Neuroimaging and neuroelectrophysiological features of music's effects on anhedonia in major depressive disorder: A minireview

Abstract

Major depressive disorder (MDD), one of the most prevalent mental illnesses, is characterized by anhedonia, the inability to experience pleasure from rewarding activities. This minireview examines the complex relationship between music, anhedonia, and neural activity from neuroimaging and neuroelectrophysiological perspectives. It synthesizes the latest advances in music neuroscience, exploring music's potential to modulate emotional responses and alleviate anhedonia in depressed individuals. Anhedonia has been linked to dysfunctional brain reward circuits. Functional magnetic resonance imaging studies have revealed that the potential mechanism by which music exerts its anti-depressive effect may involve the reactivation of the anterior cingulate cortex, while electroencephalographic studies have revealed that oscillatory network dysfunction significantly impairs music perception engagement in patients with MDD. Musical chills, representing intense emotional peaks during musical experiences, can evoke profound pleasure in healthy individuals and may offer a therapeutic modality for alleviating anhedonia in MDD. This review discusses how music therapy may support emotional regulation by activating these neural pathways and enhancing affective processing. Despite promising developments, this field remains understudied. A more nuanced research approach is urgently needed to better understand the mechanisms underlying music's effects on anhedonia and to develop effective interventions.

Key Words: Music; Major depressive disorder; Anhedonia; Neuroimage; Neuroelectrophysiology

Core Tip: Although several reviews have explored the relationship between music and neural activity, there remains a notable gap in comprehensive reviews specifically examining the association of music with anhedonia in major depressive disorder (MDD). To the best of our knowledge, this minireview provides the first systematic synthesis of music’s effects on reward function in MDD from both neuroimaging and neuroelectrophysiological perspectives, while proposing novel directions for future research.

INTRODUCTION

Major depressive disorder (MDD) is a severe mental illness that significantly impairs both physical and psychological health. MDD causes profound psychological distress, often leading to hopeless, and in severe cases, suicidal behavior. Its widespread impact poses significant challenges to economic development and social stability[1,2]. Anhedonia, one of the core symptoms of MDD, is primarily characterized by diminished motivation to seek pleasure and a reduced capacity to experience joy[3]. The limited efficacy of conventional treatments for anhedonia has prompted researchers to explore new intervention strategies.

Music is an integral aspect of human culture. It brings joy, reduces anxiety and sadness, stimulates movement, and promotes social connections. Beyond its emotional and behavioral effects, music may also enhance brain and cognitive development, improve functional well-being, optimize quality of life, and potentially mitigate symptoms of various diseases. As a non-pharmacological intervention, music therapy demonstrates unique advantages in improving mood and cognitive function. Multiple meta-analyses have confirmed music’s positive effects on MDD[4,5]. A recent meta-analysis (n = 421) demonstrated that music therapy, when combined with conventional treatment, produced significant short-term improvements in anxiety-related and depressive symptoms compared to conventional treatment alone[6]. These benefits may enhance motivation, emotional regulation, and interpersonal functioning in patients with MDD[6]. However, the mechanisms underlying music’s influence on brain activity remain unclear. Studies utilizing advanced neuroscientific techniques (e.g., electroencephalography [EEG] and functional magnetic resonance imaging [fMRI]) have yielded inconsistent results. These discrepancies reflect the inherent complexity of music’s impact on the brain.

Sound waves that reach the tympanic membrane initiate a series of complex mechanical, chemical, and neural events in the cochlea, brainstem, midbrain nuclei, and cortex to generate auditory perception[7]. Music represents a structured arrangement of sound in time, space, and intensity[8] that can stimulate emotional changes, physiological arousal (autonomic and endocrine changes), motor expressions of emotion (smiling), and action tendencies (dancing, singing, playing instruments, foot-tapping, and clapping)[9]. The complex effects of music on human physiology and behavior present significant challenges when investigating music's impact on anhedonia.

