Introduction
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity–impulsivity that interferes with functioning or development.1 Specific symptoms can include not seeming to listen when spoken to, easy distractibility, forgetfulness, making careless mistakes in work or school, procrastination, difficulty sustaining attention, difficulty completing tasks, excessive fidgetiness or restlessness, impulsivity, becoming easily bored or impatient, and blurting out answers or interrupting others.1 Although initially conceptualized as a childhood disorder, research has shown that ADHD symptoms persist in up to 70% of adults diagnosed with ADHD as children2 and that the condition affects 3%–6% of adults.3
Adults diagnosed with ADHD as children often struggle with impairments or reduced quality of social, academic, and occupational functioning.4 They are more likely than comparably matched adults without ADHD to experience unstable relationships and marital problems, leading to higher rates of separation and divorce.5 They are also at two- to three-fold increased risk compared to normal controls of being arrested, convicted, or incarcerated.6 In addition, they are more likely to engage in risky driving and sexual behavior, particularly when comorbid conduct or antisocial personality disorder are present.7 Moreover, they often experience academic underachievement, unemployment, and problems in work performance.8,9 Those with comorbid mood, anxiety, and impulse control disorders often have unrecognized ADHD that can compromise treatment adherence and disrupt daily functioning.10 Finally, they have been noted to have shorter life expectancies compared to matched cohorts without ADHD.11
Pharmacotherapy, including stimulant medication, remains the mainstay of evidence-based treatment for ADHD and has been shown to significantly improve both core ADHD symptoms and associated functional impairments in adults.12 However, over time about half of adults with ADHD discontinue medication treatment, with the most common reason being lack of perceived effectiveness.13,14 Stimulant medications can also have side effects, such as headache, irritability, insomnia, and appetite loss, that may prove unpalatable for many adults with ADHD.15 Adults may also face barriers to ADHD assessment and treatment. Some adult psychiatrists and general practitioners may be skeptical of adult ADHD, feel ill-equipped to diagnose or treat it, or be reluctant to prescribe stimulants, especially when ADHD is the primary concern.16 These barriers highlight the need for accessible, effective, and durable interventions for adult ADHD symptoms and their associated functional and quality-of-life impacts.
Physical exercise is an intervention that has received increased attention over the last three decades in the treatment of individuals with ADHD. Although numerous studies in children have documented beneficial effects of exercise on inattention, hyperactivity, and impulsivity in ADHD,17–19 the literature on exercise for adults with ADHD is comparatively scarce. The limited studies that have examined the effect of exercise on these symptoms in adults with ADHD have shown encouraging results, albeit with small sample sizes.20–22 However, two recent systematic reviews23,24 concluded that exercise has positive effects on executive function and inhibitory control in adults with ADHD, respectively.
While these findings are encouraging, further research is needed to confirm or refute the efficacy of exercise in treating inattentive, hyperactive, and impulsive symptoms in adults with ADHD. In the meantime, this paper will consider a question that, to the author's knowledge, has not been addressed in a dedicated manner to date: What are the possible mechanisms by which exercise could reduce inattentive, hyperactive, and impulsive symptoms in adults with ADHD?
Methods
The literature regarding the neurobiology of exercise in adults was reviewed and compared with the literature on the neurobiology of ADHD in adults. Information from this comparison was then used to formulate hypothesized, biologically plausible mechanisms by which exercise might influence inattentive, hyperactive, and impulsive symptoms in adults with ADHD. Comparison of these two literatures was made because direct evidence on the neurobiological effects of exercise in adults with ADHD remains very limited.
Studies providing possible support for these hypothesized mechanisms are also cited.
A narrative review approach was chosen because this paper aimed to generate mechanistic hypotheses by synthesizing heterogeneous, largely indirect literatures. The review focused on neurobiological mechanisms by which exercise might influence adult ADHD symptoms, rather than comprehensively mapping the adult exercise/ADHD literature.
Figure 1 presents a schematic of the search process used to review the literature on the neurobiology of exercise in adults. A search of PubMed from 2019 to 2025 was performed on 10 July 2025, using the search terms “exercise”, “physical activity”, “neurobiology”, and “adult”. The search was limited to the last 6 years due to the inordinate number of citations identified when using broader date ranges.
