Dopamine's Role in Neurofeedback

Dopamine is a critical neurotransmitter in the brain, with profound roles in modulating mood, attention, motivation, and movement.

It plays a central role in the brain's reward system, influencing learning processes and goal-directed behavior, making it particularly relevant to neurofeedback interventions. Neurofeedback, a technique that allows individuals to regulate their brain activity by providing real-time feedback on EEG (electroencephalogram) waveforms, may involve modulating dopamine pathways to influence certain brain functions. Understanding dopamine's involvement in neurofeedback requires a closer examination of dopamine as a neurotransmitter, its pathways, its effect on EEG waveforms, and the neuropsychiatric disorders linked to dysregulated dopamine signaling.

Dopamine: Definition and Function

Dopamine is a catecholamine neurotransmitter synthesized from the amino acid tyrosine. It acts on dopamine receptors, of which five subtypes (D1–D5) exist. Dopamine receptor graphic ©

Juan Gaertner/shutterstock.com.

They are broadly classified into two families: the D1-like receptors (D1, D5), which stimulate adenylate cyclase activity, and the D2-like receptors (D2, D3, D4), which inhibit adenylate cyclase (Beaulieu & Gainetdinov, 2011).

Around a million of the human brain's 80 to 90 billion neurons synthesize dopamine (Breedlove & Watson, 2023). Despite this small number, they exert a substantial influence on behavior. Dopamine is also thought to play roles in motivation, reward, and reinforcement. Many abused substances affect CNS dopaminergic pathways. Dopamine's role in some sympathetic ganglia is poorly understood. Its involvement in reinforcement learning highlights its connection to neurofeedback, where brainwave modulation is reinforced through feedback loops.

Dopamine is synthesized in the cytoplasm of presynaptic terminals and then transported into synaptic vesicles by VMATs. Its activity in the synaptic cleft is ended by reabsorption into the nerve terminals or neighboring glial cells through a sodium (Na+)-dependent dopamine co-transporter (DAT) (Purves, 2018).

Dopamine breakdown involves monoamine oxidase (MAO) and catechol O-methyltransferase (COMT) found in neurons and glial cells. MAO is located in the mitochondria, and COMT in the cytoplasm.

After release, dopamine triggers G-protein-coupled receptors. Most dopamine receptor subtypes turn on or off adenylyl cyclase, helping regulate complex behaviors.

Dopaminergic Pathways Relevant to Neurofeedback

Two major dopaminergic pathways in the brain, mesolimbocortical and nigrostriatal, are implicated in various aspects of behavior and cognition.

Mesolimbocortical Pathway

This pathway originates in the ventral tegmental area (VTA) and projects to the nucleus accumbens. It is heavily involved in reward processing and motivation (Volkow et al., 2011). Projections to the prefrontal cortex influence executive functions, such as decision-making, planning, and attention (Robbins & Arnsten, 2009). Mesolimbocortical pathway graphic © aipicte/Shutterstock.com.

Nigrostriatal Pathway

Originating in the substantia nigra, this pathway is critical for motor control, projecting to the striatum. Dysfunction in this pathway is a hallmark of Parkinson's disease, and neurofeedback approaches targeting motor activity may engage dopaminergic modulation in this system. Nigrostriatal pathway graphic © Vasilisa Tsoy/Shutterstock.com.

Dopamine Modulates EEG Waveforms

Dopamine influences EEG waveforms primarily by modulating cortical activity. The neurotransmitter impacts brain rhythms, particularly in the frontal cortex, where dopamine regulates high-frequency beta (13–30 Hz) and gamma (>30 Hz) activity (Kropotov, 2016). Beta waves are typically associated with alertness, active thinking, and concentration, while gamma waves are linked to higher cognitive functions, such as memory and attention.

