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OBJECTIVES: Time awareness may change depending on the mental state or disease conditions, although each individual perceives his/her own sense of time as stable and accurate. Nevertheless, the processes that consolidate altered duration production remain unclear. The present study aimed to manipulate the subjective duration production via memory consolidation through the modulation of neural plasticity. MATERIALS AND METHODS: We first performed false feedback training of duration or length production and examined the period required for natural recovery from the altered production. Next, persistent neural plasticity was promoted by quadripulse transcranial magnetic stimulation (QPS) over the right dorsolateral prefrontal cortex (DLPFC), temporoparietal junction (TPJ), and primary motor cortex (M1). We conducted the same feedback training in the individual and studied how the time course of false learning changed. RESULTS: We observed that altered duration production after false feedback returned to baseline within two hours. Next, immediate exposure to false feedback during neural plasticity enhancement revealed that in individuals who received QPS over the right DLPFC, but not over TPJ or M1, false duration production was maintained for four hours; furthermore, the efficacy persisted for at least one week. CONCLUSION: These findings suggest that, while learned altered duration production decays over several hours, QPS over the right DLPFC enables the consolidation of newly learned duration production.

Although standing plantar perception training (SPPT) may improve standing postural stability, the underlying neural mechanisms remain unclear. The authors investigated the relationship between regional cortical responses to SPPT using a balance pad and training outcomes in 32 older participants (mean ± SD:72.2 ± 6.0, range:60–87). Regional cortical activity was measured in the bilateral supplementary motor area, primary sensorimotor area, and parietal association area using near-infrared spectroscopy. Postural sway changes were compared before and after SPPT. Changes in two-point plantar discrimination and regional cortical activity during SPPT, associated with standing postural stability improvements, were examined using multiple regression and indicated improved standing postural stability after SPPT (p

Parkinson's disease (PD) impairs various cognitive functions, including time perception. Dysfunctional time perception in PD is poorly understood, and no study has investigated the rehabilitation of time perception in patients with PD. We aimed to induce the recovery of time perception in PD patients and investigated the potential relationship between recovery and cognitive functions/domains other than time perception. Sixty patients with PD (27 females) and 20 healthy controls (10 females) were recruited. The participants underwent a feedback training protocol for 4 weeks to improve the accuracy of subjective spatial distance or time duration using a ruler or stopwatch, respectively. They participated in three tests at weekly intervals, each comprising 10 types of cognitive tasks and assessments. After duration feedback training for 1 month, performance on the Go/No-go task, Stroop task, and impulsivity assessment improved in patients with PD, while no effect was observed after distance feedback training. Additionally, the effect of training on duration production correlated with extended reaction time and improved accuracy in the Go/No-go and Stroop tasks. These findings suggest that time perception is functionally linked to inhibitory systems. If the feedback training protocol can modulate and maintain time perception, it may improve various cognitive/psychiatric functions in patients with PD. It may also be useful in the treatment of diseases other than PD that cause dysfunctions in temporal processing.

Specific odors can induce memories of the past, especially those associated with autobiographical and episodic memory. Odors associated with autobiographical memories have been found to elicit stronger activation in the orbitofrontal cortex, hippocampus, and parahippocampus compared with odors not linked to personal memories. Here, we examined whether continuous odor stimuli associated with autobiographical memories could activate the above olfactory areas in older adults and speculated regarding whether this odor stimulation could have a protective effect against age-related cognitive decline. Specifically, we used functional magnetic resonance imaging to investigate the relationship between blood oxygen levels in olfactory regions and odor-induced subjective memory retrieval and emotions associated with autobiographical memory in older adults. In our group of healthy older adults, the tested odors induced autobiographical memories that were accompanied by increasing levels of retrieval and the feeling of being “brought back in time.” The strength of the subjective feelings, including vividness of the memory and degree of comfort, impacted activation of the left fusiform gyrus and left posterior orbitofrontal cortex. Further, our path model suggested that the strength of memory retrieval and of the emotions induced by odor-evoked autobiographical memories directly influenced neural changes in the left fusiform gyrus, and impacted left posterior orbitofrontal cortex activation through the left fusiform response.

