Preserved time but altered numerosity processing in epileptic patients with postoperative lesion in the inferior frontal gyrus.

Previous researches have shown that the inferior frontal gyrus (IFG) is involved in time and numerosity processing. This study aimed at examining (i) interval timing and (ii) interaction between duration and numerosity processing in four drug-resistant epileptic patients with postoperative lesions in the IFG in comparison with thirteen healthy controls. The duration reproduction and discrimination tasks performed in the sub- and supra-second ranges did not reveal any significant differences between patients and controls. The duration discrimination task of stimuli varying in numerosity (DurN) and the numerosity discrimination task of stimuli varying in duration (NumD) revealed that only numerosity judgment was altered in IFG patients. A time-order effect was notably observed in the NumD task but in opposite directions for the two groups: The second patch was perceived as more numerous than the first patch in controls and conversely as less numerous in patients. Finally in the DurN task, we observed a congruency effect which was dependent on numerical distance in patients but not in controls. These converging results suggest that the IFG would be more specifically involved in numerosity than in duration processing, possibly playing a role in numerical decision.

Relative contribution of pitch and brightness to the auditory kappa effect.

Pitch height is known to interfere with temporal judgment. This is the case in the auditory kappa effect in which the relative degree of pitch distance separating two tones extends the perceived duration of the inter-onset interval (IOI). However, pitch variations which result from manipulations of the fundamental frequency of tones are associated with variations of the spectral centroid, which is related to the perceived brightness. The present study aimed at determining the relative contribution of pitch and brightness to the auditory kappa effect. Forty-eight participants performed an AXB paradigm (tone X was shifted to be closer to either tone A or B) in three conditions: the three tones varied in both pitch and brightness (PB condition), pitch varied but brightness was fixed (P condition) or brightness varied but pitch was fixed (B condition). Pitch and brightness were modified by manipulating the fundamental frequency (F0) and the spectral centroid of the tones, respectively. In each condition, the percentage of trials in which the first IOI was perceived as shorter increased as X was closer (in pitch and/or brightness) to A. Furthermore, the magnitude of the effect was larger in PB than in P condition, while it did not differ between PB and B conditions, suggesting that brightness would contribute more than pitch height to the auditory kappa effect. This study provides the first evidence that auditory brightness interferes with duration judgment and highlights the importance to consider jointly the role of pitch height and brightness in future studies on auditory temporal processing.

Role of the supplementary motor area during reproduction of supra-second time intervals: An intracerebral EEG study.

The supplementary motor area (SMA) has been shown to be involved in interval timing but its precise role remains a matter of debate. The present study was aimed at examining, by means of intracerebral EEG recordings, the time course of the activity in this structure, as well as in other functionally connected cortical (frontal, cingulate, insular and temporal) areas, during a visual time reproduction task. Four patients undergoing stereo-electroencephalography (SEEG) for presurgical investigation of refractory focal epilepsy were enrolled. They were selected on the presence of depth electrodes implanted within the SMA. They were instructed to encode, keep in memory and then reproduce the duration (3, 5 and 7 s) of emotionally-neutral or negative pictures. Emotional stimuli were used with the aim of examining neural correlates of temporal distortions induced by emotion. Event-related potentials (ERPs) were analyzed during three periods: During and at the extinction of the target interval (TI) and at the beginning of the reproduction interval (RI). Electrophysiological data revealed an ERP time-locked to TI-offset whose amplitude varied monotonically with TI-duration. This effect was observed in three out of the four patients, especially within the SMA and the insula. It also involved the middle and anterior cingulate cortex, the superior, middle and inferior frontal gyri and the paracentral lobule. These effects were modulated by the prior TI-duration and predicted variations in temporal reproduction accuracy. In contrast, modulations of ERPs with TI-duration, emotion or temporal performance during the target or the reproduction interval were modest and less consistent across patients. These results demonstrate that, during reproduction of supra-second time intervals, the SMA, in concert with a fronto-insular network, is involved at the end of the target interval, and suggest a role in the duration categorization and decision making operations or alternatively in the preparedness of the timing of the future movement that will be executed during the reproduction phase.

Resting Heart Rate Predicts Depression and Cognition Early after Ischemic Stroke: A Pilot Study.

BACKGROUND: Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. METHODS: Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. RESULTS: Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. CONCLUSIONS: Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI.

fMRI identifies the right inferior frontal cortex as the brain region where time interval processing is altered by negative emotional arousal.