Inclusion criteria included having physical exercise as the main focus, describing neurobiological considerations in relation to exercise, focusing on adults, and being published in English. Citations not meeting all of these criteria were excluded from review. All citations were screened and reviewed for inclusion by the author (D.I.).
The initial search yielded 523 citations. Of these, 492 were excluded after reviewing titles and abstracts. Full texts of the remaining 31 citations were reviewed, with 6 articles excluded.
Reference lists of the remaining 25 articles were reviewed and led to identification of an additional 14 citations, for a total of 39 articles identified as relevant to the neurobiology of exercise in adults.
Figure 2 presents a schematic of the search process used to review the literature on the neurobiology of ADHD in adults. A search of PubMed from 2015 to 2025 was performed on 15 July 2025, using the search terms “attention deficit hyperactivity disorder”, “neurobiology”, and “adult”. The search was limited to the last 10 years to review relatively current literature.
Inclusion criteria included describing neurobiological considerations in relation to ADHD, focusing on adults, being peer-reviewed, and being published in English. Editorials, conference proceedings, and citations not meeting these inclusion criteria were excluded. All citations were screened and reviewed for inclusion by the author (D.I.).
The initial search yielded 156 citations. Of these, 110 were excluded after reviewing titles and abstracts. Full texts of the remaining 46 citations were reviewed, with 10 articles excluded.
Reference lists of the remaining 36 articles were reviewed and led to identification of an additional 14 citations, for a total of 50 articles identified as relevant to the neurobiology of ADHD in adults.
In line with standards for narrative review reporting,25 the quality of each included study was assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomized trials,26 the National Institutes of Health Quality Assessment Tool for assessing the quality of cohort and cross-sectional studies,27 the SYRCLE tool for assessing the quality of animal research,28 the Critical Appraisal Skills Programme (CASP) Systematic Review Checklist for systematic reviews,29 and the Scale for the Assessment of Narrative Review Articles (SANRA) tool for narrative reviews.30 These tools were used to assign a rating of “low”, “medium”, or “high” to the quality of each article, as shown in the last column of Tables 1 and 2.
Results
Thirty-nine articles were identified as relevant to the neurobiology of exercise in adults;31–69 these are presented in Table 1. Fifty articles were identified as relevant to the neurobiology of ADHD in adults;70–119 these are presented in Table 2.
To explore possible mechanisms by which exercise might influence inattentive, hyperactive, or impulsive symptoms in adults with ADHD, the neurobiology of exercise was reviewed first.
Neurobiology of exercise in adults
Among the 39 reviewed studies on the neurobiology of exercise in adults, 19 were experimental or interventional studies;31,32,38,39,41,42,44,49–52,56,60–63,66–68 six were observational studies;36,54,57–59,65 one used a mixed observational/experimental design;64 and 13 were reviews or evidence syntheses.33–35,37,40,43,45–48,53,55,69 Accordingly, causal or mechanistic inferences in this section are drawn primarily from experimental animal studies and human trials, whereas cross-sectional and cohort studies are interpreted as supporting associations between exercise, fitness, and neurobiological outcomes.
Exercise-induced neuroplasticity and neurogenesis
Experimental animal studies provide much of the direct mechanistic evidence linking physical activity to neuroplasticity, neurotrophic signaling, and neurogenesis, particularly in the hippocampus.31,38,49,56,61 Russo-Neustadt et al.31 showed in rodents that combining physical activity with antidepressant treatment increased brain-derived neurotrophic factor (BDNF) mRNA expression in multiple hippocampal regions beyond the effects of either intervention alone. Duman et al.38 similarly found that chronic wheel running produced antidepressant-like behavioral effects in mice through mechanisms involving BDNF, while Iqbal et al.49 reported that physical training increased neuronal proliferation and maturation in the hippocampus in a mouse model of status epilepticus. Complementary human trial evidence suggests that exercise-related changes in neurotrophic factors may correlate with brain network remodeling.
For example, Voss et al.44 found that aerobic exercise-related increases in temporal lobe functional connectivity were associated with increases in BDNF, insulin-like growth factor 1, and vascular endothelial growth factor. Together, these findings support a plausible role for exercise in neuroplastic processes, although direct evidence in adults with ADHD remains limited.
