Bruno Millet

 

 

Previous projects

 

Over the past five years, my research projects have been grounded within the framework of the “Equipe d’Accueil EA 4712 - Behaviour and Basal Ganglia”, labelled in January 2012 at the Rennes University . This team was co-founded by a neurologist and a psychiatrist (M. Vérin and B. Millet) with the objective of improving the understanding of the functional relationships between basal ganglia and the cortical structures in neuropsychiatric illnesses (Parkinson, Obsessive Compulsive Disorder (OCD), Treatment Resistant Depression (TRD)). This was made possible through studies focused upon emotional and motivational regulation.

Among the most striking results, the team has shown the involvement of sub-thalamic nucleus (STN) in emotions as well as in emotional recognition through different input modalities such as visual and auditory modalities (Drapier et al. 2008; Le Jeune et al. 2008). The role of STN has also been demonstrated in social cognition as well as in motivation (Drapier et al. 2006). With the help of metabolic neuroimaging, a correlation with brain structures has been found (Le Jeune et al. 2009). Using Deep Brain Stimulation (DBS) as an innovative therapy in severe psychiatric disorders, we participated in the discovery of the efficacy of high frequency DBS in severe OCD also obtaining information about the functional anatomical basis (Mallet et al. 2008; Le Jeune et al. 2010). At the same time, through daily routines, we have developed an in-house neuronavigation system applicable in rTMS for the treatment of psychiatric diseases (Nauczyciel et al. 2010; www.syneika.com). Finally, we have shown the potential efficacy of rTMS focused on OFC in OCD (Nauczyciel et al. 2014).

 

Current project

 

Currently, we have recently joined the Social and Affective Neuroscience research team located at the Institute of Brain and Spinal Chord (ICM) in La Pitié Salpetrière Hospital in Paris. We aim at articulating ICM research activity with our innovative therapeutic approach in resistant OCD, in Treatment Resistant Depression (TRD) as well as potentially in addictive disorders within the new Brain Stimulation Unit (STOCAD) recently promoted and built by the Assistance Publique des Hopitaux de Paris (AP-HP). In OCD, our recent works (Millet et al. 2013; Nauczyciel et al. 2014) allow us to propose the orbito-frontal cortex (OFC) as a plausible target for rTMS. We will try to identify for each patient a neuroimaging marker (potentially prefrontal activity), in order to potentialize the efficacy of rTMS. In depression, a similar work will be driven using EEG signal as a potential marker for a better use of the neuronavigated–rTMS.  In TRD as well as in ROC (resistant OCD) we are still continuing inclusion in different randomized control trials (RCTs) of high frequency DBS assessing nucleus accumbens (Millet et al. 2014), ventral striatum and STN as potential neuroanatomical targets. Those RCTs will be associated with Local Field Potentials recording discharge of neurons secondary to emotional auditory and facial recognition tasks as well as other cognitive tasks. These findings make crucial an improvement of implantation material, especially a great need for improvement of electrodes with more selective use in either the limbic or motor areas.

 

Some representative publications

 

Péron J, El Tamer S, Grandjean D, Leray E, Travers D, Drapier D, Vérin M, Millet B., “Major depressive disorder skews the recognition of emotional prosody.” Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):987-96.

 

Millet B, Vérin M, Drapier D., “Psychiatric indications of deep brain stimulation.” Bull Acad Natl Med. 2010 Mar;194(3):583-93.

 

Nauczyciel C, Hellier P, Morandi X, Blestel S, Drapier D, Ferre JC, Barillot C, Millet B., “Assessment of standard coil positioning in transcranial magnetic stimulation in depression.” Psychiatry Res. 2011 Apr 30;186(2-3):232-8.

 

Le Jeune F, Vérin M, N'Diaye K, Drapier D, Leray E, Du Montcel ST, Baup N, Pelissolo A, Polosan M, Mallet L, Yelnik J, Devaux B, Fontaine D, Chereau I, Bourguignon A, Peron J, Sauleau P, Raoul S, Garin E, Krebs MO, Jaafari N, Millet B; “French Stimulation dans le trouble obsessionnel compulsif (STOC) study group.” “Decrease of prefrontal metabolism after subthalamic stimulation in obsessive-compulsive disorder: a positron emission tomography study.” Biol Psychiatry. 2010 Dec 1;68(11):1016-22.

 

Duhameau B, Ferré JC, Jannin P, Gauvrit JY, Vérin M, Millet B, Drapier D., “Chronic and treatment-resistant depression: a study using arterial spin labelling perfusion MRI at 3 Tesla.” Psychiatry Res. 2010 May 30;182(2):111-6.

 

Péron J, Le Jeune F, Haegelen C, Dondaine T, Drapier D, Sauleau P, Reymann JM, Drapier S, Rouaud T, Millet B, Vérin M,  “Subthalamic Nucleus Stimulation Affects Theory of Mind Network: A PET Study in Parkinson's Disease.” PLoS One. 2010; 5(3): e9919.

 

Le Jeune F, Péron J, Grandjean D, Drapier S, Haegelen C, Garin E, Millet B, Vérin M., “Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study.” Eur J Nucl Med Mol Imaging. 2010 Aug;37(8):1512-20.

 

Le Jeune F, Drapier D, Bourguignon A, Péron J, Mesbah H, Drapier S, Sauleau P, Haegelen C, Travers D, Garin E, Malbert CH, Millet B, Vérin M., “Subthalamic nucleus stimulation in Parkinson disease induces apathy: a PET study.” Neurology. 2009 Nov 24;73(21):1746-51.

 

Drapier D, Péron J, Leray E, Sauleau P, Biseul I, Drapier S, Le Jeune F, Travers D, Bourguignon A, Haegelen C, Millet B, Vérin M., “Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson's disease have separate neural substrates.” Neuropsychologia. 2008 Sep;46(11):2796-801.

 

Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, du Montcel ST, Yelnik J, Chéreau I, Arbus C, Raoul S, Aouizerate B, Damier P, Chabardès S, Czernecki V, Ardouin C, Krebs MO, Bardinet E, Chaynes P, Burbaud P, Cornu P, Derost P, Bougerol T, Bataille B, Mattei V, Dormont D, Devaux B, Vérin M, Houeto JL, Pollak P, Benabid AL, Agid Y, Krack P, Millet B, Pelissolo A; STOC Study Group. “Subthalamic nucleus stimulation in severe obsessive-compulsive disorder.” N Engl J Med. 2008 Nov 13;359(20):2121-34.

 

F. Le Jeune, J. Péron, I. Biseul, S. Fournier, P. Sauleau, S. Drapier, C. Haegelen, D. Drapier, B. Millet, E. Garin, J.-Y. Herry, C.-H. Malbert, M. Vérin, “Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a pet study.” Brain. 2008 June; 131(6): 1599–1608.