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OBJECTIVE: Essential tremor (ET) is the most common movement disorder. Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (VIM) is known to improve symptoms in patients with medication-resistant ET. However, the clinical effectiveness of VIM-DBS may vary, and other targets have been proposed. The authors aimed to investigate whether the same anatomical structure is responsible for tremor control both immediately after VIM-DBS and at later follow-up evaluations. METHODS: Of 68 electrodes from 41 patients with ET, the authors mapped the distances of the active contact from the VIM, the dentatorubrothalamic tract (DRTT), and the caudal zona incerta (cZI) and compared them using Friedman's ANOVA and the Wilcoxon signed-rank follow-up test. The same distances were also compared between the initially planned target and the final implantation site after intraoperative macrostimulation. Finally, the comparison among the three structures was repeated for 16 electrodes whose active contact was changed after a mean 37.5 months follow-up to improve tremor control. RESULTS: After lead implantation, the VIM was statistically significantly closer to the active contact than both the DRTT (p = 0.008) and cZI (p < 0.001). This result did not change if the target was moved based on intraoperative macrostimulation. At the last follow-up, the active contact distance from the VIM was always significantly less than that of the cZI (p < 0.001), but the distance from the DRTT was reduced and even less than the distance from the VIM. CONCLUSIONS: In patients receiving VIM-DBS, the VIM itself is the structure driving the anti-tremor effect and remains more effective than the cZI, even years after implantation. Nevertheless, the role of the DRTT may become more important over time and may help sustain the clinical efficacy when the habituation from the VIM stimulation ensues.
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Estimulación Encefálica Profunda , Temblor Esencial , Núcleos Talámicos Ventrales , Zona Incerta , Humanos , Temblor Esencial/terapia , Temblor Esencial/cirugía , Estimulación Encefálica Profunda/métodos , Zona Incerta/cirugía , Femenino , Masculino , Persona de Mediana Edad , Anciano , Núcleos Talámicos Ventrales/cirugía , Resultado del Tratamiento , Adulto , Estudios de Seguimiento , Anciano de 80 o más AñosRESUMEN
A 65-year-old woman with a resolved history of epilepsy due to a motor vehicle accident and hippocampal sclerosis presented with recurrent de novo seizures. Brain imaging demonstrated enhancement in the left parieto-occipital lobe. At histopathological examination, the lesion displayed a diffuse lymphoid infiltrate comprised of small atypical lymphocytes, plasmacytoid lymphocytes, and scattered plasma cells with amyloid deposition. Pathology workup demonstrated a monotypic B-cell phenotype of the lymphoid infiltrate, expressing lambda light chain restriction and plasmacytic differentiation without MYD88 mutations. The patient had no systemic evidence of lymphoma, plasma cell dyscrasia, or amyloidosis. A diagnosis of low-grade B-cell lymphoma of the central nervous system with plasmacytic differentiation and amyloid deposition was made.
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Amiloidosis , Linfoma de Células B , Humanos , Encéfalo/patología , Diferenciación CelularRESUMEN
OBJECTIVES: Despite converging basic scientific and clinical evidence of the link between chronic pain and depression, existing therapies do not often take advantage of this overlap. Here, we provide a critical review of the literature that highlights the intersection in brain networks between chronic low back pain (CLBP) and depression and discuss findings from previous deep brain stimulation (DBS) studies for pain. Based on a multidimensional model of pain processing and the connectivity of the subgenual cingulate cortex (SCC) with areas that are implicated in both CLBP and depression, we propose a novel approach to the treatment of CLBP using DBS of the SCC. MATERIALS AND METHODS: A narrative review with literature assessment. RESULTS: CLBP is associated with a shift away from somatosensory representation toward brain regions that mediate emotional processes. There is a high degree of overlap between these regions and those involved in depression, including the anterior cingulate cortex, medial prefrontal cortex, nucleus accumbens, and amygdala. Whereas target sites from previous DBS trials for pain were not anatomically positioned to engage these areas and their associated networks, the SCC is structurally connected to all of these regions as well as others involved in mediating sensory, cognitive, and affective processing in CLBP. CONCLUSIONS: CLBP and depression share a common underlying brain network interconnected by the SCC. Current data and novel technology provide an optimal opportunity to develop clinically effective trials of SCC DBS for CLBP.
