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Background:
Review

Novelty Seeking in Parkinson’s Disease: A Candidate Biomarker for Cognitive Changes

by
Kyle Paulk
1,† and
Lee E. Neilson
1,2,*
1
Department of Neurology, Oregon Health and Sciences University, Portland, OR 97239, USA
2
Neurology and Research Service, VA Portland Health Care System, Portland, OR 97239, USA
*
Author to whom correspondence should be addressed.
†
Current address: Ochsner Medical Center, New Orleans, LA 70121, USA.
Int. J. Transl. Med. 2024, 4(4), 608-617; https://doi.org/10.3390/ijtm4040042
Submission received: 3 September 2024 / Revised: 29 October 2024 / Accepted: 5 November 2024 / Published: 10 November 2024
Browse Figure
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Abstract

:
Background: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by motor impairments, cognitive decline, and affective changes. Beyond the well-described motor symptoms, neuropsychiatric symptoms play a crucial role in PD disability burden. Novelty seeking, a trait extensively studied within various models of personality, may influence the manifestation of these non-motor symptoms. Methods: A narrative review of articles determined relevant by the author(s) was undertaken. Results: The literature indicates that PD patients typically exhibit low novelty seeking initially. However, dopaminergic therapies can increase novelty-seeking behaviors, sometimes leading to impulse control disorders (ICD). Studies using the Temperament and Character Inventory (TCI) suggest a complex interplay between disease state, medication, and baseline personality, which is not fully elucidated. High novelty seeking scores predict a higher risk of ICDs, yet they also correlate with a more benign clinical phenotype and improved quality of life post-DBS surgery. Conclusions: Novelty seeking is a significant trait in PD, influencing non-motor symptoms and treatment responses. Understanding its neurobiological basis and clinical implications could lead to better diagnostic and therapeutic strategies through the use of objective, practical tools for disease monitoring, individualized therapy, and pharmacological development.

1. Introduction

1.1. Parkinson’s Disease Overview

Parkinson’s disease (PD) is an age-related neurodegenerative disorder known for its progressive motor impairments [1]. Global prevalence of PD has doubled over a 25-year timeframe to 8.5 million in 2019, making it a leading cause of disability among neurological conditions [2] and reflecting its substantial impact on individuals and healthcare systems. While motor symptoms such as tremors and rigidity are prominent, cognitive and affective alterations significantly contribute to disability and can remain undetected despite their profound influence.

1.2. Personality and Parkinson’s Disease

The observation of specific patterns of cognitive and affective derangements in PD patients has attracted the attention of patients, caregivers, and physicians for some time. Early in the 20th century, notions emerged of a “Parkinson’s personality”, and this term is now sometimes used to describe patients’ traits of inflexibility, orderliness, introversion, cautiousness, and punctuality—traits which can be present early in the disease or may even precede the onset of motor symptoms [3]. This connection was substantiated in part by a large prospective study [4] of 7000 people utilizing detailed Minnesota Multiphasic Personality Inventory (MMPI) data, in which a web-based tracking tool was used to determine rates of PD nearly 40 years after personality testing. In it, the subscale for anxiety emergent in adulthood was shown to be the sole predictor for development of PD, offering nearly double the risk of disease. Other MMPI subscales offered no specific associations, including those for aggression (AGG), impulsive behavior (BXD), negative emotionality and neuroticism (NEGE-r), introversion, and low positive emotionality (INTR-r).
Numerous studies have since attempted to expand on this observation, investigating personality in the PD population at diagnosis and through the course of disease. While these studies have employed various personality measures, the majority of published studies have utilized Cloninger’s psychobiological model (PBM) or the Big Five Model (BFM) [5]. Among the common observations summarized from a recent meta-analysis of these instruments is a reduction in novelty seeking as conceptualized by PBM, as well as its related constructs, openness, and extroversion, conceptualized by the BFM [5].
This narrative review explores the evolving understanding of novelty seeking in PD, examining its neurobiological basis within Cloninger’s personality framework, its modulation by pharmacological treatments, and its implications in the management of PD. By gaining an appreciation of novelty seeking traits and behaviors, it may be possible to expand on the currently available assessments of novelty seeking which have been able to predict non-motor symptoms and influence the response to dopaminergic therapies. Our hope is that future studies will be undertaken to elucidate how novelty seeking is impacted by the intersection of disease state, medications, and baseline personality. In doing so, the personality construct may be able to move past its current clinical connotation as purely a marker of impulsivity. Rather, seeing novelty seeking as a basic biological process with potential adaptive roles may in turn assist in the development of new therapeutic strategies in the era of disease-modifying treatments.

