learning differences in Parkinson's disease, and show how these changes during learning impact subsequent value-based decision-making.

Basal ganglia contributions during the learning of a visuomotor rotation: Effect of dopamine, deep brain stimulation and reinforcement.

It is commonly thought that visuomotor adaptation is mediated by the cerebellum while reinforcement learning is mediated by the basal ganglia. In contrast to this strict dichotomy, we demonstrate a role for the basal ganglia in visuomotor adaptation (error-based motor learning) in patients with Parkinson's disease (PD) by comparing the degree of motor learning in the presence and absence of dopamine medication. We further show similar modulation of learning rates in the presence and absence of subthalamic deep brain stimulation. We also report that reinforcement is an essential component of visuomotor adaptation by demonstrating the lack of motor learning in patients with PD during the ON-dopamine state relative to the OFF-dopamine state in the absence of a reinforcement signal. Taken together, these results raise the possibility that the basal ganglia modulate the gain of visuomotor adaptation based on the reinforcement received at the end of the trial.

Different Dopaminergic Dysfunctions Underlying Parkinsonian Akinesia and Tremor.

Although the occurrence of Parkinsonian akinesia and tremor is traditionally associated to dopaminergic degeneration, the multifaceted neural processes that cause these impairments are not fully understood. As a consequence, current dopamine medications cannot be tailored to the specific dysfunctions of patients with the result that generic drug therapies produce different effects on akinesia and tremor. This article proposes a computational model focusing on the role of dopamine impairments in the occurrence of akinesia and resting tremor. The model has three key features, to date never integrated in a single computational system: (a) an architecture constrained on the basis of the relevant known system-level anatomy of the basal ganglia-thalamo-cortical loops; (b) spiking neurons with physiologically-constrained parameters; (c) a detailed simulation of the effects of both phasic and tonic dopamine release. The model exhibits a neural dynamics compatible with that recorded in the brain of primates and humans. Moreover, it suggests that akinesia might involve both tonic and phasic dopamine dysregulations whereas resting tremor might be primarily caused by impairments involving tonic dopamine release and the responsiveness of dopamine receptors. These results could lead to develop new therapies based on a system-level view of the Parkinson's disease and targeting phasic and tonic dopamine in differential ways.

The role of Dopamine in Preparatory Inhibition: What can we learn from Parkinson’s disease?

The role of Dopamine in Preparatory Inhibition: What can we learn from Parkinson’s disease?

17 Dopamine dysregulation syndrome: a systematic review

Objectives Dopamine-dysregulation syndrome (DDS) is an uncommon complication of the treatment of Parkinson’s disease, characterised by addictive behaviour and excessive use of dopamine medication. Patients may develop prominent dyskinesias, cyclothymia, psychosis and significant functional decline. There is an increasing recognition of neuropsychiatric symptoms in Parkinson’s disease, however, it is likely that DDS frequently goes unrecognised or misdiagnosed. We aim to clarify current understanding of clinical characteristics, risk factors and management of DDS to increase the recognition of this disorder. Methods Cases were identified through a search of online databases (PUBMED, EMBASE, google scholar) and a secondary search of references of identified articles. Search terms were dopaminergic dysregulation syndrome, hedonistic homeostatic dysregulation, dopamine/levodopa addiction. Cases were included if they met criteria for DDS. Case-cohort studies were also reviewed and will be discussed further. Results We reviewed 390 articles and identified a total of 98 cases of DDS. There was a predominance of male cases (83%), with an early age of onset of Parkinson’s (mean average 46 years), and a mean average duration of illness of 11 years. Past substance and psychiatric history was present in 15 and 10 cases. Co-morbid impulse control disorders were present in 61% of cases and punding in 21%. There was a large variety of management strategies utilised, with only 56% of cases documented as resolving after treatment, most of these reliant on strict caregiver supervision. Of note sodium valproate was used successfully in 5 cases. The response to deep brain stimulation was varied. Conclusions In general, DDS cases represent a diverse cohort of individuals that do not necessarily have the previously identified risk factors of past psychiatric history and substance use. Treatment of DDS is complex and may be more successful when family and caregivers are on side. Prognosis appears to be improved with early diagnosis and treatment. It is recommended that screening for DDS is considered in at risk populations. Further research is needed to clarify the true prevalence of this condition, and to identify possible preventative strategies.

Creativity Assessment in Subjects with Tourette Syndrome vs. Patients with Parkinson's Disease: A Preliminary Study.

(1) Background: Literature suggests that high levels of dopamine are associated with creative thoughts. Tourette Syndrome (TS) patients have high dopamine levels, while Parkinson’s Disease (PD) subjects have low dopamine levels. Consequently, TS individuals are supposed to have a major and PD patients less creative output. Moreover, dopamine medications may alter the level of creativity, and therefore Quality of Life, in both pathologies. (2) Methods: The aim of the study was to verify the hypothesis of TS patients having higher creative scores than PD patients. The assessment consisted of the administration of the Creative Thinking ASK Test. There were 54 participants—36 males and 18 females—i.e., 27 TS patients and 27 PD subjects. Age of the sample was 35 to 57 years old, high school certificate was required. (3) Results: TS sample (103.11 ASK average score) was more creative than PD sample (94.11 ASK average score). (4) Conclusions: The results supported the aforementioned hypothesis: TS sample resulted in having higher creative scores than PD sample. Dopamine and other neurotransmitters of TS and PS appear to affect subject’s creativity. Further studies with creative assessments in TS and PD patients are needed to support the preliminary results of our study.