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Dolor Crónico , Estimulación Encefálica Profunda , Dolor de la Región Lumbar , Encéfalo , Mapeo Encefálico , Dolor Crónico/terapia , Giro del Cíngulo/diagnóstico por imagen , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/terapiaRESUMEN
As current psychosocial and pharmacological interventions show limited efficacy in the treatment of anorexia nervosa (AN), interest in the potential value of neurosurgical intervention and neuromodulation in managing severe and enduring illness has grown. We conducted a systematic review of 20 trials of neurosurgical and neuromodulatory treatments for AN, including neurosurgical ablation, deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall, there is evidence to support the role of stereotactic ablation and DBS in the treatment of AN. In contrast, results for rTMS and tDCS have been modest and generally more mixed. Neurosurgical treatment may offer important new avenues for the treatment of AN. Additional randomized clinical trials with comparable patient populations will be needed, in which change in affective, cognitive, and perceptual symptom phenomena, and interrogation of targeted circuits, pre- and post-intervention, are carefully documented.
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Anorexia Nerviosa , Neurocirugia , Estimulación Transcraneal de Corriente Directa , Anorexia Nerviosa/psicología , Anorexia Nerviosa/terapia , Humanos , Estimulación Magnética Transcraneal , Resultado del TratamientoRESUMEN
OBJECTIVE: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016. DESIGN: Here we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses. CONCLUSION: Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.
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Trastornos Mentales/cirugía , Neurocirugia , Procedimientos Neuroquirúrgicos/métodos , Humanos , Estados UnidosRESUMEN
BACKGROUND: The thalamus has been a surgical target for the treatment of various movement disorders. Commonly used therapeutic modalities include ablative and nonablative procedures. A major clinical side effect of thalamic surgery is the appearance of speech problems. OBJECTIVE: This review summarizes the data on the development of speech problems after thalamic surgery. METHODS: A systematic review and meta-analysis was performed using nine databases, including Medline, Web of Science, and Cochrane Library. We also checked for articles by searching citing and cited articles. We retrieved studies between 1960 and September 2014. RESULTS: Of a total of 2,320 patients, 19.8% (confidence interval: 14.8-25.9) had speech difficulty after thalamotomy. Speech difficulty occurred in 15% (confidence interval: 9.8-22.2) of those treated with a unilaterally and 40.6% (confidence interval: 29.5-52.8) of those treated bilaterally. Speech impairment was noticed 2- to 3-fold more commonly after left-sided procedures (40.7% vs. 15.2%). Of the 572 patients that underwent DBS, 19.4% (confidence interval: 13.1-27.8) experienced speech difficulty. Subgroup analysis revealed that this complication occurs in 10.2% (confidence interval: 7.4-13.9) of patients treated unilaterally and 34.6% (confidence interval: 21.6-50.4) treated bilaterally. After thalamotomy, the risk was higher in Parkinson's patients compared to patients with essential tremor: 19.8% versus 4.5% in the unilateral group and 42.5% versus 13.9% in the bilateral group. After DBS, this rate was higher in essential tremor patients. CONCLUSION: Both lesioning and stimulation thalamic surgery produce adverse effects on speech. Left-sided and bilateral procedures are approximately 3-fold more likely to cause speech difficulty. This effect was higher after thalamotomy compared to DBS. In the thalamotomy group, the risk was higher in Parkinson's patients, whereas in the DBS group it was higher in patients with essential tremor. Understanding the pathophysiology of speech disturbance after thalamic procedures is a priority. © 2017 International Parkinson and Movement Disorder Society.