2. Methods

This narrative review was conducted between September 2022 and July 2024, utilizing PubMed to identify relevant studies. In the first search, we used the keywords “Parkinson’s disease”, “personality” and “impulse control disorder”, yielding 507 articles. After screening titles for relevance, 83 articles remained, of which abstracts were reviewed, leading to the inclusion of 37 articles for full-text analysis. A second search using “Parkinson’s disease” and “novelty seeking” resulted in 80 articles, of which 15 additional unique articles were deemed relevant after abstract review. Additional papers cited within these 52 were added if they were considered relevant during full text analysis, bringing the total to 59 studies included for synthesis. Data were extracted from each study, focusing on design, population characteristics, key findings, and clinical outcomes related to personality traits (e.g., novelty seeking) and ICDs in the context of PD. The findings were synthesized thematically, highlighting how personality traits influence PD progression and how ICDs arise, particularly in patients undergoing dopaminergic treatments.

3. Results

3.1. Definition of Novelty Seeking

Novelty seeking behavior, a concept pioneered by psychiatrist and geneticist Robert Cloninger in 1987, emerged within Cloninger’s psychobiological model (PBM) of personality, utilizing a standardized measure which came to be called the Temperament and Character Inventory (TCI) [6]. Novelty seeking represents a dimension of personality that increases exploratory behavior when stimuli are new or different. Cloninger assessed novelty seeking within a broad personality framework, distinct from related constructs such as sensation seeking, a previously established construct that also emphasized a “willingness to take physical and social risks for the sake of such experiences [7]”. The TCI and its revisions categorize novelty seeking into dimensions that include exploratory excitability, impulsiveness, extravagance, and disorderliness, providing a nuanced assessment of this trait.
Cloninger’s model divides personality into temperament—largely genetically determined and comprising automatic behavioral responses—and character—more environmentally influenced and maturing in adulthood [8]. Novelty seeking represents one of the four temperaments, with harm avoidance, reward dependence, and persistence representing the other domains. These temperaments, which attempt to capture basic motivations for inhibition or maintenance of behavior, were based on an unproven link to genetic polymorphisms affecting monoamine neurotransmitter receptors [9,10]. Nevertheless, this grounding in monoaminergic, and specifically dopaminergic, neurotransmission has allowed the TCI to maintain its place in the study of personality and PD, a disease noted for the loss of dopamine neurons [11].

3.2. Novelty Seeking in Parkinson’s Disease

In Parkinson’s Disease (PD), novelty seeking traits exhibit variability across disease stages and in response to dopaminergic therapies [12]. Initially, PD patients typically exhibit low novelty seeking traits, attributable to the loss of dorsal striatal dopamine neurons and minimal dopaminergic treatment [13]. However, as the disease progresses and higher doses of dopaminergic medications are required to manage motor symptoms, novelty-seeking behaviors increase. This is generally assumed to be a direct effect of dopaminergic therapy, since dopaminergic treatments themselves (i.e., levodopa and dopamine agonists) have been observed to reverse low novelty seeking states [14], but how disease progression or other medications may be playing a role has not been well elucidated.

