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1.
Transl Psychiatry ; 10(1): 139, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398699

RESUMO

Despite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated. Here, we aimed to test whether focal brain lesions in lesional mania are more often right- than left-sided, and if lesions converge on areas relevant to mood regulation. We thus performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflect diagnoses and structures of interest, as well as lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, selecting reports of adult-onset hypomania, mania or mixed state following a focal brain lesion, for pooled-analyses of individual patient data. Eligible lesion images were manually traced onto the corresponding MNI space slices, and lesion topography analyzed using standard brain atlases. Using this approach, data from 211 lesional mania patients was extracted from 114 reports. Among 201 cases with focal lesions, more patients had lesions involving exclusively the right (60.7%) than exclusively the left (11.4%) hemisphere. In further analyses of 56 eligible lesion images, while findings should be considered cautiously given the potential for selection bias of published lesion images, right-sided predominance of lesions was confirmed across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, and several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions. Such pooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected.

2.
J Neurol Neurosurg Psychiatry ; 91(5): 547-559, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32132227

RESUMO

The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres, which connects various nodes of a limbic circuitry and is believed to play a key role in cognition and episodic memory recall. As the most prevalent cause of dementia, Alzheimer's disease (AD) dramatically impairs the quality of life of patients and imposes a significant societal burden on the healthcare system. As an established treatment for movement disorders, deep brain stimulation (DBS) is currently being investigated in preclinical and clinical studies for treatment of memory impairment in AD by modulating fornix activity. Optimal target and stimulation parameters to potentially rescue memory deficits have yet to be determined. The aim of this review is to consolidate the structural and functional aspects of the fornix in the context of neuromodulation for memory deficits. We first present an anatomical and functional overview of the fibres and structures interconnected by the fornix. Recent evidence from preclinical models suggests that the fornix is subdivided into two distinct functional axes: a septohippocampal pathway and a subiculothalamic pathway. Each pathway's target and origin structures are presented, followed by a discussion of their oscillatory dynamics and functional connectivity. Overall, neuromodulation of each pathway of the fornix is discussed in the context of evidence-based forniceal DBS strategies. It is not yet known whether driving fornix activity can enhance cognition-optimal target and stimulation parameters to rescue memory deficits have yet to be determined.

3.
J Biophotonics ; 13(2): e201960083, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31710771

RESUMO

Optical coherence tomography can differentiate brain regions with intrinsic contrast and at a micron scale resolution. Such a device can be particularly useful as a real-time neurosurgical guidance tool. We present, to our knowledge, the first full-field swept-source optical coherence tomography system operating near a wavelength of 1310 nm. The proof-of-concept system was integrated with an endoscopic probe tip, which is compatible with deep brain stimulation keyhole neurosurgery. Neuroimaging experiments were performed on ex vivo brain tissues and in vivo in rat brains. Using classification algorithms involving texture features and optical attenuation, images were successfully classified into three brain tissue types.

4.
Presse Med ; 48(12): 1507-1519, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31767248

RESUMO

Vagus nerve stimulation (VNS) is an old, yet new, option for treatment-resistant depression. Despite several clinical trials over the last 15 years showing a consistent benefit-risk balance of the technic, VNS still struggles to find its place in our therapeutic algorithms. This is especially true in France, where only a few surgeries have been performed nationwide, all in the last year. The reasons behind this lag are manifolds; (1) psychiatrists usually do not consider surgical treatments, even when they are minimally invasive and reversible, (2) early VNS trials stumbled on methodological difficulties that are common to all invasive neurostimulation technics, and initially failed to provide strong evidence for its efficacy, and (3) VNS requires multidisciplinary teams involving psychiatrists and neurosurgeons that did not exist then. Nevertheless, studies of the past twenty years support VNS as a treatment of depression endowed with a unique efficacy profile: a long runner best at maintaining remission in hard-to-stabilize depression, even in the context of ECT withdrawal, and irrespective of whether it is unipolar or bipolar. Thus, VNS potentially addresses the unmet medical needs of some of the most severe and chronic patients with depression. This review aims at introducing VNS as a treatment option for depression, summarizing available evidence for its efficacy and tolerance, and delineating patient profiles that might benefit the most of such treatment.


