Abstract Background Neuropsychiatric fluctuations in Parkinson’s disease (PD) often accompany motor fluctuations, but their temporal relationship during the acute levodopa response remains unclear. Objectives To determine whether motor and neuropsychiatric responses occur synchronously during the OFF-to-ON transition. Methods Nineteen fluctuating PD patients underwent a high-resolution levodopa challenge with repeated assessments every 10 minutes for 70 minutes after levodopa administration. Motor symptoms (akinesia, rigidity) and neuropsychiatric fluctuations were quantified. Transition times (t25%-t50%-t75%-t100%) and response profiles were analyzed using correlation and clustering approaches. Results Motor and neuropsychiatric transition times were not correlated at any threshold (all FDR-corrected p>0.05; Bayes factors <1), supporting temporal dissociation. Among 18 patients with complete data, clustering revealed synchronous (6/18), neuropsychiatric-preceding (7/18), and motor-preceding (3/18) profiles. Conclusion Motor and neuropsychiatric responses to levodopa during PD fluctuations are partly independent and follow heterogeneous, patient-specific temporal profiles, supporting the search for distinct biomarkers and future individualized adaptative therapies.

Addiction is a chronic relapsing condition characterized by compulsive reward seeking and impaired behavioral control, associated with major individual and societal burden. Mechanistic investigation in humans remains constrained by ethical limitations, uncontrolled exposure histories, and ecological confounds. Parkinson's disease treated with dopamine replacement therapy provides a human framework for investigating addiction-relevant mechanisms under controlled dopaminergic modulation. We performed a narrative synthesis of clinical, neuropsychological, pharmacological, neuroimaging, and electrophysiological evidence linking impulse control disorders and dopamine dysregulation syndrome in Parkinson's disease to dimensional and circuit-based models of addiction. We examined phenotypic and neurobiological convergences, experimental opportunities, and translational relevance while outlining its boundary conditions. A subset of Parkinson's disease patients exposed to dopamine replacement treatment develops impulse control disorders and dopamine dysregulation syndrome. Impulse control disorders comprise heterogeneous behavioral phenotypes that share selected dimensions with behavioral addictions, whereas dopamine dysregulation syndrome most closely approximates pharmacological substance use disorders. These phenotypes share selected addiction-related dimensions, including craving, impaired control, compulsive reward-seeking, and persistence despite harm, while showing partial clinical and neurobiological convergence with behavioral addictions and substance use disorders. Parkinson's disease patients with neuropsychiatric fluctuations may represent a sensitized vulnerability state in which dopaminergic modulation dynamically influences reward processing, motivation, and compulsive behaviors. Parkinson's disease under dopamine replacement therapy enables within-subject dopaminergic manipulation, longitudinal observation, prospective assessment of vulnerability traits, multimodal neurobiological investigation, and reduced environmental confounding. It therefore provides a unique human window for investigating addiction-relevant mechanisms under controlled dopaminergic modulation, complementing animal models while remaining constrained by disease-specific boundary conditions.

BACKGROUND:Shame is frequent in Parkinson's disease (PD) and often overlooked. OBJECTIVE:The aim was to assess factors associated with PD-related shame. METHODS:PD-related shame was measured using the Shame and Embarrassment in PD (SPARK) scale in patients without cognitive impairment. Correlation between personal determinants (demographics, psychological traits [shame/guilt propensity, trait anxiety]), PD-related determinants (PD characteristics; motor, cognitive, and neuropsychiatric symptoms; medication; and health-related quality of life [QoL]), and SPARK was analyzed using multiple correlation analysis and generalized linear mixed models. To describe the cohort's response to shame, data-driven clustering based on SPARK was conducted, and clusters' associations with the determinants were analyzed. RESULTS:Forty-seven PD patients were included. PD-related shame correlated with psychological traits (trait anxiety, shame, and guilt propensity), clinical symptoms (dyskinesia, state anxiety, depression, and apathy), and QoL. These determinants explained 79.3% of the total variance in the subsequent linear model analysis, with QoL and anxiety as the strongest covariates of shame. Apathy positively covaried with SPARK self-esteem subscale. Cluster analysis identified 3 patient groups. Highest-intensity shame cluster demonstrated elevated scores on both motor and nonmotor symptom-related shame and was associated with higher levels in anxiety, depression, and apathy, and poorer QoL. The remaining clusters showed a dissociation, with motor symptom-related shame predominating in one and nonmotor symptom-related shame in the other. CONCLUSIONS:This study provides an in-depth understanding of shame, highlighting its multifactorial nature. Due to its impact on QoL, shame should be addressed in clinical practice through pharmacological/nonpharmacological interventions, targeting both shame and its modifiable determinants. Identifying distinct shame profiles underscores the need for tailored interventions.

