The nucleus accumbens (NAc) and the anterior limb of internal capsule (ALIC) are effective targets for treating addiction using deep brain stimulation (DBS). However, there have been no reports on the electrophysiological characteristics of addiction nuclei at the single-cell level in humans. This study aimed to investigate the electrical activity characteristics of neurons in the NAc and ALIC using microelectrode recording (MER) during DBS surgery in patients with addiction, and six patients with addiction were included (five with heroin addiction and one with alcohol addiction). The microelectrode recording trajectories were reconstructed and recording sites at different depths were determined by merging the pre- and post-operative images in the FrameLink system. The results showed that among the 256 neurons, 204 (80 %) were burst neurons. NAc neurons accounted for the majority (57 %), and the mean firing rate (MFR) was the highest (1.94 Hz). ALIC neurons accounted for the least (14 %), and MFR was the lowest (0.44 Hz). MFR increased after entering the NAc and decreased after entering the ALIC. In the patients with addiction treated using DBS, the single-cell level electrophysiological characteristics of the different nuclei were found to be distinct along the surgical trajectory.

BACKGROUND: Deep brain stimulation (DBS) is an emerging and promising therapeutic approach for treatment-refractory obsessive-compulsive disorder (OCD). The most common DBS targets include the anterior limb of internal capsule (ALIC) and nucleus accumbens (NAcc). This protocol aims to explore the efficacy and safety of the combined ALIC- and NAcc-DBS for treatment-refractory OCD.
METHODS: We will recruit 64 patients with refractory OCD from six centers, randomly allocate them to active and sham-stimulation groups through a three-month double-blind phase, then enter a three-month open-label phase. In the open-label stage, both groups experience real stimulation.
METHODS: The primary outcome will be the efficacy and safety of combined ALIC- and NAcc-DBS, determined by treatment response rate between the active and sham-stimulation groups at the double-blind stage and spontaneously reported adverse events. The secondary outcomes are comparisons of change in Y-BOCS, CGI, HAMD, and HAMA scores at the third and sixth months compared to baseline between the active and sham-control groups, as well as the scores of the third month minus the sixth month between the two groups.

Uncertainties concerning anatomy and function of cortico-subcortical projections have arisen during the recent years. A clear distinction between cortico-subthalamic (hyperdirect) and cortico-tegmental projections (superolateral medial forebrain bundle, slMFB) so far is elusive. Deep Brain Stimulation (DBS) of the slMFB (for major depression, MD and obsessive compulsive disorders, OCD) has on the one hand been interpreted as actually involving limbic (prefrontal) hyperdirect pathways. On the other hand slMFB\'s stimulation region in the mesencephalic ventral tegmentum is said to impact on other structures too, going beyond the antidepressant (or anti OCD) efficacy of sole modulation of the cortico-tegmental reward-associated pathways. We have here used a normative diffusion MRT template (HCP, n = 80) for long-range tractography and augmented this dataset with ex-vivo high resolution data (n = 1) in a stochastic brain space. We compared this data with histological information and used the high resolution ex-vivo data set to scrutinize the mesencephalic tegmentum for small fiber pathways present. Our work resolves an existing ambiguity between slMFB and prefrontal hyperdirect pathways which-for the first time-are described as co-existent. DBS of the slMFB does not appear to modulate prefrontal hyperdirect cortico-subthalamic but rather cortico-tegmental projections. Smaller fiber structures in the target region-as far as they can be discerned-appear not to be involved in slMFB DBS. Our work enfeebles previous anatomical criticism and strengthens the position of the slMFB DBS target for its use in MD and OCD.

