Brain–Behavior Relationships: Neural Mechanisms of Impulsivity and Compulsivity in Neuropsychiatric Disorders

Abstract

Impulsivity and compulsivity are multidimensional transdiagnostic constructs with relevance to neurocognitive and other neuropsychiatric disorders. Broadly, impulsivity is the tendency to react quickly, while compulsivity is the tendency to perform repetitive and contextually inappropriate behaviors. Multiple cortical and subcortical neural pathways, neurotransmitter systems, synaptic plasticity changes, genetic factors, and epigenetic interactions influence decision-making, reward processing, and cognitive control. In this narrative review, we discuss the neural circuitry and disease mechanisms implicated in impulsivity and compulsivity, including emerging evidence of the cerebellum’s influence on traditional reward circuitry. We also discuss current and emerging treatments, including neuromodulation targeted to the relevant network abnormalities. This high-level overview of impulsivity and compulsivity from a neurobiological perspective highlights the importance of furthering the understanding of the neural components and circuitry involved. Greater insight into the dynamics that modulate impulsivity and compulsivity may inform new therapeutics.

Impulsivity and compulsivity are multidimensional, transdiagnostic constructs present in multiple neuropsychiatric disorders. Impulsivity refers to the tendency to act or respond without adequate information processing, disregarding potential negative consequences (Dalley and Roiser, 2012; Moeller et al, 2001). It also includes the tendency to react rapidly and prematurely to external or internal stimuli (Moeller et al, 2001) and to rely on hasty, reward-based decision-making (Grant and Kim, 2014). Compulsivity includes repetitive actions, sometimes in reaction to unwanted thoughts, that are often excessive or unnecessary for the situation (Berlin and Hollander, 2014). These actions may include simple repetitive sensory or stereotyped movements, such as those seen in individuals with autism spectrum disorder, or complex repetitive behaviors, like the rituals performed by individuals with obsessive-compulsive disorder (OCD) (Jiujias et al, 2017).

Compulsivity has perseverative and habitual qualities, where impulsivity does not (Robins et al, 2024). Compulsive behaviors tend to have no logical relationship to an end goal (Dalley and Roiser, 2012), while impulsive behaviors likely do. For example, an individual may repeatedly perform compulsions to relieve anxiety-induced, persistent, negative thoughts despite the undesirable consequences of those compulsions. Impulsivity, on the other hand, may be motivated—at least initially—by gratification or reward, such as when making high-risk decisions involving gambling or substance use (Berlin and Hollander, 2014).

Historically, impulsivity and compulsivity were conceptualized as opposing ends of a single behavioral spectrum. In this framework, impulsivity is represented by poorly controlled, premature actions and compulsivity is represented by rigid, repetitive behaviors aimed at reducing distress. However, emerging research suggests that impulsivity and compulsivity are not mutually exclusive. Instead, they often co-occur and engage overlapping cortico-striatal-thalamo-cortical (CSTC) networks (Berlin and Hollander, 2014). Compulsivity in particular encompasses a range of behaviors characterized by repetition and perceived necessity, often driven by internal urges or unwanted thoughts.

It is crucial to recognize the dimensional and multifaceted nature of impulsivity and compulsivity to understand their neural underpinnings and relevance to various neurodevelopmental and neuropsychiatric disorders. Neuropsychiatric disorders frequently manifest with impulsivity and compulsivity. Based on the criteria provided in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-Text Revision (DSM-5-TR) (American Psychiatric Association, 2022), compulsivity is classically observed in individuals with OCD. Hyperactivity-impulsivity is one of two subtypes of attention-deficit/hyperactivity disorder (ADHD) and often manifests in individuals with ADHD through rapid decision-making and interrupting others during conversation (Patros et al, 2016).

Neurodegenerative changes in the neural circuits involved with response inhibition and reward processing may also lead to impulsivity and compulsivity. Diseases in this category include Alzheimer disease (Lai et al, 2023; Sakurai et al, 2020), frontotemporal dementia (FTD) (Lansdall et al, 2018), nonmotor symptoms in Parkinson disease (PD) (Corvol et al, 2018), Huntington disease (HD) (Galvez et al, 2017; Júlio et al, 2019), and cerebellar ataxia (Amokrane et al, 2020).

Impulsivity and compulsivity also frequently co-occur with emotional dysregulation, not only as parallel symptoms but also as mechanisms through which emotional dysregulation is expressed and perpetuated. Impulsive actions often arise in response to heightened emotional states, while rigid, compulsive behaviors may develop as a strategy to manage or suppress emotional distress. In this way, both impulsivity and compulsivity can mediate emotional dysregulation, linking affective instability to maladaptive patterns of behavior (Kenézlői et al, 2025; Mantilla et al, 2022; Mitchell et al, 2012; Schreiber et al, 2012).

Impulsivity and compulsivity can also refer to state-independent personality traits (Chamberlain et al, 2018; Steinberg et al, 2013). For example, some individuals exhibit consistently higher or lower baseline scores on impulsivity measures that remain stable across time and context (Kraemer et al, 1994; Pan et al, 2021). State impulsivity, however, refers to a temporary change and fluctuation in impulsive behaviors influenced by situational or emotional factors (Nguyen et al, 2018).

Research has increasingly focused on identifying the specific brain mechanisms underlying impulsivity and compulsivity, which recruit distinct, yet partially overlapping, neural networks that engage multiple regions of the brain. As such, impulsivity and compulsivity may manifest as core features across a wide range of neurocognitive and neuropsychiatric disorders, highlighting their transdiagnostic relevance. Furthermore, emerging evidence from recent studies has begun to uncover distinct neuro-biochemical substrates and circuit-level mechanisms underlying these behaviors, offering new opportunities to refine our understanding of their pathophysiology and identify novel therapeutic targets.

For these reasons, we chose to focus on impulsivity and compulsivity in this narrative review. Here we will explore the relevant neurological pathways, identify their possible mechanisms, and examine manifestations of impulsivity and compulsivity in selected neuropsychiatric disorders. Finally, we will discuss current and promising emerging treatments for impulsivity and compulsivity, with the intent to inform possible future directions for research.

DISCUSSION

Relevant Neurologic Pathways

Structural and Functional Networks

A complex network of cortical and subcortical regions has been implicated in both impulsivity and compulsivity (Hüpen et al, 2024; McDonald et al, 2017; Montigny et al, 2013). Structurally, these behaviors have been linked to dysfunction in the CSTC network and related cortico-striatal circuits. These structural pathways provide the anatomical scaffolding for top-down modulation of behavior and are thought to support hierarchical regulation of motor, cognitive, and affective processes (Badre and Nee, 2017; Cruz et al, 2021; Peters et al, 2016). Key nodes in these circuits include the dorsolateral and ventromedial prefrontal cortices, the anterior cingulate cortex (ACC), the orbitofrontal cortex (OFC), the thalamus, and the striatum. These regions are critical for cognitive control, reward evaluation, and behavioral inhibition (Bourne et al, 2012; Robbins et al, 2024; van den Heuvel et al, 2016).

Artificial activation of the CSTC network through optogenetic stimulation has been studied in mice (Ahmari et al, 2013). Over time, hyperactivation of the CSTC network led to increased firing of neurons in the ventromedial striatum and the emergence of repetitive grooming behavior, a phenotype analogous to OCD in mice. Complementing these structural findings, functional connectivity analyses—particularly those utilizing resting-state fMRI—have identified large-scale brain networks that are differentially implicated in impulsivity and compulsivity (Heine et al, 2012; Uddin et al, 2019). For example, the default mode network, often associated with self-referential thought and introspection, may be dysregulated in compulsivity, reflecting excessive internal monitoring or rumination (Menon, 2023).