Assuntos
Depressão/terapia , Estimulação do Nervo Vago , Depressão/epidemiologia , Depressão/etiologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Transtorno Depressivo/terapia , França/epidemiologia , Humanos , Resultado do Tratamento , Nervo Vago/fisiologia , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/métodos , Estimulação do Nervo Vago/tendências
6.
Brain Stimul ; 12(1): 119-128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30344109

RESUMO

BACKGROUND: The therapeutic options for treatment-resistant depression (TRD) encompass a range of neuromodulatory techniques, including repetitive transcranial magnetic stimulation (rTMS). While rTMS is safe and has documented short-term efficacy, durability of antidepressant effects is poorly established. OBJECTIVE: Assess existing evidence regarding durability of rTMS-induced antidepressant response. METHODS: We performed a systematic review of studies reporting antidepressant outcome measures collected three or more months after the end of an induction course of rTMS for depression. Among responders to the induction course, we used a meta-analytic approach to assess response rates at 3 (m3), 6 (m6) or 12 (m12) months after induction, and studied predictors of responder rates using meta-regression. RESULTS: Nineteen studies published between 2002 and 2018 were included. Eighteen were eligible for analysis at m3 (732 patients) and m6 (695 patients) and 9 at m12 (247 patients). Among initial responders, 66.5% sustained response at m3 (95% CI = 57.1-74.8%, I2 = 27.6%), 52.9% at m6 (95% CI = 40.3-65%, I2 = 0%), and 46.3% at m12 (95% CI = 32.6-60.7%, I2 = 0%), in the absence of any major bias. Random-effects meta-regressions further demonstrated that a higher proportion of women, as well as receipt of maintenance treatment, predicted higher responder rates at specific time-points. CONCLUSIONS: rTMS is a durable treatment for depression, with sustained responder rates of 50% up to 1 year after a successful induction course of treatment. Maintenance treatment may enhance the durability of the antidepressant effects of rTMS, and should be considered in clinical practice, as well as systematically explored in future clinical trials.


Assuntos
Transtorno Depressivo Resistente a Tratamento/psicologia , Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Feminino , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
7.
Trends Neurosci ; 41(7): 418-428, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735372

RESUMO

Pharmacological neuromodulation strategies have shown limited efficacy in treating memory deficits related to Alzheimer's disease (AD). Despite encouraging results from a few preclinical studies, clinical trials investigating open-loop deep brain stimulation (DBS) for AD have not been successful. Recent refinements in understanding the various phases of memory processes, animal studies investigating phase-specific modulation of hippocampal activity during memorization, and clinical studies using closed-loop DBS strategies to treat patients with movement disorders, all point to the need to investigate closed-loop fornical DBS strategies to better understand memory dynamics and potentially treat memory deficits in AD preclinical models.


Assuntos
Doença de Alzheimer/terapia , Estimulação Encefálica Profunda/métodos , Fórnice , Doença de Alzheimer/fisiopatologia , Animais , Fórnice/fisiopatologia , Humanos
9.
Sci Rep ; 7: 43997, 2017 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-28276522

RESUMO

Optogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic effects and did not trigger non-physiological functional activation. This study demonstrates the ability to illuminate cortical layers to a depth of several millimeters using pulsed red light without detrimental thermal damages.


Assuntos
Córtex Cerebral/efeitos da radiação , Luz , Optogenética/métodos , Animais , Córtex Cerebral/fisiologia , Temperatura Alta/efeitos adversos , Luz/efeitos adversos , Neurônios/fisiologia , Neurônios/efeitos da radiação , Optogenética/efeitos adversos , Ratos Wistar , Pesquisa Médica Translacional
11.
Int J Radiat Oncol Biol Phys ; 95(2): 721-8, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-26960748