Introduction Pathological abnormalities first appear in the medial temporal regions including entorhinal cortex and parahippocampus in patients with Alzheimer's disease. Previous studies showed that olfactory decline in elderly subjects was associated with volume reductions in the left hippocampus and left parahippocampus without cognitive impairment. The aim of this study is to investigate the link between olfaction and volume reductions in the medial temporal regions including the parahippocampus, entorhinal cortex, and hippocampal subfields. Method 27 elderly subjects and 27 young controls were measured olfaction acuity, cognitive function, and structural magnetic resonance imaging. Image processing and gray matter volumetric segmentation were performed with FreeSurfer. Volume data were analyzed with SPSS Statistics software. Results Interesting results of this study were that volume reduction in the entorhinal cortex was not directly linked with declining olfactory ability. Volume reduction in the left entorhinal cortex was correlated with volume reduction in the left parahippocampus and dentate gyrus. However, left parahippocampus volume reduction had the greatest impact on olfactory decline, and the entorhinal cortex and dentate gyrus might additionally contribute to olfactory decline. Conclusion Our results indicate that olfactory decline may be directly reflected in the medial temporal regions as reduced parahippocampus volumes, rather than as morphological changes in the entorhinal cortex and hippocampus. The parahippocampus may play an important role in the association between memory retrieval and olfactory identification., Left: Visualization of brain segmentation in a single subject with FreeSurfer. The entorhinal cortex (ENT) is indicated in red, and the parahippocampus (para‐HI) is indicated in green. Right: Visualization of hippocampal subfield segmentation in a single subject with each subfield represented by a different color.

Although animal studies and studies on Parkinson’s disease (PD) suggest that dopamine deficiency slows the pace of the internal clock, which is corrected by dopaminergic medication, timing deficits in parkinsonism remain to be characterized with diverse findings. Here we studied patients with PD and progressive supranuclear palsy (PSP), 3–4 h after drug intake, and normal age-matched subjects. We contrasted perceptual (temporal bisection, duration comparison) and motor timing tasks (time production/reproduction) in supra- and sub-second time domains, and automatic versus cognitive/short-term memory–related tasks. Subjects were allowed to count during supra-second production and reproduction tasks. In the time production task, linearly correlating the produced time with the instructed time showed that the “subjective sense” of 1 s is slightly longer in PD and shorter in PSP than in normals. This was superposed on a prominent trend of underestimation of longer (supra-second) durations, common to all groups, suggesting that the pace of the internal clock changed from fast to slow as time went by. In the time reproduction task, PD and, more prominently, PSP patients over-reproduced shorter durations and under-reproduced longer durations at extremes of the time range studied, with intermediate durations reproduced veridically, with a shallower slope of linear correlation between the presented and produced time. In the duration comparison task, PD patients overestimated the second presented duration relative to the first with shorter but not longer standard durations. In the bisection task, PD and PSP patients estimated the bisection point (BP50) between the two supra-second but not sub-second standards to be longer than normal subjects. Thus, perceptual timing tasks showed changes in opposite directions to motor timing tasks: underestimating shorter durations and overestimating longer durations. In PD, correlation of the mini-mental state examination score with supra-second BP50 and the slope of linear correlation in the reproduction task suggested involvement of short-term memory in these tasks. Dopamine deficiency didn’t correlate significantly with timing performances, suggesting that the slowed clock hypothesis cannot explain the entire results. Timing performance in PD may be determined by complex interactions among time scales on the motor and sensory sides, and by their distortion in memory.

The aim of this study was to investigate the relationship between olfactory recognition and morphological changes in olfactory brain regions including the amygdala, hippocampus, rectus, parahippocampus, orbitofrontal cortex, and medial frontal cortex in 27 elderly subjects and 27 younger healthy controls. The specific aim of the study was to determine which brain areas are associated with the initial decline of olfaction in elderly subjects, which occurs before the onset of dementia. All subjects underwent magnetic resonance imaging to measure anatomical brain volume and cortical thickness, and subjects were assessed using tests of olfactory acuity and cognitive function measured with the Montreal Cognitive Assessment. Overall brain volume reductions were observed in elderly subjects compared with young healthy controls, but only reduction in the volume of the left hippocampus was associated with decreased olfactory ability. The parahippocampus of elderly subjects was not different from that of controls; the extent of the reduction of parahippocampus volume varied among individuals, and reduction in this region was associated with olfactory decline. Similarly, parahippocampus thinning was associated with decreased olfactory function. The path analysis showed direct and indirect effects of hippocampus and parahippocampus volume on olfactory ability and that volume reductions in these areas were not associated with cognitive function. Parahippocampus volume reduction and thinning exhibited individual variation; this may be the first appearance of pathological changes and may lead to dysfunction in the connection of olfactory memory to the neocortex. Parahippocampus change may reflect the first sign of olfactory impairment prior to pathological changes in the hippocampus, amygdala and orbitofrontal cortex.

