Deep-brain stimulation of the human nucleus accumbens-medial septum enhances memory formation.

Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.

Nucleus Accumbens Stimulation Modulates Inhibitory Control by Right Prefrontal Cortex Activation in Obsessive-Compulsive Disorder.

Inhibitory control is considered a compromised cognitive function in obsessive-compulsive (OCD) patients and likely linked to corticostriatal circuitry disturbances. Here, 9 refractory OCD patients treated with deep brain stimulation (DBS) were evaluated to address the dynamic modulations of large-scale cortical network activity involved in inhibitory control after nucleus accumbens (NAc) stimulation and their relationship with cortical thickness. A comparison of DBS "On/Off" states showed that patients committed fewer errors and exhibited increased intraindividual reaction time variability, resulting in improved goal maintenance abilities and proactive inhibitory control. Visual P3 event-related potentials showed increased amplitudes during Go/NoGo performance. Go and NoGo responses increased cortical activation mainly over the right inferior frontal gyrus and medial frontal gyrus, respectively. Moreover, increased cortical activation in these areas was equally associated with a higher cortical thickness within the prefrontal cortex. These results highlight the critical role of NAc DBS for preferentially modulating the neuronal activity underlying sustained speed responses and inhibitory control in OCD patients and show that it is triggered by reorganizing brain functions to the right prefrontal regions, which may depend on the underlying cortical thinning. Our findings provide updated structural and functional evidence that supports critical dopaminergic-mediated frontal-striatal network interactions in OCD.

Personalized striatal targets for deep brain stimulation in obsessive-compulsive disorder.

BACKGROUND: Psychiatric conditions currently treated with deep brain stimulation (DBS), such as obsessive-compulsive disorder (OCD), are heterogeneous diseases with different symptomatic dimensions, indicating that fixed neuroanatomical DBS targets for all OCD cases may not be efficacious. OBJECTIVE/HYPOTHESIS: We tested whether the optimal DBS target for OCD is fixed for all patients or whether it is individualized and related to each patient's symptomatic content. Further, we explored if the optimal target can be predicted by combining functional neuroimaging and structural connectivity. METHODS: In a prospective, randomized, double-blinded study in 7 OCD patients, symptomatic content was characterized pre-operatively by clinical interview and OCD symptom-provocation during functional MRI. DBS electrode implantation followed a trajectory placing 4 contacts along a striatal axis (nucleus accumbens to caudate). Patients underwent three-month stimulation periods for each contact (and sham), followed by clinical evaluation. Probabilistic tractography, applied to diffusion-weighted images acquired pre-operatively, was used to study the overlap between projections from the prefrontal areas activated during symptom provocation and the volume of activated tissue of each electrode contact. RESULTS: Six patients were classified responders, with median symptomatic reduction of 50% achieved from each patient's best contact. This was located at the caudate in 4 cases and at the accumbens in 2. Critically, the anatomical locus of the best contact (accumbens or caudate) was related to an index derived by combining functional MRI responses to prevailing symptom provocation and prefronto-cortico-striatal projections defined by probabilistic tractography. CONCLUSION: Our results therefore represent a step towards personalized, content-specific DBS targets for OCD.

Deep brain stimulation for obsessive-compulsive disorder: is the side relevant?

BACKGROUND: Deep brain stimulation for obsessive-compulsive disorder (OCD) has targeted several subcortical nuclei, including the subthalamic nucleus (STN) and the nucleus accumbens. While the most appropriate target is still being looked for, little attention has been given to the side of the stimulated hemisphere in relationship to outcome. METHODS: We report 2 patients diagnosed with OCD, one having symmetry obsessions and the other one with sexual-religious obsessive thoughts. They were implanted bilaterally with deep electrodes located at both STN and nuclei accumbens. The effectiveness of the stimulation was tested for every possible paired combination of electrodes guided by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score reduction. RESULTS: In both cases, the combination of electrodes which best relieved the OCD symptoms was both the left STN and left accumbens. In case 1, the preoperative Y-BOCS score was 33, and 1 month after stimulation it was 16. In case 2, the Y-BOCS scores were 33 and 3, respectively, with the patient being free of obsessions. CONCLUSION: Some reports suggest that lesion stimulation or stimulation of only the right side relieves OCD symptoms. However, anatomical and functional studies are not conclusive as to which side is most affected in OCD. Possibly, each OCD patient has an individualized optimal side to stimulate.

Psicosis inducidas por estados excepcionales de conciencia / No disponible

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Estados excepcionales de conciencia y consumo de sustancias psicotropas / No disponible

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