Background: Learning by conditioning is a key ability of animals and humans for acquiring novel behavior necessary for survival in a changing environment. Aberrant conditioning has been considered a crucial factor in the etiology and maintenance of panic disorder with agoraphobia (PD/A). Cognitive-behavioral therapy (CBT) is an effective treatment for PD/A. However, the neural mechanisms underlying the effects of CBT on conditioning processes in PD/A are unknown. Methods: In a randomized, controlled, multicenter clinical trial in medication-free patients with PD/A who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before and after CBT. Quality-controlled fMRI data from 42 patients and 42 healthy subjects were obtained. Results: After CBT, patients compared to control subjects revealed reduced activation for the conditioned response (CS+ > CS–) in the left inferior frontal gyrus (IFG). This activation reduction was correlated with reduction in agoraphobic symptoms from t1 to t2. Patients compared to control subjects also demonstrated increased connectivity between the IFG and regions of the “fear network” (amygdalae, insulae, anterior cingulate cortex) across time. Conclusions: This study demonstrates the link between cerebral correlates of cognitive (IFG) and emotional (“fear network”) processing during symptom improvement across time in PD/A. Further research along this line has promising potential to support the development and further optimization of targeted treatments.

The aim of this thesis was to investigate the input-specificity of sensory-induced plasticity in humans. This was achieved by varying the characteristics of sine gratings so that they selectively targeted distinct populations of neurons in the visual cortex. In Experiments 1-3, specificity was investigated with electroencephalography using horizontally- and vertically-oriented sine gratings (Experiment 1) or gratings of differing spatial frequency (Experiments 2 & 3). Increases in the N1b potential were observed only for sine gratings that were the same in orientation or spatial frequency as that used as the tetanus, suggesting that the potentiation is specific to the visual pathways stimulated during the induction of the tetanus. However, the increase in the amplitude of the N1b in Experiment 1 was not maintained when tested again at 50 minutes post-tetanus. This may have been due to depotentiation caused by the temporal frequency of stimulus presentation in the first post-tetanus block. To try to circumvent this potential confound, immediate and maintained (tested 30 minutes post-tetanus) spatial-frequency-specific potentiation were tested separately in Experiments 2 and 3, respectively. Experiment 3 demonstrated that the increased N1b was maintained for up to half an hour post-tetanus. In addition, the findings from Experiment 1, as well as the pattern of results from Experiments 2 and 3, indicate that the potentiation must be occurring in the visual cortex rather than further upstream at the lateral geniculate nucleus. In Experiment 4 functional magnetic resonance imaging was used to more accurately localise where these plastic changes were taking place using sine gratings of differing spatial frequency. A small, focal post-tetanic increase in the blood-oxygen-level-dependent (BOLD) response was observed for the tetanised grating in the right temporo-parieto-occipital junction. For the non-tetanised grating, decreases in BOLD were found in the primary visual cortex and bilaterally in the cuneus and pre-cuneus. These decreases may have been due to inhibitory interconnections between neurons tuned to different spatial frequencies. These data indicate that tetanic sensory stimulation selectively targets and potentiates specific populations of neurons in the visual cortex.

The aim of this thesis was to investigate the input-specificity of sensory-induced plasticity in humans. This was achieved by varying the characteristics of sine gratings so that they selectively targeted distinct populations of neurons in the visual cortex. In Experiments 1-3, specificity was investigated with electroencephalography using horizontally- and vertically-oriented sine gratings (Experiment 1) or gratings of differing spatial frequency (Experiments 2 & 3). Increases in the N1b potential were observed only for sine gratings that were the same in orientation or spatial frequency as that used as the tetanus, suggesting that the potentiation is specific to the visual pathways stimulated during the induction of the tetanus. However, the increase in the amplitude of the N1b in Experiment 1 was not maintained when tested again at 50 minutes post-tetanus. This may have been due to depotentiation caused by the temporal frequency of stimulus presentation in the first post-tetanus block. To try to circumvent this potential confound, immediate and maintained (tested 30 minutes post-tetanus) spatial-frequency-specific potentiation were tested separately in Experiments 2 and 3, respectively. Experiment 3 demonstrated that the increased N1b was maintained for up to half an hour post-tetanus. In addition, the findings from Experiment 1, as well as the pattern of results from Experiments 2 and 3, indicate that the potentiation must be occurring in the visual cortex rather than further upstream at the lateral geniculate nucleus. In Experiment 4 functional magnetic resonance imaging was used to more accurately localise where these plastic changes were taking place using sine gratings of differing spatial frequency. A small, focal post-tetanic increase in the blood-oxygen-level-dependent (BOLD) response was observed for the tetanised grating in the right temporo-parieto-occipital junction. For the non-tetanised grating, decreases in BOLD were found in the primary visual cortex and bilaterally in the cuneus and pre-cuneus. These decreases may have been due to inhibitory interconnections between neurons tuned to different spatial frequencies. These data indicate that tetanic sensory stimulation selectively targets and potentiates specific populations of neurons in the visual cortex.

