Published online Jun 19, 2026. doi: 10.5498/wjp.v16.i6.116800
Revised: February 21, 2026
Accepted: March 20, 2026
Published online: June 19, 2026
Processing time: 189 Days and 4.2 Hours
Major depressive disorder (MDD) is characterized by persistent low mood and anhedonia, indicative of fundamental disruptions in emotion regulation and reward processing. With advancements in high-temporal resolution electrophysiological techniques, electroencephalography/event-related potentials have become crucial for identifying the dynamic neural signatures associated with these dysfunctions. This review synthesizes recent evidence regarding the electrophysiological underpinnings, abnormal patterns, neural circuitry, and molecular mechanisms that contribute to emotional and reward processing deficits in MDD. It further explores the potential of these deficits to serve as endophenotypes and transdiagnostic features, and it outlines mechanism-based interventions and translational findings. Current research reveals extensive electrophysiological abnormalities across various stages of emotional and reward processing, impli
Core Tip: This review elucidates electrophysiological evidence indicating that major depressive disorder is characterized by widespread abnormalities in emotional and reward processing. By synthesizing event-related potentials markers with disruptions in prefrontal-limbic and mesocorticolimbic circuits, it identifies these deficits as potential endophenotypes and transdiagnostic features. Furthermore, the review provides a summary of emerging mechanism-based interventions that demonstrate promising translational potential.
- Citation: Han JM, Zhang JZ, Wu YW, Zhang J, Wang XY, Liu XH, Wang J, Zhou ZH. Advances in electrophysiological research on emotional and reward processing in major depressive disorder. World J Psychiatry 2026; 16(6): 116800
- URL: https://www.wjgnet.com/2220-3206/full/v16/i6/116800.htm
- DOI: https://dx.doi.org/10.5498/wjp.v16.i6.116800
Major depressive disorder (MDD) represents a significant global health burden characterized by persistent low mood and loss of interest or pleasure, known as anhedonia. A growing body of evidence indicates that dysfunctions in both emotional and reward processing systems are fundamental characteristics of MDD, potentially offering crucial insights into its underlying pathophysiology. Instead of operating as isolated mechanisms, emotional and reward processing are integrated within an extensive regulatory network, primarily involving the prefrontal cortex (PFC), cingulate cortex, striatal, and limbic circuitry[1].
Emotional processing encompasses the perception, evaluation, experience, and regulation of emotional information, primarily mediated by a neural network that includes the PFC, amygdala, anterior cingulate cortex (ACC), and hippocampus[2]. Individuals diagnosed with MDD often display diminished efficiency within this neural network, particularly during the initial stages of perceptual processing and in later phases associated with sustained emotional engagement. Studies utilizing event-related potentials (ERPs) have revealed reduced amplitudes of P1, N170, and late positive potential (LPP), suggesting impairments in the attention to and experience of positive emotional stimuli[3,4]. These electrophysiological patterns closely align with clinical symptoms such as blunted affect and a negativity bias.
In a similar vein, reward processing encompasses several phases - namely anticipation, motivation, acquisition, and consummation - underpinned by a complex neural circuit that includes PFC, ACC, nucleus accumbens (NAc), ventral tegmental area (VTA), and basolateral amygdala[5,6]. Individuals diagnosed with MDD consistently exhibit reduced activity within this circuitry, particularly during the phases of reward anticipation and outcome processing. Electrophysiological evidence indicates a reduction in reward positivity (RewP), among other abnormalities, which closely correlates with clinical manifestations of anhedonia and motivational deficits[7-9].
Neurophysiological techniques, such as ERPs and local field potentials, characterized by their high temporal resolution, have emerged as powerful methodologies for investigating the dynamic processes underlying emotional and reward functions. In the context of emotional processing, early visual components, including P1, N170, and P200, are indicative of initial perceptual encoding and attentional allocation; reductions in these components suggest early-stage impairments in facial representation and emotional cue detection[3]. Later components, such as the LPP, are associated with sustained emotional engagement and meaning extraction, which are consistently attenuated in MDD[4]. Within the realm of reward processing, RewP component - regarded as a subcomponent of the feedback-related negativity (FRN) - captures rapid neural responses to reward feedback, with diminished amplitudes indicating decreased reward sensitivity[7-9]. Additional components, such as the contingent negative variation (CNV), and the stimulus-preceding negativity (SPN), as well as P3, and LPP[10-13], offer further insights into the anticipatory and consummatory phases of reward processing[14-16].