3.2.1. Novelty Seeking and Impulse Control Disorders

Levodopa and dopamine agonists, the cornerstones of PD treatment, can influence novelty-seeking behaviors by way of their ability to induce some of the most extreme manifestations of novelty seeking: impulse control disorders (ICD) [15]. Common ICDs in PD include problematic gambling, sexual behaviors, shopping, and eating, all of which can result in severe financial and inter-personal consequences, significantly impairing the quality of life of PD patients and their families. Traditional models for understanding the emergence of ICDs in PD describe a “dopamine overdose” of the ventral striatum, which does not experience as early or as rapidly a loss of dopamine neurons in PD as compared with the dorsal striatum. The relatively intact ventral striatum is therefore overwhelmed with exogenous dopamine, altering reward processing and, ultimately, impulse control [11].
Dopamine agonists, which carry the highest risk among pharmacologic agents for inducing ICD, continue to have a clinical role in PD for symptom management, including indications for the cardinal motor symptoms along with sleep, pain, apathy, and depression [16]. Therefore, understanding the intersection of novelty seeking and ICD could inform PD management, particularly because discontinuation of the offending dopaminergic medication remains the primary approach to managing these disorders [17]. We do know that most of the currently available dopamine agonists have a higher affinity for D2-type dopamine receptors, which may explain some the increased risk of ICD seen with these drugs since D1-type and D2-type dopamine receptors vary widely in their expression among brain regions served by mesocortical and mesolimbic projections [17]. Younger patients, those with earlier disease onset, males, and patients with personal or family history of addiction have higher rates of ICD in PD, and more recent work has continued to expand on our understanding of ICD risk. One recent study utilizing machine learning and genomic data was able to produce a clinic-genetic risk calculator, deemed the “ICD-risk score”, incorporating just seven easily obtained clinical variables and genotypes at two single nucleotide polymorphisms [18]. The genes related to the kappa opioid receptor and tryptophan hydroxylase—notably involved in monoaminergic transmission—are implicated. Despite the known risk factors described, clinicians still observe significant variability in dopamine agonist tolerability, with some patients unable to tolerate agonists even at low doses.
Importantly, the degree to which baseline personality, disease progression, medication dose, and neuromodulation (deep brain stimulation) influence novelty seeking traits and ICD risk remains poorly understood. Firstly, the association of ICD with novelty seeking personality has largely been described in patients already on dopaminergic treatments [19,20,21]. Additionally, in a more recent study in young (mean age 58) de novo PD patients, higher novelty seeking on the TCI was described to be more characteristic of a benign phenotype. This group was modestly, but notably, less impulsive than a “neuropsychiatric” phenotype that had lower novelty seeking [22]. The benign group also had better motor scores on the UPDRS (Unified Parkinson’s Disease Rating Scale). It is possible that low novelty seeking at the onset of disease may paradoxically be a risk factor for ICD, as these patients may experience a more sudden and sizeable increase in novelty seeking traits incongruent with their baseline personality (Figure 1).
Deep brain stimulation (DBS), a treatment for advanced PD, also likely affects novelty-seeking behaviors. While several studies have evaluated cognitive and affective outcomes before and after DBS to the two common brain targets in PD [23], published data utilizing comprehensive personality measures have exclusively reported outcomes after DBS of the subthalamic nucleus (STN). Patients undergoing STN DBS appear to have no change in overall novelty seeking scores as measured by the TCI [24]. This is unexpected given the significant drop in oral dopaminergic therapy post-STN DBS, and this observation raises the prospect of a novelty promoting effect of deep brain stimulation itself. This also fits with the observation that DBS can induce or worsen ICD independent of changes in dopaminergic medication [25].
Interestingly, a possible personality effect of DBS may be grounded in basic novelty processing. Recent research in animal models has identified the Zona Incerta (ZI), often stimulated in STN DBS as a critical neural locus driving novelty seeking behavior, distinct from traditional reward-based motivational systems. In mice, activation of inhibitory GABAergic neurons in the ZI promoted interaction with novel objects, suggesting direct involvement in novelty seeking behavior [26]. This finding was extended to primates, where a study involving eye tracking tasks demonstrated that neurons in the ZI, particularly in the caudal lateral ZI, predicted future gaze shifts toward objects that would lead to novel experiences [27]. The anatomy of the STN, including its associative and limbic functional subregions [28] as well its proximity to the ZI, may become critical considerations for DBS programming in the future, and such considerations may rely on our ability to measure novelty seeking.
Novelty seeking has additional relevance to neuromodulation in PD, apart from any association with ICD, by way of its ability to predict post-DBS prognosis [29]. PD patients with high NS prior to surgery have greater improvement in the subjective mobility component on quality-of-life measures after STN-DBS, which are paradoxically improved compared to objective motor examination expected for their perceived changes. This may be a reflection of the tendency of high NS patients to respond positively and with excitation toward a new situation or stimulus. As STN-DBS poses a significant and abrupt change in patients’ lives, this personality construct may simply be enhancing the placebo effect of such an intervention. Exploring novelty seeking personality and DBS outcomes stands to inform patient selection by way of its ability to predict such subjective responses to stimulation. Future research could also shed light on the intersection of personality, speech, and language before and after DBS, since reductions in verbal fluency represent one of the most commonly reported side effects after STN-DBS [30].