Enhancement of functional connectivity and cognitive networks
Human experimental and observational studies suggest that exercise and higher cardiorespiratory fitness are associated with differences in large-scale functional connectivity networks relevant to cognition. In a randomized trial of older adults, Voss et al.41 found that aerobic walking and non-aerobic stretching/toning interventions were associated with increased functional connectivity within the default mode network (DMN) and frontal executive network, with connectivity changes corresponding to improved executive function. Observational studies provide complementary association-level evidence.
Kronman et al.54 found that cardiorespiratory fitness predicted stronger connectivity between the hippocampus and DMN nodes (ventromedial prefrontal cortex, posterior cingulate, and temporal cortices) in young adults, while Hendrikse et al.57 reported that higher levels of exercise and cardiorespiratory fitness were associated with improved hippocampal structure and function in young to middle-aged adults. These findings suggest that exercise and fitness may be linked to functional network characteristics relevant to attention and executive function, but observational findings should not be interpreted as establishing causality.
Modulation of neurotransmitter systems
Evidence that exercise influences neurotransmitter systems derives largely from animal studies and narrative syntheses, with some supportive human observational and interventional evidence. Meeusen et al.35 noted, based on microdialysis data from animal models, that exercise increases extracellular concentrations of dopamine, norepinephrine, and serotonin in the striatum, hippocampus, and frontal cortex, with both intensity and duration affecting neurotransmitter release. Review-level evidence has also linked exercise to endocannabinoid and opioid signaling pathways that may be relevant to mood, reward, and motivation.34,40,43,46 In humans, Plini et al.58 found that higher VO2 max (maximal aerobic capacity, a type of aerobic fitness marker) was associated with increased locus coeruleus signal intensity, suggesting a possible relationship between fitness and noradrenergic system integrity.
Because much of this neurotransmitter evidence is animal-based, observational, or review-level, these findings are best interpreted as supporting mechanistic plausibility rather than definitive clinical effects in adults with ADHD.
Effects on stress axis regulation and mood
Evidence linking exercise to hypothalamic–pituitary–adrenal (HPA) axis function includes animal mechanistic work, observational human data, and pre-post intervention studies. Stranahan et al.37 proposed, based on animal models, that exercise may improve HPA-axis negative feedback, potentially reducing corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol responses. In a cross-sectional human study, Rimmele et al.36 found that physically trained men exhibited lower cortisol and heart-rate responses to a laboratory stressor than untrained men, along with better mood and lower state anxiety.
Drogos et al.52 using a single-group pre-post intervention design in older adults, found that aerobic exercise increased the cortisol awakening response, and that increases in this response were associated with reduced subjective stress. These findings suggest that exercise may relate to stress regulation, but the strength of causal inference varies by study design.
Antioxidant and anti-inflammatory effects
Exercise has been linked to antioxidant and anti-inflammatory pathways through experimental, observational, and review-level evidence. In a randomized controlled human study of adults with Parkinson's disease, Bloomer et al.39 found that resistance exercise was associated with trends toward reduced oxidative stress and increased antioxidant capacity. In a systematic review and meta-analysis of animal studies, de Souza et al.53 reported that endurance training increased antioxidant enzymes, including superoxide dismutase and catalase.
In a large prospective cohort study, Jiao et al.65 found that higher total and leisure-time physical activity were associated with lower incident Parkinson's disease risk. Although these findings support a possible role for exercise in oxidative-stress and inflammatory pathways, the cohort findings remain associational, and extrapolation to adults with ADHD should be made cautiously.
Enhancement of reward, motivation, and mood-related neurocircuitry
Evidence relating exercise to reward and motivation circuitry includes narrative reviews, human experimental studies, and disease-specific intervention studies. Dietrich and McDaniel34 reviewed animal and human literature linking exercise to endocannabinoid activity and potential anxiolytic or mood-related effects, with dense CB1 receptor expression in the prefrontal cortex—critical for integration of emotion and cognition. Sacheli et al.51 in a randomized controlled study of adults with Parkinson's disease, found that aerobic exercise increased ventral striatal activity and repetitive transcranial magnetic stimulation-evoked dopamine release in the caudate.