Emotional prosody is defined as suprasegmental and segmental changes in voice and related acoustic parameters that can inform the listener about the emotional state of the speaker. Despite a large corpus of literature in psychological and brain mechanisms in emotional prosody perception, the perspective of embodied cognition in these mechanisms have been largely neglected. Here we investigated the influence of induced bodily vibrations in the categorization of ambiguous emotional vocalizations in an event-related potential study (N=24). The factorial design included Vocal emotion [anger and fear] and external Vibration [anger, fear, and none] as fixed factors. Emotional voices were morphed between a fearful expression with the speaker identity-matching angry expression, creating blends of emotions in each voice. Emotional congruent and incongruent vibrations were delivered on the skin through transducers placed close to the vocal cords. We hypothesized that induced bodily vibrations would constitute an interoceptive and proprioceptive feedbacks that would influence the perception of emotions, especially for more ambiguous voices as ambiguity would favour the processing of other available sensory information, here toward the tactile sensory modality. Behavioural results revealed that induced vibrations skewed the participants emotional ratings by biasing responses congruent with the vibration. Event-related potentials results indicated that N100 and P200 components subtending the early processing of emotional prosody were significantly modulated by induced vibrations in the congruent setting, which could be considered as a facilitation effect for emotion recognition at early stage of processing. A significant modulation of the late positive component was also observed in the incongruent setting, suggesting an error processing mechanism. EEG source reconstruction highlighted significant contrasts between vibration types in prefrontal, motor, somatosensory, and insular cortices. Altogether, our results suggest that voice-associated vibrations would play a significant role in vocal emotion perception and recognition through embodied mechanisms at both behavioral and neural levels. ### Competing Interest Statement The authors have declared no competing interest.

Preterm newborns' autonomic response to dynamic auditory stimuli is poorly understood. To examine how cardiac and respiratory systems adjust their rhythms in response to music, we assessed 18 preterm infants (gestational age 37.73 ± 0.80 weeks) and 19 adults across music listening. Heart rate dynamics, respiratory sinus arrhythmia (RSA), and cardiorespiratory coupling were analyzed. Studying the power spectral density of the interpolated interbeat interval series, both groups showed decreased high-frequency power during music listening. In preterm infants, RSA increased (p = 0.005), possibly suggesting a state of calm alertness, where the infant is physiologically prepared for interaction with environmental stimuli, while adults had decreased RSA (p = 0.003) and concomitant increased values of the low-frequency/high-frequency power ratio, possibly reflecting heightened alertness. While frequency domain cardiovascular responses to music were similar between preterms and adults, only the investigation of RSA and cardiorespiratory coupling measures revealed the delicate balance of autonomic dynamics in preterm newborns.