Significantly, these abnormalities are not confined to individuals diagnosed with MDD but are also evident in high-risk populations. Adolescents with a familial predisposition or children exhibiting early depressive symptoms frequently demonstrate a reduced RewP and a diminished capacity for positive emotional experiences[7,9,17,18]. These deficits may serve as endophenotypes indicative of inherited vulnerability. Moreover, environmental stressors interact with these biological vulnerabilities, further exacerbating deficits in reward reactivity and intensifying negative emotional biases[8,18].
As the mechanistic understanding of these processes’ advances, novel intervention strategies have been developed, targeting abnormal emotional and reward circuits. These strategies include cognitive-behavioral therapy (CBT), transcranial electrical stimulation, deep brain stimulation (DBS), and pharmacological innovations. Furthermore, electrophysiological markers are increasingly being investigated as potential biomarkers for predicting treatment response and monitoring therapeutic progress[6,19-21].
This review offers an extensive synthesis of recent electrophysiological research concerning the mechanisms of emotion and reward processing in MDD. We summarize atypical neural signatures, examine their associated circuits and molecular pathways, assess their potential as endophenotypes and transdiagnostic features, and underscore emerging interventions grounded in mechanistic understanding. Finally, we delineate current challenges and propose future directions to advance the field of precision psychiatry.
MDD is distinguished by systematic abnormalities across various stages of emotional and reward processing. These alterations are observable not only during symptomatic episodes but also in individuals at heightened risk, indicating their potential role as vulnerability markers. Investigating the temporal dynamics of ERP components offers crucial insights into the progression of deficits from initial perceptual encoding to higher-order emotional evaluation and motivational engagement.
Within the emotional processing pathway, individuals with MDD typically demonstrate a series of impairments characterized. During the early perceptual stage, occurring within the first 200 milliseconds, patients often exhibit diminished neural encoding of emotional cues. This is evidenced by reduced amplitudes in face-sensitive components such as P1, N170, and P200, which are indicative of initial visual processing and the cross-modal integration of emotional information[3]. These reductions imply early-stage deficits in attentional allocation and the structural representation of emotional stimuli. Interestingly, individuals with elevated negative affectivity may exhibit the opposite pattern, such as enhanced N170 responses or delayed P100 latency to threatening stimuli, suggesting an automatic and preferential allocation of attention to negative emotional cues[22]. These findings support the existence of a negativity-biased perceptual style in individuals with MDD.
During the mid-to-late emotional evaluation stage (300-600 milliseconds and beyond), individuals diagnosed with MDD consistently demonstrate reduced amplitudes of LPP. The LPP is indicative of sustained attention, the extraction of emotional significance, and the integration of affective experiences. A decrease in LPP amplitudes suggests a compromised capacity to maintain engagement with emotional stimuli, particularly those of a positive nature, resulting in attenuated emotional reactivity and challenges in sustaining positive affective states[4,12]. These electrophysiological anomalies closely correspond with clinical symptoms such as emotional numbing and a diminished experience of positive emotions.
An integrated schematic model illustrating ERP alterations in emotional and reward processing in MDD, along with their associated neural circuits, molecular and cellular mechanisms, and potential intervention targets, is presented in Figure 1. A complementary structured summary of ERP features is provided in Table 1.