Cosgrove et al.68 found that 12 weeks of exercise altered neurocircuitry supporting reward-based decision-making in adults with overweight or obesity, including regions such as the dorsolateral prefrontal cortex and anterior cingulate cortex. These findings support the possibility that exercise can influence reward-related neural systems, although the extent to which these effects generalize to adults with ADHD warrants further evaluation.
Synaptic plasticity, epigenetic effects, and gene expression
Experimental animal and mixed-design studies suggest that exercise or exercise-like interventions may influence synaptic plasticity, gene expression, and epigenetic regulation. Oroszi et al.60 found that whole-body vibration increased hippocampal cholinergic activity and synaptophysin expression in mice, alongside improved spatial-memory performance. La Tour et al.61 found that intermittent exercise in mice was associated with persistent cognitive benefits and increased hippocampal expression of genes involved in long-term memory.
Zhao et al.64 using a mixed design combining observational human data with animal experimental components reported that exercise training could prevent and reverse alternative splicing of LDL-receptor pre-mRNA, suggesting a role for exercise in beneficial epigenetic effects leading to improved cholesterol metabolism. In a small, single-arm pilot study in adults with amyotrophic lateral sclerosis, Jawdat et al.62 found that exercise was associated with changes in muscle transcriptomic profiles. These findings support biological plausibility for exercise-related molecular adaptation, but most are not directly derived from adult ADHD samples.
Clinical and neurocognitive benefits in aging and disease
Human trials suggest that exercise interventions may influence cognition, brain structure, or functional outcomes in aging and neurologic disease populations. Shadyab et al.66 found that exercise interventions were associated with reduced prefrontal volume loss relative to a propensity-matched external comparison cohort in older adults with mild cognitive impairment. Baker et al.67 reported that both moderate-to-high-intensity aerobic exercise and lower-intensity stretching/balance exercise were associated with stable cognition and minimal hippocampal volume loss in adults with mild cognitive impairment.
In Parkinson's disease, exercise interventions have been associated with improvements in depressive symptoms, motor outcomes, and functional brain measures.32,48,51 These findings support the broader neurocognitive relevance of exercise but should be treated as indirect evidence when considering adult ADHD.
Next, the neurobiology of ADHD in adults is considered.
Neurobiology of adult ADHD
Among the 50 reviewed studies on the neurobiology of adult ADHD, four were experimental or controlled mechanistic studies;92,111,117,119 34 were observational studies;71–80,82–87,89,90,93,96–102,104,108,110,112–115,118 and 12 were reviews or evidence syntheses.70,81,88,91,94,95,103,105–107,109,116 Therefore, most conclusions in this section are framed as observational associations between ADHD and neurobiological features, while experimental evidence is used more narrowly to support mechanistic plausibility regarding attention control, dopaminergic signaling, epigenetic regulation, and striatal proteomic changes.
Structural brain differences in adults with ADHD
Structural neuroimaging findings in adult ADHD were derived almost entirely from observational case-control, cross-sectional, longitudinal cohort, and mega-analytic studies.72–74,77,80,85,86,96,104,110,115,118 These studies therefore support associations between ADHD and structural brain differences rather than causal conclusions. Several studies and reviews have reported reduced or altered volumes in regions implicated in attention and executive function, including the prefrontal cortex, basal ganglia, cerebellum, and corpus callosum.70,74,88,96,105,118 For example, Franke et al.88 in their narrative review highlighted magnetic resonance imaging (MRI) findings suggesting decreased basal ganglia and cerebellar volume and persistent frontal–parietal hypoactivation in ADHD. Kasparek et al.70 noted a trend toward normalization of the caudate with age but reported that differences in total brain volume, particularly in the prefrontal cortex and cerebellum, may persist into adulthood.
Some large-scale studies, such as Hoogman et al.96 did not observe statistically significant cortical surface-area or thickness differences in adults with ADHD, suggesting possible normalization with age or effects too subtle to detect with available methods.