Music can elicit strong pleasurable sensations. Many individuals report experiencing chills or “goosebumps”—referred to as musical chills—when listening to emotionally evocative passages. This phenomenon is associated with increased activity in the brain's reward system[10]. Unlike primary (e.g., food, sex) or secondary (e.g., money, power) rewards, music is thought to engage the reward network through distinct neural pathways[11,12]. By contrast, individuals with musical anhedonia exhibit intact auditory perception yet report no pleasure from musical stimuli, despite normal hedonic responses to non-musical rewards[13]. Significant progress has been made in musical anhedonia research over the past decade[12-15]. One seminal study identified a cohort of healthy individuals without depression or general anhedonia who, despite normal music perception capabilities, derived no subjective pleasure from enjoyable music while maintaining intact hedonic responses to monetary rewards[16]. A meta-analysis revealed distinct activation patterns: The right ventromedial striatum, right superior temporal gyrus (STG), and prefrontal cortex (PFC) showed more reliable activation to music, whereas the left insula, bilateral putamen, and right amygdala were more consistently activated by food rewards[11]. These findings collectively suggest that music engages reward functions through pathways distinct from those activated by other reward stimuli. This growing body of evidence provides novel therapeutic insights for remitting anhedonia in patients with MDD.

This minireview synthesizes existing evidence on the effects of music intervention on anhedonia in MDD from neuroimaging and neuroelectrophysiological perspectives, providing novel insights to inform future research and clinical practice.

NEUROIMAGING FEATURES OF MDD AND ANHEDONIA

Anhedonia is closely associated with reward processing, involving both structural and functional aspects of the dopaminergic mesolimbic reward circuit[3]. The dopaminergic mesolimbic system originates in the ventral tegmental area and projects to the ventral striatum (VS) including the nucleus accumbens (NAcc) and dorsal striatum (e.g., caudate nucleus, putamen), subsequently extending to various subregions of the orbitofrontal cortex (OFC), dorsolateral PFC, and anterior cingulate cortex (ACC)[17]. Structural neuroimaging studies have revealed volume reductions in multiple brain regions among patients with MDD, including the ventromedial PFC (vmPFC)[18-20], ACC[21], caudate nucleus[22], and amygdala[23,24]. These structural alterations of key reward-related brain regions may contribute to anhedonia.

Functional neuroimaging studies have further revealed abnormalities in neural circuitry among patients with MDD. Although some findings are inconsistent, accumulating evidence demonstrates altered functional connectivity among default mode, salience, and central executive networks in MDD[25-27]. Particularly during reward processing, reduced activation has been observed in key regions including the VS, ACC, and OFC[28], and is closely associated with anhedonia. These neuroimaging findings provide crucial clues for understanding the neural mechanisms underlying anhedonia while also offering objective biomarkers for evaluating the effects of music-based interventions.

NEUROIMAGING FEATURES OF MUSIC-INDUCED NEURAL ACTIVITY

Music-based interventions significantly modulate brain activity, particularly in reward-related circuits. fMRI studies demonstrate that listening to pleasurable music robustly activates key components of the reward system, including the VS, midbrain regions, amygdala, OFC, vmPFC, NAcc, and ACC[10,29] (Figure 1). Notably, self-selected music elicits stronger activation in auditory and reward systems compared to experimenter-chosen stimuli[30]. Subjects listening to preferred music exhibit enhanced functional connectivity between the NAcc and STG and increased coupling with bilateral auditory cortices[31]. The degree of activation in these regions positively correlates with subjective pleasure ratings, suggesting that music may alleviate anhedonia by normalizing reward circuit function, enhancing auditory-reward integration, and facilitating positive emotional processing.

Figure 1 Key components of the reward system activated by pleasurable music. ACC: Anterior cingulate cortex; NAcc: Nucleus accumbens; OFC: Orbitofrontal cortex; vmPFC: Ventromedial prefrontal cortex; VS: Ventral striatum.