A growing number of brain imaging studies show functional connectivity (FC) between regions during emotional and cognitive tasks in humans. However, emotions are accompanied by changes in physiological parameters such as heart rate and respiration. These changes may affect blood oxygen level-dependent signals, as well as connectivity between brain areas. This study aimed to clarify the effects of physiological noise on the connectivity between areas related to the default mode network using resting-state functional magnetic resonance imaging (rs-fMRI). Healthy adult volunteers (age range: 19–51 years, mean age: 26.9 ± 9.1 years, 8 males and 8 females) underwent rs-fMRI for 10 min using a clinical 3T scanner (MAGNETOM Trio A Tim System, Siemens) with simultaneously recorded respiration and cardiac output. Physiological noise signals were subsequently removed from the acquired fMRI data using the DRIFTER toolbox. Image processing and analysis of the FC between areas related to the default mode network were performed using DPARSF. Network-Based Statistic (NBS) analysis of the functional connectome of the DMN and DMN-related area was used to perform three groups of comparison: without physiological noise correction, with cardiac noise correction, and with cardiac and respiratory noise correction. NBS analysis identified 36 networks with significant differences in three conditions in FC matrices. Post hoc comparison showed no differences between the three conditions, indicating that all three had the same networks. Among the 36 networks, strength of FC of 8 networks was modified under physiological noise correction. Connectivity between left and right anterior medial frontal regions increased strength of connectivity. These areas are located on the medial cerebral hemisphere, close to the sagittal sinus and arteries in the cerebral hemispheres, suggesting that medial frontal areas may be sensitive to cardiac rhythm close to arteries. The other networks observed temporal regions and showed a decrease in their connectivity strength by removing physiological noise, indicating that physiological noise, especially respiration, may be sensitive to BOLD signal in the temporal regions during resting state. Temporal lobe was highly correlated with anxiety-related respiration changes (Masaoka and Homma, 2000), speech processing, and respiratory sensation. These factors may affect the rs-fMRI signaling sensitivity.

Objective: To investigate whether the number of cerebral microbleeds (CMB) could be a useful indicator to predict glymphatic system dysfunction in Alzheimer’s disease (AD) patients, by comparing the degree of cerebral spinal fluid (CSF) and interstitial fluid (ISF) stasis. Methods: Forty probable AD patients were included, with those exhibiting two or more CMB were included in the multiple CMB group (mCMB, n = 21, mean = 11.1), and none or one CMB included in the non-multiple CMB group (nmCMB, n = 19, mean = 0.84). CMB were defined in axial gradient recalled echo (GRE) T2*-weighted images. Evans index (EI) was calculated to measure lateral ventricle enlargement, Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) software was used to determine the extent of gray and white matter atrophy, and Fazekas scale (FS) was used to determine white matter hyperintensities (WMH). Results: EI was significantly larger in mCMB than in nmCMB, while the gray and white matter volume was not different between groups. Thus, the difference in lateral ventricle enlargement between AD with and without multiple CMB reflects a combination of the degree of brain atrophy and the extent of CSF stasis. FS was higher in mCMB than in the nmCMB, suggesting the failure of ISF elimination was more severe in mCMB cases. Conclusion: The difference in lateral ventricle enlargement and WMH between AD with or without multiple CMB may reflect a difference in the degree of CSF/ISF stagnation.