Dopaminergic modulation of these waveforms occurs through several mechanisms. For example, dopamine enhances cortical excitability, which can increase beta and gamma wave activity. This excitatory influence may be particularly relevant in neurofeedback sessions to improve attention or cognitive control. In contrast, reductions in dopamine activity can lead to an increase in lower-frequency theta (4–8 Hz) and delta (1–4 Hz) rhythms, which are often observed in disorders like ADHD (Arns et al., 2013). Neurofeedback protocols targeting the reduction of theta waves, common in ADHD treatment, may enhance dopamine activity in cortical regions, helping to restore the balance between excitation and inhibition in these circuits.

Furthermore, dopamine plays a role in regulating the reward-related theta-alpha (6–12 Hz) oscillations, which are crucial in feedback learning (Cavanagh & Frank, 2014). These mid-range frequencies are thought to be involved in processing reward prediction errors, which are essential for reinforcing learning during neurofeedback (NFB) training.

Disorders Involving Abnormal Dopamine Signaling

Several neuropsychiatric disorders are characterized by dysregulated dopamine signaling, and many of these are targets for neurofeedback interventions. These include Attention-Deficit/Hyperactivity Disorder, Parkinson's Disease, Schizophrenia, Depression, and Substance Use Disorders.

Attention-Deficit/Hyperactivity Disorder (ADHD)

ADHD is often associated with reduced dopamine transmission in the prefrontal cortex, which manifests as excessive theta wave activity and insufficient beta wave activity (Arns et al., 2013). NFB protocols designed to increase beta activity or reduce theta activity can help improve attention and reduce hyperactivity in individuals with ADHD.

Based on six RCTs, Stefanie Enriquez-Geppert and colleagues rated NFB for ADHD as efficacious and specific in Evidence-Based Practice in Biofeedback and Neurofeedback (4th ed.).

NFB interventions included training to decrease the theta/beta ratio and increase sensorimotor rhythm (SMR) activity or slow cortical potential (SCP) activity.

NFB training resulted in beneficial post-treatment changes in ADHD symptoms, including the Attention Deficit Disorders Evaluation Scale (ADDES). Participants also increased IQ scores, improved TOVA measures of attentiveness, impulse control, and response variability, and strengthened school-related performance, as seen in Wide Range Achievement Test results.

Parkinson’s Disease

Parkinson's is marked by the degeneration of dopaminergic neurons in the nigrostriatal pathway, leading to motor symptoms like tremors, rigidity, and bradykinesia. Motor symptoms have cognitive analogs such as bradyphrenesia, which is the slowness of thought processes. Neurofeedback approaches targeting motor cortex activity might influence dopamine-mediated motor control mechanisms, offering a non-pharmacological method to alleviate symptoms (Subramanian, 2014). Parkinson's graphic © Kateryna Kon/Shutterstock.com.

Schizophrenia

Schizophrenia involves hyperactive dopamine signaling in the mesolimbic pathway, contributing to positive symptoms like hallucinations and delusions, while hypoactivity in the mesocortical pathway contributes to cognitive deficits (Howes & Kapur, 2009). In schizophrenia, structural changes in both gray and white matter are closely linked to the cognitive deficits and negative symptoms commonly observed in affected individuals (Stucky, Kirkwood, & Donders, 2014).

Gray matter, which consists of neuronal cell bodies, synapses, and dendrites, shows a notable reduction in volume in key brain regions. These areas include the prefrontal cortex, temporal lobes, and hippocampus—regions critical for cognitive functions such as memory, attention, and executive control. The thinning and loss of gray matter in these regions contribute to impairments in working memory, attention deficits, and difficulties in decision-making, all hallmark cognitive symptoms of schizophrenia. Furthermore, gray matter reductions in the prefrontal cortex are thought to play a role in the blunting of emotional expression and social withdrawal, which are central to the negative symptoms of schizophrenia.

White matter, composed of myelinated axons that facilitate communication between different brain regions, also exhibits abnormalities in schizophrenia. Disruptions in white matter integrity, particularly in the frontal and temporal lobes, have been associated with the disorganized thinking and impaired information processing that underlie the cognitive symptoms of the disorder. Diffusion tensor imaging (DTI) studies have revealed reduced white matter coherence, indicating a loss of connectivity between brain regions. This reduction in connectivity may further exacerbate cognitive dysfunction by impairing the brain's ability to integrate and process information efficiently. In addition, compromised white matter pathways, such as the corpus callosum, affect the coordination between brain hemispheres, contributing to the severity of cognitive and negative symptoms. Neurofeedback aimed at enhancing prefrontal cortex activity could potentially ameliorate some of the cognitive impairments associated with this disorder.