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Estimulación Encefálica Profunda/efectos adversos , Trastornos del Movimiento/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/etiología , Trastornos del Habla/etiología , Tálamo/cirugía , Estimulación Encefálica Profunda/estadística & datos numéricos , Humanos , Trastornos del Movimiento/epidemiología , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Trastornos del Habla/epidemiologíaRESUMEN
OBJECT: Knowledge of the costs incurred through the delivery of neurosurgical care has been lagging, making it challenging to design impactful cost-containment initiatives. In this report, the authors describe a detailed cost analysis for pituitary surgery episodes of care and demonstrate the importance of such analyses in helping to identify high-impact cost activities and drive value-based care. METHODS: This was a retrospective study of consecutively treated patients undergoing an endoscopic endonasal procedure for the resection of a pituitary adenoma after implementation and maturation of quality-improvement initiatives and the implementation of cost-containment initiatives. RESULTS: The cost data pertaining to 27 patients were reviewed. The 2 most expensive cost activities during the index hospitalization were the total operating room (OR) and total bed-assignment costs. Together, these activities represented more than 60% of the cost of hospitalization. Although value-improvement initiatives contributed to the reduction of variation in the total cost of hospitalization, specific cost activities remained relatively variable, namely the following: 1) OR charged supplies, 2) postoperative imaging, and 3) use of intraoperative neuromonitoring. These activities, however, each contributed to less than 10% of the cost of hospitalization. Bed assignment was the fourth most variable cost activity. Cost related to readmission/reoperation represented less than 5% of the total cost of the surgical episode of care. CONCLUSIONS: After completing a detailed assessment of costs incurred throughout the management of patients undergoing pituitary surgery, high-yield opportunities for cost containment should be identified among the most expensive activities and/or those with the highest variation. Strategies for safely reducing the use of the targeted resources, and related costs incurred, should be developed by the multidisciplinary team providing care for this patient population.
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Adenoma/economía , Hospitalización/economía , Neuroendoscopía/economía , Neoplasias Hipofisarias/economía , Neoplasias Hipofisarias/cirugía , Adenoma/cirugía , Adolescente , Adulto , Anciano , Control de Costos/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quirófanos/economía , Rol del Médico , Estudios Retrospectivos , Adulto JovenRESUMEN
Deep Brain Stimulation (DBS) is an experimental treatment for medication-refractory neuropathic pain. The ventral posteromedial (VPM) and ventral posterolateral (VPL) nuclei of the thalamus are popular targets for the treatment of facial and limb pain, respectively. While intraoperative testing is used to adjust targeting of patient-specific pain locations, a better understanding of thalamic somatotopy may improve targeting of specific body regions including the individual trigeminal territories, face, arm, and leg. To elucidate the somatotopic organization of the ventral nuclear group of the dorsal thalamus using in vivo macrostimulation data from patients undergoing DBS for refractory neuropathic pain. In vivo macrostimulation data was retrospectively collected for 14 patients who underwent DBS implantation for neuropathic pain syndromes at our institution. 56 contacts from 14 electrodes reconstructed with LeadDBS were assigned to macrostimulation-related body regions: tongue, face, arm, or leg. 33 contacts from 9 electrodes were similarly assigned to one of three trigeminal territories: V1, V2, or V3. MNI coordinates in the x, y, and z axes were compared by using MANOVA. Across the horizontal plane of the ventral nuclear group of the dorsal thalamus, the tongue was represented significantly medially, followed by the face, arm, and leg most laterally (p < 0.001). The trigeminal territories displayed significant mediolateral distribution, proceeding from V1 and V2 most medial to V3 most lateral (p < 0.001). Along the y-axis, V2 was also significantly anterior to V3 (p = 0.014). While our results showed that the ventral nuclear group of the dorsal thalamus displayed mediolateral somatotopy of the tongue, face, arm, and leg mirroring the cortical homunculus, the mediolateral distribution of trigeminal territories did not mirror the established cortical homunculus. This finding suggests that the facial homunculus may be inverted in the ventral nuclear group of the dorsal thalamus.
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Estimulación Encefálica Profunda , Neuralgia , Humanos , Núcleos Talámicos Ventrales , Estimulación Encefálica Profunda/métodos , Estudios Retrospectivos , Tálamo/fisiología , Neuralgia/terapiaRESUMEN
[This corrects the article DOI: 10.3389/fnimg.2022.1009399.].
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Deep brain stimulation (DBS) of the thalamic nuclei for the treatment of drug-resistant epilepsy (DRE) has been investigated for decades. In recent years, DBS targeting the anterior nucleus of the thalamus (ANT) was approved by CE and FDA for the treatment of focal-onset DRE in light of the results from the multicentric randomized controlled SANTE trial. However, stereotactic targeting of thalamic nuclei is not straightforward because of the low contrast definition among thalamic nuclei on the current MRI sequences. When the FGATIR sequence is added to the preoperative MRI protocol, the mammillothalamic tract can be identified and used as a visible landmark to directly target ANT. According to the current evidence, the trans-ventricular trajectory allows the placement of stimulating contact into the nucleus more frequently than the trans-cortical trajectory. Another thalamic nucleus whose stimulation for the treatment of generalized DRE is receiving increasing attention is the centromedian nucleus (CM). CM-DBS seems to be particularly efficacious in patients suffering from Lennox-Gastault syndrome (LGS) and the recent monocentric randomized controlled ESTEL trial also described a beneficial "sweet-spot". However, CM targeting is still based on indirect stereotactic coordinates, since acquisition times and post-processing techniques of the actual MRI sequences are not applicable in clinical practice. Moreover, the results of the ESTEL trial await confirmation from similar studies accounting for epileptic syndromes other than LGS. Therefore, novel neuroimaging approaches are advisable to improve the surgical targeting of CM and potentially tailor the stimulation based on the patient's specific epileptic phenotype.