| Domain | ERP component | Time window scalp (typical) | Indexed function | Typical MDD abnormality | Putative neural circuits | Intervention/translation links |
| Emotion | P1 | < 200 milliseconds; occipital (early visual) | Initial perceptual encoding & attentional allocation to emotional cues | Reduced amplitude; blunted early attention to positive cues; sometimes negativity bias in high negative affectivity | Early visual cortex to ventral visual stream; modulation by PFC/ACC-limbic network (PFC/ACC ↔ amygdala/hippocampus) | CBT and prefrontal neuromodulation may enhance top-down control and normalize early attentional allocation |
| Emotion | N170 | Approximately 140-200 milliseconds; occipito-temporal (face-sensitive) | Structural encoding of faces; early facial representation; emotion cue detection | Reduced amplitude to positive faces; possible enhanced responses to threat in subgroups (negativity bias) | Occipito-temporal face network; interaction with amygdala and PFC/ACC during emotional face processing | CBT; neuromodulation (e.g., DLPFC-tDCS) associated with improved emotion recognition/ERP indices |
| Emotion | P200 | Approximately 150-250 milliseconds; fronto-central/centro-parietal (task-dependent) | Early attentional selection; cross-modal integration of emotional information | Reduced amplitude reflecting early-stage impairment in emotional cue detection/attentional allocation | Distributed attentional network; PFC/ACC contributions to selection/integration; limbic modulation | Mechanism-based neuromodulation targeting prefrontal control networks; CBT |
| Emotion | LPP (emotion) | ≥ 300 milliseconds (often 300-600+ milliseconds); centro-parietal | Sustained emotional engagement, meaning extraction, affective salience | Attenuated LPP; reduced sustained engagement with emotional/positive stimuli; blunted affective salience | Prefrontal-limbic regulation (DLPFC/vmPFC/ACC ↔ amygdala/hippocampus/insula) | CBT; prefrontal stimulation (tDCS); pharmacological modulation reported to enhance late positive activity |
| Reward | CNV | Slow negative potential during anticipation (S1-S2/pre-outcome); fronto-central | Motivational preparation & temporal expectancy during reward anticipation | Attenuated CNV, especially for high-value social rewards; associated with poorer performance/engagement | Mesocorticolimbic preparation network (PFC/ACC ↔ striatum/NAc) with motivational drive from VTA | Behavioral activation/social-reward paradigms; circuit-based neuromodulation; translational social-feedback interventions |
| Reward | SPN | Slow negativity immediately preceding feedback/outcome revelation; often fronto-central (task-dependent) | Informational anticipation (anticipatory attention/motivation toward impending feedback/outcome information) | Emerging evidence of blunted SPN during reward anticipation; suggests reduced anticipatory engagement for reward-related information; needs standardized replication | Expectancy/anticipatory attention networks involving medial/Lateral PFC and ACC; task-dependent insula/parietal contributions; interaction with valuation circuitry | Candidate treatment-sensitive readout for interventions targeting anticipatory reward processing (behavioral activation, prefrontal neuromodulation, social-feedback training) |
| Reward | RewP (FRN subcomponent) | Approximately 250-500 milliseconds post-feedback; fronto-central | Rapid reward sensitivity/outcome valuation (reward vs non-reward) | Reduced RewP; correlates with anhedonia and motivational deficits; present in MDD and high-risk groups | Mesocorticolimbic reward circuit (VTA to NAc/ventral striatum to vmPFC/OFC/ACC) | Mechanism-based interventions targeting reward circuitry; pharmacological and neuromodulation approaches; potential biomarker of treatment response |
| Reward | FRN | Approximately 200-350 milliseconds post-feedback; fronto-central | Feedback evaluation/negative prediction error signaling | Altered FRN in social feedback; effects may be stronger for social vs monetary outcomes | ACC-centered monitoring with striatal inputs; interacts with mesocorticolimbic circuitry | Social-feedback interventions (e.g., robot-mediated paradigms) may normalize feedback-related processing |
| Reward | P3 (reward) | Approximately 300-600 milliseconds; centro-parietal (task-dependent) | Motivational salience allocation & updating of stimulus significance | Attenuated P3 to reward feedback, particularly in social reward tasks | Distributed salience/attention network; PFC/ACC and parietal integration; striatal contribution via motivational salience | Pharmacological/neuromodulation readouts; social-feedback interventions |
| Reward | LPP (reward feedback) | Late sustained positivity after feedback; centro-parietal | Sustained evaluative processing & affective integration of reward outcomes | Reduced LPP to reward outcomes; together with RewP predicts depression severity via distinct pathways | Mesocorticolimbic valuation with prefrontal integration; interaction with limbic affect systems; LHb anti-reward modulation | Astrocyte-/LHb-targeting strategies (e.g., Kir4.1/CB1R modulation, LHb-DBS in TRD); pharmacological approaches; potential biomarker of treatment effects |
In addition to deficits in emotional processing, individuals with MDD exhibit impairments in reward processing across various temporal stages, notably during reward anticipation, consumption, and evaluation. The processing of reward feedback, occurring between 250-500 milliseconds, is crucial in this context. The RewP component is one of the most extensively studied electrophysiological indicators of reward function, typically peaking at frontocentral electrodes approximately 250-500 milliseconds after reward feedback. Research consistently demonstrates that patients with MDD, or those exhibiting elevated depressive symptoms, show reduced RewP amplitudes. This reduction is interpreted as indicative of diminished reward sensitivity and serves as an electrophysiological marker of anhedonia[7-9,12]. Importantly, this attenuation is not confined to adults; it is also observed in adolescents[9,18] and even in preschool-aged children with early-onset depression[21,23], underscoring its developmental continuity and significance as an early indicator of vulnerability.