Diffusion tensor imaging studies provide additional observational evidence for altered white matter microstructure in adult ADHD. Findings frequently include decreased fractional anisotropy—a marker of disrupted white matter integrity—in the corpus callosum, corona radiata, thalamic radiations, and superior longitudinal fasciculus.72,73,77,110 Shaw et al.73 found that lower fractional anisotropy in the left uncinate and inferior fronto-occipital fasciculus was associated with persistent inattention in adulthood. Onnink et al.72 linked decreased fractional anisotropy and increased mean diffusivity in these tracts to impaired inhibition and increased impulsive decision-making.
These findings suggest that white matter differences may be linked to persistent ADHD symptoms, but whether they are causes, consequences, correlates, or compensatory features of ADHD is unclear.
Abnormal functional connectivity and network dynamics
Evidence for altered functional connectivity and attentional-network dynamics in adult ADHD comes primarily from observational neuroimaging and electrophysiologic studies, with one controlled experimental task-based EEG study contributing more direct experimental evidence.75,76,79,82,84,89,90,92,98,112,113 Sudre et al.82 utilized functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in a prospective cohort to show that persistence of ADHD symptoms was associated with hypoactive functional connectivity within the DMN, as well as hyperactive connectivity between the DMN and frontoparietal and attentional networks. These patterns were linked to behavioral manifestations such as distractibility and impulsivity. Mostert et al.76 found that adults with ADHD presented significantly stronger resting-state connectivity in the anterior cingulate gyrus and notable trends for increased cerebellar connectivity, with correlations between hyperactivity/impulsivity symptoms and connectivity strength.
Sidlauskaite et al.79 found hyperconnectivity between ventral and dorsal attention networks and within the DMN in adults with ADHD, suggesting possible imbalance between stimulus-driven (ventral) and goal-directed (dorsal) attentional systems. Schneidt et al.92 using a controlled experimental paradigm with EEG, found that adults with ADHD were more susceptible to distraction by salient irrelevant stimuli, particularly under conditions requiring top-down control. Thus, while most network findings are observational, the experimental task-based evidence supports the plausibility that altered attentional control may contribute to distractibility in adults with ADHD.
Reviews synthesizing this literature similarly suggest that resting-state and task-based studies converge in implicating frontoparietal, frontostriatal, frontocerebellar, and DMN abnormalities, though these conclusions remain largely based on observational imaging studies.94,95
Neurotransmitter involvement
Neurotransmitter-related claims in adult ADHD are supported by observational positron emission tomography (PET), EEG/event-related potential (ERP), genetic, imaging, and spectroscopy studies, as well as review-level syntheses; experimental animal work provides additional mechanistic plausibility.78,87,89,101,105,107,109,111,112,113,116,119 Dopamine and norepinephrine remain prominent in models of ADHD neurobiology, particularly in relation to reward processing, motivation, attention, and executive control.81,105,116 Cherkasova et al.87 combined MRI and PET imaging and found that among adults with ADHD, decreased cortical thickness was associated with lower dopamine D2/3 receptor availability—a pattern opposite to that found in healthy controls. However, their modest sample size (15 adults) and higher depression rates in the ADHD group temper the impact of these findings. Vidor et al.107 in a systematic review and meta-analysis of spectroscopy studies found evidence of altered glutamate/glutamine concentrations in the medial prefrontal cortex among individuals with ADHD.
Studies using transcranial magnetic stimulation and EEG suggest that cortical excitability and arousal instability may also be relevant to ADHD symptomatology, potentially reflecting glutamate/gamma-amino-butyric acid (GABA) imbalance.89,109 Experimental animal evidence from Liu et al.111 supports a possible mechanistic link between circadian gene variation, dopamine D1 receptor signaling, and ADHD-like behaviors. Overall, these studies support involvement of neurotransmitter systems in ADHD but do not establish a single causal pathway.
Genetic and epigenetic mechanisms
Genetic, transcriptomic, and epigenetic findings in adult ADHD are largely observational, including genome-wide association, genetic association, transcriptomic, methylation, and post-mortem case-control studies.71,83,93,97,99–101,108,114,115 Demontis et al.93,114 identified multiple genome-wide significant loci associated with ADHD, with implicated genes enriched for expression in the frontal cortex during brain development and involved in synaptic and neuronal signaling. Sánchez-Mora et al.71 identified FBXO33 as a candidate susceptibility gene for persistent ADHD, while Merker et al.83 implicated SLC2A3 variants in ADHD risk and cognitive processing. Epigenetic studies also suggest possible involvement of DNA methylation in ADHD.