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Núcleos Talámicos Anteriores , Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsia , Humanos , Estimulación Encefálica Profunda/métodos , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Núcleos Talámicos Anteriores/fisiología , Epilepsia/terapia , Imagen por Resonancia Magnética , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: Epilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candidates. Recently, the effect of CM- deep brain stimulation (DBS) in DRE patients was investigated in the Electrical Stimulation of Thalamus for Epilepsy of Lennox-Gastaut phenotype (ESTEL) trial, a monocentric randomized-controlled study. The same authors described a 'cold-spot' and a 'sweet-spot', which are defined as the volume of stimulation in the thalamus yielding the least and the best clinical response, respectively. However, it remains unclear which structural connections may contribute to the anti-seizure effect of the stimulation. Objective: We investigated the differences in structural connectivity among CM, the sweet-spot and the cold-spot. Furthermore, we tried to validate our results in a cohort of DRE patients who underwent CM-DBS or CM-RNS (responsive neurostimulation). We hypothesized that the sweet-spot would share similar structural connectivity with responder patients. Methods: By using the software FMRIB Software Library (FSL), probabilistic tractography was performed on 100 subjects from the Human Connectome Project to calculate the probability of connectivity of the whole CM, the sweet-spot and the cold-spot to 45 cortical and subcortical areas. Results among the three seeds were compared with multivariate analysis of variance (MANOVA). Similarly, the structural connectivity of volumes of tissue activated (VTAs) from eight DRE patients was investigated. Patients were divided into responders and non-responders based on the degree of reduction in seizure frequency, and the mean probabilities of connectivity were similarly compared between the two groups. Results: The sweet-spot demonstrated a significantly higher probability of connectivity (p < 0.001) with the precentral gyrus, superior frontal gyrus, and the cerebellum than the whole CM and the cold-spot. Responder patients displayed a higher probability of connectivity with both ipsilateral (p = 0.011) and contralateral cerebellum (p = 0.04) than the non-responders. Conclusion: Cerebellar connections seem to contribute to the beneficial effects of CM-neuromodulation in patients with drug-resistant generalized epilepsy.
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Focused ultrasound is a novel brain stimulation modality that combines the noninvasiveness of repetitive transcranial magnetic stimulation and the precision of deep brain stimulation. In this review, the authors examine low-intensity focused ultrasound for brain mapping and neuromodulation. They also discuss high-intensity focused ultrasound, which is used for incisionless surgeries, such as capsulotomies for obsessive-compulsive disorder. Future potential applications of focused ultrasound are also presented.
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Neuromodulation of peripheral nerves has been clinically used for a wide range of indications. Wireless and batteryless stimulators offer important capabilities such as no need for reoperation, and extended life compared to their wired counterparts. However, there are challenging trade-offs between the device size and its operating range, which can limit their use. This study aimed to examine the functionality of newly designed wirelessly powered and controlled implants in vagus nerve stimulation for pigs. The implant used near field inductive coupling at 13.56 MHz industrial, scientific, and medical band to harvest power from an external coil. The circular implant had a diameter of 13 mm and weighed 483 mg with cuff electrodes. The efficiency of the inductive link and robustness to distance and misalignment were optimized. As a result, the specific absorption rate was orders of magnitude lower than the safety limit, and the stimulation can be performed using only 0.1 W of external power. For the first time, wireless and batteryless VNS with more than 5 cm operation range was demonstrated in pigs. A total of 84 vagus nerve stimulations (10 s each) have been performed in three adult pigs. In a quantitative comparison of the effectiveness of VNS devices, the efficiency of systems on reducing heart rate was similar in both conventional (75%) and wireless (78.5%) systems. The pulse width and frequency of the stimulation were swept on both systems, and the response for physiological markers was drawn. The results were easily reproducible, and methods used in this study can serve as a basis for future wirelessly powered implants.