Abnormalities in reward anticipation extend to the anticipatory stage of reward processing. The CNV, a slow-wave component that indexes motivational preparation and expectation, is attenuated in individuals exhibiting depressive symptoms, particularly in high-value social reward scenarios. These individuals demonstrate lower CNV amplitudes and diminished behavioral performance, such as reduced hit rates, indicating impaired anticipatory processing for socially salient rewards[10,11]. Interestingly, these deficits are less evident in monetary reward contexts, suggesting a potential specific sensitivity to impairments in social reward processing associated with depression.
Beyond the general motivational preparation indexed by the CNV, the SPN provides a complementary marker of anticipatory processing related to the expectation of impending outcome information. Whereas the CNV is classically linked to motor/response preparation and temporal expectancy in S1-S2 paradigms, the SPN is a slow negative potential that develops immediately before informative stimuli such as feedback or outcome revelation, and is commonly interpreted as reflecting anticipatory attention and motivational engagement (i.e., informational anticipation). SPN is often maximal over fronto-central sites and may show right-hemisphere predominance depending on task demands. Circuit-wise, SPN has been associated with anticipatory attention networks involving medial/Lateral PFC and ACC, with task-dependent contributions from insular and parietal regions, potentially shaping subsequent outcome evaluation indexed by RewP/FRN and later P3/LPP. Emerging evidence suggests that MDD is characterized by blunted SPN during reward anticipation, consistent with reduced informational anticipation for reward-related feedback; however, standardized paradigms are needed to clarify modality specificity (e.g., social vs monetary) and relationships with downstream outcome components[13-16].
The consumption of rewards at later stages and the allocation of motivational resources are critical areas of study. The ERP components associated with later processing stages, such as P3 and LPP, are diminished in individuals with MDD. The P3 component is indicative of the allocation of motivational salience, while the LPP component reflects sustained emotional evaluation and affective engagement. Attenuated P3 and LPP responses to reward feedback suggest inadequate motivational engagement and diminished affective integration of reward outcomes[12,24]. Recent research indicates that RewP and LPP predict the severity of depression through distinct neural pathways, suggesting they represent different aspects of reward dysfunction[12].
Furthermore, abnormalities are observed in resting-state and baseline conditions. Beyond deficits related to specific tasks, alterations in reward-related circuits are also evident during rest. In rodents predisposed to depression, the basolateral amygdala displays diverse spontaneous neural ensemble activity patterns capable of decoding an animal's stress history and susceptibility[5], underscoring the pervasive dysregulation in reward-related neural dynamics.
Electrophysiological markers have been found to correlate with various aspects of depressive symptoms and treatment outcomes. Specifically, RewP is associated with the severity of anhedonia[6,12], while LPP is linked to impairments in emotional reactivity[12] and predicts treatment outcomes, with larger baseline LPP indicating greater remission in early-childhood depression[21]. Furthermore, these markers are predictive of future trajectories of depressive symptoms, particularly under conditions of stress exposure[8,9,18].
Interaction between emotional and reward deficits: Emotional and reward processing abnormalities exhibit a significant interaction. Negative emotional states have been shown to suppress the responsiveness of the reward system, and a diminished sensitivity to reward further exacerbates negative affect. Empirical studies demonstrate that inducing a negative mood prior to a reward task results in decreased activation of the ventral striatum and reduced RewP amplitudes compared to neutral mood conditions[25]. This bidirectional inhibitory mechanism may contribute to the chronic nature and treatment resistance often observed in MDD.
Collectively, these findings demonstrate that various neuroelectrophysiological markers are highly sensitive in detecting abnormalities across different stages of emotional and reward processing in depression. These abnormalities manifest in multiple dimensions, including emotional processing (e.g., negative bias, inadequate regulation) and reward processing (e.g., diminished motivation, decreased reactivity). Furthermore, these markers exhibit stability across developmental stages and possess certain predictive value, offering significant insights into the pathophysiological mechanisms underlying depression and informing the development of novel therapeutic strategies.
Emotional processing abnormalities in MDD are primarily attributed to functional imbalances among critical limbic and prefrontal regions, notably the PFC, amygdala, and hippocampus. Emotional regulation is contingent upon the dynamic interaction between the amygdala-driven emotional reactivity system and the top-down regulatory control exerted by the PFC. In individuals with MDD, the amygdala often demonstrates hyperactivation and increased sensitivity to negative stimuli, while the regulatory influence of the PFC is significantly diminished[26]. Specifically, the reduction in inhibitory control from the dorsolateral PFC to the amygdala - facilitated through pathways such as the superior longitudinal fasciculus II - contributes to impaired emotional regulation and the persistence of negative affect[27].