Müller et al.108 reported lower global DNA methylation in adults with ADHD, and Shastri et al.115 found overlap between genes differentially methylated in the caudate and genes previously implicated by ADHD genome-wide association studies. Animal experimental work provides additional mechanistic support for methylation and molecular pathway changes,117,119 though human evidence remains primarily associational.
Executive dysfunction, working memory, and arousal regulation
Studies examining executive function, working memory, and arousal regulation in adult ADHD are primarily observational, with convergent evidence from EEG, ERP, fMRI, and behavioral paradigms.75,78,80,84,89,90,98,112,113 Barth et al.90 identified distinct EEG-based neurophysiological profiles among adults with ADHD, including subgroups characterized by attention/inhibitory dysregulation with compensatory prefrontal activation, arousal/vigilance instability, and efficient attention allocation. Mayer et al.78 found reduced contingent negative variation amplitude and increased reaction-time variability in adults with ADHD, interpreted as markers of cortical underarousal and attentional instability. Roman-Urrestarazu et al.80 reported caudate structural and functional differences associated with working-memory performance in young adults diagnosed with ADHD in adolescence.
These findings are consistent with clinically observed executive dysfunction in ADHD, although they should be interpreted as correlational neurophysiological patterns rather than direct causal explanations.
Inflammation and immune system involvement
Evidence linking inflammation and immune pathways to adult ADHD remains emerging and is largely observational or review-based. Mortimer et al.99 used transcriptome profiling and identified genes differentially expressed in adults with ADHD, including genes involved in immune response, synaptic function, and dopamine/glutamate signaling. Park,106 reviewing studies on the kynurenine pathway, identified that pro-inflammatory cytokines such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) can drive the neurotoxic branch of tryptophan metabolism, potentially leading to oxidative stress and neuronal dysfunction in regions critical for attention.
These findings suggest possible immune and inflammatory involvement in ADHD neurobiology, but direct causal evidence in adults remains limited.
Mitochondrial dysfunction and metabolic pathways
A smaller body of evidence suggests possible involvement of mitochondrial and metabolic pathways in ADHD. Khoury et al.105 reviewed evidence for oxidative stress and mitochondrial dysfunction in ADHD, possibly disrupting neuronal energy balance and neurotransmitter synthesis. Custodio et al.119 in a controlled animal model of predominantly inattentive ADHD-like behavior found striatal proteomic alterations involving dopamine and glutamate signaling, synaptic vesicle cycling, and mitochondrial energy homeostasis.
These findings support a possible role for metabolic inefficiency in neural systems relevant to attention and motivation, although human adult ADHD data remain sparse.
Heterogeneity, sex differences, and subtype variability
Observational studies indicate substantial neurobiological heterogeneity in adult ADHD, including differences by symptom persistence, sex, and clinical subtype.77,82,90,96,98,112,118 Luders et al.77 reported that thinning of the corpus callosum showed sexually dimorphic patterns, with more pronounced relationships between callosal size and ADHD symptoms in men. Barth et al.90 proposed neurophysiological subtypes based on EEG profiles, and Lee et al.112 found sex-related differences in prefrontal and striatal activation during a Stroop task120 among medication-naïve adults with ADHD. Such heterogeneity may help explain inconsistent findings across studies and suggests that aggregating across sex, symptom profile, medication history, and persistence/remission status may obscure meaningful neurobiological differences.
Discussion
In comparing the neurobiology of ADHD with the neurobiology of physical exercise, several hypothesis-generating mechanisms emerge by which exercise might plausibly influence inattentive, hyperactive, or impulsive symptoms in adults with ADHD. However, these proposed mechanisms should be interpreted cautiously. Most adult ADHD neurobiology studies reviewed were observational, and much of the mechanistic exercise evidence was derived from animal studies, non-ADHD adult samples, or clinical populations other than adults with ADHD.