Depression

Dysregulated dopamine transmission in the mesocortical and mesolimbic pathways is implicated in major depressive disorder, particularly with anhedonia (the inability to experience pleasure; Nestler & Carlezon, 2006). Neurofeedback protocols that target mood regulation through reward system modulation may help alleviate depressive symptoms by normalizing dopamine signaling.

Based on 10 RCTs, Zachary Meehan, Fred Shaffer, and Christopher Zerr rated BFB and NFB for major depressive disorder (MDD) as efficacious and specific in Evidence-Based Practice in Biofeedback and Neurofeedback (4th ed.). NFB interventions included alpha asymmetry reduction, alpha/theta increase, and real-time functional MRI (rtfMRI) to increase left or right ventromedial prefrontal cortex, insula, dorsolateral prefrontal cortex, medial temporal lobe, or orbitofrontal cortex activity.

Substance Use Disorders

Addictive behaviors are linked to dopamine dysregulation in the mesolimbic pathway, particularly in the nucleus accumbens, which is critical for reward-seeking behavior. Neurofeedback may modulate reward circuits, offering a novel approach to reduce cravings and improve self-regulation (Coffey et al., 2015). Estate M. Sokhadze and David Trudeau rated NFB for SUD as probably efficacious based on an RCT (N = 121) using the Scott–Kaiser NFB protocol. The Scott-Kaiser protocol, which starts with NF ADHD training and then progresses to the Peniston protocol, has improved retention and abstinence in these hard-to-treat populations. Participants increased abstinence, quality of life, self-efficacy, time in the program, and TOVA (continuous attention), and reduced addiction severity and craving.

The Scott-Kaiser modification of the Peniston Protocol can be classified as probably efficacious with residential or office-based rehabilitation and opioid replacement for alcohol, opioid, mixed-substance, and stimulant abusers.

Conclusion

Dopamine plays a pivotal role in regulating mood, motivation, attention, and movement through its complex interactions within the brain’s reward and motor pathways. The neurotransmitter’s influence on EEG waveforms, particularly in the frontal cortex, highlights its importance in neurofeedback interventions to modulate brain activity. By targeting dopamine-related pathways, neurofeedback can help alleviate symptoms in a range of neuropsychiatric disorders, such as ADHD, Parkinson's disease, schizophrenia, depression, and substance use disorders. Since the mesolimbic system projects frontally, neurofeedback may be a promising intervention for prefrontal cortex-mediated cognitive and affective symptoms.

Understanding dopamine’s impact on brain function and its role in feedback learning offers promising avenues for refining neurofeedback techniques, making it a valuable tool for cognitive and behavioral modulation. Further research into these mechanisms will enhance the efficacy of neurofeedback in therapeutic settings.

Glossary

adenylate cyclase: an enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP). It plays a key role in cellular signal transduction, particularly in response to neurotransmitters like dopamine, by triggering a cascade of intracellular events.

alpha-asymmetry depression protocol: a neurofeedback protocol used in the treatment of depression. It focuses on increasing left frontal alpha activity relative to right frontal alpha activity, based on research suggesting that individuals with depression often show greater right frontal activity, which is associated with difficult emotions. bradykinesia: a clinical feature of Parkinson's disease, referring to slowness of movement and difficulty in initiating or maintaining motor activity.

bradyphrenia: the slowness of thought processes. It is a symptom commonly associated with neurological conditions such as Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders. Individuals with bradyphrenia may experience delayed cognitive responses, difficulty in processing information, and slower decision-making or problem-solving abilities. It differs from bradykinesia, which specifically refers to slowed physical movement.

catecholamine: a class of neurotransmitters that includes dopamine, norepinephrine, and epinephrine.

catechol O-methyltransferase (COMT): an enzyme that degrades catecholamines such as dopamine, epinephrine, and norepinephrine by methylation, thereby regulating the levels of these neurotransmitters in the brain and periphery.

cognitive deficits in schizophrenia: Impairments in attention, memory, executive function, and other cognitive abilities, which are common in individuals with schizophrenia and are thought to be related to abnormalities in prefrontal cortex function and dopamine dysregulation.

cortical excitability: the ability of neurons in the cortex to become active or "excited" in response to stimulation.