Dysfunctional connectivity involving the dorsal and median raphe nuclei further diminishes the prefrontal regulation of limbic structures. Serotonergic projections from the dorsal raphe nucleus to the basolateral amygdala modulate sociability and emotional responses in a bidirectional manner, with disruptions in this serotonergic signaling predisposing individuals to negative emotional states[28,29]. In addition to neuronal dysfunction, astrocytes play a crucial modulatory role in serotonergic signaling. In depressive states, astrocytic uptake and recycling of serotonin are impaired, resulting in reduced synaptic serotonin availability and exacerbated emotional dysregulation[30].
Molecular imaging studies support these findings, showing decreased serotonin 1A receptor density and binding affinity in MDD, particularly among individuals with treatment-resistant depression[31,32]. This reduction undermines top-down inhibitory control within PFC-amygdala circuits, thereby intensifying negative emotional experiences and prolonging emotional recovery.
In addition to monoaminergic dysfunction, imbalances in glutamatergic and gamma-aminobutyric acidergic (GABAergic) neurotransmission play a significant role in the deficits observed in emotional regulation. Abnormal concentrations of glutamate, combination of glutamate and glutamine, or gamma-aminobutyric acid (GABA) have been consistently documented in PFC, ACC, and hippocampus of individuals diagnosed with MDD[33-35]. A reduction in prefrontal glutathione, a critical regulator of oxidative stress, has been specifically linked to decreased positive affect, suggesting an interaction between excitatory neurotransmission and redox imbalance in emotional dysfunction[36]. Notably, neuromodulatory interventions such as intermittent theta-burst stimulation have the potential to induce plastic changes in glutamate and GABA acid metabolism, indicating that these neurochemical abnormalities are, to some extent, reversible and amenable to clinical intervention[37].
At the molecular level, the disrupted signaling of brain-derived neurotrophic factor (BDNF) is critically implicated in abnormalities related to emotional processing. In depressive states, there is a noted reduction in BDNF expression within the hippocampus and PFC, which results in decreased synaptic plasticity, diminished structural connectivity, and impaired neurogenesis[38]. The dysregulation of the BDNF-tropomyosin receptor kinase B pathway adversely impacts emotional regulation and cognitive function, while also contributing to decreased reward sensitivity and motivational drive. Importantly, the enhancement of BDNF expression through antidepressant medications, rapid-acting agents such as ketamine, and even physical exercise underscores its pivotal role as a central molecular target across various therapeutic interventions[38].
Abnormalities in reward processing associated with MDD primarily originate from dysfunctions within the mesocorticolimbic dopamine system, encompassing the VTA, NAc, and PFC[39-41]. During reward learning tasks, individuals with MDD exhibit reduced feedback-locked neural responses within the ACC and NAc, as evidenced by attenuated electrophysiological activity within the 250-500 milliseconds time window, along with decreased delta (1-5 Hz) and alpha/beta (9-17 Hz) power. These findings indicate pervasive impairments in reward-related neural processing[39].
The lateral habenula (LHb), recognized as a pivotal anti-reward center, has been identified as a crucial structure in the dysfunction of reward systems associated with depression. In individuals predisposed to depression, LHb neurons demonstrate heightened burst firing, contributing to aversive learning and a reduction in reward responsiveness[42]. This pathological burst activity is partially driven by the upregulation of the astrocytic Kir4.1 potassium channel, which modifies extracellular potassium concentrations and enhances neuronal excitability. Targeted manipulation of Kir4.1 expression within LHb astrocytes can bidirectionally modulate neuronal bursting and behaviors resembling depression, highlighting the significance of neuron-glia interactions in the pathophysiology of depression[42].
At the molecular level, the functioning of reward circuits is influenced by multiple neurotransmitter systems. The GABAergic system, particularly α5-containing GABA subtype A (GABAA) receptors, has been associated with stress-induced anhedonia. Selective negative allosteric modulators targeting α5-GABAA benzodiazepine sites have been shown to rapidly reverse anhedonic behavior and restore synaptic strength in hippocampal temporoammonic-CA1 circuits. These effects are absent in α5 knockout mice, thereby confirming the specificity of the target[43].
Additionally, the endocannabinoid system plays a role in the regulation of reward mechanisms. Specifically, astrocytic cannabinoid type 1 receptor in LHb affect synaptic plasticity and habenular activity, highlighting a potential target for novel antidepressant strategies[19].