The reason why human beings are inclined to overestimate the duration of highly arousing negative events remains enigmatic. The issue about what neurocognitive mechanisms and neural structures support the connection between time perception and emotion was addressed here by an event-related neuroimaging study involving a localizer task, followed by the main experiment. The localizer task, in which participants had to categorize either the duration or the average color of visual stimuli aimed at identifying the neural structures constitutive of a duration-specific network. The aim of the main experiment, in which participants had to categorize the presentation time of either neutral or emotionally negative visual stimuli, was to unmask which parts of the previously identified duration-specific network are sensitive to emotionally negative arousal. The duration-specific network that we uncovered from the localizer task comprised the cerebellum bilaterally as well as the orbitofrontal, the anterior cingulate, the anterior insular, and the inferior frontal cortices in the right hemisphere. Strikingly, the imaging data from the main experiment underscored that the right inferior frontal cortex (IFC) was the only region within the duration-specific network whose activity was increased in the face of emotionally negative pictures compared to neutral ones. Remarkably too, the extent of neural activation induced by emotionally negative pictures (compared to neutral ones) in this region correlated with a behavioral index reflecting the extent to which emotionally negative pictures were overestimated compared to neutral ones. The results are discussed in relation to recent models and studies suggesting that the right anterior insular cortex/IFC is of central importance in time perception.

Distortion of time interval reproduction in an epileptic patient with a focal lesion in the right anterior insular/inferior frontal cortices.

This case report on an epileptic patient suffering from a focal lesion at the junction of the right anterior insular cortex (AIC) and the adjacent inferior frontal cortex (IFC) provides the first evidence that damage to this brain region impairs temporal performance in a visual time reproduction task in which participants had to reproduce the presentation duration (3, 5 and 7s) of emotionally-neutral and -negative pictures. Strikingly, as compared to a group of healthy subjects, the AIC/IFC case considerably overestimated reproduction times despite normal variability. The effect was obtained in all duration and emotion conditions. Such a distortion in time reproduction was not observed in four other epileptic patients without insular or inferior frontal damage. Importantly, the absolute extent of temporal over-reproduction increased in proportion to the magnitude of the target durations, which concurs with the scalar property of interval timing, and points to an impairment of time-specific rather than of non temporal (such as motor) mechanisms. Our data suggest that the disability in temporal reproduction of the AIC/IFC case would result from a distorted memory representation of the encoded duration, occurring during the process of storage and/or of recovery from memory and leading to a deviation of the temporal judgment during the reproduction task. These findings support the recent proposal that the anterior insular/inferior frontal cortices would be involved in time interval representation.

Postoperative recovery of hippocampal contralateral diffusivity in medial temporal lobe epilepsy correlates with memory functions.

This study aimed at determining if the recovery of mean diffusivity (MD) in the contralateral non sclerotic hippocampus is correlated with a change in memory outcome after surgery in patients with medial temporal lobe epilepsy (MTLE). Verbal and non-verbal memory scores and MD were assessed in 23 patients with MTLE before and after surgical treatment of epilepsy. The recovery of MD in the left hippocampus was correlated with the performance on verbal memory tests, and the recovery of MD in all patients was correlated with the performance on non-verbal memory tests. This finding strengthens the hypothesis that reversible diffusion abnormalities in the contralateral hippocampus in MTLE are linked to the active epileptic process that seems to interfere with memory abilities.

Abnormal pitch--time interference in congenital amusia: evidence from an implicit test.

Congenital amusia, characterized by a severe problem in detecting anomalies in melodies, is a lifelong disorder that has been ascribed to an acoustical pitch deficit. In the present study, we investigated how the perception of a duration is altered when it is bounded by tones varying in pitch. The results show that temporal accuracy is impaired by pitch variations as small as a quarter of a semitone in control participants, whereas it is impaired only when pitch variations are increased to 4 semitones in congenital amusics. Furthermore, control participants associate intervals bounded by low- and high-pitched tones with long and short durations, respectively. Amusic participants do not make this connection, even with large pitch differences, pointing to a deficit in pitch-time integration. Thus, our results are consistent with the notion that congenital amusia is linked to a neurogenetic anomaly that impairs pitch processing, independently of task factors.

The birth of musical emotion: a depth electrode case study in a human subject with epilepsy.

Intracranial electroencephalography was recorded in an epileptic patient when he was listening to dissonant and consonant chords and to minor and major chords. Changes in dissonance induced event-related potentials (ERPs) in the auditory areas from 200 ms onward, in the orbito-frontal cortex (500-1000 ms), and later in the amygdala and anterior cingulate gyrus (1200-1400 ms), suggesting the sequential involvement of these brain structures in implicit emotional judgment of musical dissonance. Changes in musical mode induced ERPs only in the orbito-frontal cortex (500-1000 ms), emphasizing the implication of this frontal region in emotional judgment of pleasant music.

Brain activity during interval timing depends on sensory structure.