In contrast, impulsivity has been associated with alterations in the salience and executive control networks (Grodin et al, 2017; Schimmelpfennig et al, 2023). The salience network mediates the dynamic switching between internal and external attention, while the executive control network governs goal-directed behavior and inhibitory control. Although structural and functional connectivity often converge, discrepancies between the two can offer insight into disease-specific patterns of dysregulation.

For example, functional decoupling of structurally intact circuits may reveal compensatory or maladaptive mechanisms. Taken together, the interplay between CSTC structural networks and large-scale resting-state networks highlights the importance of examining both anatomical and functional connectivity. This multimodal framework provides a better lens to understand the neural substrates of impulsivity and compulsivity as transdiagnostic constructs across neuropsychiatric and neurodegenerative conditions.

The Orbitofrontal Cortex

Damage to the frontal lobes is associated with changes in impulsivity, as exemplified by the classic case of Phineas Gage (Teles, 2020). Individuals with prefrontal cortex lesions have difficulty with planning and risky decision-making (Manes et al, 2002). Specifically, the OFC is crucial for reward-based decision-making. OFC circuitry abnormalities have been identified in several psychiatric disorders, such as major depressive disorder, OCD, ADHD, and substance use disorder (SUD) (Beucke et al, 2013; Bracht et al, 2021; Fettes et al, 2017; Frodl et al, 2010; Yang et al, 2019). Interestingly, the OFC exhibits diverse patterns of connectivity with other frontal and subcortical regions across species, reflecting its functional heterogeneity (Barreiros et al, 2021; Du et al, 2020; Oh et al, 2020; Öngür and Price, 2000; Zald et al, 2014).

Anatomical and functional studies reveal medial-lateral and anterior-posterior gradients within the OFC (Barreiros et al, 2021; Echevarria-Cooper and Kahnt, 2025; Hirose et al, 2016). While the medial OFC is more involved in visceral-autonomic and reward valuation processes, the lateral OFC is linked to evaluative, affective, and decision-making functions. Along the anterior-posterior axis, there is a shift from integrative, abstract processing in anterior regions to more stimulus-driven, specific representations in posterior regions (Barreiros et al, 2021). This gradient-based organization is further supported by findings that associate the anterior OFC with behavioral flexibility (Butkovich et al, 2025), and the medial OFC with reward-seeking behavior and cost-benefit decision-making (Kringelbach, 2005; Wan et al, 2020).

Task-based and functional connectivity studies provide insight into the functional network components that are dysregulated in individuals with impulsive or compulsive behaviors. Frontal lobe regions play a pivotal role in action initiation, inhibition, and cognitive processing. Heightened prefrontal cortex activity during behavioral inhibition tasks is correlated with lower impulsivity (Asahi et al, 2004). Effective response inhibition corresponded to greater engagement of the right inferior frontal gyrus and reduced activation in the ventral striatum, along with changes in their functional connectivity (Behan et al, 2015). These findings suggest that distinct, yet neighboring, areas of the right inferior frontal gyrus are involved in impulsive decision-making and response, along with functional coupling between the right inferior frontal gyrus and ventral striatum.

The Anterior Cingulate Cortex

Heightened activity in the ACC has been associated with greater gain and more valuable rewards in decision-making tasks (Bush et al, 2002; Rogers et al, 2004). The ACC is anatomically and functionally heterogeneous, with subregions including the subgenual, perigenual, and dorsal ACCs contributing to impulsivity, compulsivity, and emotional regulation in different ways. For example, during a computer-simulated task in rhesus monkeys, neuronal activity in the dorsal ACC was attenuated based on prior reward history, suggesting a key role in reward-based decision-making (Bush et al, 2002; Seo and Lee, 2007).

Functional neuroimaging studies further delineate the dorsal ACC’s involvement in emotional appraisal and processing, while the ventral ACC—including the subgenual portion—is more engaged in top-down regulation of emotional conflict (Etkin et al, 2011; Hua et al, 2021). Anatomical specificity is also evident in ACC–amygdala connectivity. The subgenual ACC projects primarily to the lateral and accessory basal nuclei of the amygdala, whereas the perigenual and dorsal ACC send the majority of their projections to the basal nucleus (Kim et al, 2018). These distinctions highlight the importance of considering regional substructures when interpreting the role of the ACC in impulsivity and compulsivity.

Compulsivity involves frontal and subcortical areas linked to habit formation and repetitive behaviors, including the dorsal striatum (Graybiel and Grafton, 2015; Jahanshahi et al, 2015). For example, lower neuronal activation levels in the subthalamic nucleus have been associated with repetitive behavior in mice (Lewis et al, 2018). Past studies of functional connectivity in individuals with OCD revealed distinct patterns of altered connectivity between frontal, dorsal striatal, and ventral striatal regions, which may underlie repetitive symptoms (Anticevic et al, 2014; Harrison et al, 2013). One study found resting functional connectivity hyperactivity in the dorsal ACC (McGovern and Sheth, 2017), while another found low spontaneous neuronal activity of perigenual ACC in patients with OCD (Long et al, 2020).

Neurochemical Pathways

The dopaminergic and serotonergic pathways are critical for modulating the neural circuits involved with impulse control and habit formation at the neurochemical level. For example, studies have shown that lower serotonin (5HT) levels are associated with increased impulsive or aggressive behavior (Dalley and Roiser, 2012; Virkkunen et al, 1994). In rodent studies, dopamine hyperactivity led to hypoactivity in the frontal cortex, which was associated with decreased self-grooming and increased inhibition (Casado-Sainz et al, 2022). Additional studies have shown that reduced D2 receptor availability in individuals with OCD may implicate dysregulation of the dopaminergic system in compulsivity (Dong et al, 2020). Likewise, selective serotonin reuptake inhibitors (SSRIs) are the standard treatment of choice for individuals with OCD because they enhance serotonin synthesis, which leads to symptom improvement (Lissemore et al, 2018).

A recent resting-state functional connectivity study highlighted differences in regional brain specialization in individuals with OCD, showing increased autonomy index values in the right insula and right superior temporal gyrus when compared to a control group (Liu et al, 2023). These differences were linked to serotonin receptor density distribution, with significant correlations observed for 5-HT1A and 5-HT4 receptors, suggesting that serotonin plays a key role in the altered functional architecture seen in individuals with OCD. Unique neuroimaging patterns in individuals with OCD have also been linked to other neurotransmitters, such as the dopaminergic system and norepinephrine (Tao et al, 2024). Overall, evidence from both animal and human studies underscores the importance of the serotonergic and dopaminergic systems in impulsive-compulsive behavior.

Cerebellar Involvement

Recently, the role of the cerebellum in nonmotor functions has gained increasing attention in neuroscience research. The cerebellum is essential for modulating motor, cognitive, social, and affective functions, integrating predictive mechanisms (such as temporal and reward prediction errors) through interactions with cortical and subcortical structures (Manto et al, 2024; Wagner et al, 2017). Lesions in the posterior cerebellar vermis have been shown to impair forward internal models and habit formation, disrupting executive function and behavioral flexibility, and underscoring the cerebellum’s role in adaptive behavioral control (Miquel et al, 2019). In the sections below, we will explore in further detail how the cerebellum modulates dopaminergic activity and influences behavior.