Thus, the following mechanisms should be regarded as biologically plausible but not yet established as causal pathways in adult ADHD. Exercise might enhance neuroplasticity in brain regions implicated in ADHD. Experimental animal studies and some human exercise trials suggest that physical activity can influence neuroplasticity, neurotrophic signaling, and hippocampal or cortical network function, including pathways involving BDNF, IGF-1, and VEGF.31,38,44,49,50,56,61 Separately, observational studies of adult ADHD have associated ADHD with structural differences in prefrontal, striatal, cerebellar, and white matter systems.70,72–74,85,86,96,104,118 Taken together, these literatures raise the possibility that exercise-related neuroplastic effects could be relevant to neural systems implicated in ADHD, although direct evidence in adults with ADHD is needed.Exercise could influence functional connectivity in networks relevant to attention and executive control.
Human exercise trials and observational fitness studies have linked exercise or higher cardiorespiratory fitness to functional connectivity in the default mode, frontal executive, hippocampal, and temporal networks.41,44,54,57 Adult ADHD studies, largely observational, have associated ADHD with altered default mode, frontoparietal, frontostriatal, salience, and attentional network connectivity.75,76,79,82,84,98 This overlap suggests a plausible network-level mechanism through which exercise might affect attention or executive control. From a behavioral outcomes standpoint, Yang et al.24 in a systematic review and meta-analysis concluded that both acute and chronic exercise improve inhibitory control in adults with ADHD. However, whether exercise normalizes or compensates for ADHD-related connectivity differences remains unproven.Exercise-related neurotransmitter effects might be relevant to ADHD-associated dopamine and norepinephrine pathways.
Animal and review-level exercise studies suggest that exercise could influence dopamine, norepinephrine, serotonin, endocannabinoid, and opioid signaling.34,35,40,43 Human studies provide more limited but supportive evidence linking exercise or fitness to dopaminergic and noradrenergic systems.51,58 In adult ADHD, observational imaging, genetic, and review-level evidence implicates dopamine and norepinephrine pathways in reward processing, attention, and executive control.81,87,101,105,116 These parallel literatures, while not establishing causality, suggest a plausible neurotransmitter-based rationale for exercise as an adjunctive intervention in adult ADHD. Supporting this from a behavioral outcomes perspective, Gapin et al.21 found that a single session of moderate aerobic exercise was associated with improved inhibitory control on the Stroop task120 among college students with ADHD. Future research is needed, however, to establish whether exercise actually improves adult ADHD symptoms via neurotransmitter effects.Exercise may be relevant to stress regulation and arousal systems.
Exercise has been associated with altered HPA-axis function and stress responsivity in animal, observational, and pre-post intervention studies.36,37,52 Adult ADHD has also been associated with arousal dysregulation, attentional instability, and variability in neurophysiological markers of vigilance.78,89,90 These findings suggest that exercise-related changes in stress physiology or arousal regulation could plausibly influence attention or impulsivity, especially in individuals whose symptoms fluctuate with stress. Supporting this from a behavioral outcomes standpoint, Rassovsky and Alfassi22 found that moderate-intensity exercise during a continuous auditory attention task was associated with faster reaction times and fewer omission errors among adults with ADHD. However, future research is needed to determine if in fact exercise impacts stress or arousal regulation and thereby helps with attention and impulsivity in adults with ADHD.Exercise might intersect with oxidative-stress, inflammatory, and metabolic pathways implicated in ADHD.
Experimental and review-level exercise studies suggest that exercise can increase antioxidant capacity and influence oxidative-stress pathways.39,53 Cohort data also link higher physical activity to lower risk of neurodegenerative disease, though such findings are observational.65 In adult ADHD, transcriptomic and review-level evidence suggests possible involvement of immune, inflammatory, oxidative-stress, and metabolic pathways.99,105,106,119 These converging findings raise the possibility that exercise could affect biological processes relevant to ADHD, but direct trials examining inflammatory or oxidative biomarkers in exercising adults with ADHD are lacking.Exercise could influence reward and motivation circuitry relevant to ADHD. Exercise has been linked to endocannabinoid, opioid, dopaminergic, and reward-related neural systems in review-level and experimental studies.34,40,51,68 Adult ADHD has been associated with altered reward processing, delay discounting, motivational regulation, and striatal–prefrontal circuitry.81,87,101,113,116 These findings suggest that exercise could plausibly support reward and motivation systems relevant to ADHD. Supporting this from a behavioral outcomes standpoint, Fuermaier et al.20 found that 2 min of passive whole-body vibration acutely improved inhibitory control among adults with ADHD and healthy controls, with larger effects in the ADHD group.