3.2.2. Novelty Seeking and Cognition

Beyond its implications in ICD, novelty seeking may also have relevance for cognition more generally. Historically, it was thought that all individuals possess varying degrees of each type of temperament, with extremes of any one temperament posing a risk for problem behaviors and psychological disorders, including cognitive dysfunction. In fact, Cloninger himself hypothesized that the monoaminergic transmission differences in early life may influence “pre-semantic perception”, which in-turn results in differences in the encoding of concrete visuospatial information and affective valence of stimuli [31]. The same study of de novo PD noted less impulsivity in patients with higher novelty seeking and observed fewer cognitive deficits [22]. Additionally, one study of de novo PD patients with initially low novelty seeking scores on the TCI showed a reversal of low performance in reward learning tasks following 12 weeks of dopamine agonist therapy, which simultaneously increased novelty seeking scores [14]. Though novelty seeking measured with the TCI has not specifically correlated with cognitive performance on a number of neuropsychological tests [32,33], the highly related construct of openness measured using the Big Five Model of personality has shown correlations with verbal fluency in PD patients [34]. Little is known about how disease phenotypes might intersect with personality and cognition, but akinetic-rigid phenotypes with higher risk of cognitive decline do demonstrate more BFM introversion and neuroticism, generally considered to correlate with low TCI novelty seeking, compared to tremor-predominant PD [35].

3.3. Neurobiological Mechanisms Underlying Novelty Seeking Behavior

3.3.1. Preclinical Models of Novelty Seeking

Our understanding of novelty seeking behavior has been significantly advanced by models such as the HR/LR model, originating from Piazza et al. (1989), which categorizes rats into High Responders (HRs) and Low Responders (LRs) based on their locomotor responses to novel environments [36,37]. HRs, exhibiting high exploration of novel environments, mirror humans with novelty seeking traits, sharing neurobiological similarities particularly involving dopamine and serotonin neurotransmitter systems. These systems, extensively studied in HR/LR rat models, reveal an intricate interplay crucial for understanding addiction and impulsivity, where elevated mesolimbic dopamine activity is a common feature [38].
Genetically, HR rats exhibit lower D2 receptor mRNA concentrations in the nucleus accumbens and striatum, suggesting alterations in dopamine receptor function [39]. Additionally, genes implicated in hippocampal neurogenesis differ between HR and LR rats, with HR rats showing reduced expression of the hippocampal glucocorticoid receptor, indicating that HR rats may explore novel environments because of a dampened neuro-endocrine response to the inherent stress of a novel environment [40]. This lack of glucocorticoid receptor response may ultimately be driving elevated steroid hormone levels and an increase in mesolimbic dopamine release, which is positively reinforcing for stress and novelty.
On the circuit level, novelty processing engages both thalamocortical circuits for sensory integration and mesial temporal lobe structures for encoding and discrimination of familiar versus novel stimuli [41]. Dopaminergic projections from the substantia nigra and ventral tegmental area modulate these processes, influencing motivation and behavioral responses. It is possible that the aforementioned ZI is the integrative node for such diverse functions as sensory processing, arousal, attention shifting, and behavioral outputs including posture and locomotion [42]. A second layer of complexity is habituation: the process by which repeated exposure to a stimulus attenuates the novelty response, allowing an individual to focus on more relevant stimuli [43]. Ordinarily, spontaneous firing of midbrain dopaminergic neurons increases in response to the introduction of a novel stimulus, and this increase is necessary to generate novelty-seeking behaviors. Habituation, or the rapid decline in firing rates that occurs with the continuous presence of the stimulus, then allows the brain to mark a stimulus as familiar. Age seems to impair habituation, thus reducing novelty seeking by impairing the transition of stimuli from novel to familiar, but whether the ventral tegmental area and the substantia nigra pars compacta [44] or other midbrain structures such as the interpeduncular nucleus are important for modulating the habituation process is unknown [45].