Underlying Disease Mechanisms

Molecular Mechanisms

In this section, we outline potential mechanisms of changes in the brain that may give rise to impulsivity and compulsivity. Dopamine is widely known to modulate motor movement, learning, and reward behavior (Ianni et al, 2023; Muehlberg et al, 2024; Wise, 2004). The disruption of the traditional dopaminergic reward circuits, including the mesolimbic and nigrostriatal pathways, has been implicated as the major cause of impulsivity and compulsivity (Figure 1) (Elliott et al, 2022; Goutaudier et al, 2023; Hathaway et al, 2024; Navalpotro-Gomez et al, 2019; Sharkey et al, 2019). Studies utilizing PET have shown that diminished midbrain D2/D3 autoreceptor binding predicted higher trait impulsivity in healthy individuals, indicating that dopamine receptor availability is inversely correlated with the degree of impulsivity (Buckholtz et al, 2010).

FIGURE 1.

Traditional dopaminergic reward pathways with modulating effects from the cerebellum.

In another study, gene polymorphisms in the D2 receptor gene were correlated with impulsive-addictive-compulsive behaviors in individuals with disorders such as Tourette syndrome (Blum et al, 1995). On the other hand, polymorphisms in the D3 receptor gene have also been linked to impulsivity and compulsivity in individuals with early PD, suggesting that genetic predisposition may influence these behaviors (Theis et al, 2023). Similarly, variations in the D4 receptor gene have been associated with impulse-control disorders (ICDs) induced by dopamine agonists in individuals with PD. This indicates that genetic differences in dopamine receptors may affect susceptibility to ICDs (Cao et al, 2021; Theis et al, 2023; Torres et al, 2024; Vallelunga et al, 2012).

Neural Circuitry Imbalance

Imbalances in the excitatory/inhibitory processes occurring in neural circuits, such as the CSTC network or the fronto-striatal circuits, are also relevant to impulsivity and compulsivity (Table 1). Glutamate, the primary excitatory neurotransmitter, regulates excitatory/inhibitory balance (Sears and Hewett, 2021; Wen et al, 2022). Disruptions in glutamatergic signaling and the excitatory/inhibitory balance may result in an inability to regulate the neural circuitry subserving impulse control (Bauer et al, 2018; Schmaal et al, 2012). Using magnetic resonance spectroscopy, increased glutamate levels in the ACCs of individuals with ADHD were found to be correlated with the severity of impulsivity (eg, self-reported scores on the ADHD hyperactivity/impulsivity subset scale) (Bauer et al, 2018; Naaijen et al, 2015) as well as other psychiatric disorders, such as bipolar disorder (Hoerst et al, 2010).

TABLE 1.

Summary of Large-scale Brain Networks and Their Contributions to Impulsivity and Compulsivity^†

Network‡	Components	Neurotransmitters	Role in Impulsivity	Role in Compulsivity
Default Mode Network§†	Medial prefrontal cortex, posterior cingulate, precuneus	GABA, glutamate	Manages self-referential thoughts, affecting self-control; decreased activity linked to impulsivity	Disrupted deactivation can reinforce compulsive rumination and repetitive thoughts
Salience Network||	Anterior insula, dorsal anterior cingulate	Dopamine, norepinephrine	Enhances attention to relevant stimuli, leading to impulsive responses when hyperactive	Amplifies the detection of errors, which may reinforce obsessive behaviors and ritualistic actions
Cortico-Striatal Network¶	Prefrontal cortex, striatum (caudate, putamen)	Dopamine	Central to reward processing and decision-making, promoting impulsive actions when dysregulated	Altered pathways lead to habitual behaviors, characteristic of compulsive disorders
Limbic Network#	Amygdala, hippocampus, ventromedial prefrontal cortex	Serotonin, dopamine	Increases emotional reactivity, often underlying emotional impulsivity	Heightens emotional attachment to routines, contributing to compulsive behaviors
Visuospatial Network††	Parietal and occipital lobes, prefrontal cortex	Acetylcholine, dopamine	Disruptions impair spatial judgment and planning, causing impulsive spatial decisions in navigation	Fixations on spatial patterns or errors potentially reinforce compulsive visual scanning behaviors in OCD

^†Canonical networks, such as the default mode network and the salience network, are labeled according to commonly used intrinsic connectivity frameworks. Other circuits, such as the cortico-striatal and limbic networks, are included based on their well-established relevance in neuroanatomical and neurochemical models of impulsivity and compulsivity. This table integrates both intrinsic connectivity and circuit-level conceptualizations to capture a comprehensive view of relevant network dynamics.

^‡Yeo et al (2011).

^§Beucke et al (2014); Blomberg et al (2002); Catani and Dell’acqua (2013); Whitfield-Gabrieli and Ford (2012); Zhao et al. (2017).

^||Blomberg et al (2022); Grodin et al (2017); Peters et al (2016).

^¶Ahmari et al (2013); Davis et al (2013); Fettes et al (2017); van den Heuvel et al (2016).

^#Morgane et al (2005); van den Heuvel et al (2016).

^††de Graaf et al (2010); Wang et al (2023).

GABA = gamma-aminobutyric acid. OCD = obsessive-compulsive disorder.

Dopaminergic Modulation

The cerebellum regulates reward processing and homeostasis, with regions like lobules VI–VII and the vermis playing key roles in loss aversion and reward sensitivity (Manto et al, 2024). Abnormalities in cerebellar-prefrontal-thalamic and CSTC networks have been linked to compulsive and impulsive behaviors in individuals with neuropsychiatric disorders such as OCD, ADHD, autism, and SUD. Emerging research into cerebellar connections to the reward system—particularly the ventral tegmental area (VTA)—suggests additional dopaminergic influences on the circuitry underlying impulsivity and compulsivity (Figure 1) (Baek et al, 2022; Carta et al, 2019).

Chronic activation of inhibitory Purkinje cells in Crus I (which project to the dentate nucleus, then to neurons in the VTA) has been shown to prevent the emergence of stress-induced depression-like behaviors in mice (Baek et al, 2022), likely by suppressing dentate nucleus activity and modulating downstream VTA circuits involved in mood regulation. In mice, excitatory signaling from the cerebellar dentate nucleus to the VTA has also been associated with behavioral preference related to reward and social behavior (Carta et al, 2019). Taken together, these findings from rodent studies suggest the cerebellum may modulate the dopaminergic system via cerebello-VTA connections.

Synaptic Plasticity Alterations

Synaptic plasticity is essential for neurodevelopment, learning, and recovery following injury. It involves strengthening and pruning of neural connections to promote brain network adaptability (Citri and Malenka, 2008; Kolb, 1999). Abnormalities in the process of synaptic plasticity leading to maladaptive neuromolecular changes have also been implicated in disorders of impulsivity and compulsivity (Baik, 2013; Kyzar and Pandey, 2015; Lüscher and Malenka, 2011; Mameli and Lüscher, 2011).

For example, SUD begins with impulsivity, where behavior is driven by immediate reward, then evolves into compulsivity, where actions become habitual and aim to relieve distress (Koob and Volkow, 2010; Wise and Koob, 2014). Studies involving SUD have shown that alcohol use alters the density of dendritic spines in the amygdala, with increased density during alcohol use and decreased density upon withdrawal (Kyzar and Pandey, 2015). Substance use also impacts the mesolimbic reward system, particularly through dopamine release and modulation in the VTA (Baik, 2013). Drug-evoked synaptic plasticity may involve multiple mechanisms and prominently targets glutamatergic excitation. Two well-established mechanisms are dopamine release, where dopamine transporters are targeted by amphetamine, cocaine, or MDMA (3,4-methylenedioxymethamphetamine), and dopamine neuron depolarization (Lüscher and Malenka, 2011; Mameli and Lüscher, 2011).

