[Show abstract][Hide abstract] ABSTRACT: Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations.
Frontiers in Human Neuroscience 03/2015; 9:171. DOI:10.3389/fnhum.2015.00171 · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Leucin-rich, glioma inactivated 1 (LGI1) is a secreted protein linked to human seizures of both genetic and autoimmune aetiology. Mutations in the LGI1 gene are responsible for autosomal dominant temporal lobe epilepsy with auditory features, whereas LGI1 autoantibodies are involved in limbic encephalitis, an acquired epileptic disorder associated with cognitive impairment. We and others previously reported that Lgi1-deficient mice have early-onset spontaneous seizures leading to premature death at 2–3 weeks of age. Yet, where and when Lgi1 deficiency causes epilepsy remains unknown. To address these questions, we generated Lgi1 conditional knockout (cKO) mice using a set of universal Cre-driver mouse lines. Selective deletion of Lgi1 was achieved in glutamatergic pyramidal neurons during embryonic (Emx1-Lgi1cKO) or late postnatal (CaMKIIα-Lgi1cKO) developmental stages, or in gamma amino butyric acidergic (GABAergic) parvalbumin interneurons (PV-Lgi1cKO). Emx1-Lgi1cKO mice displayed early-onset and lethal seizures, whereas CaMKIIα-Lgi1cKO mice presented late-onset occasional seizures associated with variable reduced lifespan. In contrast, neither spontaneous seizures nor increased seizure susceptibility to convulsant were observed when Lgi1 was deleted in parvalbumin interneurons. Together, these data showed that LGI1 depletion restricted to pyramidal cells is sufficient to generate seizures, whereas seizure thresholds were unchanged after depletion in gamma amino butyric acidergic parvalbumin interneurons. We suggest that LGI1 secreted from excitatory neurons, but not parvalbumin inhibitory neurons, makes a major contribution to the pathogenesis of LGI1-related epilepsies. Our data further indicate that LGI1 is required from embryogenesis to adulthood to achieve proper circuit functioning.
[Show abstract][Hide abstract] ABSTRACT: Certain motor activities - like walking or breathing - present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks - including various frontal lobe areas - subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the "resting state" pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active maintenance of cortical control over a continuous motor activity impacts on brain functioning and cognition.
PLoS ONE 09/2014; 9(9):e107850. DOI:10.1371/journal.pone.0107850 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Between seizures the brain of patients with epilepsy generates pathological patterns of synchronous activity, designated as interictal epileptiform discharges (ID). Using microelectrodes in the hippocampal formations of 8 patients with drug-resistant temporal lobe epilepsy, we studied ID by simultaneously analyzing action potentials from individual neurons and the local field potentials (LFPs) generated by the surrounding neuronal network. We found that ~30% of the units increased their firing rate during ID and 40% showed a decrease during the post-ID period. Surprisingly, 30% of units showed either an increase or decrease in firing rates several hundred of milliseconds before the ID. In 4 patients, this pre-ID neuronal firing was correlated with field high-frequency oscillations at 40-120 Hz. Finally, we observed that only a very small subset of cells showed significant coincident firing before or during ID. Taken together, we suggested that, in contrast to traditional views, ID are generated by a sparse neuronal network and followed a heterogeneous synchronization process initiated over several hundreds of milliseconds before the paroxysmal discharges.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to explore auditory cortical oscillation properties in developmental dyslexia. We recorded cortical activity in 17 dyslexic participants and 15 matched controls using simultaneous EEG and fMRI during passive viewing of an audiovisual movie. We compared the distribution of brain oscillations in the delta, theta and gamma ranges over left and right auditory cortices. In controls, our results are consistent with the hypothesis that there is a dominance of gamma oscillations in the left hemisphere and a dominance of delta-theta oscillations in the right hemisphere. In dyslexics, we did not find such an interaction, but similar oscillations in both hemispheres. Thus, our results confirm that the primary cortical disruption in dyslexia lies in a lack of hemispheric specialization for gamma oscillations, which might disrupt the representation of or the access to phonemic units.
