Abstract The objectives were to study ultrasound (US), magnetic resonance imaging (MRI), single photon emission tomography (SPET) and brainstem auditory evoked potentials (BAEP) as structural and functional imaging methods for the prediction of later neuromotor outcome and to assess the reliability of auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free-field auditory behavioural responses (FF) for the prediction of permanent hearing loss. The series comprised 51 surviving very low birth weight preterm infants born at < 34 gestational weeks with a birth weight < 1500 grams, taking 52 full-term infants as controls with respect to hearing screening and 21 with respect to brainstem function. The imaging examinations and hearing screening were performed at term age and follow-up continued to a corrected age of 18 months for the evaluation of neurodevelopment and hearing. MRI images were analysed with regard to the degree of myelination, parenchymal lesions, ventricular-brain ratios and widths of the extracerebral spaces, and the predictive value of the findings for later neuromotor development was assessed by comparison with US. In the SPET examinations (on 34 infants) relative regional perfusion levels and hemispheric asymmetries were evaluated in slices. The predictive value of perfusion defects in SPET was similarly assessed relative to US abnormalities. Brainstem size was measured by MRI, and brainstem function evaluated by BAEP, and results being used to predict neurosensory disability. Hearing was screened by means of TEOAE, ABR and FF, and the results used to predict permanent hearing loss. Parenchymal lesions in MRI predicted cerebral palsy (CP) with a sensitivity of 82% and a specificity of 97%, the corresponding figures for US being 58% and 100%. Delayed myelination, ventricular-brain ratios and widths of the extracerebral spaces failed to predict CP. The sensitivity of perfusion defects in SPET for predicting CP was 82% and the specificity 70%, and correspondingly US attained a sensitivity of 73% and a specificity of 83%. The best brainstem dimensions for predicting neurosensory disability reached at sensitivity of 23-31% and a specificity of 97-100%. The best predictors in BAEP gave the sensitivity of 93% with a specificity of 57-59%. Bilateral failure in TEOAE predicted hearing loss with a sensitivity of 50% and with a specificity of 84%, and that in ABR with a sensitivity of 100% and a specificity of 98%. The FF examination showed a sensitivity of 50% and a specificity of 98%. In conclusion, out of the brain imaging methods used here MRI was the best for predicting abnormal neuromotor outcome. Brainstem dimensions in MRI appear to predict neurosensory disability poorly, however, whereas BAEP shows a better prediction value, but is limited by a low specificity. ABR seems to be the best hearing screening method because it includes retrocochlear involvements in preterm infants.

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Deep brain stimulation (DBS) is a neurosurgical intervention now established for the treatment of movement disorders. For the treatment of chronic pain refractory to medical therapies, several prospective case series have been reported, but few centres worldwide have published findings from patients treated during the last decade using current standards of technology. This thesis seeks to survey the current clinical status of DBS for pain, investigate its mechanisms and their interactions with autonomic function, its clinical limitations and ablative alternatives. Presented first is a review of the current status of analgesic DBS including contemporary clinical studies. The historical background, scientific rationale, patient selection and assessment methods, surgical techniques and results are described. The clinical outcomes of DBS of the sensory thalamus and periventricular / periaqueductal grey (PAVG) matter in two centres are presented including results from several pain and quality of life measures. A series of translational investigations in human subjects receiving DBS for pain elucidating mechanisms of analgesic DBS and its effects upon autonomic function are then presented. Single photon emission tomography comparing PAVG, VP thalamus and dual target stimulation is described. Somatosensory and local field potential (LFP) recordings suggesting PAVG somatotopy are shown. ABPM results demonstrating changes with PAVG DBS are given and Portapres studies into heart rate variability changes with ventral PAVG DBS are detailed. Investigations using naloxone are then shown to hypothesise separate dorsal opioidergic and ventral parasympathetic analgesic streams in the PAVG. Finally, cingulotomy in lung cancer to relieve pain and dyspnoea results are discussed in the context of altering pain and autonomic function by functional neurosurgery. Pain and autonomic interactions and mechanisms in deep brain surgery for pain are then discussed alongside its limitations with proposals made for optimising treatment and improving outcomes.

La pharmaco-résistance est une complication évolutive fréquente de l'épisode dépressif majeur. La rTMS est une technique de stimulation cérébrale innovante dont l'efficacité antidépressive est maintenant établie.Le premier objectif de notre travail de thèse a été de caractériser les substrats fonctionnels de la dépression pharmaco-résistante à l'aide de la technique TEMP, afin d'identifier des patterns d'anomalies cérébrales qui leur sont propres. Dans un second temps, et sur la base des travaux existant sur les mécanismes d'action de la rTMS, nous avons étudié la valeur prédictive de marqueurs fonctionnels en neuro-imagerie TEMP et par EEG. Enfin, nous avons relié l'effet cérébral de la rTMS révélé par la neuro-imagerie fonctionnelle à son efficacité antidépressive, et de façon plus globale à la qualité de vie, comme recommandé actuellement.Nos résultats montrent l'existence d'un pattern de perfusion cérébrale commun aux patients pharmaco-résistants quel que soit le type de dépression, impliquant les régions fronto-temporales et le cervelet. L'étude TEMP de la perfusion cérébrale et de l'activité cérébrale en l'EEG dans sa bande alpha semble pouvoir prédire de façon satisfaisante, avant traitement, l'amélioration clinique individuelle des patients dépressifs pharmaco-résistants traités par rTMS. L'efficacité antidépressive de la rTMS apparait équivalente quel que soit le côté stimulé, entrainant des modifications de perfusion cérébrale comparables. Enfin, nos résultats ont permis d'identifier des régions cérébrales dysfonctionnelles distinctes et confirment l'interet d'une approche complémentaire de la dépression, par l'évaluation de la qualité de vie. / Treatment-resistance is a common outcome of a major depressive episode. Repetitive transcranial magnetic stimulation has been put forward as a new technique to treat this debilitating illness. The first objective of our thesis was to characterize the functional substrates of treatment-resistant depression (TRD) using SPECT technique, in order to identify specific patterns of brain abnormalities. In a second part, based on existing work on the antidepressant mechanisms of rTMS, we investigated the predictive value of two neurofunctional biomarkers: SPECT and EEG. Finally, we studied brain SPECT perfusion changes underlying therapeutic efficiency and improvement of quality of life, as currently recommended. Our results showed the existence of a common pattern of brain perfusion in treatment-resistant patients involving the fronto-temporal regions and the cerebellum, regardless the type of depression. At baseline, SPECT brain perfusion and alpha EEG band power could predict individual clinical improvement in TRD-patients treated with rTMS. Regardless the stimulated side, the antidepressant efficacy of rTMS consisted in similar changes in cerebral perfusion. Finally, our results have identified distinct dysfunctional brain regions and confirm the interest of a complementary approach to depression, by assessing quality of life.