Azusa Shiromaru-Sugimoto,1 Hidetomo Murakami,1 Akinori Futamura,1 Motoyasu Honma,2 Takeshi Kuroda,1 Mitsuru Kawamura,1,3 Kenjiro Ono1 1Division of Neurology, Department of Internal Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan; 2Department of Physiology, Kyorin University School of Medicine, Tokyo 181-0004, Japan; 3Neurology, Okusawa Hospital and Clinics, Tokyo 158-0083, Japan Background: The relationship between dementia and time perception impairment is unknown. Aim: This study aims to explore subjective perception of the passage of time in patients with Alzheimer’s disease (AD). Methods: We conducted semi-structured interviews with 11 AD patients. Grounded theory, a qualitative research methodology, was used for data analysis. Results: Based on interview transcripts, five categories were designated: {Live according to a private clock}, {The past comes up}, {Move back and forth between the present and the past}, {Cannot imagine the future}, and {Bid farewell to this world as early as tomorrow}. Discussion: Our results suggest that AD patients alternate past and present without complete awareness and cannot imagine a future other than one ending in death. Keywords: dementia, grounded theory, neuropsychology, qualitative study, mind time, interview

Bright light (BL) not only regulates human emotion and circadian physiology but can also directly modulate emotional memories. Impaired fear extinction and enhanced fear acquisition and consolidation are hallmarks of fear-circuitry disorders; thus, we tested whether BL facilitates fear extinction and inhibits fear acquisition. We randomly exposed 29 healthy humans to high- (9000 lx) or low-intensity light (500 lx) for 15 min, near the nadir of the phase response to light, in a single-blind manner. Simultaneously with the light exposure, subjects performed fear extinction training and second fear acquisition, where a visual conditioned stimulus (CS), previously paired with an electric shock unconditioned stimulus (US), was presented without the US, while another CS was newly paired with the US. Conditioned responses (CRs) and changes in prefrontal cortex (PFC) activity were determined during encoding and delayed recall sessions. BL-exposed subjects exhibited lower extinction-related PFC activity and marginally higher acquisition-related PFC activity during light exposure than subjects exposed to control light. Twenty-four hours later, BL reduced CRs to both the extinguished and non-extinguished CSs with marginally lower extinction-related PFC activation, suggesting that BL enhanced fear extinction, while suppressing fear acquisition. Further, BL sustained tolerance to fear re-conditioning. Our results demonstrate that a single and brief BL exposure, synchronized with fear extinction and acquisition, instantaneously influences prefrontal hemodynamic responses and alleviates fear expression after 24 h. Although the specificity of BL effects deems further investigation, our findings indicate the clinical relevance of adjunctive BL intervention in exposure-based cognitive-behavioral therapy for fear-circuitry disorders.

ObjectiveTo determine whether Parkinson disease (PD) affects cross-modal function of vision and olfaction because it is known that PD impairs various cognitive functions, including olfaction.MethodsWe conducted behavioral experiments to identify the influence of PD on cross-modal function by contrasting patient performance with age-matched normal controls (NCs). We showed visual effects on the strength and preference of odor by manipulating semantic connections between picture/odorant pairs. In addition, we used brain imaging to identify the role of striatal presynaptic dopamine transporter (DaT) deficits.ResultsWe found that odor evaluation in participants with PD was unaffected by visual information, while NCs overestimated smell when sniffing odorless liquid while viewing pleasant/unpleasant visual cues. Furthermore, DaT deficit in striatum, for the posterior putamen in particular, correlated to few visual effects in participants with PD.ConclusionsThese findings suggest that PD impairs cross-modal function of vision/olfaction as a result of posterior putamen deficit. This cross-modal dysfunction may serve as the basis of a novel precursor assessment of PD.

Autism spectrum disorder (ASD) presents certain hallmark features associated with cognitive and social functions, however, the ability to estimate self-generated distance and duration in individuals with ASD are unclear. We compared the performance of 20 ASD individuals with 20 typical developments (TDs) with respect to two tasks: (1) the drawing of a line of a specified distance (10 or 20 cm) and (2) waiting for a specified time (10 or 20 s). We observed that both the line distances and waiting times were substantially shorter in the ASD group than in the TD group. Furthermore, a trait of “attention to detail,” as measured by the Autism-Spectrum Quotient, correlated with some distance and duration productions observed in individuals with ASD. We suggest that attentional functions are related to the contraction of distance and duration in ASD.