Frontiers in Human Neuroscience 08/2013; 7:454. DOI:10.3389/fnhum.2013.00454 · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neural oscillations in the alpha band (8-12 Hz) are increasingly viewed as an active inhibitory mechanism that gates and controls sensory information processing as a function of cognitive relevance. Extending this view, phase synchronization of alpha oscillations across distant cortical regions could regulate integration of information. Here, we investigated whether such long-range cross-region coupling in the alpha band is intrinsically and selectively linked to activity in a distinct functionally specialized brain network. If so, this would provide new insight into the functional role of alpha band phase synchrony. We adapted the phase-locking value to assess fluctuations in synchrony that occur over time in ongoing activity. Concurrent EEG and functional magnetic resonance imaging (fMRI) were recorded during resting wakefulness in 26 human subjects. Fluctuations in global synchrony in the upper alpha band correlated positively with activity in several prefrontal and parietal regions (as measured by fMRI). fMRI intrinsic connectivity analysis confirmed that these regions correspond to the well known fronto-parietal (FP) network. Spectral correlations with this network's activity confirmed that no other frequency band showed equivalent results. This selective association supports an intrinsic relation between large-scale alpha phase synchrony and cognitive functions associated with the FP network. This network has been suggested to implement phasic aspects of top-down modulation such as initiation and change in moment-to-moment control. Mechanistically, long-range upper alpha band synchrony is well suited to support these functions. Complementing our previous findings that related alpha oscillation power to neural structures serving tonic control, the current findings link alpha phase synchrony to neural structures underpinning phasic control of alertness and task requirements.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2012; 32(41):14305-14310. DOI:10.1523/JNEUROSCI.1358-12.2012 · 6.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Songbirds constitute a powerful model system for the investigation of how complex vocal communication sounds are represented and generated, offering a neural system in which the brain areas involved in auditory, motor and auditory-motor integration are well known. One brain area of considerable interest is the nucleus HVC. Neurons in the HVC respond vigorously to the presentation of the bird's own song and display song-related motor activity. In the present paper, we present a synthesis of neurophysiological studies performed in the HVC of one songbird species, the canary (Serinus canaria). These studies, by taking advantage of the singing behavior and song characteristics of the canary, have examined the neuronal representation of the bird's own song in the HVC. They suggest that breeding cues influence the degree of auditory selectivity of HVC neurons for the bird's own song over its time-reversed version, without affecting the contribution of spike timing to the information carried by these two song stimuli. Also, while HVC neurons are collectively more responsive to forward playback of the bird's own song than to its temporally or spectrally modified versions, some are more broadly tuned, with an auditory responsiveness that extends beyond the bird's own song. Lastly, because the HVC is also involved in song production, we discuss the peripheral control of song production, and suggest that interspecific variations in song production mechanisms could be exploited to improve our understanding of the functional role of the HVC in respiratory-vocal coordination.
Journal of Physiology-Paris 08/2012; 107. DOI:10.1016/j.jphysparis.2012.08.004 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has recently been conjectured that dyslexia arises from abnormal auditory sampling. What sampling rate is altered and how it affects reading remains unclear. We hypothesized that by impairing phonemic parsing abnormal low-gamma sampling could yield phonemic representations of unusual format and disrupt phonological processing and verbal memory. Using magnetoencephalography and behavioral tests, we show in dyslexic subjects a reduced left-hemisphere bias for phonemic processing, reflected in less entrainment to ≈30 Hz acoustic modulations in left auditory cortex. This deficit correlates with measures of phonological processing and rapid naming. We further observed enhanced cortical entrainment at rates beyond 40 Hz in dyslexics and show that this particularity is associated with a verbal memory deficit. These data suggest that a single auditory anomaly, i.e., phonemic oversampling in left auditory cortex, accounts for three main facets of the linguistic deficit in dyslexia.