Importantly, synaptic plasticity may also be induced through glutamatergic excitation (Hunt and Castillo, 2013; Park et al, 2015; Sapoznik et al, 2006). It has been established that cocaine use results in an increase in the ratio of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) to NMDA (N-methyl-D-aspartate) receptors (Liu et al, 2005; van Huijste and Mansvelder, 2015). Thus, glutamatergic transmission serves a dual role: it provides the excitatory drive that induces plasticity and represents a key locus where addictive drugs exert lasting synaptic modifications. This pattern demonstrates the maladaptive reinforcement of reward circuits, solidifying compulsive behaviors in SUD (Gipson et al, 2014). Ultimately, synaptic plasticity represents another pathway through which compulsive behaviors become sustained addictive behaviors.

Genetic and Epigenetic Factors

Genetic influences on impulsivity and compulsivity include polymorphisms in neurotransmitter receptor genes (Bevilacqua and Goldman, 2013; Walitza et al, 2014). Epigenetic mechanisms affect gene expression and are shaped by environmental factors (Liu et al, 2008). Research involving neurotransmitter systems—particularly dopaminergic, serotonergic, and glutamatergic systems—has uncovered associations between receptor gene variations and impulsive and compulsive disorders (Miguel et al, 2005; Walitza et al, 2014).

The gene for the serotonin transporter, SLC6A4, is among the most extensively studied in relation to OCD due to its role in a particular polymorphism, 5-HTTLPR, which involves an insertion or deletion affecting gene expression. Traditionally, alleles of 5-HTTLPR are classified as long (L), linked to higher expression, or short (S), linked to lower expression. More recently, these long alleles have been further distinguished into L_A, referring to a common A substitution of the L allele (Hu et al, 2006). One study identified increased transmission of an L_A allele within the serotonin transporter gene among children with early-onset OCD, suggesting a genetic predisposition to OCD phenotypes (Walitza et al, 2014). Additional gene variations associated with increased risk of OCD phenotypes involve genes that encode for key enzymes in the dopaminergic and norepinephrine pathways (Karayiorgou et al, 1997).

Gene polymorphisms have been identified in individuals with various subtypes of OCD. For example, the early-onset OCD phenotype is associated with 5-HT2A gene polymorphism, while the tic-related OCD phenotype is related to D2 and D4 receptor genes (Miguel et al, 2005). Studies involving individuals with SUD have shown genetic associations with altered resting-state functional connectivity within the default-mode network and between the default-mode and fronto-parietal networks (Kayış et al, 2024).

Genetic predispositions are also influenced by external or environmental factors that induce epigenetic changes (Barros and Offenbacher, 2009; Liu et al, 2008). DNA methylation, for example, is an epigenetic process that modulates gene expression and has been linked to impulsive/compulsive phenotypes in animal studies and studies of individuals with ADHD (Meijer et al, 2023; Rajala et al, 2014). In nonhuman primates, DNA methylation within the dopamine transporter gene at single-nucleotide polymorphisms was found to be associated with impulsivity, suggesting an epigenetic contribution to these behaviors (Rajala et al, 2014). This finding has also been observed in the internal nucleus of the globus pallidus and results in higher dopamine transporter availability.

Studies of individuals with ADHD also highlight prenatal and perinatal influences, such as maternal diet and psychosocial adversities (Mill and Petronis, 2008). In one large epidemiologic study, family history of psychiatric disorders, maternal diagnosis of ADHD, and gestational diabetes were associated with the ADHD phenotype, specifically the hyperactivity-impulsivity type (Roigé-Castellví et al, 2021). Other studies have reported associations between pregnancy complications, testosterone exposure, and ADHD (Bitsko et al, 2024). Overall, environmental factors can amplify genetic predispositions, enhancing susceptibility to impulsive and compulsive phenotypes.

Impulsivity and Compulsivity in Neuropsychiatric Disorders

A variety of neurodegenerative and neuropsychiatric disorders present with symptoms along the spectra of impulsivity and compulsivity. Various neural networks are implicated in the emergence of impulsivity and compulsivity associated with specific neurodegenerative and psychiatric disorders (Table 2).

TABLE 2.

Neuropsychiatric and Neurodegenerative Disorders Associated With Impulsivity and Compulsivity

Disorder	Characteristics of Impulsivity/Compulsivity	Key Neurobiological Findings
ADHD	High impulsivity, impaired executive function†	Reduced dopaminergic activity in prefrontal regions‡
OCD	Compulsive rituals, rigid behaviors§	Hyperactivity in the OFC and striatum; increased glutamate levels||
SUD	Early impulsivity/disinhibition, impaired top-down control¶	Decreased dopamine binding in the ventral striatum#
AD	Agitation, verbal aggression, lack of premeditation††	Reduced serotonin binding‡‡
PD	Impulse control disorders§§	Altered dopamine regulation in basal ganglia||||
PSP	Disinhibition, premature motor movements (ie, standing)¶¶	Frontal cortex atrophy##
HD	Disinhibition in pre-manifest stage; obsessive-compulsive behaviors emerge with disease progression†††	Atrophy of fronto-striatal networks‡‡‡
Cerebellar Ataxia	Disruption of reward modulation§§§	Cerebellar neuron projections onto VTA||||||
FTD	Disinhibition, compulsive and repetitive behaviors¶¶¶	Atrophy of fronto-temporal cortex, insula, ACC; hypometabolism in ACC
Post-stroke Sequelae	Post-stroke anger proneness, post-stroke emotional incontinence, dysexecutive functioning††††	Low MAO-A activity, ischemic changes to the frontal cortex and internal capsule‡‡‡‡

^†Nikolaidis et al (2022); Ortiz et al (2015).

^‡Yokokura et al (2021).

^§American Psychiatric Association (2022).

^||Li et al (2023); Naaijen et al (2015).

^¶Li et al (2023); Koob and Volkow (2010).

^#Tanabe et al (2019); Volkow et al (2015).

^††Lai et al (2003); Rochat et al (2008).

^‡‡Lai et al (2003).

^§§Weintraub et al (2012); Corvol et al (2018).

^||||Theis et al (2023).

^¶¶Cordato et al (2002); Burrell et al (2014); Ahn et al (2023).

^##Cordato et al (2002).

^†††Galvez et al (2017); Júlio et al (2019); Anderson et al (2001).

^‡‡‡Dominguez et al (2016); Tan et al (2022).

^§§§Amokrane et al (2020); Lai et al (2023).

^||||||Baek et al (2022); Carta et al (2019).

^¶¶¶Lansdall et al (2018); Rascovsky et al (2011).

^###Hornberger et al (2012); Planche et al (2023); Rouse et al (2025); Chu et al (2021); Pompanin et al (2014); van Engelen et al (2023).

^††††Jones et al (2025); Kim (2005); Scheffer et al (2016).

^‡‡‡‡Choi-Kwon et al (2013); Kim (2016).

ACC = anterior cingulate cortex. ADHD = attention-deficit/hyperactivity disorder. FTD = frontotemporal dementia. HD = Huntington disease. MAO-A = monoamine oxidase A. OCD = obsessive-compulsive disorder. OFC = orbitofrontal cortex. PD = Parkinson disease. PSP = Progressive Supranuclear Palsy. SUD = substance use disorder. VTA = ventral tegmental area.