RESUMO

PURPOSE: To analyze the relationship between dosimetric characteristics and symptoms related to trigeminal neuropathy (TN) observed after radiosurgery (RS) for vestibular schwannomas (VS); to propose guidelines to optimize planification in VS RS regarding TN preservation; and to detail the mechanism of TN impairment after VS RS. METHODS AND MATERIALS: One hundred seventy-nine patients treated between 2011 and 2013 for VS RS and without trigeminal impairment before RS were included in a retrospective study. Univariate and multivariate analyses were performed to determine predictors of TN among characteristics of the patients, the dosimetry, and the VS. RESULTS: There were 20 Koos grade 1, 99 grade 2, 57 grade 3, and 3 grade 4. Fourteen patients (7.8%) presented a transitory or permanent TN. Between the patients with and without TN after VS RS, there was no significant difference regarding dosimetry or VS volume itself. Significant differences (univariate analysis P<.05, Mann-Whitney test) were found for parameters related to the cisternal portion of the trigeminal nerve: total integrated dose, maximum dose, mean dose, volume of the Vth nerve (Volv), and volume of the Vth nerve receiving at least 11 Gy (VolVcist>11Gy), but also for maximal dose to the Vth nerve nucleus and intra-axial portion (Dose maxVax). After multivariate analysis, the best model predicting TN included VolVcist>11Gy (P=.0045), Dose maxVax (P=.0006), and Volv (P=.0058). The negative predictive value of this model was 97%. CONCLUSIONS: The parameters VolVcist>11Gy, Dose maxVax, and Volv should be checked when designing dosimetry for VS RS.


Assuntos
Neuroma Acústico/radioterapia , Radiocirurgia/efeitos adversos , Doenças do Nervo Trigêmeo/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos
12.
Biol Cybern ; 110(1): 55-71, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26837751

RESUMO

This paper develops a new closed-loop firing rate regulation strategy for a population of neurons in the subthalamic nucleus, derived using a model-based analysis of the basal ganglia. The system is described using a firing rate model, in order to analyse the generation of beta-band oscillations. On this system, a proportional regulation of the firing rate reduces the gain of the subthalamo-pallidal loop in the parkinsonian case, thus impeding pathological oscillation generation. A filter with a well-chosen frequency is added to this proportional scheme, in order to avoid a potential instability of the feedback loop due to actuation and measurement delays. Our main result is a set of conditions on the parameters of the stimulation strategy that guarantee both its stability and a prescribed delay margin. A discussion on the applicability of the proposed method and a complete set of mathematical proofs is included.


Assuntos
Gânglios da Base/fisiologia , Retroalimentação Fisiológica/fisiologia , Modelos Biológicos , Inibição Neural/fisiologia , Neurônios/fisiologia , Humanos , Doença de Parkinson/fisiopatologia
13.
J Neurosurg ; 125(2): 472-80, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26745490

RESUMO

OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for motor symptoms in patients with pharmacoresistant Parkinson's disease (PD). However, the procedure, which requires multimodal perioperative exploration such as imaging, electrophysiology, or clinical examination during macrostimulation to secure lead positioning, remains challenging because the STN cannot be reliably visualized using the gold standard, T2-weighted imaging (T2WI) at 1.5 T. Thus, there is a need to improve imaging tools to better visualize the STN, optimize DBS lead implantation, and enlarge DBS diffusion. METHODS Gradient-echo sequences such as those used in T2WI suffer from higher distortions at higher magnetic fields than spin-echo sequences. First, a spin-echo 3D SPACE (sampling perfection with application-optimized contrasts using different flip angle evolutions) FLAIR sequence at 3 T was designed, validated histologically in 2 nonhuman primates, and applied to 10 patients with PD; their data were clinically compared in a double-blind manner with those of a control group of 10 other patients with PD in whom STN targeting was performed using T2WI. RESULTS Overlap between the nonhuman primate STNs segmented on 3D-histological and on 3D-SPACE-FLAIR volumes was high for the 3 most anterior quarters (mean [± SD] Dice scores 0.73 ± 0.11, 0.74 ± 0.06, and 0.60 ± 0.09). STN limits determined by the 3D-SPACE-FLAIR sequence were more consistent with electrophysiological edges than those determined by T2WI (0.9 vs 1.4 mm, respectively). The imaging contrast of the STN on the 3D-SPACE-FLAIR sequence was 4 times higher (p < 0.05). Improvement in the Unified Parkinson's Disease Rating Scale Part III score (off medication, on stimulation) 12 months after the operation was higher for patients who underwent 3D-SPACE-FLAIR-guided implantation than for those in whom T2WI was used (62.2% vs 43.6%, respectively; p < 0.05). The total electrical energy delivered decreased by 36.3% with the 3D-SPACE-FLAIR sequence (p < 0.05). CONCLUSIONS 3D-SPACE-FLAIR sequences at 3 T improved STN lead placement under stereotactic conditions, improved the clinical outcome of patients with PD, and increased the benefit/risk ratio of STN-DBS surgery.