Light has attracted increasing attention as a critical determinant of memory processing. While sleep selectively consolidates newly encoded memories according to their future relevance, the role of light in human memory consolidation is largely unknown. Here, we report how bright light (BL), provided during encoding, influences online and offline consolidation of motor skill learning. We sought to determine whether relatively slower and faster key-press transitions within individuals were differentially consolidated by BL. Healthy human subjects were briefly exposed to either BL (8000 lx) or control light (CL;500 lx) during memory encoding at 13:00 h, when light minimally affects circadian phase-shifting, and were retested 24 h later. The effects of BL on online and offline performance gains were determined by accuracy and speed. BL-exposed subjects showed better overall performance accuracy during training and lower overnight accuracy gains after a subsequent night of sleep than did CL-exposed subjects. BL preferentially improved the initially most difficult individual key-press transitions during practice; these were only improved overnight under CL. By contrast, accuracy during what had been the easiest key-press transitions at the beginning of the experiment was unaffected by light conditions or online/offline learning processes. BL effects were not observed for performance speed, mood, or sleep-wake patterns. Brief BL exposure during training may advance motor memory selection and consolidation that optimally meet individual requirements for potential gains, which would otherwise depend on post-training sleep. This suggests a new way of enhancing brain plasticity to compensate for impaired sleep-dependent memory consolidation in neuropsychiatric conditions.

Diagonistic apraxia is a corpus callosal disconnection syndrome. Callosal lesions in Neuromyelitis optica spectrum disorder (NMOSD) have been reported, but callosal disconnection syndrome are rare. A 48-year-old woman was treated for fever and a cough before hospitalization. Her fever abated immediately, but she had balance problems in walking and standing. She also had slurred speech. On neurological examination, she had diagonistic apraxia. Her left hand moved in an uncoordinated way when she moved her right hand: changing her clothes for example or using a knife and fork. She had to instruct her left hand to stop. She had dysarthria and her gait was wide-based. She also had many callosal disconnection syndrome symptoms such as alexia of left visual field, left ear extinction, crossed optic ataxia. Using FLAIR and DWI MRI, a mixture of low and high signals, a so-called “marbled pattern,” was seen in the corpus callosum. Since the patient was positive for anti-aquaporin-4 antibody, she was diagnosed with NMOSD. After two courses of steroid pulse therapy, the symptoms improved. Here we report diagonistic apraxia and other symptoms of callosal disconnection syndrome in anti-AQP4-positive NMOSD.

Lesions of the medio‐parietal lobes are linked with topographical and temporal disorientation, and are of interest to understanding mental time. We examined a 39‐year‐old man who worked as a driving instructor before cerebral hemorrhage, and followed his case for 8 years including neuropsychological testing and brain imaging. The patient had mild anterograde episodic amnesia, but no semantic amnesia. He felt that time passed too quickly, and developed a compulsive routine to compensate, although he was able to count time at a normal speed. Furthermore, he was unable to accurately sketch the layout of his house and to make a cross‐reference type timetable for the future. Brain magnetic resonance imaging showed lesions of the left anterior–posterior cingulate gyrus, and N‐isopropyl‐[123I] p‐iodoamphetamine single‐photon emission computed tomography showed decreased blood flow mainly of the left medio‐parietal lobe.

In daily life, we sometimes select temporal cues of one sort while suppressing others. This study investigated the mechanism of suppression by examining a split-brain patient's perception of target intervals while ignoring distractor intervals. A patient with agenesis of corpus callosum and five age- and sex-matched control subjects participated in reproduction of target intervals while ignoring distractors displayed in the visual field either ipsilateral or contralateral to target. In the patient, the distractor interfered with reproduction performance more strongly when contralateral rather than ipsilateral. Our results suggest that the corpus callosum plays an inhibitory role in interhemispheric interference and that temporal interval information can be transferred via subcortical structures when there are no direct interhemispheric pathways.

To produce coordinated manual actions within specific space and time, their relationship must be properly dealt with in a sensorimotor system. This study examined how such a coordination system might be impaired in normal aging and in Parkinson's disease (PD). Using a tablet device, young participants, elderly participants, and patients with PD were tested for concurrent production of distance and duration as well as single production of distance or duration alone. Results were analyzed in relation to deficiency of presynaptic dopamine transporter (DaT) in the striatum. We observed different patterns of impairment between normal aging and PD. Elderly participants exhibited duration overproduction when they had to produce distance and duration concurrently, but were normal in single production of either distance or duration. In contrast, PD patients exhibited normal distance production and marked underproduction of duration when either distance or duration was produced alone, but both duration and distance were underproduced when they were concurrently produced. These findings suggest that aging yields impaired performances in both elderly people and PD patients, but that temporal underproduction in PD patients entrains spatial production as if the distance to be produced were made consistent with their duration underproduction. We also observed that striatal DaT deficit was correlated with the extent of duration underproduction in PD patients. The deficit may be associated with the severe time compression and the entrainment during spatiotemporal production in PD patients.

