Time perception in schizophrenia and bipolar disorder. A case-control study.

Background: Models of time perception are inherently modular, comprising specialized mechanisms that represent the temporal relationships among events. Humans can perceive time duration through adaptive functions that engage specific neural regions organized according to the duration of stimuli encountered. Time perception relies on the interaction between cortical structures associated with the internal clock and areas involved in specific tasks. It is crucial to revisit foundational concepts that encompass both subjective and intersubjective dimensions of temporality, especially in relation to significant psychiatric conditions. This subject is regarded as original and highly relevant for research. This case-control study aims to investigate disturbances in time perception in individuals with Bipolar Disorder (BD) and Schizophrenia (SZ). Aims of the study: The study aimed to achieve several goals: first, to characterize sub-second temporal processing abilities in individuals with bipolar disorder and schizophrenia and their correlation with clinical and psychopathological variables. Second, it sought to compare different acquisition methods or tasks. Finally, it focused on characterizing sub-second temporal processing abilities in bipolar disorder and schizophrenia and examining their relationship with cerebello-thalamo-cortical functional connectivity. Material and Methods: To facilitate the comparison of various task methods, we recruited two populations. A range of psychopathological scales were employed to assess patient symptomatology at the time of testing, including the Hamilton Depression Rating Scale (HAM-D) (Hamilton, 1960), the Young Mania Rating Scale (YMRS) (Young et al., 1978), and the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987). The Temporal Order Judgment Task (TOJ) or Ventriloquist Apparatus was used, providing visual, auditory, and vibrotactile stimuli through a custom-designed serial-controlled stimulator measuring 20 mm × 20 mm, securely attached to the back of the dominant hand with transparent film that did not interfere with the stimuli . The visual stimulus consisted of a high-brightness blue LED with a diameter of 1.5 cm, activated for 10 ms. The vibrotactile stimulus produced a continuous pure vibration lasting 10 ms at a frequency of 112 Hz, while the auditory stimulus was a 10 ms burst of a 926 Hz pure tone pulsed at a frequency of 5 Hz. All stimuli were generated and precisely timed using MATLAB with the Psychtoolbox-3 package, with timings verified by an oscilloscope prior to testing. Additionally, we utilized the Antares PsySuite Method, a mobile app designed to deliver multimodal stimuli, including auditory, visual, and tactile inputs. This user-friendly Android application combines the convenience of a common device with the rigorous methods of psychophysics, which studies the quantitative relationships between psychological experiences and physical events. Within PsySuite, a temporal interval discrimination (TID) test was included to assess and enhance temporal skills in both auditory and tactile sensory modalities, employing classical psychophysical methods such as Two-Alternative Forced-Choice (2AFC) tasks. MRI recordings were conducted using a 3-T GE scanner with a standard head coil, utilizing foam pads to minimize head movement and reduce scanner noise. Three-dimensional T1-weighted anatomical images were acquired in a sagittal orientation via a 3D-SPGR sequence, achieving an in-plane resolution of 256x256 and a slice thickness of 1 mm. Functional images were obtained using a gradient echo Echo Planar Imaging (EPI) sequence sensitive to BOLD contrast, capturing whole-brain volumes in 33 contiguous slices, each 4 mm thick. Each participant underwent 6 minutes of fMRI scanning, totaling 150 scans. Results: This study investigated temporal precision in a Temporal Order Judgment (TOJ) task involving 21 patients with schizophrenia (SZ), 20 with bipolar disorder (BD), and 21 healthy controls (HC). Participants assessed pairs of audio-tactile, visuo-tactile, and audio-visual stimuli with varying stimulus onset asynchronies (SOAs). Results indicated that both SZ and BD patients exhibited significantly poorer temporal precision compared to HC across all conditions. A permutation-based ANOVA revealed a significant main effect of group (F = 4.06, p = 0.02), with significant differences between HC and both BD (t = -5.5, p < 0.001) and SZ (t = -6.1, p < 0.001), but not between the two patient groups. Age was not a significant factor. Furthermore, correlational analyses showed a significant association between individual just noticeable differences (JNDs) and the positive subscale of the PANSS, explaining approximately 47% of the variance in scores. No significant associations were found between medication dosages and temporal precision. These findings highlight the impact of psychiatric conditions on temporal processing and its relationship with symptomatology. The MRI study examined differences in amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) between bipolar disorder (BD) patients and healthy controls (HC) with adjustments for age and gender. A widespread pattern of differences was observed in both ALFF and fALFF measures. No significant differences were noted when analyzing BD patients based on their clinical phase. Additionally, in BD patients, fALFF demonstrated a negative correlation with both the Young Mania Rating Scale (YMRS) and disease duration, while no significant correlations were found for ALFF. Subject-level seed-based functional connectivity (SBFC) analysis was performed, revealing that connectivity from the Crus II region of the cerebellum negatively correlated with YMRS scores in a frontal region (p = 0.04, k = 149, MNI coordinates: -24, 18, 50). This suggests that greater disconnection between the right Crus II and the left frontal region is linked to higher YMRS scores in BD patients. No significant correlations were found from the other seed regions. Limitations: This study has several limitations. The primary limitation is the absence of longitudinal evaluations, which restricts the generalizability of the results. Additionally, information regarding patients' medication types and dosages prior to the examination was not rigorously collected for all patients, preventing us from correcting for any potential confounding effects. Discussion: This study replicates previous findings of sub-second timing deficits in schizophrenia (SZ) patients while offering new insights. Both SZ and bipolar disorder (BD) patients exhibited a similarly wider temporal binding window (TBW) compared to healthy controls, contrary to prior studies. The key finding is that alterations in multisensory temporal binding correlate with specific psychotic symptoms, such as delusions and hallucinations, rather than being exclusive to SZ or BD diagnoses. These results support the idea that low-level temporal integration is essential for coherent higher-level perceptions, with impaired temporal binding potentially leading to fragmented perceptions and clinical symptoms. Furthermore, these findings suggest a continuum between affective and non-affective psychoses, indicating that TBW amplitude may reflect the severity of psychotic symptoms. No significant relationships were found between temporal binding precision and medication dosages. Additionally, reduced functional connectivity between the right cerebellar Crus II and frontal regions was observed in individuals with more severe manic symptoms, highlighting its role in timing thoughts, emotions, and actions. This weakened connection may disrupt the cerebello-thalamo-cortical pathway, impairing the cerebellum's regulatory functions. Overall, the study suggests shared network dysfunction across psychotic disorders, supporting a unified psychosis model. Conclusion: In conclusion, this study confirms sub-second timing deficits in schizophrenia and reveals that both schizophrenia and bipolar disorder patients have a wider temporal binding window than healthy controls. This suggests shared characteristics rather than distinct diagnoses. Alterations in temporal binding are linked to specific psychotic symptoms, highlighting the role of low-level temporal integration in perception. No significant relationship was found between temporal binding precision and medication, indicating that these effects are not solely pharmacological. The right cerebellar Crus II is vital for temporal perception, with reduced connectivity to frontal regions in individuals with severe manic symptoms. Future research should explore connections between specific symptoms, subjective time experience, and temporal processing deficits, aiming to enhance understanding and inform treatment strategies for better patient outcomes.