Parkinson’s disease (PD) encompasses motor (e.g., bradykinesia) and non-motor (e.g., apathy) symptoms. We aimed to use reflexive and voluntary saccades as a proxy for bradykinesia and apathy. Seventeen PD patients and thirteen controls (matched for age and educational level) were recruited. We assessed apathy using the Dimensional Apathy Scale (DAS) and bradykinesia using MDS-UPDRS III. Subjects were asked to fixate successively two green points (cues, 40° apart) alternating at 1 Hz. After 20 s, all stimuli disappeared, and participants were required to continue fixating on the previous locations of the cues at the same frequency for another 20 s. We measured the Maximal Amplitude (MA) (saccade amplitude from side to side) and its period. Linear mixed models assessed the effect of the group (patient/control), cue, DAS, and bradykinesia score. Overall, the DAS was similarly correlated to the period (p = 0.0157) and the MA (p = 0.0002) in the absence of a cue. However, this correlation was significant only in the patient subgroup for the MA (p = 0.0005). In the absence of cue, bradykinesia was similarly correlated to the period (p = .0001) and the MA (p = 0.0004). However, the period was better correlated to bradykinesia than the DAS. While the saccade period best correlates with bradykinesia, maximal amplitude in the absence of cue better reflects the severity of apathy. Our paradigm may be a promising objective biomarker for assessing bradykinesia and apathy in PD.

Human social interaction relies on the ability to detect and predict the temporal organization of sensory events. Although these abilities change markedly across infancy, little is known about their underlying neural mechanisms. This systematic review aims to define the neural signatures of temporal prediction in newborns and infants and to identify gaps that should guide future longitudinal research. Eight peer-reviewed studies were included, with 228 infants from birth to 9 months of age. Across studies, neural signatures of temporal prediction have been reported in broad cortical areas, including the anterior and medial parts of the brain, particularly within the frontal and central regions. Current evidence suggests that infants' neural responses to temporal regularities likely reflect a combination of early sensory-driven responses and emerging top-down processes. Importantly, gaps in the literature highlight the need for systematic, longitudinal approaches to clarify how neural mechanisms of temporal prediction develop and how biological predispositions and early experiences, including rhythmic and musical interactions, may contribute to this trajectory.

Introduction: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID. Case Presentation: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region. Conclusion: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.

To understand the consequences of prematurity on language perception, it is fundamental to determine how atypical early sensory experience affects brain development. At term equivalent age, ten preterm and ten fullterm newborns underwent high-density EEG during mother or stranger speech presentation, in the forward or backward order. A general group effect terms > preterms is evident in the theta frequency band, in the left temporal area, with preterms showing significant activation for strangers' and terms for the mother's voice. A significant group contrast in the low and high theta in the right temporal regions indicates higher activations for the stranger's voice in preterms. Finally, only full terms presented a late gamma band increase for the maternal voice, indicating a more mature brain response.EEG time-frequency analysis demonstrate that preterm infants are selectively responsive to stranger voices in both temporal hemispheres, and that they lack selective brain responses to their mother's forward voice.

There is growing evidence that both the basal ganglia and the cerebellum play functional roles in emotion processing, either directly or indirectly, through their connections with cortical and subcortical structures. However, the lateralization of this complex processing in emotion recognition remains unclear. To address this issue, we investigated emotional prosody recognition in individuals with Parkinson's disease (model of basal ganglia dysfunction) or cerebellar stroke patients, as well as in matched healthy controls (n = 24 in each group). We analysed performances according to the lateralization of the predominant brain degeneration/lesion. Results showed that a right (basal ganglia and cerebellar) hemispheric dysfunction was likely to induce greater deficits than a left one. Moreover, deficits following left hemispheric dysfunction were only observed in cerebellar stroke patients, and these deficits resembled those observed after degeneration of the right basal ganglia. Additional analyses taking disease duration / time since stroke into consideration revealed a worsening of performances in patients with predominantly right-sided lesions over time. These results point to the differential, but complementary, involvement of the cerebellum and basal ganglia in emotional prosody decoding, with a probable hemispheric specialization according to the level of cognitive integration.