Parkinson's disease (PD) is associated with various cognitive impairments. However, the nature of cognitive modification in patients with PD remains to be elucidated. In the present study, we examined whether patients with PD could correct and maintain subjective time duration and line length estimation. After training sessions, in which participants repeatedly memorized either a duration or a length, we compared a learning performance in 20 PD patients with 20 healthy controls. In the case of duration in the PD patients, the learned durations immediately returned to baseline of pre-training within a few minutes. However, the patients' ability to learn length estimation remained unimpaired. In contrast, healthy controls were able to retain the learned duration and length estimations. Time compression in PD's internal clock may become entrained to their altered duration estimation even after learning of accurate time duration. These deficits may be associated with disrupting cognitive modification in PD.

Plasticity is essential in body perception so that physical changes in the body can be accommodated and assimilated. Multisensory integration of visual, auditory, tactile, and proprioceptive signals contributes both to conscious perception of the body’s current state and to associated learning. However, much is unknown about how novel information is assimilated into body perception networks in the brain. Sleep-based consolidation can facilitate various types of learning via the reactivation of networks involved in prior encoding or through synaptic down-scaling. Sleep may likewise contribute to perceptual learning of bodily information by providing an optimal time for multisensory recalibration. Here we used methods for targeted memory reactivation (TMR) during slow-wave sleep (SWS) to examine the influence of sleep-based reactivation of experimentally induced alterations in body perception. The rubber-hand illusion (RHI) was induced with concomitant auditory stimulation in 24 healthy participants on 3 consecutive days. While each participant was sleeping in his or her own bed during intervening nights, electrophysiological detection of SWS prompted covert stimulation with either the sound heard during illusion induction, a counterbalanced novel sound, or neither. TMR systematically enhanced spatial recalibration of perceived hand location during subsequent inductions of the RHI. Illusory feelings of body ownership for the rubber hand also differed as a function of whether the novel or RHI-associated sound was played on the prior night. This evidence for sleep-based modulation of a body-perception illusion demonstrates that the recalibration of multisensory signals can be altered overnight to modify new learning of bodily representations. Sleep-based memory processing may thus constitute a fundamental component of body-image plasticity.

The sense of body ownership constantly adapts to new environments, and awareness of a distinction between oneself and others is a fundamental ability. However, it remains unclear whether plasticity in the sense of body ownership is dependent on genetic factors. The present study investigated the influence of the catechol-O-methyltransferase (COMT) Val158Met genotype on illusory learning of a sense of body ownership and dissociation. 76 healthy Japanese participants experienced the rubber hand illusion (RHI), which is produced by sensory integration of conflicting modalities, with the intent to experimentally alter objective perceived locations and subjective ownership ratings. We found that Val/Val homozygous participants had more intense RHI experiences than Val/Met heterozygous and Met homozygous participants. Furthermore, RHI sensation was correlated with a dissociative personality trait in Val/Val homozygous participants. Our findings indicate an interaction between COMT genotype, RHI sensation, and dissociative personality traits: Val/Val genotypes were associated with RHI induction and greater vulnerability to dissociation. The findings suggest that Val/Val homozygous individuals may be more flexible regarding self-attribution/body ownership and that biological factors may contribute to reduced awareness regarding the distinction between self and others.

Patients with Parkinson’s disease (PD) often underestimate time intervals, however it remains unclear why they underestimate rather than overestimate them. The current study examined time underestimation and counting in patients with PD, in relation to dopamine transporter (DaT) located on presynaptic nerve endings in the striatum. Nineteen non-dementia patients with PD and 20 age- and sex-matched healthy controls performed two time estimation tasks to produce or reproduce time intervals with counting in the head, to examine dysfunctional time counting processing. They also performed tapping tasks to measure cycles of counting with 1 s interval with time estimation. Compared to controls, patients underestimated time intervals above 10 s on time production not reproduction tasks and the underestimation correlated with fast counting on the tapping task. Furthermore, striatal DaT protein levels strongly correlated with underestimation of time intervals. These findings suggest that distortion of time intervals is guided by cumulative output of fast cycle counting and that this is linked with striatal DaT protein deficit.