Human social activities are realized by a synergy of neuronal activity over various regions of the brain, which is supported by their connectivity. In the present study, we examined associations between social activities, represented by work hours, and brain connectivity as quantified using diffusion tensor imaging (DTI). In 483 healthy participants, DTI analysis was performed using 3 T magnetic resonance imaging, and work hours were calculated, considering hours of paid employment (the \"Work for Pay\" category), hours of housework (the \"Work at Home\" category), and hours of school-related study (the \"Student\" category). The correlations between each class of work time and DTI indices were analyzed. The mean diffusivity (MD) values of the anterior limb of the internal capsule (ALIC) and the superior fronto-occipital fasciculus (SFO) were negatively correlated with total work hours (ALIC: r = -0.192, p =  2.3 × 10-5; SFO: r = -0.161, p =  3.8 × 10-4). We also found that the MD values of the ALIC and the SFO were correlated with work hours in the Work for Pay category (ALIC: r = -0.211, p =  3.2 × 10-6; SFO: r = -0.163, p =  3.4 × 10-4) but not with those in the Work at Home category or the Student category. These results suggest that social activity is associated with the white matter microstructure of the ALIC and the SFO. The main difference between \"Work for Pay\" and the other two social activities appears to be the type of motivation-for example, external versus internal. Therefore, the white matter microstructure of the ALIC and SFO may be related to externally motivated social activities.

Gilles de la Tourette syndrome (GTS) is a neurobehavioral disorder comprising motor and vocal tics. In most cases it is associated with other disorders such as obsessive-compulsive disorder (OCD). In refractory cases deep brain stimulation (DBS) is a valid treatment option. This paper describes the case of a 15-year-old adolescent with an extremely refractory GTS with associated OCD. The patient developed catatonia associated with OCD, which partially remitted after electroconvulsive therapy. At the peak of the disease the Yale Global Tic Severity Scale (YGTSS) was 100 and the patient required sedation and intubation. All medical treatment options were unsuccessful. Bilateral DBS of the anterior limb of internal capsule (ALIC)/bed nucleus of stria terminalis (BST) region was performed, using a target below the BST and a trajectory through the ALIC, with stimulation of contacts 0 and 3. Two weeks after surgery sedatives were suspended and the patient was successfully extubated. One year after surgery the patient reached a YGTSS of 19, representing an 81% improvement. OCD completely resolved. Adverse events were a superficial infection and weight gain. In conclusion, this ALIC/BST stimulation appears to have been an effective and safe treatment for GTS with OCD in this case. Young age should not be an exclusion criterion for DBS in severe GTS and OCD. Further studies should be pursued for this target.