In recent years, there has been increasing evidence of cerebellar involvement in emotion processing. Difficulties in the recognition of emotion from voices (i.e., emotional prosody) have been observed following cerebellar stroke. However, the interplay between sensory and higher-order cognitive dysfunction in these deficits, as well as possible hemispheric specialization for emotional prosody processing, has yet to be elucidated. We investigated the emotional prosody recognition performances of patients with right versus left cerebellar lesions, as well as of matched controls, entering the acoustic features of the stimuli in our statistical model. We also explored the cerebellar lesion-behavior relationship, using voxel-based lesion-symptom mapping. Results revealed impairment of vocal emotion recognition in both patient subgroups, particularly for neutral or negative prosody, with a higher number of misattributions in patients with right-hemispheric stroke. Voxel-based lesion-symptom mapping showed that some emotional misattributions correlated with lesions in the right Lobules VIIb and VIII and right Crus I and II. Furthermore, a significant proportion of the variance in this misattribution was explained by acoustic features such as pitch, loudness, and spectral aspects. These results point to bilateral posterior cerebellar involvement in both the sensory and cognitive processing of emotions.

The subthalamic nucleus (STN) is involved in different aspects of emotional processes and more specifically in emotional prosody recognition. Recent studies on the behavioral effects of deep brain stimulation (DBS) in patients with Parkinson's disease (PD) have uncovered an asymmetry in vocal emotion decoding in PD, with left-onset PD patients showing deficits for the processing of happy voices. Whether and how PD asymmetry affects STN electrophysiological responses to emotional prosody, however, remains unknown.In the current study, local field potential activity was recorded from eight left- and six right-lateralized motor-onset PD patients (LOPD/ROPD) undergoing DBS electrodes implantation, while they listened to angry, happy and neutral voices.Time-frequency decomposition revealed that theta (2–6 Hz), alpha (6–12 Hz) and gamma (60–150 Hz) band responses to emotion were mostly bilateral with a differential pattern of response according to patient's sides-of onset. Conversely, beta-band (12–20 Hz and 20–30 Hz) emotional responses were mostly lateralized in the left STN for both patient groups. Furthermore, STN theta, alpha and gamma band responses to happiness were either absent (theta band) or reduced (alpha and gamma band) in the most affected STN hemisphere (contralateral to the side-of onset), while a late low-beta band left STN happiness-specific response was present in ROPD patients and did not occur in LOPD patients.Altogether, in this study, we demonstrate a complex pattern of oscillatory activity in the human STN in response to emotional voices and reveal a crucial influence of disease laterality on STN low-frequency oscillatory activity.

While the role of the cerebellum in emotion recognition has been explored with facial expressions, its involvement in the auditory modality (i.e., emotional prosody) remains to be demonstrated. The present study investigated the recognition of emotional prosody in 15 patients with chronic cerebellar ischaemic stroke and 15 matched healthy controls, using a validated task, as well as clinical, motor, neuropsychological, and psychiatric assessments. We explored the cerebellar lesion-behaviour relationship using voxel-based lesion-symptom mapping. Results showed a significant difference between the stroke and healthy control groups, with patients giving erroneous ratings on the Surprise scale when they listened to fearful stimuli. Moreover, voxel-based lesion-symptom mapping revealed that these emotional misattributions correlated with lesions in right Lobules VIIb, VIIIa,b and IX. Interestingly, the posterior cerebellum has previously been found to be involved in affective processing, and Lobule VIIb in rhythm discrimination. These results point to the cerebellum's functional involvement in vocal emotion decoding.

Acute dyskinesias elicited by STN‐DBS, here referred to as stimulation‐induced dyskinesias, predict optimal clinical outcome in PD. However, it remains elusive whether stimulation‐induced dyskinesias can guide DBS programming.

The ability to monitor our own errors is mediated by a network that includes dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI). However, the dynamics of the underlying neurophysiological processes remain unclear. In particular, whether AI is on the receiving or driving end of the error-monitoring network is unresolved. Here, we recorded intracerebral electroencephalography signals simultaneously from AI and dmPFC in epileptic patients while they performed a stop-signal task. We found that errors selectively modulated broadband neural activity in human AI. Granger causality estimates revealed that errors were immediately followed by a feedforward influence from AI onto anterior cingulate cortex and, subsequently, onto presupplementary motor area. The reverse pattern of information flow was observed on correct responses. Our findings provide the first direct electrophysiological evidence indicating that the anterior insula rapidly detects and conveys error signals to dmPFC, while the latter might use this input to adapt behavior following inappropriate actions.