From a computational neuroscience standpoint, it is increasingly evident that the dysregulation of reward prediction error (RPE) signals may play a significant role in the manifestation of depressive states. Within social defeat models, the loss of social status generates negative RPE signals that are conveyed from the lateral hypothalamus to the LHb, subsequently inhibiting activity in the medial PFC. This inhibition diminishes social motivation and fosters withdrawal behaviors[44]. Such disruptions in RPE signaling result in discrepancies between anticipated and actual rewards, thereby contributing to anhedonia and deficits in motivation.
Recent research challenges the traditional assumptions regarding the segregation of reward and aversion coding within NAc. It has been demonstrated that both D1-type and D2-type medium spiny neurons possess the capacity to modulate reward and aversion bidirectionally, contingent upon their activation patterns[40]. Specifically, brief activation of these neurons promotes reward-related behaviors, whereas prolonged activation induces aversion. These effects are mediated through distinct downstream pathways, involving κ-opioid receptors in VTA for D1 pathways and δ-opioid receptors in the ventral pallidum for D2 pathways[40]. Such findings elucidate a more nuanced and dynamic architecture of reward encoding in MDD.
The findings elucidate intricate neural circuits and molecular mechanisms that underlie the dysregulation of mood and reward processing in depression. This involves the precise regulation of various brain regions, neurotransmitter systems, and cell types. A comprehensive understanding of these mechanisms not only enhances insight into the pathophysiology of depression but also identifies potential targets for the development of novel therapeutic strategies.
Emotional processing deficits are widely regarded as a significant endophenotype and transdiagnostic characteristic of MDD. From an endophenotypic standpoint, individuals with MDD consistently exhibit impairments in emotion recognition, marked by an increased sensitivity to negative emotional cues and a diminished ability to recognize positive emotions. For example, patients are more prone to misinterpret neutral facial expressions as negative and demonstrate slower or less accurate identification of happy faces, indicative of a pervasive negativity bias during the perceptual and evaluative stages of emotional processing[17]. These behavioral tendencies are closely associated with abnormalities in emotion-related neural circuits, including hyperactivation of the amygdala and reduced regulatory control from the PFC, reflecting an imbalance between emotion evaluation and top-down regulation systems[26,27].
Emotional processing deficits, as a transdiagnostic feature, are not confined to MDD but are also prevalent across various psychiatric disorders, including social anxiety disorder and bipolar disorder. Individuals with these conditions exhibit differing levels of impairment in emotion recognition, emotional reactivity, and emotion regulation[45]. For instance, individuals with social anxiety disorder tend to be hypervigilant to threatening social cues, such as angry or disapproving faces, while often overlooking positive social information[45]. Conversely, those with MDD typically display diminished responses to positive emotional stimuli and an enhanced negativity bias. These common patterns indicate that altered emotional processing may represent a shared neurocognitive substrate among psychiatric disorders. Notably, these biases are subject to modification; interventions such as cognitive training and emotional working memory exercises have demonstrated efficacy in reducing threat-related attentional biases and enhancing emotional processing, underscoring their potential as therapeutic targets[45].
Deficits in reward processing present significant potential as endophenotypes for MDD, serving as intermediate phenotypes that connect genetic predisposition with clinical manifestations. Electrophysiological markers of reward responsiveness, particularly RewP and components associated with late-stage reward evaluation, have been closely linked to inherited risk factors. In adolescents, polygenic scores for attention-deficit/hyperactivity disorder correlate with electrophysiological indicators of affective-motivational processing, such as the LPP amplitude and alpha event-related desynchronization, independent of comorbid anxiety, depression severity, or overlapping genetic risk factors[46]. These findings imply that electrophysiological signatures related to reward processing may represent a broader neurodevelopmental vulnerability, functioning as cross-disorder endophenotypes.
Abnormalities in reward processing are evident across various psychiatric conditions. In both MDD and schizophrenia, individuals exhibit impaired reward learning, which is characterized by diminished learning flexibility and a predisposition toward hypersensitive or slow-decaying learning rates. This impairment increases their susceptibility to misleading feedback. Computational modeling and trial-level EEG analyses reveal a shared deficiency in the neural tracking of expected value signals in both disorders[47], underscoring a transdiagnostic impairment in learning dynamics.
Concurrently, disorder-specific patterns are observed: Schizophrenia is marked by an approach bias toward maladaptive cues, whereas individuals with MDD demonstrate heightened sensitivity to disconfirmation feedback, such as actual losses or counterfactual missed rewards[47]. Consequently, reward deficits display both cross-diagnostic commonality and disorder-specific dissociations.