3.3.2. Neuroimaging Findings

Neuroimaging studies utilizing structural and functional MRI have provided several illuminating observations regarding novelty seeking in both healthy individuals and PD patients. Among healthy individuals, structural MRIs have demonstrated a positive correlation of novelty seeking scores with cortical thickness and grey matter volume in the prefrontal cortex [46,47]. This observation fits with studies showing an association of novelty seeking scores with increased prefrontal cortex as well as subcortical activation in the striatum, substantia nigra, and ventral tegmental area on fMRI [48]. More recent work has expanded this simplistic association, showing that novelty seeking is associated with stronger cerebellar connectivity to the thalamus, putamen, and several cortical structures, as well as more robust connectivity between visual and sensorimotor cortices [49]. This suggests that modulating basic functions of perception and motor planning may modulate novelty seeking.
Three studies of PD patients have evaluated the uptake of radiolabeled forms of dopamine in patients compared to controls, finding no significant association between striatal dopamine uptake and global novelty seeking scores [50], though one of the three did find an association of one subscale of novelty seeking with ventral striatal uptake [51]. A separate PET study utilizing 11C-CFT [52] also showed no correlation between striatal dopamine receptor availability and personality; however, novelty seeking correlated positively with the connectivity of the striatum with the hippocampus and amygdala in both patients and controls. Lastly, an fMRI study evaluating dynamic functional connectivity in treated PD patients with and without impulse control disorders showed that those with ICD exhibited a lack of inter-network connections at the expense of strong within-network connections, most pronounced in nodes of the salience network consisting of frontoinsular and cingulate cortices [53]. This tendency within PD-ICD patients was also positively correlated with novelty seeking on the TCI.

4. Discussion: Challenges and Future Directions

4.1. Limitations of Clinical Assessment Tools

If novelty seeking is to serve as a clinical biomarker with relevance to clinical phenotype, disease progression, and response to clinical treatments, more practical means of capturing the construct are needed. Measuring novelty seeking with the traditional TCI has several limitations. Even in its revised form, it is a 140-item questionnaire and not practical for use during a routine clinic visit. It also requires interpretation by the foundation which owns the copyright for the scale. Additionally, the questionnaire was designed to quantify a stable and inherited feature of personality, limiting its interpretation regarding personality changes that result from dynamic factors such as medication dosing, DBS, or progression of a disease [12,24]. Alternatives to measuring the novelty seeking construct do exist, and several have been applied to the study of PD patients (Table 1). However, there are notable limitations to employing some of these tasks in the PD population. Attentional orienting tasks using paired visual stimuli require a push-button response, which may be delayed in a hypokinetic disorder such as PD and therefore cause a spurious result [54]. Similarly, behavioral pattern monitors using accelerometers to measure locomotor activity and interaction with novel objects within a fixed space can be confounded in PD for similar reasons [55]. Three-arm bandit tasks—a paradigm which measures how patients weigh the value of novelty without relying on motor skills—force patients to choose visual images which they perceive to be of the highest value before and after trials involving reward feedback.
This can thus measure how much reward value novelty itself plays in forced-choice situations. Although such tasks do not rely on a motor response, they do require significant patient engagement through a series of trials [56].
One promising and objective measure of novelty preference utilizing eye tracking methodologies is the visual paired comparison (VPC) task. It has previously been applied extensively in the Alzheimer’s disease population. This task involves the presentation of paired visual stimuli in a series of slides, with test slides comprising a mix of new images and previously presented images. The VPC evaluates a patient’s visual scanning behavior, noting the proportion of time a patient attends to new images compared to previously presented images. Healthy adults have a tendency to unconsciously prioritize novel images in their ordinary scanning behavior. Patients with Alzheimer’s disease and mild cognitive impairment, on the other hand, exhibit a relative novelty indifference, and eye movement data from VPC tasks in patients already known to have MCI can predict cognitive decline with the use of machine learning algorithms [57,58]. Only one published study has included PD patients in a VPC paradigm. Though it showed no difference between people with PD and healthy controls, the study included only those with normal cognition and was under-powered to detect a difference [59].

4.2. Diagnostic and Therapeutic Opportunities

If novelty seeking could be measured with a practical, objective, and validated tool, the construct may be able to serve a greater role in diagnosis and treatment of PD. An eye tracking assessment or something similar could be employed to predict clinical phenotype, determine candidacy or target selection for DBS, identify or predict cognitive impairment, or identify patients at high risk of impulse control disorder with certain dopaminergic therapies.