Attention-Deficit/Hyperactivity Disorder

According to the DSM-5-TR, ADHD is characterized by inattention, hyperactivity, and impulsivity that interfere with an individual’s daily life (American Psychiatric Association, 2022). Impulsivity in ADHD includes behaviors such as interrupting others or blurting out answers before a question is finished. Alterations in impulse inhibition and control have been linked to dysfunction within the fronto-striatal and CSTC networks (Nikolaidis et al, 2022). Studies have shown anatomical differences in the striatum of individuals with ADHD and hypoactivation in the prefrontal cortex and ACC (Casey, Castellanos, et al, 1997; Ortiz et al, 2015). Dysfunction in these networks during attention-based tasks is present in both childhood and adulthood, suggesting that neural differences may persist as individuals with ADHD age (Cubillo et al, 2012). Various allele profiles of the D4 gene have been linked to specific fronto-striatal functional connectivity patterns in individuals with ADHD (Qian et al, 2018).

Obsessive-Compulsive Disorder

OCD is characterized by obsessions, unwanted thoughts, and compulsions, or repetitive behaviors in response to obsessions (American Psychiatric Association, 2022). Compulsivity is a hallmark symptom of OCD, often involving the OFC, ACC, and striatum within the CSTC network (Bourne et al, 2012; Maia and Cooney, 2008). Structural studies consistently report regional differences in gray matter volumes within this circuit, including reduced gray matter in the medial OFC and left insulo-opercular region, but increased gray matter volume in the ventral putamen and anterior cerebellum (Picó-Pérez et al, 2020; Pujol et al, 2004). Beyond anatomical variations, unique patterns of activity across the CSTC network in individuals with OCD are also evident, including decreased functional connectivity between the subthalamic nucleus and striatum (Calzà et al, 2019; Zhao et al, 2021).

SPECT with HMPAO (technetium-99m) imaging has revealed decreased cerebral blood flow in the head of the caudate nucleus in individuals with OCD, while FDG-PET revealed increased glucose metabolism in the same region (Whiteside et al, 2004). This suggests a possible uncoupling of glucose metabolism and blood flow in individuals with OCD. According to a recent meta-analysis, increased activity in the OFC is associated with OCD and hypothesized to represent dysfunction in the CSTC network (Li et al, 2023). Interestingly, treatment with Cognitive Behavioral Therapy has been shown to reduce this hyperactivity in studies using regional homogeneity, a method to measure the coherence of local, intrinsic spontaneous brain activity on resting-state fMRI (Yang et al, 2015).

Substance Use Disorder

Both impulsivity and compulsivity are prominent in SUD. Disinhibition is defined as a lack of inhibitory control to suppress or restrain inappropriate or unwanted behaviors, thoughts, or impulses (Jones et al, 2013). It is a key element identified in both impulsivity and compulsivity and is particularly evident in alcohol use disorder and gambling disorder (Lee et al, 2019). SUD is conceptualized as involving three stages: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation (Kwako and Koob, 2017). Initial stages of SUD reflect impulsivity, with compulsivity manifesting later as the individual attempts to alleviate the stress of withdrawal and cravings, as compulsive behaviors may become habits that are relatively “value free” (Li et al, 2023).

This shift may reflect a decline in top-down executive control while the brain’s reward circuitry is simultaneously and continuously activated (Koob and Volkow, 2010). Dysfunction within the frontal-executive and mesolimbic reward circuits contributes to these behaviors, potentially modulated by imbalances in neurotransmitters like glutamate, GABA (gamma-aminobutyric acid), and dopamine (Kozak et al, 2019). In chronic SUD, the binding availability of dopamine D2 receptors diminishes within the ventral striatum (Tanabe et al, 2019; Volkow et al, 2015). This suggests that dynamic changes to mesolimbic and frontal circuitry underpin the evolution of impulsive and compulsive tendencies over time.

Alzheimer Disease

In community-dwelling individuals, increased impulsivity has been closely associated with cognitive decline, particularly in those with suspected dementia (Boyle et al, 2012; Sakurai et al, 2020). This suggests that heightened impulsivity may be an early indicator of cognitive deterioration in older adults (Sakurai et al, 2020). In AD, reduced 5-HT1A binding in the temporal cortex has been linked to agitation and aggression (Lai et al, 2003), which increases over time as the disease progresses (Bidzan et al, 2008, 2012). When compared to a control group, individuals with Alzheimer disease exhibited higher impulsivity, with a lack of premeditation and perseverance (Rochat et al, 2008). Additionally, these dimensions of impulsivity correlate with neuropsychological measures of inhibition, set-shifting, and working memory (Rochat et al, 2013). Each of these cognitive processes is subserved by the networks discussed above, and the alteration of these networks likely contributes to impulsive behaviors.

Frontotemporal Dementia

FTD is characterized by progressive decline in executive and behavioral functioning (Bang et al, 2015; Boeve et al, 2022). It encompasses a spectrum of clinical syndromes, including behavioral-variant FTD, nonfluent primary progressive aphasia (PPA), and semantic-variant PPA (Bang et al, 2015). Individuals with behavioral-variant FTD typically exhibit prominent changes in personality and behavior, with core diagnostic features including apathy, loss of empathy, disinhibition, and repetitive or compulsive behaviors (Lansdall et al, 2018; Rascovsky et al, 2011). Repetitive behaviors are well-documented in individuals with behavioral-variant FTD and in those with semantic-variant PPA, differentiating these syndromes from other dementias, such as Alzheimer disease (Mendez et al, 1997; Snowden et al, 2001). Individuals with semantic-variant PPA may present with motor stereotypies (eg, lip-smacking, repetitive singing or clapping) or true compulsions, such as rigid routines that cause distress when interrupted (Snowden et al, 2001).

Neuroanatomical correlates of FTD include atrophy in the prefrontal cortex, insula, amygdala, ACC, and anterior temporal cortex (Hornberger et al, 2012; Planche et al, 2023; Rouse et al, 2025). Hypometabolism and hypoperfusion of the ACC have been consistently observed in individuals with behavioral-variant FTD and are associated with core symptoms, such as compulsive behaviors and executive dysfunction (Chu et al, 2021; Pompanin et al, 2014; van Engelen et al, 2023). Additionally, reward-seeking behaviors are markedly increased in individuals with behavioral-variant FTD. One study reported prevalence as high as 82%, including manifestations such as hyperphagia, increased preference for sweet foods, and heightened substance use (Perry et al, 2014). In the same study, these behaviors were significantly associated with volume loss in the right ventral putamen and pallidum.

Parkinson Disease

ICDs in individuals with PD include pathological gambling, shopping, hypersexuality, binge eating, hobbyism, punding, and dopamine dysregulation syndrome (ie, excessive use or abuse of dopaminergic drugs) (Weintraub et al, 2012). A multi-centered study based in France reported a 46% cumulative incidence rate of ICDs in individuals with PD over 5 years before significant adjustment of PD medications (Corvol et al, 2018). The prevalence of ICDs in PD varied from 14% to 36% (Biundo et al, 2017; Isaias et al 2008; Weintraub et al, 2010).

Individuals with PD who also have ICD display altered connectivity between the meso-cortico-limbic system and temporal regions (Verger et al, 2018), indicating that larger network-level changes may underlie these behaviors. In individuals with PD and gambling disorder, decision-making under risky or ambiguous conditions is impaired compared to those without gambling disorder (Biundo et al, 2017). This may be linked to the effects of dopamine replacement therapy on the ventromedial prefrontal cortex and amygdala-ventral striatum system.