Reward-related endophenotypes possess predictive utility for treatment outcomes. In the context of early-childhood depression, elevated baseline LPP amplitudes in response to pleasant images are indicative of greater symptom remission following parent-child interaction therapy. This suggests that preserved neural responsiveness to positive stimuli is associated with a more favorable treatment prognosis[21]. Likewise, heightened baseline neural reward responsiveness, as measured by RewP amplitude and dorsomedial ACC activation, forecasts improvements in overall quality of life over time among individuals with mood disorders. This improvement is mediated by reductions in the severity of anhedonia[6].
Deficits in social reward processing are notably pertinent to depressive symptomatology. Individuals exhibiting depressive symptoms demonstrate impairments in both the anticipation and consumption of social rewards, as evidenced by reduced hit rates, attenuated CNV responses, and diminished FRN and P3 amplitudes during tasks involving social feedback[11]. These abnormalities are more pronounced for social rewards compared to monetary rewards, indicating that disruptions in social reward systems may serve as particularly sensitive markers of depression. These findings underscore the importance of integrating social reward paradigms into the assessment and conceptualization of depressive psychopathology.
Collectively, these findings indicate that deficits in emotional and reward processing in MDD function as robust endophenotypes with significant genetic, developmental, and transdiagnostic implications. These endophenotypes elucidate underlying vulnerability mechanisms, contribute to understanding the heterogeneity across psychiatric conditions, and hold substantial potential for enhancing early identification, personalized risk stratification, and the development of targeted intervention strategies.
As the understanding of the neural mechanisms underlying depressive emotions and reward processing deepens, researchers are increasingly exploring novel intervention strategies and translating these mechanisms into treatment modalities.
CBT remains one of the most prevalent psychological interventions for MDD and is particularly effective in altering maladaptive cognitive and emotional processing styles. Early implementation of CBT has demonstrated efficacy in correcting negative cognitive biases, enhancing sensitivity to positive emotional cues, and facilitating the re-evaluation of pleasurable experiences[48]. Neuroimaging evidence indicates that successful CBT is associated with enhanced prefrontal regulation of limbic structures; for instance, increased PFC control over amygdala reactivity has been observed post-treatment, reflecting improved emotional regulation and reduced limbic hyperactivation[49]. Electrophysiological data similarly suggest improved efficiency in emotional processing following CBT.
In conjunction with psychological interventions, noninvasive brain stimulation methods, including transcranial direct current stimulation (tDCS), have garnered attention as promising therapeutic alternatives. By modulating cortical excitability via low-intensity electrical currents, tDCS administered over the dorsolateral PFC has demonstrated efficacy in enhancing emotional recognition performance and augmenting ERP indices of emotional processing in individuals diagnosed with depression[50]. These findings highlight the potential of neuromodulation to restore disrupted emotional circuits.
DBS constitutes a more invasive yet highly promising intervention for treatment-resistant depression. The LHb, a pivotal node in anti-reward and aversive signaling pathways, has demonstrated significant clinical benefits when targeted. In an open-label trial, bilateral LHb-DBS resulted in a 49% reduction in depressive and anxiety symptoms within one month, alongside enhancements in functional impairment and quality of life[20]. Despite high dropout rates and variability in treatment responses, the improvements in symptoms were largely maintained over time. Importantly, local field potential oscillatory patterns within the LHb were found to correlate with baseline symptom severity and are currently being investigated as potential biomarkers for monitoring disease state and treatment efficacy[20].
Recent pharmacological advancements have elucidated novel pathways for addressing reward and emotional dysfunction. Studies have demonstrated that low doses of lysergic acid diethylamide (LSD) - specifically 13 μg or 26 μg - can enhance reward-related ERP components, such as RewP, feedback-related P3, and LPP, in healthy adults[24]. Notably, these effects appear to be largely independent of subjective drug experiences, indicating that microdosed LSD may enhance reward processing and hold potential as an antidepressant intervention.
Another promising avenue involves the modulation of the GABAergic system. Negative allosteric modulators targeting α5-containing GABAA receptors (GABA-negative allosteric modulators) have been shown to rapidly reverse stress-induced anhedonia and restore synaptic function in hippocampal reward circuits[43]. The effects of these modulators are absent in α5-knockout mice and can be inhibited by benzodiazepine-site antagonists, thereby confirming their receptor specificity and translational relevance.