[Show abstract][Hide abstract] ABSTRACT: In songbirds, neurons in the song nucleus HVC exhibit a striking example of selective auditory response, firing more to playback of the bird's own song (BOS) than to conspecific songs. This song selectivity has been found in various songbird species, both those that sing a single individual-specific song as well as those, such as the canary, in which both song structure and individual-identity encoding in song is more complex. In the present study, we investigated how the BOS is represented in the HVC of anesthetized long-day canaries by using temporal and spectral variants of the BOS stimulus. We addressed the question of how selective HVC neurons were by quantifying the number of song elements, called phrases, that evoked auditory responses. Phrases that were individual-specific or that were frequently delivered in an individual's songs did not drive HVC neurons to a greater degree than others. Reordering phrases or altering their acoustic structure caused a decrease in the auditory responsiveness of HVC neurons. This sensitivity to the spectral and temporal features of the BOS involved neurons that failed to respond to BOS variants or were driven by a reduced number of phrases, as well as neurons whose auditory responsiveness extended beyond the features of the individual's song, responding to phrases that were not sung by the bird itself. Therefore, the neural strategy by which BOS structure is represented in the canary HVC may require something other than a strict representation of the repertoire of song components. We suggest that the individual's song could be coded, at least in part, by an ensemble of broadly tuned neurons.
[Show abstract][Hide abstract] ABSTRACT: The physiological basis of human cerebral asymmetry for language remains mysterious. We have used simultaneous physiological and anatomical measurements to investigate the issue. Concentrating on neural oscillatory activity in speech-specific frequency bands and exploring interactions between gestural (motor) and auditory-evoked activity, we find, in the absence of language-related processing, that left auditory, somatosensory, articulatory motor, and inferior parietal cortices show specific, lateralized, speech-related physiological properties. With the addition of ecologically valid audiovisual stimulation, activity in auditory cortex synchronizes with left-dominant input from the motor cortex at frequencies corresponding to syllabic, but not phonemic, speech rhythms. Our results support theories of language lateralization that posit a major role for intrinsic, hardwired perceptuomotor processing in syllabic parsing and are compatible both with the evolutionary view that speech arose from a combination of syllable-sized vocalizations and meaningful hand gestures and with developmental observations suggesting phonemic analysis is a developmentally acquired process.
Proceedings of the National Academy of Sciences 10/2010; 107(43):18688-93. DOI:10.1073/pnas.1007189107 · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Trial-by-trial variability in perceptual performance on identical stimuli has been related to spontaneous fluctuations in ongoing activity of intrinsic functional connectivity networks (ICNs). In a paradigm requiring sustained vigilance for instance, we previously observed that higher prestimulus activity in a cingulo-insular-thalamic network facilitated subsequent perception. Here, we test our proposed interpretation that this network underpins maintenance of tonic alertness. We used simultaneous acquisition of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) in the absence of any paradigm to test an ensuing hypothesis, namely that spontaneous fluctuations in this ICN's activity (as measured by fMRI) should show a positive correlation with the electrical signatures of tonic alertness (as recorded by concurrent EEG). We found in human subjects (19 male, 7 female) that activity in a network comprising dorsal anterior cingulate cortex, anterior insula, anterior prefrontal cortex and thalamus is positively correlated with global field power (GFP) of upper alpha band (10-12 Hz) oscillations, the most consistent electrical index of tonic alertness. Conversely, and in line with earlier findings, alpha band power was negatively correlated with activity in another ICN, the so-called dorsal attention network which is most prominently involved in selective spatial attention. We propose that the cingulo-insular-thalamic network serves maintaining tonic alertness through generalized expression of cortical alpha oscillations. Attention is mediated by activity in other systems, e.g., the dorsal attention network for space, selectively disrupts alertness-related suppression and hence manifests as local attenuation of alpha activity.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 07/2010; 30(30):10243-50. DOI:10.1523/JNEUROSCI.1004-10.2010 · 6.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In songbirds, experience of social and environmental cues during a discrete period after birth may dramatically influence song learning. In the canary, the ability to learn new songs is assumed to persist throughout life. The aim of the present study was to investigate whether social context could guide changes in adult song. Three groups of canaries were kept in different social and temporal conditions. Results showed that the multiple hierarchical levels of the canary song structure were affected by social environment: songs of males housed together for 2 years were more similar than those of males that spent the same time in individual cages in regard to acoustic parameters, syllable repertoire and repertoire of sequences of two-syllable types. However, social housing did not result in the emergence of a group-specific vocal signature within songs. In conclusion, these results suggested that under the influence of social factors, a copying process could allow adult canaries to adjust, at least in part, their songs to those of other individuals.