NEUROIMAGING FEATURES OF MUSIC INTERVENTION IN MDD

Research on music and reward processing has progressed remarkably, yet most studies have evaluated healthy participants, leaving the effects of music on anhedonia in MDD patients relatively understudied. Current evidence suggests that music may exert its anti-depressive effect by reactivating the ACC[32]. An fMRI study employing both positive and negative valence musical and non-musical stimuli revealed heightened ACC activation among patients with MDD, particularly in dorsal regions, in response to negative non-musical stimuli[32]. However, conflicting findings emerged from a similar study demonstrating that both patients with MDD and healthy controls exhibited stronger ACC activation in response to positive vs negative music, with patients with MDD showing no significant difference in ACC activation between negative music and baseline conditions[33]. Additional research has identified specific neural correlates of anhedonia in MDD during musical stimulation. One study found that the severity of anhedonia was associated with deficient activation of the posterior vmPFC and mesolimbic reward system during pleasurable music listening[34]. Jenkins et al[35] reported reduced activation of the left NAcc in patients with MDD compared to healthy controls when exposed to classical music. Furthermore, Deng et al[36] discovered that patients with MDD exhibited decreased functional connectivity in emotional recognition brain regions across different music valences, with statistically significant differences in connectivity patterns between patients and controls particularly evident during negative music stimulation.

NEUROELECTROPHYSIOLOGICAL FEATURES OF MDD AND ANHEDONIA

Neuroelectrophysiological studies have revealed significant associations between anhedonia and specific event-related potential (ERP) components. Stimulus-preceding negativity (SPN), a right-lateralized frontocentral slow-wave negativity, is implicated not only in anticipatory affective and motivational processing but is also potentially linked to dopaminergic activity during reinforcement learning stages. Another reward-related ERP component, feedback-related negativity (FRN), primarily reflects the evaluation of reward feedback valence (loss vs gain). Reduced amplitudes of both SPN and FRN have been consistently observed in patients with MDD[37,38]. Furthermore, patients with MDD exhibit attenuated P3 and late positive potential components that are positive waves that index attentional resource allocation and higher-order processing of emotional stimuli[39,40]. These ERP components may potentially serve as biomarkers for assessing the severity of anhedonia.

NEUROELECTROPHYSIOLOGICAL FEATURES OF MUSIC-INDUCED NEURAL ACTIVITY

Electrophysiological studies have consistently demonstrated that music elicits distinct neural responses measurable through EEG and ERP techniques. In the frequency domain, theta-band (4-8 Hz) phase synchronization between the right temporal and frontal regions increases proportionally with subjective pleasure ratings during music listening[41]. Additionally, frontal beta (13-30 Hz) and gamma (30-100 Hz) oscillations closely track prediction-error signals in musical reward processing[42].

Time-domain analyses reveal important differences between neural responses to musical vs monetary rewards. Compared to financial stimuli, music evokes smaller P2 amplitudes but larger N2 components, suggesting distinct patterns of early sensory processing and conflict monitoring. Interestingly, FRN shows no significant differences between different valences of music, nor were there significant differences in P3 amplitudes between monetary and musical rewards[43]. Music perception particularly engages specialized ERP components that reflect different levels of auditory processing. Unexpected chord progressions can elicit both early right anterior negativity (ERAN) and mismatch negativity (MMN) components[44-46]. MMN appears to reflect violations of immediate musical patterns (such as rhythmic structures and melodic contours), whereas ERAN is more specifically associated with deviations from learned musical syntax rules, which represent violations of acquired structural knowledge of music[47,48]. Recent evidence robustly confirms that while MMN and ERAN share common predictive coding mechanisms, they represent distinct neural processes[46,49]. This theoretical distinction is crucial as it elucidates how the resolution or violation of musical expectations contribute to emotional responses through tension mechanisms.

NEUROELECTROPHYSIOLOGICAL FEATURES OF MUSIC INTERVENTION IN MDD

EEG-based investigations of music's effects on patients with MDD remain limited. One study found that during music perception, patients with MDD exhibited reduced connectivity patterns in the delta band but increased connectivity in the beta band, along with an absence of the left-hemisphere lateralization effect observed in healthy individuals[50]. Additional studies on neural oscillations have revealed that dysfunctional oscillatory networks may impair engagement with music perception in patients with MDD[51].