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Estimulación del Nervio Vago , Tecnología Inalámbrica , Animales , Electrodos , Nervios Periféricos/fisiología , Prótesis e Implantes , Porcinos , Nervio VagoRESUMEN
Obsessions and compulsions are central components of obsessive-compulsive disorder (OCD) and obsessive-compulsive related disorders such as body dysmorphic disorder (BDD). Compulsive behaviours may result from an imbalance of habitual and goal-directed decision-making strategies. The relationship between these symptoms and the neural circuitry underlying habitual and goal-directed decision-making, and the arbitration between these strategies, remains unknown. This study examined resting state effective connectivity between nodes of these systems in two cohorts with obsessions and compulsions, each compared with their own corresponding healthy controls: OCD (nOCD = 43; nhealthy = 24) and BDD (nBDD = 21; nhealthy = 16). In individuals with OCD, the left ventrolateral prefrontal cortex, a node of the arbitration system, exhibited more inhibitory causal influence over the left posterolateral putamen, a node of the habitual system, compared with controls. Inhibitory causal influence in this connection showed a trend for a similar pattern in individuals with BDD compared with controls. Those with stronger negative connectivity had lower obsession and compulsion severity in both those with OCD and those with BDD. These relationships were not evident within the habitual or goal-directed circuits, nor were they associated with depressive or anxious symptomatology. These results suggest that abnormalities in the arbitration system may represent a shared neural phenotype across these two related disorders that is specific to obsessive-compulsive symptoms. In addition to nosological implications, these results identify potential targets for novel, circuit-specific treatments.
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Trastorno Dismórfico Corporal , Trastorno Obsesivo Compulsivo , Humanos , Negociación , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , PutamenRESUMEN
BACKGROUND: Anorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations-a critical component of hedonic responding-has never been studied in AN. METHODS: This multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12-22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired. DISCUSSION: This study will be the first to interrogate appetitive conditioning in AN-a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward. TRIAL REGISTRATION: Pending. INTENDED REGISTRY: Clinicaltrials.gov.
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Diminished motivation to pursue and obtain primary and secondary rewards has been demonstrated in anorexia nervosa (AN). However, the neurobehavioral mechanisms underlying the behavioral activation component of aberrant reward motivation remains incompletely understood. This work aims to explore this underexplored facet of reward motivation in AN. We recruited female adolescents with AN, restricting type (n = 32) and a healthy control group (n = 28). All participants underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. Diffusion MRI data was also collected to examine the reward motivation circuit's structural connectivity. Behavioral results demonstrated slower speed of reward-seeking behavior in those with AN compared with controls. Accompanying this was lower functional connectivity and reduced white matter structural integrity of the connection between the ventral tegmental area/substantia nigra pars compacta and the nucleus accumbens within the mesolimbic circuit. Further, there was evidence of neurobehavioral decoupling in AN between reward-seeking behavior and mesolimbic regional activation and functional connectivity. Aberrant activity of the bed nucleus of the stria terminalis (BNST) and its connectivity with the mesolimbic system was also evident in AN during the reward motivation period. Our findings suggest functional and structural dysconnectivity within a mesolimbic reward circuit, neurofunctional decoupling from reward-seeking behavior, and abnormal BNST function and circuit interaction with the mesolimbic system. These results show behavioral indicators of aberrant reward motivation in AN, particularly in its activational component. This is mediated neuronally by mesolimbic reward circuit functional and structural dysconnectivity as well as neurobehavioral decoupling. Based on these findings, we suggest a novel circuit-based mechanism of impaired reward processing in AN, with the potential for translation to developing more targeted and effective treatments in this difficult-to-treat psychiatric condition.