The aim of this thesis was to investigate the input-specificity of sensory-induced plasticity in humans. This was achieved by varying the characteristics of sine gratings so that they selectively targeted distinct populations of neurons in the visual cortex. In Experiments 1-3, specificity was investigated with electroencephalography using horizontally- and vertically-oriented sine gratings (Experiment 1) or gratings of differing spatial frequency (Experiments 2 & 3). Increases in the N1b potential were observed only for sine gratings that were the same in orientation or spatial frequency as that used as the tetanus, suggesting that the potentiation is specific to the visual pathways stimulated during the induction of the tetanus. However, the increase in the amplitude of the N1b in Experiment 1 was not maintained when tested again at 50 minutes post-tetanus. This may have been due to depotentiation caused by the temporal frequency of stimulus presentation in the first post-tetanus block. To try to circumvent this potential confound, immediate and maintained (tested 30 minutes post-tetanus) spatial-frequency-specific potentiation were tested separately in Experiments 2 and 3, respectively. Experiment 3 demonstrated that the increased N1b was maintained for up to half an hour post-tetanus. In addition, the findings from Experiment 1, as well as the pattern of results from Experiments 2 and 3, indicate that the potentiation must be occurring in the visual cortex rather than further upstream at the lateral geniculate nucleus. In Experiment 4 functional magnetic resonance imaging was used to more accurately localise where these plastic changes were taking place using sine gratings of differing spatial frequency. A small, focal post-tetanic increase in the blood-oxygen-level-dependent (BOLD) response was observed for the tetanised grating in the right temporo-parieto-occipital junction. For the non-tetanised grating, decreases in BOLD were found in the primary visual cortex and bilaterally in the cuneus and pre-cuneus. These decreases may have been due to inhibitory interconnections between neurons tuned to different spatial frequencies. These data indicate that tetanic sensory stimulation selectively targets and potentiates specific populations of neurons in the visual cortex.

The aim of this thesis was to investigate the input-specificity of sensory-induced plasticity in humans. This was achieved by varying the characteristics of sine gratings so that they selectively targeted distinct populations of neurons in the visual cortex. In Experiments 1-3, specificity was investigated with electroencephalography using horizontally- and vertically-oriented sine gratings (Experiment 1) or gratings of differing spatial frequency (Experiments 2 & 3). Increases in the N1b potential were observed only for sine gratings that were the same in orientation or spatial frequency as that used as the tetanus, suggesting that the potentiation is specific to the visual pathways stimulated during the induction of the tetanus. However, the increase in the amplitude of the N1b in Experiment 1 was not maintained when tested again at 50 minutes post-tetanus. This may have been due to depotentiation caused by the temporal frequency of stimulus presentation in the first post-tetanus block. To try to circumvent this potential confound, immediate and maintained (tested 30 minutes post-tetanus) spatial-frequency-specific potentiation were tested separately in Experiments 2 and 3, respectively. Experiment 3 demonstrated that the increased N1b was maintained for up to half an hour post-tetanus. In addition, the findings from Experiment 1, as well as the pattern of results from Experiments 2 and 3, indicate that the potentiation must be occurring in the visual cortex rather than further upstream at the lateral geniculate nucleus. In Experiment 4 functional magnetic resonance imaging was used to more accurately localise where these plastic changes were taking place using sine gratings of differing spatial frequency. A small, focal post-tetanic increase in the blood-oxygen-level-dependent (BOLD) response was observed for the tetanised grating in the right temporo-parieto-occipital junction. For the non-tetanised grating, decreases in BOLD were found in the primary visual cortex and bilaterally in the cuneus and pre-cuneus. These decreases may have been due to inhibitory interconnections between neurons tuned to different spatial frequencies. These data indicate that tetanic sensory stimulation selectively targets and potentiates specific populations of neurons in the visual cortex.