NEUROIMAGING AND NEUROELECTROPHYSIOLOGICAL FEATURES OF MUSICAL CHILLS

Musical chills represent a peak physiological response to intense musical pleasure[10,52], analogous to tearful emotional reactions. During chill episodes, individuals report strong subjective pleasure experiences accompanied by measurable changes in heart rate and skin conductance[12,53]. Neuroimaging studies have disclosed that music chills activate an evolutionarily conserved brain network involving the limbic system, striatum, and midbrain structures[10]. A positron emission tomography imaging study specifically demonstrated a correlation of the intensity of chills with neural activity in the VS, amygdala, and medial PFC[54]. Research by Mori[52] revealed that chill responses can be triggered by violations of rhythmic expectations, while harmonious acoustic spectra may induce tearfulness. These effects emerge from carefully constructed musical tension created through variations in rhythm, dynamics, melody, harmony, and timbre. In tonal music, the tension specifically related to melodic and harmonic motion is termed tonal tension[55]. Psychological studies have established that the resolution of tonal tension or violation of listeners' expectations constitutes a key mechanism for eliciting musical emotions[56,57]. fMRI evidence further shows that increasing musical tension correlates with enhanced blood oxygen level-dependent signals in the left lateral OFC and activates the right superficial amygdala[58].

An EEG study of musical chills revealed distinct theta-band activity in prefrontal regions, with source localization identifying significantly greater activation in the insula, OFC, and supplementary motor area (SMA). These findings provide further evidence for the involvement of bilateral insula, OFC, vmPFC, SMA, and ventral/dorsal striatum in mediating musical chills[59].

These findings collectively demonstrate that musical chills provide an objective, physiologically measurable indicator of peak reward experiences during music listening, with distinct neural correlates in reward and emotional processing circuits. This phenomenon offers valuable insights into understanding the neurobiological basis of aesthetic experiences and may inform music-based therapeutic interventions to mitigate reward processing deficits.

DISCUSSION

Anhedonia, as one of the core symptoms of MDD, shows limited responsiveness to pharmacological treatments. Music, as an effective non-pharmacological intervention for mood modulation, holds significant potential for alleviating anhedonia. Although the precise mechanisms underlying music's effects on reward processing remain unclear, neuroimaging studies have demonstrated its ability to activate multiple brain regions within the reward circuitry that include the VS, midbrain, amygdala, OFC, vmPFC, NAcc, and ACC. Current research has predominantly focused on healthy populations, with relatively few studies investigating individuals with MDD. Future studies should prioritize examining MDD populations to better understand music's therapeutic potential. While fMRI offers superior spatial resolution, its temporal resolution is relatively limited. Given that reward processing can be subdivided into distinct phases, such as decision, appetitive, consummatory, and learning phases[20] that require precise temporal characterization, future research could employ magnetoencephalography (MEG) to investigate the relationship between music and reward processing, as MEG provides both high temporal and spatial resolution.

Many electrophysiological studies using musical stimuli have adopted stimulus onset (time-zero) at the beginning of musical playback for time-domain analysis. However, unlike discrete stimuli such as images or brief tones (e.g., beeps), music unfolds over time, making onset-locked event marking theoretically problematic. This approach is particularly questionable in valence judgment paradigms, as listeners cannot determine a musical piece's emotional valence solely from its initial notes. Future research should implement more rigorous experimental designs with temporally appropriate event markers that better capture music's dynamic emotional progression.

Musical chills can evoke profound pleasure in healthy individuals. However, whether patients with MDD retain this capacity remains unexplored. Current evidence suggests that distinct neural pathways mediate music-derived pleasure compared to conventional rewards (e.g., money/food). This raises a compelling possibility: If patients with MDD can indeed experience musical chills, such responses might engage alternative reward-processing mechanisms, potentially bypassing the dysfunctional circuits underlying anhedonia to restore hedonic capacity.

CONCLUSION

Music can activate multiple brain regions. Unlike other reward stimuli, music may engage reward-related brain circuits through unique pathways. This provides new insights for alleviating anhedonia in patients with MDD who exhibit diminished reward responses to money and food. Notably, musical chills—an intensely pleasurable experience—could serve as a potential tool for improving anhedonia in individuals with MDD.