D1-like receptors: a class of dopamine receptors (including D1 and D5) that primarily stimulate cAMP production via adenylate cyclase activation, typically associated with excitatory neurotransmission in brain areas related to motor control and cognition.

D2-like receptors: a class of dopamine receptors (including D2, D3, and D4) that inhibit adenylate cyclase activity and reduce cAMP production. These receptors are involved in modulating inhibitory neurotransmission and are important in motor control and reward processing.

diffusion tensor imaging (DTI): a specialized form of magnetic resonance imaging (MRI) that measures the diffusion of water molecules in brain tissue. It is particularly useful for studying white matter tracts, as the movement of water is more restricted along the direction of axonal fibers due to the myelin sheath. DTI provides detailed information about the integrity and organization of white matter by analyzing how water diffuses in different directions (anisotropy). This technique is commonly used to assess connectivity between brain regions, detect abnormalities in neural pathways, and study conditions like multiple sclerosis, schizophrenia, and traumatic brain injury where white matter integrity is compromised. dorsolateral prefrontal cortex (DLPFC): a region of the prefrontal cortex involved in executive functions such as working memory, cognitive flexibility, decision-making, and planning. The DLPFC plays a critical role in goal-directed behavior and higher cognitive processes.

EEG (electroencephalogram): a method used to measure electrical activity in the brain by recording brain wave patterns.

executive functions: a set of cognitive processes essential for controlling and regulating behavior. These functions enable individuals to plan, make decisions, solve problems, manage time, and engage in goal-directed behaviors.

gamma waves: high-frequency brain waves associated with higher cognitive functions, such as attention and memory.

gray matter: neuronal cell bodies, dendrites, unmyelinated axons, synapses, and glial cells. It is primarily involved in processing information in the brain. Gray matter is found in regions such as the cerebral cortex, which governs higher cognitive functions like decision-making, sensory perception, and voluntary motor activities.

high-frequency beta: brainwave activity in the beta frequency range (approximately 13-30 Hz). Elevated beta activity has been associated with motor control and, in some cases, with rigidity and tremors in Parkinson's disease.

insula: a region of the brain located deep within the lateral sulcus, involved in interoception (the sense of internal body states), emotional processing, empathy, and decision-making. The insula integrates information from the body and the external environment to influence behavior and emotions. medial temporal lobe: a region of the brain that includes structures such as the hippocampus and amygdala. It is primarily involved in memory formation and emotional processing, particularly long-term memory consolidation and spatial navigation.

mesolimbic pathway: a dopamine pathway involved in reward processing and motivation.

mesolimbocortical pathway: a dopaminergic pathway in the brain that projects from the ventral tegmental area (VTA) to various limbic structures (such as the nucleus accumbens) and the prefrontal cortex. It is involved in regulating motivation, reward, and higher cognitive functions.

monoamine oxidase-A (MAO-A): an enzyme found in the outer membrane of mitochondria that is responsible for the breakdown of monoamines such as serotonin, norepinephrine, and dopamine. MAO-A preferentially degrades serotonin and norepinephrine and plays a key role in regulating mood and emotional responses. Inhibitors of MAO-A are used in the treatment of depression and anxiety disorders due to their ability to increase the availability of these neurotransmitters in the brain.

monoamine oxidase-B (MAO-B): an enzyme also located in the outer mitochondrial membrane that breaks down monoamines, with a preference for dopamine. MAO-B is primarily involved in the degradation of dopamine and plays a critical role in maintaining dopaminergic balance in the brain, particularly in areas related to motor control. Inhibitors of MAO-B are often used to treat Parkinson's disease to increase dopamine levels and improve motor function. motor cortex activity: electrical activity in the motor cortex of the brain, which is responsible for planning, controlling, and executing voluntary movements.

