Micha Pfeuty

Neural Network Involved in Time Perception: An fMRI Study Comparing Long and Short Interval Estimation

In this study, long (∼1,300 ms) and short duration (∼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 Brocas 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. Hum. Brain Mapping, 2005.

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.

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.

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. Hum Brain Mapp 36:981–995, 2015.

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.

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.

Impulsive aggressive obsessions following cerebellar strokes: a case study.

Out of the total ischemic stroke events, about 4 % of them affect the cerebellum [1]. Traditionally, studies on cerebellar function have focused on the motor functions. It is clear now that the cerebellum underlies numerous nonmotor networks [2] and has a role not only in higher cognitive functions [3], but also in emotional and behavioral processing [4]. ‘‘Mr. M’’ is a 56-year-old left-handed man with 11 years of educational level and was professionally active (baker). His medical history reveals neither significant previous medical history nor any mental disorder. He was admitted for a sudden vertigo and dysarthria and left paresthesia. Brain MRI showed a right cerebellar punctiform infarction (lobule VI). A stroke recurrence occurred few days later, with similar minor symptoms. Brain MRI demonstrated a new ischemic lesion in the left superior cerebellar artery territory (lobule VI), and in a right perforating branch of the pons (pyramidal tract) (Fig. 1). In the acute phase of stroke, Mr. M presented a moderate level of anxiety, but he had no apathy, depression or cognitive disorders when assessed by reliable scales (data available on request). Five months after stroke, the patient started to experience invasive obsessive thoughts leading to an important distress. The content of these obsessions focus on an unacceptable theme: stabbing a relative. The intensity of these obsessions was associated with daily life alteration, avoidance behavior and anxiety. In the distress to an immediate hetero-aggressive gesture by cold steel on his daughter, he committed impulsive suicide attempts by drowning. In this context, he was hospitalized in a psychiatric hospital with the final diagnosis of obsessive– compulsive disorder (OCD) complicated by a major depressive disorder (MDD). Following the recent guidelines for pharmacotherapy in OCD [5], first-line selective serotonin reuptake inhibitor (SSRI) (escitalopram, sertraline, paroxetine) then second-line antidepressant (venlafaxine) until the dosage of 225 mg/day with antipsychotic as adjunctive therapy (risperidone 2 mg/day) were tried but they failed. At last, the combination of diazepam (20 mg/day), paroxetine (40 mg/day) and quetiapine (100 mg/day) was efficient for MDD but failed to significantly improve the impulsive aggressive obsessions leading to recurrent hospitalizations. Cognitive behavioral therapy (CBT) was tried but was unfortunately poorly efficient on obsessions. A meta-analysis in 2008 reported that lobule VI is involved in emotional processing by a cerebellar-limbic circuit [6]. Chronology and infarct localization suggest that the second cerebellar stroke, involving lobules VI and Crus I, was preferentially responsible of the onset of psychiatric disorder and fully supports our hypothesis. However, we cannot exclude the potential influence of the first stroke’s stress, or the influence of bilateral lesions. The cerebellum seems to be less activated in patients with OCD [7, 8], but there is a lack of studies exploring the clinical implications of this phenomenon. Several studies & Arnaud Tessier atessier@ch-perrens.fr