5. Conclusions

Parkinson’s disease is a common neurodegenerative disorder characterized by progressive motor impairments, affective changes, and cognitive decline. Non-motor neuropsychiatric symptoms significantly impact patient disability and are often undetected despite their profound influence. Novelty-seeking behaviors have been studied in PD patients and clearly evolve with disease duration and by type of treatment, but the intersection of genotype differences, disease state, medications, and baseline personality remains poorly understood. The traditional understanding of novelty seeking as purely a marker of impulsivity and risk for ICD may lose sight of the adaptive role of novelty seeking as a basic biological process. While sensitive and objective measurements of the novelty seeking construct are in development, their advent may herald a new era in improving disease monitoring, individualized therapy selection, and pharmacological development.

Author Contributions

K.P. and L.E.N.; Conceptualization, K.P.; methodology, K.P. and L.E.N.; writing—original draft preparation, K.P.; writing—review and editing, L.E.N.; supervision, L.E.N. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by VA CSR&D CDA2 IK2 CX00253-01A1 (to L.E.N.) and OHSU PCO Pilot Grant (K.P.). This work was also supported by the Parkinson’s Disease Research, Education, and Clinical Centers at the VA Portland Health Care System.

Institutional Review Board Statement

Not applicable.

Acknowledgments

The authors would like to extend their heartfelt gratitude to the faculty and staff of the Oregon Health & Science University, Division of Movement Disorders, for their exceptional contributions as educators and physicians. Their profound expertise in Parkinson’s disease and dedication to patient care have been instrumental in shaping our understanding of the complex interplay between neurological disorders and personality changes. The insights and support provided by the team have significantly enriched the development of this narrative review.

Conflicts of Interest

The authors declare no conflicts of interest.

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Ijtm 04 00042 g001
Figure 1. A proposed model for novelty seeking as it relates to disease progression in PD. The PD patients which maintain a higher degree of novelty seeking after onset of disease have better motor and cognitive scores than the low novelty seeking group. The abrupt increases in novelty seeking after initiation of dopaminergic therapies or DBS (denoted by the shaded region) represent periods of increased risk for impulse control disorders, with steeper increases producing more risk.
Figure 1. A proposed model for novelty seeking as it relates to disease progression in PD. The PD patients which maintain a higher degree of novelty seeking after onset of disease have better motor and cognitive scores than the low novelty seeking group. The abrupt increases in novelty seeking after initiation of dopaminergic therapies or DBS (denoted by the shaded region) represent periods of increased risk for impulse control disorders, with steeper increases producing more risk.
Ijtm 04 00042 g001
Table 1. Neuropsychiatric measures of the construct of novelty seeking and novelty preference which do not rely on subjective questionnaires. Several methods of presenting novelty can be employed. Various levels of physical engagement are required by the subject in these tasks.
Table 1. Neuropsychiatric measures of the construct of novelty seeking and novelty preference which do not rely on subjective questionnaires. Several methods of presenting novelty can be employed. Various levels of physical engagement are required by the subject in these tasks.
MeasureMethodOutcome
Behavioral Pattern Monitor Scattered physical objects within an enclosed environmentLocomotor activity and interaction with novel objects using accelerometer output
Attentional Orienting TaskPaired visual stimuliPush-button reaction times
Three-armed Bandit TaskReinforcement learning of visual stimuli Calculates reward value of novel stimuli before reward feedback
Visual Paired Comparison (VPC) TaskPaired visual stimuliEye tracking and visual novelty preference
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Paulk, K.; Neilson, L.E. Novelty Seeking in Parkinson’s Disease: A Candidate Biomarker for Cognitive Changes. Int. J. Transl. Med. 2024, 4, 608-617. https://doi.org/10.3390/ijtm4040042

AMA Style

Paulk K, Neilson LE. Novelty Seeking in Parkinson’s Disease: A Candidate Biomarker for Cognitive Changes. International Journal of Translational Medicine. 2024; 4(4):608-617. https://doi.org/10.3390/ijtm4040042

Chicago/Turabian Style

Paulk, Kyle, and Lee E. Neilson. 2024. "Novelty Seeking in Parkinson’s Disease: A Candidate Biomarker for Cognitive Changes" International Journal of Translational Medicine 4, no. 4: 608-617. https://doi.org/10.3390/ijtm4040042

APA Style

Paulk, K., & Neilson, L. E. (2024). Novelty Seeking in Parkinson’s Disease: A Candidate Biomarker for Cognitive Changes. International Journal of Translational Medicine, 4(4), 608-617. https://doi.org/10.3390/ijtm4040042

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