negative symptoms: deficits or reductions in normal emotional and behavioral functioning, commonly seen in schizophrenia. These include diminished emotional expression (flat affect), social withdrawal, lack of motivation (avolition), and a decrease in speech output (alogia). These symptoms contrast with positive symptoms like hallucinations and delusions, which represent excesses in behavior or perception. neurofeedback: a type of biofeedback that uses real-time monitoring of brain activity (e.g., EEG) to train individuals to regulate their own brain functions.

nucleus accumbens: a brain structure located in the basal forebrain that plays a central role in the brain's reward circuit, processing rewarding stimuli and reinforcing behavior. It receives dopaminergic input from the VTA.

orbitofrontal cortex (OFC): a region of the prefrontal cortex located above the eye sockets, involved in decision-making, emotion regulation, and the evaluation of rewards and punishments. The OFC helps integrate emotional and sensory information to guide behavior.

Parkinson's disease: a neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, bradykinesia, and postural instability, resulting from the progressive loss of dopaminergic neurons in the substantia nigra.

prefrontal cortex: the part of the frontal lobe of the brain involved in higher cognitive functions such as decision-making, planning, working memory, and social behavior. Dopamine plays a key role in its function. real-time functional MRI (rtfMRI): a neurofeedback technique that uses real-time data from functional magnetic resonance imaging to allow individuals to regulate brain activity. This method provides feedback on brain regions associated with specific cognitive or emotional processes.

rigidity: increased muscle tone that causes resistance to movement, commonly seen in Parkinson's disease. This symptom is associated with abnormalities in the brain's motor pathways, including the basal ganglia.

Scott-Kaiser modification of the Peniston protocol: a neurofeedback protocol modified from the original Peniston Protocol, which was developed for the treatment of alcoholism and PTSD. The Scott-Kaiser modification tailors the protocol to include more individualized neurofeedback settings, particularly for addressing attentional and emotional regulation issues. self-efficacy: a psychological construct referring to an individual's belief in their ability to successfully execute specific actions or tasks. Self-efficacy influences motivation, effort, and persistence in the face of challenges. sensorimotor rhythm (SMR): a type of brainwave frequency (12-15 Hz) typically associated with relaxed but focused states, often targeted in neurofeedback protocols to improve attention, reduce hyperactivity, and enhance cognitive control, particularly in disorders such as ADHD. slow cortical potential (SCP) activity: slow voltage shifts in the EEG that reflect changes in cortical excitability. SCP neurofeedback trains individuals to regulate these shifts, which can enhance cognitive control and has been used in treating conditions like epilepsy, ADHD, and migraines.

sodium (Na+)-dependent dopamine co-transporter (DAT): a membrane protein that is responsible for the reuptake of dopamine from the synaptic cleft back into the presynaptic neuron, helping to terminate dopamine signaling.

substantia nigra: a brain structure located in the midbrain that plays a critical role in movement control. It contains dopaminergic neurons, the degeneration of which is a hallmark of Parkinson's disease. Test of Variables of Attention (TOVA): a neuropsychological assessment tool that measures attention and response control. The TOVA is commonly used to diagnose ADHD by assessing response times and errors in sustained attention tasks. theta waves: low-frequency brain waves associated with relaxation, drowsiness, and attentional lapses. theta-alpha oscillations: brainwaves in the 6-12 Hz range. These oscillations are often associated with cognitive processes such as attention, feedback learning, memory, and relaxation. theta/beta ratio: a metric used in neurofeedback and ADHD research, reflecting the ratio of slow theta waves (4–8 Hz) to faster beta waves (13–30 Hz) in EEG recordings. Elevated theta/beta ratios are associated with attention deficits, and neurofeedback often aims to reduce this ratio to improve focus and cognitive performance.

tremors: involuntary rhythmic muscle contractions that cause shaking movements, often observed in Parkinson's disease. Tremors are typically more pronounced at rest and are related to dysfunction in dopaminergic pathways.