Precise timing is crucial for accurate perception and action in the range of hundreds of milliseconds. One still unresolved question concerns the influence of sensory information content on timing mechanisms. Numerous studies have converged to suggest that the CNV (Contingent Negative Variation), a slow negative wave that develops between two events, notably reflects temporal processing of the interval between these two events. The present study aimed at investigating CNV activity in duration discrimination tasks using either filled (continuous tones) or empty intervals (silent periods bounded by two brief tones). Participants had to compare a test duration with a 600-ms standard. Time perception was markedly better in the 'empty' than in the 'filled' condition. Electrophysiological analyses performed on the longest test duration (794 ms) of the comparison phase revealed an effect of the sensory structure on both the CNV amplitude and CNV time-course. The CNV amplitude was larger for filled than for empty intervals, suggesting a superimposition of timing-dependent activity and sensory sustained activity. Furthermore, the CNV time-course paralleled the temporal structure of the memorized sensory event: for filled intervals, the CNV amplitude stopped increasing at 600 ms, i.e. the expected end of the continuous tone; for empty intervals, in contrast, the CNV amplitude precisely increased at 600 ms, i.e. the expected onset of the second brief tone. These results suggest that the CNV reflects the mental rehearsal of the memorized sensory event, in line with the idea that temporal processing in the sub-second range is based on sensory information.

Relationship between CNV and timing of an upcoming event.

This study reports an analysis of the Contingent Negative Variation (CNV) recorded on the human scalp during the comparison of a test duration with a previously memorized duration. Results show that CNV activity peaks at the end of the memorized duration, and that its slope varies inversely with the length of this duration. These features of CNV activity are similar to those of climbing neuronal activity observed through intracerebral recordings in animals, and suggest that both activities reflect how the brain encodes the timing of an upcoming event. These results also show that the time-course of the CNV in timing tasks is compatible with a pacemaker-accumulator model of temporal processing.

Neural network involved in time perception: an fMRI study comparing long and short interval estimation.

In this study, long ( approximately 1,300 ms) and short duration ( approximately 450 ms) estimation trials in an event-related functional MRI (fMRI) study were contrasted in order to reveal the regions within a time estimation network yielding increased activation with the increase of the duration to be estimated. In accordance with numerous imaging studies, our results showed that the presupplementary motor area (preSMA), the anterior cingulate, the prefrontal and parietal cortices, and the basal ganglia were involved in the estimation trials whatever the duration to be estimated. Moreover, only a subset of the regions within this distributed cortical and subcortical network yielded increased activation with increasing time, namely, the preSMA, the anterior cingulate cortex, the right inferior frontal gyrus (homolog to Broca's area), the bilateral premotor cortex, and the right caudate nucleus. This suggests that these regions are directly involved in duration estimation. We propose that the caudate-preSMA circuit, the anterior cingulate, and the premotor-inferior frontal regions may support a clock mechanism, decision and response-related processes, and active maintenance of temporal information, respectively.

When time is up: CNV time course differentiates the roles of the hemispheres in the discrimination of short tone durations.

Numerous studies have suggested that the CNV (contingent negative variation), a negative slow wave developing between a warning and an imperative stimulus, reflects, among other things, temporal processing of the interval between these two stimuli. One aim of the present work was to specify the relationship between CNV activity and the perceived duration. A second aim was to establish if this relationship is the same over the left and right hemispheres. Event-related potentials (ERPs) were recorded for 12 subjects performing a matching-to-sample task in which they had to determine if the duration of a tone (490 ms, 595 ms, 700 ms, 805 ms, and 910 ms) matched that of a previously presented standard (700 ms). CNV activity measured at the FCZ electrode was shown to increase until the standard duration had elapsed. By contrast, right frontal activity increased until the end of the current test duration, even when the standard duration had elapsed. Moreover, for long test durations (805 ms and 910 ms), correlations were observed between CNV peak latency and subjective standard, over left and medial frontal sites. We propose that left and medial frontal activity reflects an accumulation of temporal information that stops once the memorized standard duration is over, while right frontal activity subserves anticipatory attention near the end of the stimulus.

Processes involved in tempo perception: a CNV analysis.

The purpose of this research was to study the mechanisms underlying tempo perception, by looking at their electrophysiological brain correlates. The subjects' task consisted of comparing the tempos of two isochronous tone sequences made up of either three (condition 13) or six (condition 16) 600-ms intervals. Contingent negative variation (CNV), known to be linked to the judgment of a single interval, kept increasing in amplitude for three intervals during tempo encoding, thereby providing evidence of the occurrence of CNVs also for several intervals in succession. This CNV increase could reflect the use of interval-based processes in the building of the interval memory trace. During the comparison phase, a CNV decrease was observed in condition 16, suggesting that subjects did not build a new memory trace, but used beat-based processes to check whether the beats of the new tempo occurred at the times they anticipated.