Assuntos
Estimulação Encefálica Profunda/métodos , Imagem por Ressonância Magnética , Doença de Parkinson/terapia , Núcleo Subtalâmico , Animais , Método Duplo-Cego , Eletrodos Implantados , Humanos , Imageamento Tridimensional , Macaca mulatta , Estudos Prospectivos
14.
Front Neurosci ; 9: 237, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26217171

RESUMO

Several disorders are related to pathological brain oscillations. In the case of Parkinson's disease, sustained low-frequency oscillations (especially in the ß-band, 13-30 Hz) correlate with motor symptoms. It is still under debate whether these oscillations are the cause of parkinsonian motor symptoms. The development of techniques enabling selective disruption of these ß-oscillations could contribute to the understanding of the underlying mechanisms, and could be exploited for treatments. A particularly appealing technique is Deep Brain Stimulation (DBS). With clinical electrical DBS, electrical currents are delivered at high frequency to a region made of potentially heterogeneous neurons (the subthalamic nucleus (STN) in the case of Parkinson's disease). Even more appealing is DBS with optogenetics, which is until now a preclinical method using both gene transfer and deep brain light delivery and enabling neuromodulation at the scale of one given neural network. In this work, we rely on delayed neural fields models of STN and the external Globus Pallidus (GPe) to develop, theoretically validate and test in silico a closed-loop stimulation strategy to disrupt these sustained oscillations with optogenetics. First, we rely on tools from control theory to provide theoretical conditions under which sustained oscillations can be attenuated by a closed-loop stimulation proportional to the measured activity of STN. Second, based on this theoretical framework, we show numerically that the proposed closed-loop stimulation efficiently attenuates sustained oscillations, even in the case when the photosensitization effectively affects only 50% of STN neurons. We also show through simulations that oscillations disruption can be achieved when the same light source is used for the whole STN population. We finally test the robustness of the proposed strategy to possible acquisition and processing delays, as well as parameters uncertainty.

15.
Stereotact Funct Neurosurg ; 93(2): 94-101, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25720954

RESUMO

Background/Aims: Evaluation of tremor constitutes a crucial step from the diagnosis to the initial treatment and follow-up of patients with essential tremor. The severity of tremor can be evaluated using clinical rating scales, accelerometry, or electrophysiology. Clinical scores are subjectively given, may be affected by intra- and interevaluator variations due to different experience, delays between consultations, and subtle changes in tremor severity. Existing medical devices are not routinely used: they are expensive, time-consuming, not easily accessible. We aimed at showing that a smartphone application using the accelerometers embedded in smartphones is effective for quantifying the tremor of patients presenting with essential tremor. Methods: We developed a free iPhone/iPod application, Itremor, and evaluated different parameters on 8 patients receiving deep brain stimulation of the ventral intermediate nucleus of the thalamus: average and maximum accelerations, time above 1 g of acceleration, peak frequency, typical magnitude of tremor, for postural and action tremors, on and off stimulation. Results: We demonstrated good correlations between the parameters measured with Itremor and clinical score in all conditions. Itremor evaluation enabled higher discriminatory power and degree of reproducibility than clinical scores. Conclusion: Itremor can be used for routine objective evaluation of essential tremor, and may facilitate adjustment of the treatment. © 2015 S. Karger AG, Basel.

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