However, direct adult ADHD trials with reward-based neural outcomes are needed.Exercise could influence white matter, synaptic plasticity, and gene expression. Animal and mixed-design studies suggest that exercise or exercise-like interventions may affect synaptic density, hippocampal gene expression, and molecular pathways related to plasticity.56,60,61,64 Adult ADHD observational studies have linked persistent symptoms to altered white matter microstructure and structural connectivity.72,73,110 These findings suggest a possible structural and synaptic pathway by which exercise could impact ADHD symptoms. Consistent with this, from a behavioral outcomes standpoint, Singh et al.23 concluded from their systematic review and meta-analysis that exercise significantly improves executive function among children and adults with ADHD compared to the general population.
However, evidence that exercise improves ADHD-related white matter or synaptic markers in adults has not been established.Exercise might influence epigenetic or gene-expression pathways relevant to ADHD risk and symptom expression. Molecular studies suggest possible effects of exercise on gene expression and epigenetic regulation.62,64 Separately, adult ADHD studies have identified polygenic, transcriptomic, and epigenetic associations.71,83,93,99,108,114,115 Animal ADHD models also support possible roles for methylation and striatal proteomic changes in ADHD.117,119 These findings support biological plausibility but remain preliminary and indirect with respect to exercise effects in adult ADHD.
Limitations
Several limitations should be considered when interpreting the findings and proposed mechanisms in this review. First, much of the mechanistic evidence for the neurobiological effects of exercise is based on animal studies, healthy adults, older adults, or neurologic populations rather than adults with ADHD, limiting direct applicability to this group. Second, the adult ADHD neurobiology literature reviewed here was dominated by observational case-control, cross-sectional, cohort, genetic, and neuroimaging studies; therefore, most ADHD-related neurobiological findings should be interpreted as associations rather than causal mechanisms.
Third, while the literature searches were systematic and transparent, the single-author screening process and restrictions by date and language raise risks of publication and selection bias. Fourth, the studies reviewed were heterogeneous in design, sample characteristics, exercise parameters, and methodological rigor, making formal synthesis or meta-analysis difficult. However, as noted earlier, the aim of this narrative review was to generate mechanistic hypotheses regarding how exercise might influence adult ADHD symptoms, rather than to systematically map the adult exercise/ADHD literature.
A future scoping review may be valuable for characterizing the breadth, design features, and methodological quality of studies examining exercise in adults with ADHD, particularly as this literature continues to expand. Fifth, there was substantial heterogeneity in the type, frequency, intensity, and format of exercise examined across studies. Finally, there remains a scarcity of intervention studies directly testing whether exercise-induced neurobiological changes mediate improvements in inattentive, hyperactive, or impulsive symptoms in adults with ADHD.
Conclusion
This review explored possible mechanisms by which exercise might influence inattentive, hyperactive, and impulsive symptoms in adults with ADHD. The reviewed evidence suggests several biologically plausible pathways, including neuroplasticity, functional connectivity, neurotransmitter signaling, stress regulation, oxidative-stress and inflammatory pathways, reward and motivation circuitry, white matter integrity, and epigenetic or gene-expression mechanisms. However, the current evidence remains largely indirect.
The exercise literature includes a mixture of experimental, observational, animal, and review-level evidence, while the adult ADHD neurobiology literature is predominantly observational. Therefore, the proposed mechanisms should be viewed as hypotheses rather than established causal pathways.
Future research should prioritize adequately powered, well-controlled exercise trials in representative adult ADHD samples. Such trials should examine different exercise types, intensities, durations, and delivery formats while incorporating multimodal neurobiological and behavioral outcomes. Studies that test whether neurobiological changes mediate improvements in ADHD symptoms would be especially valuable.
If supported by future evidence, exercise could become an accessible complementary intervention with potential benefits for both ADHD symptoms and broader physical and mental health outcomes.