[Show abstract][Hide abstract] ABSTRACT: In songbirds, auditory neurons of the nucleus HVC respond selectively to a particular complex sound, the bird's own song (BOS). In the canary, this song selectivity did not exclude responses to conspecific songs. Here, we recorded single units in nucleus HVC of adult canaries to assess to what extent repertoire sharing among birds contributed to auditory responsiveness to birds' songs other than the BOS. Results indicated that song phrases driving auditory responses could differ from bird's own phrases suggesting that a subset of neurons were not strictly tuned to acoustic features of self-generated song components. In the canary, auditory representation of the BOSs might be more complex than that which has been described for birds with a small repertoire.
[Show abstract][Hide abstract] ABSTRACT: Through variations in features, both within and between individuals, songs of male passerines provide information on the identity of the singer. In domesticated canaries (Serinus canaria), these variations remain, for a large part, to be investigated. This led us to question whether individual identity might be coded at one or more hierarchical levels of song organization, i.e. in acoustic parameters, in the syllable repertoire and in the delivery order of syllables. A song as a whole had numerous individual distinctive acoustic features. However, the structure of its individual signature appeared to be complex. A repertoire combined syllables never sung by other individuals with those shared by other birds. But, most of the individual-specific syllables that accounted for 16% of a repertoire did not recur frequently. Variation in sequences of multiple syllable types appeared to reflect the individual identity of a male canary. Nearly all sequences larger than three syllable types were specific to the individual that produced them. Some of these occurred recurrently in songs and differed in their acoustic structure between individuals. Focusing upon recurrent sequences might allow vocal recognition of an individual without requiring the knowledge of its full repertoire. However, acoustic parameters and repertoire composition might also serve as additional cues to limit confusion between individuals.
[Show abstract][Hide abstract] ABSTRACT: Song geographic variation and Neighbour-Stranger (N-S) discrimination have been intensively but separately studied in bird species, especially in those with small- to medium-sized repertoires. Here, we establish a link between the two phenomena by showing that dialect features are used for N-S recognition in a territorial species with a large repertoire, the skylark Alauda arvensis. In this species, during the breeding season, many pairs settle in stable and adjoining territories gathered in locations spaced by a few kilometres. In a first step, songs produced by males established in different locations were recorded, analyzed and compared to identify possible microgeographic variation at the syntax level. Particular common sequences of syllables (phrases) were found in the songs of all males established in the same location (neighbours), whereas males of different locations (strangers) shared only few syllables and no sequences. In a second step, playback experiments were conducted and provided evidence for N-S discrimination consistent with the dear-enemy effect, i.e. reduced aggression from territorial birds towards neighbours than towards strangers. In addition, a similar response was observed when a ;chimeric' signal (shared phrases of the location artificially inserted in the song of a stranger) and a neighbour song were broadcast, indicating that shared sequences were recognized and identified as markers of the group identity. We thus show experimentally that the shared phrases found in the songs of neighbouring birds constitute a group signature used by birds for N-S discrimination, and serve as a basis for the dear-enemy effect.