Dopamine agonists, such as pramipexole and ropinirole, are associated with an increased risk of ICDs, likely due to overstimulation of D3 receptors in the ventral striatum, leading to over-activation of the reward pathway (Kelly et al, 2020; Wu et al, 2009). While the use of a dopamine agonist can increase the risk of ICDs in individuals with PD, ICDs also manifest in those who did not receive dopaminergic therapy (Ávila et al, 2011; Ondo and Lai, 2008). However, this is much less common, implying multifactorial causations (Chen et al, 2022).

Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) is classified as an atypical Parkinsonism disorder classically presenting with postural instability, axial rigidity, vertical gaze palsy, and speech dyspraxia or severe dysarthria (Dickson et al, 2007). Frontal circuitry dysfunction is a core feature of PSP, leading to symptoms such as emotional lability, impulsivity, and apathy (Cordato et al, 2002). One recent study found that impulsivity and apathy co-occur in up to two-thirds of individuals with PSP (Kok et al, 2021). In individuals with PSP, the frequent impulse to stand and walk often leads to falls (Burrell et al, 2014). Impulsivity in individuals PSP can be measured as premature clapping prior to a signal (Ahn et al, 2023). Individuals who clap prematurely are more likely to experience falls, tend to score lower on frontal lobe batteries, and have a greater fiber density between the nucleus accumbens core and the medial orbitofrontal gyrus, as measured by diffusion tensor imaging.

Huntington Disease

HD is a neurodegenerative movement disorder marked by progressive motor, cognitive, and psychiatric symptoms (McDonell et al, 2020; Paulsen et al, 2001). Individuals with HD have difficulty with inhibition control tasks, even in the pre-manifest and prodromal stages (Galvez et al, 2017; Júlio et al, 2019). Obsessive-compulsive behaviors may also emerge as the disease progresses (Anderson et al, 2001). Structural and functional alterations in the striatum, angular gyrus, inferior temporal gyrus, and superior frontal gyrus of individuals with HD lead to a frontal-subcortical pattern of cognitive decline due to cortico-striatal dysfunction (Liu et al, 2016). Atrophy of the striatum and white matter tract changes in fronto-striatal circuitry in individuals with HD suggest a neurodegeneration of circuitries involved in executive function and control (Dominguez et al, 2016; Tan et al, 2022). Impulsivity and compulsivity in individuals with HD may result from alterations in CSTC networks, leading to subsequent impairments in executive control, planning, and inhibition.

Cerebellar Ataxia

Traditionally, the cerebellum has been considered a region of the brain primarily responsible for motor function and coordination, and cerebellar ataxia is characterized by incoordination of gait, speech, and limb dexterity (Radmard et al, 2023; Manto et al, 2012; Paulin, 1993). Emerging research highlights the cerebellum’s role beyond motor control, however, implicating it in reward prediction, attention, and decision-making (Miquel et al, 2019; Rudolph et al, 2023; Schmahmann, 2004). It remains to be determined whether the cerebellum’s contribution to the reward system belongs to a separate entity, or a broader spectrum of the cerebellar cognitive affective syndrome (Argyropoulos et al, 2020; Manto et al, 2024). As mentioned above, the cerebellum participates in modulating the traditional reward system through cerebello-VTA connectivity.

Various cerebellar neurons play essential roles in reward processing: granule cells signal both anticipation and receipt of reward, climbing fibers transmit information about prediction errors, and Purkinje cells contribute strongly to reinforcement learning (Garcia-Garcia et al, 2024; Heffley et al, 2018; Kostadinov et al, 2019; Ohmae and Medina, 2015; Sendhilnathan et al, 2020; Sendhilnathan et al, 2021; Sendhilnathan et al, 2022; Wagner et al, 2017). The bilateral anterior lobes, posterior vermis, lobule VI and crus I of the cerebellum are active during reward anticipation and outcome in both humans and mice, suggesting that the cerebellum is more involved in reward prediction than initially thought (Kruithof et al, 2023).

Additionally, cerebellar disorders often lead to a frontal-subcortical pattern of cognitive decline due to disruptions in the executive loop that connects the cerebellum with the prefrontal lobe (Badaly et al, 2022; Mannarelli et al, 2023). This decline is likely further influenced by neurodegeneration of the circuitry involved in executive function control. Thus, impulsivity and compulsivity may manifest as primary symptoms for individuals with cerebellar dysfunction due to the disruption of reward modulation (Amokrane et al, 2020; Lai et al, 2023).

Individuals with cerebellar ataxia not only develop heightened impulsivity-compulsivity behaviors, but have been shown to manifest these behaviors in a relatively domain-specific manner compared to the global pattern of manifestation evidence in individuals with PD (Amokrane et al, 2020; Chen et al, 2022). For example, on the QUIP-RS, individuals with cerebellar ataxia demonstrated heightened impulsivity and compulsivity in pathological gambling, hobbyism/punding, and compulsive medication overuse, while individuals with PD demonstrated these symptoms in eating, shopping, and hypersexuality (Amokrane et al, 2020).

Similar findings have been reported when using the Barratt Impulsiveness Scale (BIS-11) (Patton et al, 1995). When compared to a control group, individuals with cerebellar ataxia demonstrated impulsivity in the nonplanning domain, while individuals with PD showed impulsivity across nonplanning, attentional, and motor domains (Chen et al, 2022). Taken together, these findings imply that the cerebellum and basal ganglia exert distinct influences on impulsive behaviors, with the cerebellum shaping the neural circuits of impulsivity in a domain-specific way.

Poststroke Sequelae

Poststroke impulsivity is relatively uncommon and remains less well-studied compared to other neurologic conditions. However, poststroke sequelae offer important insights into localization and neural substrates of impulsive symptoms (Jones et al, 2025). Specific manifestations of impulsivity after cerebrovascular events include syndromes such as poststroke anger proneness, poststroke emotional incontinence, alien hand syndrome, and atypical ICDs (Jones et al, 2025; Kim, 2005). In one study, up to 32% of patients with prior unilateral stroke experienced poststroke anger proneness, while 34% exhibited poststroke emotional incontinence (Kim, 2005).

Poststroke emotional incontinence, which includes emotional lability and uncontrollable laughter and/or crying, has been linked to lesions in the anterior cortex, internal capsule, basal ganglia, and ventral brainstem circuits (Kim, 2016). A rare form of poststroke impulsivity, pathological generosity, has been reported in an individual with a left lenticulocapsular stroke (Ferreira-Garcia et al, 2013). Similarly, poststroke aggression and anger proneness have been associated with overlapping lesion sites and may also be linked to genetic polymorphisms involving low monoamine oxidase A (MAO-A) activity (Choi-Kwon et al, 2013; Kim, 2016).

Executive dysfunction and impaired decision-making may also result from a stroke affecting the frontal or nonfrontal regions, including the temporal and parietal lobes, subcortical structures, and the cerebellum (Scheffer et al, 2016). In one study, individuals with a history of stroke who were rated as “dysexecutive” made significantly more errors on Go/No-Go tasks assessing inhibitory control than a control group, regardless of whether their lesions were located in frontal or nonfrontal regions (Scheffer et al, 2016). As reviewed above, the frontal cortex, cerebellum, and subcortical structures—such as the thalamus—all play key roles in executive control, and disruptions in these areas can significantly impair inhibitory processing.