Emerging evidence underscores the significance of glia-neuron interactions in the pathophysiology of depression. The upregulation of astrocytic Kir4.1 channels within LHb has been shown to precipitate pathological burst firing in ha
From a social neuroscience standpoint, human-robot interaction represents an innovative avenue for therapeutic intervention. In comparison to human-human interactions, depressive symptoms have a less pronounced negative impact on reward processing during human-robot interactions. In tasks involving social rewards, individuals with depressive symptoms exhibit various abnormalities under human-feedback conditions, such as decreased hit rates, reduced CNV amplitudes, and altered FRN and P3 responses. However, these abnormalities are significantly reduced when feedback is provided by a robot, with only the FRN remaining affected[10]. This observation suggests that robot-mediated social feedback may be less vulnerable to depressive biases and could be effectively utilized in therapeutic contexts. Col
This review integrates recent electrophysiological findings on the mechanisms of emotional and reward processing in MDD, highlighting the pivotal role these systems play in the disorder’s pathophysiology. Various electrophysiological markers, including P1, N170, P200, and LPP have been demonstrated to sensitively indicate abnormalities across different stages of emotional processing, such as emotional regulation, recognition, and sustained affective engagement[3,4,22]. Similarly, reward-related components like RewP, CNV/SPN[7-9,12,13], FRN, P3[14-16,18], and LPP[21,23] effectively capture deficits in reward anticipation, consumption, and motivational processing. These abnormalities are developmentally stable, manifesting as early as preschool age and persisting into adulthood, and they possess predictive value for future depressive symptoms, clinical progression, and treatment response.
At the neurobiological level, emotional and reward processing deficits in MDD are attributed to dysfunctions across distributed neural circuits, including the PFC, amygdala, hippocampus, mesocorticolimbic dopamine pathways, and the LHb[26,27,39-42]. These circuit-level abnormalities are further exacerbated by molecular mechanisms, such as imbalances in serotonergic[19,28,29], glutamatergic, and GABAergic systems[30,33-35], along with disruptions in BDNF signaling and astrocyte-mediated modulation[38,42,43]. Additionally, computational theories propose that impaired processing of RPE signals may contribute to discrepancies between expected and actual outcomes, thereby playing a role in the development of anhedonia and motivational deficits[44].
Abnormalities in emotional and reward processing exhibit significant endophenotypic and transdiagnostic characteristics, manifesting across mood, psychotic, and anxiety disorders. These abnormalities align with shared mechanisms, including negativity bias, impaired reward learning, and diminished responsiveness to positive stimuli[11,17,45,47]. Concurrently, disorder-specific patterns, such as the increased sensitivity to social reward deficits observed in MDD, indicate that these biomarkers can aid in elucidating clinical heterogeneity and informing personalized phenotyping strategies.
Emerging intervention strategies based on these mechanistic insights - including neuromodulation techniques (e.g., tDCS, DBS), pharmacological approaches (e.g., GABA-negative allosteric modulators, microdosed LSD), and astrocyte-targeted interventions - demonstrate promising translational potential[20,24,43,50]. Additionally, social neuroscience approaches, such as robot-mediated feedback, further expand the possibilities for addressing social reward deficits in depression. Collectively, these advancements underscore the potential to advance toward mechanism-informed, personalized, and precision-based treatment models.
Despite these advancements, numerous challenges persist. Firstly, it is imperative to conduct large-sample, multi-site studies to validate the reliability, specificity, and clinical utility of electrophysiological markers as biomarkers. Secondly, longitudinal research designs must rigorously investigate the causal and bidirectional relationships between emotional/reward deficits and depressive symptoms[9]. Thirdly, the translation of findings across species necessitates careful consideration, as results derived from rodent models may not adequately reflect the complexity of human emotional and reward processing[39]. Fourthly, individual differences, including developmental stage, sex, and sociocultural context, need to be systematically incorporated into study designs to enhance generalizability[9,10]. Lastly, the integration of electrophysiological indicators into clinical decision-making requires the development of user-friendly tools, the establishment of clinically meaningful thresholds, and the combination of these markers with genetic, neuroimaging, and clinical data to construct multidimensional predictive models.
Future research should persist in exploring the molecular and cellular mechanisms underlying emotional and reward deficits, with the aim of developing targeted interventions informed by these mechanisms. Additionally, it is crucial to integrate electrophysiological markers with multimodal data to further the advancement of precision psychiatry. Such endeavors have the potential to significantly enhance the field's capacity to offer more effective and individualized prevention and treatment strategies for patients with MDD.
The authors express their gratitude to the Affiliated Mental Health Center of Jiangnan University for its institutional support.
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