ventral tegmental area (VTA): a group of neurons located in the midbrain that produce dopamine and project to various brain regions, including the nucleus accumbens and prefrontal cortex. The VTA is critical in the regulation of reward, motivation, and cognitive processes.

ventromedial prefrontal cortex (vmPFC): a brain region involved in processing risk, decision-making, emotional regulation, and social cognition. The vmPFC integrates emotional and cognitive inputs to guide behavior, particularly in contexts involving reward and punishment.

vesicular monoamine transporters (VMATs): proteins that transport monoamines (including dopamine, serotonin, and norepinephrine) into synaptic vesicles within neurons, facilitating their release into the synaptic cleft during neurotransmission.

white matter: myelinated axons, which are responsible for transmitting signals between different regions of the brain and spinal cord. The myelin sheath around these axons facilitates faster communication between neurons, enabling efficient information processing and coordination across various brain areas.

References

Arns, M., Conners, C. K., & Kraemer, H. C. (2013). A decade of EEG Theta/Beta ratio research in ADHD: A meta-analysis. Journal of Attention Disorders, 17(5), 374-383. https://doi.org/10.1177/1087054712460087

Beaulieu, J. M., & Gainetdinov, R. R. (2011). The physiology, signaling, and pharmacology of dopamine receptors. Pharmacological Reviews, 63(1), 182-217. https://doi.org/10.1124/pr.110.002642

Breedlove, S. M., & Watson, N. V. (2023). Behavioral neuroscience (10th ed.). Sinauer Associates, Inc.

Cavanagh, J. F., & Frank, M. J. (2014). Frontal theta as a mechanism for cognitive control. Trends in Cognitive Sciences, 18(8), 414-421. https://doi.org/10.1016/j.tics.2014.04.012

Coffey, S. F., Schumacher, J. A., Baschnagel, J. S., Hawk, L. W., & Holloman, G. (2015). Impulsivity and risk-taking in substance use disorder treatment. Journal of Substance Abuse Treatment, 48(1), 50-61. https://doi.org/10.1016/j.jsat.2014.07.008

Enriquez-Geppert, S., Brown, T., Henrich, H., Arns, M., & Pimenta, M. G. (2023). Attention Deficit Hyperactivity Disorder. In I. Khazan, F. Shaffer, D. Moss, R. Lyle, & S. Rosenthal (Eds). Evidence-based practice in biofeedback and neurofeedback (4th ed.). Association for Applied Psychophysiology and Biofeedback.

Howes, O. D., & Kapur, S. (2009). The dopamine hypothesis of schizophrenia: Version III—The final common pathway. Schizophrenia Bulletin, 35(3), 549-562. https://doi.org/10.1093/schbul/sbp006

Kropotov, J. D. (2016). Functional neuromarkers for psychiatry: Applications for diagnosis and treatment. Academic Press. https://doi.org/10.1016/C2013-0-16657-2

Meehan, Z. M., Shaffer, F., & Zerr, C. L. (2023). Depression. In I. Khazan, F. Shaffer, D. Moss, R. Lyle, & S. Rosenthal (Eds). Evidence-based practice in biofeedback and neurofeedback (4th ed.). Association for Applied Psychophysiology and Biofeedback.

Nestler, E. J., & Carlezon, W. A. (2006). The mesolimbic dopamine reward circuit in depression. Biological Psychiatry, 59(12), 1151-1159. https://doi.org/10.1016/j.biopsych.2005.09.018

Purves, D. (2018). Neuroscience (6th ed.). Oxford University Press Academic.

Sokhadze, E. M., & Trudeau, D. (2023). Alcohol and drug dependence. In I. Khazan, F. Shaffer, D. Moss, R. Lyle, & S. Rosenthal (Eds). Evidence-based practice in biofeedback and neurofeedback (4th ed.). Association for Applied Psychophysiology and Biofeedback.

Stucky, K. J., Kirkwood, M. W., & Donders, J. (Eds.). (2014). Neuropsychology study guide and board review. Oxford University Press.

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