The aim of this thesis was to investigate the input-specificity of sensory-induced plasticity in humans. This was achieved by varying the characteristics of sine gratings so that they selectively targeted distinct populations of neurons in the visual cortex. In Experiments 1-3, specificity was investigated with electroencephalography using horizontally- and vertically-oriented sine gratings (Experiment 1) or gratings of differing spatial frequency (Experiments 2 & 3). Increases in the N1b potential were observed only for sine gratings that were the same in orientation or spatial frequency as that used as the tetanus, suggesting that the potentiation is specific to the visual pathways stimulated during the induction of the tetanus. However, the increase in the amplitude of the N1b in Experiment 1 was not maintained when tested again at 50 minutes post-tetanus. This may have been due to depotentiation caused by the temporal frequency of stimulus presentation in the first post-tetanus block. To try to circumvent this potential confound, immediate and maintained (tested 30 minutes post-tetanus) spatial-frequency-specific potentiation were tested separately in Experiments 2 and 3, respectively. Experiment 3 demonstrated that the increased N1b was maintained for up to half an hour post-tetanus. In addition, the findings from Experiment 1, as well as the pattern of results from Experiments 2 and 3, indicate that the potentiation must be occurring in the visual cortex rather than further upstream at the lateral geniculate nucleus. In Experiment 4 functional magnetic resonance imaging was used to more accurately localise where these plastic changes were taking place using sine gratings of differing spatial frequency. A small, focal post-tetanic increase in the blood-oxygen-level-dependent (BOLD) response was observed for the tetanised grating in the right temporo-parieto-occipital junction. For the non-tetanised grating, decreases in BOLD were found in the primary visual cortex and bilaterally in the cuneus and pre-cuneus. These decreases may have been due to inhibitory interconnections between neurons tuned to different spatial frequencies. These data indicate that tetanic sensory stimulation selectively targets and potentiates specific populations of neurons in the visual cortex.

A ce jour, six millions de français sont atteints de troubles de l'audition. Face à ce problème de santé publique, des outils performants d'exploration de la fonction auditive sont indispensables. La Speech ABR (Speech Auditory Brainstem Response ou Réponse du tronc cérébral auditif à la parole) est un outil prometteur, comme marqueur électrophysiologique fin de l'encodage neuronal de la parole. Cependant, sa méthodologie reste peu développée, son origine neuronale incertaine et elle n'a jamais été enregistrée chez le malentendant porteur d'aides auditives. Le premier axe de cette thèse porte sur les générateurs neuronaux de la Speech ABR. Le développement d'une méthodologie de recueil topographique de cette réponse jusqu'alors décrite comme strictement sous-corticale, a d'abord suggéré la possibilité d'un générateur cortical. Une étude en stéréo-électroencéphalographie a ensuite confirmé l'existence d'une activité Speech ABR dans les cortex auditifs primaires bilatéraux. Ce résultat apporte un éclairage nouveau sur la représentation des sons de parole par système nerveux auditif. Le second axe concerne l'étude de la Speech ABR chez le malentendant appareillé. Après avoir développé une méthodologie de stimulation acoustique directement au travers des aides auditives, nous avons étudié la plasticité neuronale induite par le port d'aides auditives. Les résultats montrent une amélioration de l'identification des phonèmes amplifiés, liée à une représentation corticale modifiée et à un encodage fréquentiel rééquilibré. Ces toutes premières preuves de plasticité neuronales dès les 4 premiers mois d'utilisation des aides auditives ouvrent de nouveaux espoirs thérapeutiques / To date, six million French are hearing impaired. To address this public health issue, efficient tools for exploration of the hearing function are essentials. Speech ABR (Speech Auditory Brainstem Response) is a promising tool, being a fine electrophysiological marker of the neuronal encoding of speech. Though, its methodology remains underdeveloped, its neural origin is still uncertain, and it has never been recorded in hearing aid users. The first axis of this thesis focuses on the neural generators of Speech ABR. The development of a methodology for recording topographies of this response, up to now described as strictly subcortical, first suggested the possibility of a cortical generator. A stereo-electroencephalography study then confirmed the existence of Speech ABR activity in bilateral primary auditory cortices. This result sheds a new light on the representation of speech sounds within the auditory nervous system. The second axis concerns the study of Speech ABR in hearing aid users. After having developed a methodology of acoustic stimulation directly through hearing aids, we investigated neural plasticity induced by hearing aid use. Results show an improvement in the identification of amplified phonemes, linked to an altered cortical representation and a rebalanced frequency encoding. This very first evidence of neural plasticity as soon as the first four months of hearing aid use opens up new therapeutic hopes