[Show abstract][Hide abstract] ABSTRACT: Among songbird species, the canary, Serinus canaria, is considered to be an ‘open-ended’ song learner because adults continue to change their syllable repertoire throughout their lives. However, it remains unclear whether the capacity to alter the syllable repertoire allows birds to acquire new song material to correct abnormal song characteristics that result from auditory isolation during development. To address this question, we reared males without any experience of typical adult conspecific song models from fledging to sexual maturity. They were then placed for at least 2 years in an aviary that included adult conspecific males. Discriminant function analyses on songs indicated that features describing the fine structure of syllables showed significant differences between isolation-reared and control birds. Analysis of syllable repertoires attributed differences to a higher proportion of multiple-element syllables in songs of isolation-reared males than in songs of control males. Isolation-reared birds were able to modify their syllable repertoire throughout their lives. However, the proportion of multiple-element syllables, instead of decreasing during the years spent in the aviary, continued to form a large part of the songs. The ability of isolation-reared canaries to change their repertoires failed to rectify, at least in large part, the syllable abnormalities caused by the lack of a song model during their first year of life. Therefore, new and previously acquired syllables might result from similar underlying processes that would set limits to the kinds of syllables produced in adulthood.
[Show abstract][Hide abstract] ABSTRACT: To what extent seasonal factors modify the neuronal functional properties within the nuclei of the avian song system remains an open question. In adult songbirds, neurons of the song premotor nucleus HVC (used as a proper name) exhibit selective responses for the bird's own song (BOS). Here we examine whether, outside the breeding season, when songs are less stereotyped, HVC neurons of male canaries still respond selectively to the BOS produced during this period. In an initial experiment, single-unit recordings (n = 114) revealed that the neuronal selectivity for the current BOS was attenuated in males exposed to a short-day photoperiod (typical of the nonbreeding season) compared with that found in males exposed to a long-day photoperiod. In long-day conditions, 35% of the cells responded to the BOS, whereas only 12% did in short-day conditions; there were four times more selective cells (d' > 1) in long-day than in short-day conditions. To determine whether these effects were the consequence of differences in acoustic features between breeding and nonbreeding songs, neurons (n = 72) recorded in short-day conditions were tested with both a short-day BOS and a long-day BOS. A low percentage of neurons exhibited responses to short-day or to long-day BOS (11% for each song). Responses of putative interneurons (spike duration < 0.4 ms) and of putative relay cells were similarly attenuated by the short-day conditions. These results strongly suggest that, in canary, rather than being a fixed property, the selectivity for the BOS moves along a continuum and peaks when the day length mimics the breeding conditions.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 05/2005; 25(20):4952-63. DOI:10.1523/JNEUROSCI.4847-04.2005 · 6.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The neuronal selectivity observed in the avian song system for the Bird's Own Song progressively emerged as an extraordinary fruitful model to investigate the neural code underlying the recognition of complex stimuli and the occurrence of learned behaviors. In adult zebra finch, neurons from the HVC (used as a proper name) show very selective auditory responses, firing more to presentation of the Bird's Own Song (BOS) than to reverse BOS or other conspecific songs. However, as adult zebra finches always produce the same stereotyped song, the presence of such highly selective neurons in birds with larger repertoire still remains an open question. Data presented here show that neurons selective for the BOS can be found in adult canary, a seasonal breeding bird which display a large repertoire. More precisely, we found that a large proportion of neurons (29/36) exhibits higher responses to presentation of the forward than to the reverse BOS, and that 22% of the cells were identified as selective on the basis of the d' value. For a cell that was extensively studied, we evaluated to what extent temporal stimulus-related structure predicts the acoustic stimulus using linear or non-linear artificial neural networks (ANN). These analyses indicated that the temporal structure contained in spike trains characterizes more accurately the stimulus than the firing rate. The limitations of applying ANN analyses to electrophysiological data are discussed and potential solutions to increase the confidence in these analysis are proposed.
Journal of Physiology-Paris 07/2004; 98(4-6):395-406. DOI:10.1016/j.jphysparis.2005.09.011 · 2.35 Impact Factor