Assessment and Treatment

Neuropsychological Assessments

A variety of self-report psychometric and neuropsychological tests are used to assess impulsivity and compulsivity in both clinical and research settings (Table 3).

TABLE 3.

Neuropsychological Assessments and Experimental Tasks for Evaluation of Impulsivity and Compulsivity

Item	Type	Target
BIS-11†	Self-report questionnaire	Impulsivity across attentional, motor, and nonplanning facets
UPPS-P‡	Self-report questionnaire	Impulsivity across five dimensions: negative urgency, positive urgency, lack of premeditation, lack of perseverance, and sensation seeking
OCI§	Self-report questionnaire	Presence and severity of OCD symptoms across various domains
CIA||	Self-report questionnaire, disorder-specific	Impulsivity and compulsivity in cerebellar dysfunction in decision-making, planning ability, irresponsibility, conversation interruption, and self-control
Y-BOCS¶	Clinician-administered	Severity of OCD symptoms across five dimensions: time spent, interference, distress, resistance, and control
QUIP-RS#	Clinician-administered, disorder-specific	Impulsivity and compulsivity in PD across various domains, including gambling, sex, buying, eating, hobbyism/punding, and compulsive medication overuse
Stop-Signal Task††	Experimental task	Response inhibition when asked to stop responding to a signal
Go/No-Go Task‡‡	Experimental task	Impulsivity when asked to respond to certain stimuli but not others
Delayed Discounting Task§§	Experimental task	Decision-making when choosing between immediate and delayed rewards
Iowa Gambling Task||||	Experimental task	Decision-making under uncertainty
Balloon Analogue Risk Task¶¶	Experimental task	Risk-taking behavior
Marshmallow Test##	Experimental task	Delf-control through delayed gratification
Two-Choice Impulsivity Paradigm†††	Experimental task	Choice impulsivity
Simon Task‡‡‡	Experimental task	Cognitive control

^†Patton et al (1995).

^‡Lynam et al (2006).

^§Foa et al (1998).

^||Lin et al (2023).

^¶Goodman et al (1989).

^#Weintraub et al (2012).

^††Congdon et al (2012).

^‡‡Bezdjian et al (2009).

^§§Green and Myerson (2004).

^||||Bechara et al (1994).

^¶¶Lejuez et al (2002).

^##Mischel and Ebbesen (1970).

^†††Dougherty et al (2003; 1999); Marsh et al (2002).

^‡‡‡Simon and Rudell (1967).

BIS-11 = Barratt Impulsiveness Scale. CIA = Cerebellar Impulsivity-Compulsivity Assessment Scale. OCD = obsessive-compulsive disorder. OCI = Obsessive-Compulsive Inventory. PD = Parkinson disease. QUIP-RS = Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease-Rating Scale. UPPS-P = Urgency, Premeditation, Perseverance, Sensation, and Positive Urgency Impulsive Behavior Scale. Y-BOCS = Yale-Brown Obsessive-Compulsive Scale.

For example, the Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease-Rating Scale (QUIP-RS) is a validated scale to assess ICDs in PD (Weintraub et al, 2009; Weintraub et al, 2012). To specifically assess manifestations of impulsivity and compulsivity in cerebellar ataxia, a Cerebellar Impulsivity-Compulsivity Assessment Scale was recently developed and validated for bedside and clinical trial use (Li, Lin, et al, 2023).

The BIS-11 measures the construct of impulsivity (Patton et al, 1995). First created in 1959, the most recent version is a self-report scale consisting of 30 items used to measure impulsivity in individuals with SUD, ADHD, and ICDs (Stanford et al, 2009). The BIS-11 has become a cornerstone for studying impulsivity in various neuropsychiatric disorders due to its robust psychometric properties and multidimensional structure (Patton et al, 1995). It categorizes impulsivity into attentional, motor, and nonplanning facets and provides critical insights into trait versus state impulsivity. This allows researchers and clinicians to study long-standing personality characteristics and their contribution to context-dependent behaviors. The versatility and ease of administration of the BIS-11 have made it one of the most widely used scales for advancing our understanding of the cognitive and behavioral underpinnings of impulsivity.

The Urgency, Premeditation, Perseverance, Sensation, and Positive Urgency Impulsive Behavior Scale also measures components of impulsivity (Lynam et al, 2006) and is available in an abbreviated version (Cyders et al, 2014). The Impulsive Behavior Scale is a self-report questionnaire that assesses impulsivity across five dimensions: negative urgency, positive urgency, lack of premeditation, lack of perseverance, and sensation seeking. It evaluates the individual’s tendency to act rashly when experiencing strong emotions, difficulty with planning or sustaining focus, and the pursuit of novel, risky experiences. Widely used in research and clinical settings, this scale provides insight into personality traits related to impulsive behaviors in neuropsychiatric disorders.

The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (Goodman, Price, Rasmussen, Mazure, Delgado et al, 1989; Goodman, Price, Rasmussen, Mazure, Fleischmann, et al, 1989) is a clinician-administeredscale consisting of 10 items evaluating the severity of OCD symptoms (Goodman, Price, Rasmussen, Mazure, Fleischmann et al, 1989). It evaluates obsessions and compulsions across five dimensions: time spent, interference, distress, resistance, and control, resulting in a total score from 0 to 40, with higher scores indicating greater symptom severity. Administered as a semi-structured interview, it also includes a symptom checklist to identify specific obsessions and compulsions. The Y-BOCS is widely used to diagnose OCD, monitor symptom changes, and assess treatment efficacy. It is considered the gold standard for the assessment of OCD severity due to its reliability and adaptability across various patient populations and contexts.

The Obsessive-Compulsive Inventory (OCI) is a self-report questionnaire used to assess the presence and severity of OCD symptoms across various domains, including checking, washing, hoarding, ordering, obsessing, and neutralizing (Foa et al, 1998). The OCI-Revised is an 18-item tool that measures symptoms on a Likert scale to quantify distress and severity. Easy to administer, it is widely used in clinical and research settings for screening, treatment planning, and monitoring symptom changes over time. The OCI and OCI-Revised are effective for identifying OCD symptoms and distinguishing them from related disorders.

Experimental Task Paradigms

In addition to surveys and scales, experimental tasks have been used to assess impulsivity and compulsivity. An effective way to measure impulsivity is through response inhibition, which is frequently assessed with Stop-signal and Go/No-Go tasks (Congdon et al, 2012). In the stop-signal task, individuals are asked to respond to a signal as quickly as possible, but to refrain from responding when a “stop” stimulus is presented after the signal (Lipszyc and Schachar, 2010). Individuals with ADHD and OCD have difficulty with response inhibition during this task (Lipszyc and Schachar, 2010).

In the Go/No-Go task, individuals are asked to press a button when specific stimuli are present and, like the stop-signal task, to refrain from pressing the button when shown a different stimulus (Bezdjian et al, 2009). Errors in response inhibition during the Go/No-Go task have been associated with the hyperactive-impulsive ADHD subtype specifically (Bezdjian et al, 2009).

The Delayed Discounting Task (Green et al, 2014) and Temporal Discounting Paradigm (Green and Myerson, 2004) measure decision-making and the ability to delay gratification by choosing between smaller immediate rewards and larger delayed ones. The Iowa Gambling Task (Bechara et al, 1994) and Probabilistic Reversal Learning Task (Cools et al, 2002) are often used in substance use and mood disorder research to evaluate decision-making under uncertainty and adaptability to changing reward contingencies. The Balloon Analogue Risk Task (Lejuez et al, 2002) measures risk-taking behavior, while the Marshmallow Test (Mischel and Ebbesen, 1970) assesses self-control.

