Offline ventral subiculum-ventral striatum serial communication is required for spatial memory consolidation.

The hippocampal formation is considered essential for spatial navigation. In particular, subicular projections have been suggested to carry spatial information from the hippocampus to the ventral striatum. However, possible cross-structural communication between these two brain regions in memory formation has thus far been unknown. By selectively silencing the subiculum-ventral striatum pathway we found that its activity after learning is crucial for spatial memory consolidation and learning-induced plasticity. These results provide new insight into the neural circuits underlying memory consolidation and establish a critical role for off-line cross-regional communication between hippocampus and ventral striatum to promote the storage of complex information.

Anatomic Review of the Ventral Capsule/Ventral Striatum and the Nucleus Accumbens to Guide Target Selection for Deep Brain Stimulation for Obsessive-Compulsive Disorder.

BACKGROUND: Disturbances in the reward network of the brain underlie addiction, depression, and obsessive-compulsive disorder. The ventral capsule/ventral striatum and nucleus accumbens (NAc) region is a clinically approved target for deep brain stimulation for obsessive-compulsive disorder. METHODS: We performed a comprehensive literature review to define clinically relevant anatomy and connectivity of the ventral capsule/ventral striatum and NAc region to guide target selection for deep brain stimulation. RESULTS: Architecturally and functionally, the NAc is divided into the core and the shell, with each area having different connections. The shell primarily receives limbic information, and the core typically receives information from the motor system. In general, afferents from the prefrontal cortex, hippocampus, and amygdala are excitatory. The dopaminergic projections to the NAc from the ventral tegmental area modulate the balance of these excitatory inputs. Several important inputs to the NAc converge at the junction of the internal capsule (IC) and the anterior commissure (AC): the ventral amygdalofugal pathways that run parallel to and underneath the AC, the precommissural fornical fibers that run anterior to the AC, axons from the ventral prefrontal cortex and medial orbitofrontal cortex that occupy the most ventral part of the IC and embedding within the NAc and AC, and the superolateral branch of the medial forebrain bundle located parallel to the anterior thalamic radiation in the IC. CONCLUSIONS: The caudal part of the NAc passing through the IC-AC junction may be an effective target for deep brain stimulation to improve behavioral symptoms associated with obsessive-compulsive disorder.

Differential Effects of Deep Brain Stimulation of the Internal Capsule and the Striatum on Excessive Grooming in Sapap3 Mutant Mice.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for patients with obsessive-compulsive disorder (OCD) that do not respond to conventional therapies. Although the precise mechanism of action of DBS remains unknown, modulation of activity in corticofugal fibers originating in the prefrontal cortex is thought to underlie its beneficial effects in OCD. METHODS: To gain more mechanistic insight into DBS in OCD, we used Sapap3 mutant mice. These mice display excessive self-grooming and increased anxiety, both of which are responsive to therapeutic drugs used in OCD patients. We selected two clinically relevant DBS targets through which activity in prefronto-corticofugal fibers may be modulated: the internal capsule (IC) and the dorsal part of the ventral striatum (dVS). RESULTS: IC-DBS robustly decreased excessive grooming, whereas dVS-DBS was on average less effective. Grooming was reduced rapidly after IC-DBS onset and reinstated upon DBS offset. Only IC-DBS was associated with increased locomotion. DBS in both targets induced c-Fos expression around the electrode tip and in different regions of the prefrontal cortex. This prefronto-cortical activation was more extensive after IC-DBS, but not associated with behavioral effects. Furthermore, we found that the decline in grooming cannot be attributed to altered locomotor activity and that anxiety, measured on the elevated plus maze, was not affected by DBS. CONCLUSIONS: DBS in both the IC and dVS reduces compulsive grooming in Sapap3 mutant mice. However, IC stimulation was more effective, but also produced motor activation, even though both DBS targets modulated activity in a similar set of prefrontal cortical fibers.

Removing and reimplanting deep brain stimulation therapy devices in resistant OCD (when the patient does not respond): case report.

BACKGROUND: Deep brain stimulation (DBS) is emerging as a promising tool in the treatment of refractory obsessive-compulsive disorder (OCD) but the search for the best target still continues. This issue is especially relevant when particularly resistant profiles are observed in some patients, which have been ascribed to individual responses to DBS according to differential patterns of connectivity. As patients have been implanted, new dilemmas have emerged, such as what to do when the patient does not respond to surgery. CASE PRESENTATION: Here we describe a 22-year-old male with extremely severe OCD who did not respond to treatment with DBS in the nucleus accumbens, but who did respond after explanting and reimplanting leads targeting the ventral capsule-ventral striatum region. Information regarding the position of the electrodes for both surgeries is provided and possible brain structures affected during stimulation are reviewed. To our knowledge this case is the first in the literature reporting the removal and reimplantation of DBS leads for therapeutical benefits in a patient affected by a mental disorder. CONCLUSION: The capability for explantation and reimplantation of leads should be considered as part of the DBS therapy reversibility profile in resistant mental disorders, as it allows application in cases of non-response to the first surgery.

Variability and anatomical specificity of the orbitofrontothalamic fibers of passage in the ventral capsule/ventral striatum (VC/VS): precision care for patient-specific tractography-guided targeting of deep brain stimulation (DBS) in obsessive compulsive disorder (OCD).

Deep Brain Stimulation (DBS) is a neurosurgical procedure that can reduce symptoms in medically intractable obsessive-compulsive disorder (OCD). Conceptually, DBS of the ventral capsule/ventral striatum (VC/VS) region targets reciprocal excitatory connections between the orbitofrontal cortex (OFC) and thalamus, decreasing abnormal reverberant activity within the OFC-caudate-pallidal-thalamic circuit. In this study, we investigated these connections using diffusion magnetic resonance imaging (dMRI) on human connectome datasets of twenty-nine healthy young-adult volunteers with two-tensor unscented Kalman filter based tractography. We studied the morphology of the lateral and medial orbitofrontothalamic connections and estimated their topographic variability within the VC/VS region. Our results showed that the morphology of the individual orbitofrontothalamic fibers of passage in the VC/VS region is complex and inter-individual variability in their topography is high. We applied this method to an example OCD patient case who underwent DBS surgery, formulating an initial proof of concept for a tractography-guided patient-specific approach in DBS for medically intractable OCD. This may improve on current surgical practice, which involves implanting all patients at identical stereotactic coordinates within the VC/VS region.

Smile without euphoria induced by deep brain stimulation: a case report.

Poststroke central pain (PSCP) can be a debilitating medication-refractory disorder. We report a single case where right unilateral ventral capsule/ventral striatum (VC/VS) deep brain stimulation was used to treat PSCP and inadvertently induced a smile without euphoria. The patient was a 69 year-old woman who had a stroke with resultant dysesthesia and allodynia in her left hemibody and also a painful left hemibody dystonia. In her case, VC/VS stimulation induced a smile phenomenon, but without a euphoric sensation. This phenomenon was different from the typical smile responses we have observed in obsessive-compulsive disorder cases. This difference was considered to be possibly attributable to impairment in the emotional smile pathway.