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Background: Understanding the structural connectivity of key brainstem nuclei with limbic cortical regions is essential to the development of therapeutic neuromodulation for depression, chronic pain, addiction, anxiety and movement disorders. Several brainstem nuclei have been identified as the primary central nervous system (CNS) source of important monoaminergic ascending fibers including the noradrenergic locus coeruleus, serotonergic dorsal raphe nucleus, and dopaminergic ventral tegmental area. However, due to practical challenges to their study, there is limited data regarding their in vivo anatomic connectivity in humans. Objective: To evaluate the structural connectivity of the following brainstem nuclei with limbic cortical areas: locus coeruleus, ventral tegmental area, periaqueductal grey, dorsal raphe nucleus, and nucleus tractus solitarius. Additionally, to develop a group average atlas of these limbic brainstem structures to facilitate future analyses. Methods: Each nucleus was manually masked from 197 Human Connectome Project (HCP) structural MRI images using FSL software. Probabilistic tractography was performed using FSL's FMRIB Diffusion Toolbox. Connectivity with limbic cortical regions was calculated and compared between brainstem nuclei. Results were aggregated to produce a freely available MNI structural atlas of limbic brainstem structures. Results: A general trend was observed for a high probability of connectivity to the amygdala, hippocampus and DLPFC with relatively lower connectivity to the orbitofrontal cortex, NAc, hippocampus and insula. The locus coeruleus and nucleus tractus solitarius demonstrated significantly greater connectivity to the DLPFC than amygdala while the periaqueductal grey, dorsal raphe nucleus, and ventral tegmental area did not demonstrate a significant difference between these two structures. Conclusion: Monoaminergic and other modulatory nuclei in the brainstem project widely to cortical limbic regions. We describe the structural connectivity across the several key brainstem nuclei theorized to influence emotion, reward, and cognitive functions. An increased understanding of the anatomic basis of the brainstem's role in emotion and other reward-related processing will support targeted neuromodulatary therapies aimed at alleviating the symptoms of neuropsychiatric disorders.
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We examined the safety and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) of the right orbitofrontal cortex (OFC) in patients with refractory obsessive-compulsive disorder (OCD) and comorbid Major Depressive Disorder. All participants (n = 26) received excitatory stimulation of the left dorsolateral prefrontal cortex followed by inhibitory stimulation of bilateral supplementary motor area for 10 sessions. In 18 patients with poor early OCD response, treatment was augmented with OFC inhibitory stimulation after the tenth treatment session. Augmentation with OFC stimulation was well-tolerated, and associated with further alleviation of both OCD and depression symptoms, particularly in individuals with more severe illnesses.
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Trastorno Depresivo Mayor , Corteza Motora , Trastorno Obsesivo Compulsivo , Humanos , Estimulación Magnética Transcraneal , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/terapia , Corteza Prefrontal , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/terapia , Resultado del TratamientoRESUMEN
Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships.
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Anorexia Nerviosa/fisiopatología , Toma de Decisiones/fisiología , Sustancia Blanca/fisiología , Adolescente , Adulto , Anorexia Nerviosa/psicología , Encéfalo/metabolismo , Encéfalo/fisiología , Conducta Compulsiva/fisiopatología , Imagen de Difusión Tensora/métodos , Femenino , Hábitos , Humanos , Masculino , Sustancia Blanca/metabolismo , Adulto JovenRESUMEN
Accurate localization of complex human experiences such as emotions, dreaming, creativity, and consciousness to specific cerebral structures or neural networks has remained elusive despite technological advances. We report the use of acute deep brain stimulation (DBS) to evoke behavioral and emotional effects by applying electrical stimulation (ES) at various voltage strengths to the basolateral and central subnuclei of the amygdala in addition to the head of hippocampus (HC) for two subjects with medically refractory post-traumatic stress disorder (PTSD). Our results suggest that the amygdala could be a node in a neural network responsible for the generation of complex vivid mental imagery and integrated sensory experiences similar to John Hughlings Jackson's "dreamy state" and "double consciousness," which have been classically associated with temporal lobe epilepsy during uncinate seizures. That we were able to elicit similar vivid, dynamic, complex, bizarre, and original mental imagery with ES in non-epileptic subjects suggests that Jackson's seizure related "dreamy state" and "double consciousness" may arise from heightened innate brain mechanisms with the amygdala acting as a node in the neural network responsible for physiologic dreaming and creative functions. Furthermore, our subjects experienced different emotions with different stimulation strengths at various electrode contacts. Our results suggest that higher voltage stimulation of the amygdala and HC at 4-5 V leads to predominantly negative responses and 2-4 V stimulation showed inversely coupled positive and negative responses of the amygdala in either hemisphere which may imply hemispheric dominance of emotional valences without relation to handedness. Due to the unique and complex responses dependent on location and strength of stimulation, we advise that all patients receiving DBS of the amygdala undergo acute stimulation mapping in a monitored setting before selecting therapeutic parameters for chronic stimulation.