The Two-Choice Impulsivity Paradigm (Dougherty et al, 2003; Dougherty et al, 1999; Marsh et al, 2002) assesses choice impulsivity (Marsh et al, 2002; Mathias et al, 2002) and the Simon Task (Simon and Rudell, 1967) assesses cognitive control. Reward sensitivity tasks, such as the Monetary Incentive Delay Task (Schultz, 1998), examine reactions to rewards and punishments, and the Continuous Performance Test (Beck et al, 1956) evaluates attentional impulsivity.

Each of these tasks can be performed during MRI to provide additional brain response measurements (Butti et al, 2006; Cao et al, 2019; Casey, Trainer, et al, 1997; Cools et al, 2002; Georgiou-Karistianis et al, 2007; Knutson et al, 2000; Li et al, 2020; Power et al, 2012). Together, these tasks provide a comprehensive understanding of impulsivity across its decision-making, motor inhibition, and reward sensitivity aspects.

Pharmacologic Therapies

Pharmacotherapies targeting dopaminergic, serotoninergic, and glutaminergic systems are often used to manage impulsivity and compulsivity across neuropsychiatric diseases. SSRIs, including fluoxetine, sertraline, and paroxetine, are the first-line therapy for individuals with OCD (Goddard et al, 2008). Serotonin-norepinephrine reuptake inhibitors, such as duloxetine (Dougherty et al, 2015) and venlafaxine (Hollander, Friedberg, et al, 2003) may be considered as a second-line therapy, especially in treatment-resistant cases. Glutamatergic agents, such as memantine, N-acetylcysteine, and riluzole, have also been explored as possible medication options, showing benefit as add-on therapy, although the results from controlled studies vary (Pittenger, 2015).

A meta-analysis of eight studies on memantine found an overall decrease in obsessive compulsive scale ratings following treatment (Modarresi et al, 2019), further providing an alternative option for inividuals with SSRI treatment resistance. While second-generation antipsychotics have been used off-label to treat ICDs (Beduin and de Haan, 2010), they may paradoxically cause such disorders, especially aripiprazole (Voelker, 2016). Mood stabilizers, especially carbamazepine and valproate, may be considered for the treatment of impulsivity (Hollander, Tracy, et al, 2003; Mestre-Bach and Potenza, 2024).

Psychotherapeutic Modalities

Cognitive-behavioral therapy (CBT) and related psychotherapies are also effective for compulsive behaviors. Across the literature, CBT is effective in reducing symptom severity in individuals with OCD (Olatunji et al, 2013). Multiple imaging studies have reported decreased metabolism in the caudate nucleus following CBT (Thorsen et al, 2015). Given that OCD has been associated with increased activity in the caudate nucleus (Saxena et al, 1998), the changes seen with CBT may reflect more normal functioning of the neural circuitry.

Both SSRIs and CBT result in improvements in clinical symptoms of OCD and are associated with increased 5-HT synthesis capacities in treatment responders (Lissemore et al, 2018). A recent study used task-based fMRI to examine the effects of SSRIs and CBT on response inhibition tasks, demonstrating that CBT and SSRIs had opposite effects on the OFC, middle frontal gyrus, and lingual gyrus, with CBT increasing and SSRIs decreasing activity in these regions (van der Straten et al, 2024). These findings suggest distinct neural pathways may underlie the effects of each treatment, indicating a need for personalized approaches.

Neuromodulation Techniques

Neuromodulation of CSTC networks and reward networks via deep brain stimulation (DBS) and repetitive transcranial magnetic stimulation (rTMS) has also been applied to the treatment of impulsivity and compulsivity in multiple neuropsychiatric diseases. One meta-analysis showed that subthalamic nucleus DBS can reduce the severity of ICDs in individuals with PD, as measured by the QUIP-RS (Razmkon et al, 2021). DBS has also been shown to reduce the severity of symptoms in individuals with treatment-resistant OCD (Gadot et al, 2022). Furthermore, models of the predictability of periodic neural activity can classify responders to DBS and may be used in the future to measure the effectiveness of DBS therapy (Provenza et al, 2024).

One meta-analysis showed that rTMS had small but significant effects on impulsivity, measured by several of the above-mentioned experimental tasks in adults without ICDs (Yang et al, 2018). Additionally, rTMS to the dorsolateral prefrontal cortex yielded improvement in compulsive behaviors across studies (Protasio et al, 2015), including in individuals with methamphetamine SUD (Liu et al, 2022). Other meta-analytic studies, however, have shown no overall effect of rTMS on impulsivity among individuals with mental health disorders (Yang et al, 2020).

Future Directions

Current therapeutic approaches to impulsivity and compulsivity are largely derived from studies involving individuals with OCD and it remains uncertain if individuals with other neuropsychiatric disorders involving impulsivity and compulsivity will benefit equally, highlighting a need for further exploration. As our understanding of the brain circuitry involved in impulsivity and compulsivity has increased, neuromodulation techniques targeting these specific brain areas may be considered. More research is needed to assess the efficacy of neuromodulation therapies on specific facets of impulsivity and compulsivity in individuals with neuropsychiatric disorders.

Further studies should elucidate the precise neural dynamics driving impulsivity and compulsivity, particularly through real-time imaging of CSTC network activity during inhibition or reward-based tasks. For movement disorders such as PD, HD, and cerebellar ataxia, longitudinal research into impulsivity and compulsivity symptom evolution could inform the timing of potential therapeutic interventions. Additionally, more investigation into the role of the glutamatergic system in SUD, ADHD, and CSTC network dysfunction is warranted.

Personalized treatments targeting unique neural pathways are a promising avenue. For treatment-resistant individuals, neuromodulation beyond standard pharmacotherapy may offer benefits, especially by targeting neural circuits underlying impulsivity and compulsivity symptoms.

CONCLUSION

Impulsivity and compulsivity involve multiple frontal-subcortical, limbic, and cerebellar neural networks. The functioning of these networks is influenced by neurotransmitter systems and genetic and epigenetic factors. Impulsive and compulsive symptoms may manifest across various disorders, and further elucidation of the underlying neural and molecular mechanisms may inform treatment strategies. Current therapies—from pharmacotherapy to neuromodulation—show promise in managing these behaviors, but additional research is needed to refine approaches to treatment from a transdisciplinary perspective.

GLOSSARY

ACC

anterior cingulate cortex

ADHD

attention-deficit/hyperactivity disorder

BIS-11

Barratt Impulsiveness Scale

CBT

cognitive-behavioral therapy

CSTC

cortico-striatal-thalamo-cortical

DBS

deep brain stimulation

DSM-5-TR

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition—Text Revision

FTD

frontotemporal dementia

HD

Huntington disease

ICD

impulse-control disorder

OCI

Obsessive-Compulsive Inventory

OCD

obsessive-compulsive disorder

OFC

orbitofrontal cortex

PD

Parkinson disease

PPA

primary progressive aphasia

PSP

progressive supranuclear palsy

QUIP-RS

Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease–Rating Scale

rTMS

repetitive transcranial magnetic stimulation

SSRI

selective serum serotonin reuptake inhibitor

SUD

substance use disorder

VTA

ventral tegmental area

Y-BOCS

Yale-Brown Obsessive-Compulsive Scale