Major depression (MD) and obsessive-compulsive disorder (OCD) are psychiatric diseases with a huge impact on individual well-being. Despite optimal treatment regiments a subgroup of patients remains treatment resistant and stereotactic surgery (stereotactic lesion surgery, SLS or Deep Brain Stimulation, DBS) might be an option. Recent research has described four networks related to MD and OCD (affect, reward, cognitive control, default network) but only on a cortical and the adjacent sub-cortical level. Despite the enormous impact of comparative neuroanatomy, animal science and stereotactic approaches a holistic theory of subcortical and cortical network interactions is elusive. Because of the dominant hierarchical rank of the neocortex, corticofugal approaches have been used to identify connections in subcortical anatomy without anatomical priors and in part confusing results. We here propose a different corticopetal approach by identifying subcortical networks and search for neocortical convergences thereby following the principle of phylogenetic and ontogenetic network development.
This work used a diffusion tensor imaging data from a normative cohort (Human Connectome Project, HCP; n = 200) to describe eight subcortical fiber projection pathways (PPs) from subthalamic nucleus (STN), substantia nigra (SNR), red nucleus (RN), ventral tegmental area (VTA), ventrolateral thalamus (VLT) and mediodorsal thalamus (MDT) in a normative space (MNI). Subcortical and cortical convergences were described including an assignment of the specific pathways to MD/OCD-related networks. Volumes of activated tissue for different stereotactic stimulation sites and procedures were simulated to understand the role of the distinct networks, with respect to symptoms and treatment of OCD and MD.
The detailed course of eight subcortical PPs (stnPP, snrPP, rnPP, vlATR, vlATRc, mdATR, mdATRc, vtaPP/slMFB) were described together with their subcortical and cortical convergences. The anterior limb of the internal capsule can be subdivided with respect to network occurrences in ventral-dorsal and medio-lateral gradients. Simulation of stereotactic procedures for OCD and MD showed dominant involvement of mdATR/mdATRc (affect network) and vtaPP/slMFB (reward network).
Corticofugal search strategies for the evaluation of stereotactic approaches without anatomical priors often lead to confusing results which do not allow for a clear assignment of a procedure to an involved network. According to our simulation of stereotactic procedures in the treatment of OCD and MD, most of the target regions directly involve the reward (and affect) networks, while side-effects can in part be explained with a co-modulation of the control network.
The here proposed corticopetal approach of a hierarchical description of 8 subcortical PPs with subcortical and cortical convergences represents a new systematics of networks found in all different evolutionary and distinct parts of the human brain.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder featuring repetitive intrusive thoughts and behaviors associated with a significant handicap. Of patients, 20% are refractory to medication and cognitive behavioral therapy. Refractory OCD is associated with suicidal behavior and significant degradation of social and professional functioning, with high health costs. Deep brain stimulation (DBS) has been proposed as a reversible and controllable method to treat refractory patients, with meta-analyses showing 60% response rate following DBS, whatever the target: anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), nucleus accumbens (NAcc), anteromedial subthalamic nucleus (amSTN), or inferior thalamic peduncle (ITP). But how do we choose the \"best\" target? Functional neuroimaging studies have shown that ALIC-DBS requires the modulation of the fiber tract within the ventral ALIC via the ventral striatum, bordering the bed nucleus of the stria terminalis and connecting the medial prefrontal cortex with the thalamus to be successful. VC/VS effective sites of stimulation were found within the VC and primarily connected to the medial orbitofrontal cortex (OFC) dorsomedial thalamus, amygdala, and the habenula. NAcc-DBS has been found to reduce OCD symptoms by decreasing excessive fronto-striatal connectivity between NAcc and the lateral and medial prefrontal cortex. The amSTN effective stimulation sites are located at the inferior medial border of the STN, primarily connected to lateral OFC, dorsal anterior cingulate, and dorsolateral prefrontal cortex. Finally, ITP-DBS recruits a bidirectional fiber pathway between the OFC and the thalamus. Thus, these functional connectivity studies show that the various DBS targets lie within the same diseased neural network. They share similar efficacy profiles on OCD symptoms as estimated on the Y-BOCS, the amSTN being the target supported by the strongest evidence in the literature. VC/VS-DBS, amSTN-DBS, and ALIC-DBS were also found to improve mood, behavioral adaptability and potentially both, respectively. Because OCD is such a heterogeneous disease with many different symptom dimensions, the ultimate aim should be to find the most appropriate DBS target for a given refractory patient. This quest will benefit from further investigation and understanding of the individual functional connectivity of OCD patients.

Deep brain stimulation (DBS) is currently used to treat addiction, with the nucleus accumbens (NAc) as one promising target. The anterior limb of the internal capsule (ALIC) is also a potential target, as it carries fiber tracts connecting the mesocorticolimbic circuits that are crucially involved in several psychiatric disorders, including addiction. Stimulating the NAc and ALIC simultaneously may have a synergistic effect against addiction.
Eight patients with a long history of heroin use and multiple relapses, despite optimal conventional treatments, were enrolled. Customized electrodes were implanted through the ALIC into the NAc, and deep brain stimulation (DBS) treatment began two weeks after surgery. The patients were followed for at least 24 months. The duration of drug-free time, severity of drug cravings, psychometric evaluations, and PET studies of glucose metabolism before and after DBS were conducted. All adverse events were recorded.
With DBS, five patients were abstinent for more than three years, two relapsed after abstaining for six months, and one was lost of follow-up at three months. The degree of cravings for drug use after DBS was reduced if the patients remained abstinent (p < 0.001). Simultaneous DBS of the NAc and ALIC also improved the quality of life, alleviated psychiatric symptoms, and increased glucose metabolism in addiction-related brain regions. Moreover, stimulation-related adverse events were few and reversible.
Simultaneous DBS of the NAc and ALIC appears to be safe, with few side effects, and may prevent long-term heroin relapse after detoxification in certain patients. (This trial was registered at ClinicalTrials.gov, NCT01274988).

The nucleus accumbens (NAc) is known to regulate the motivation and underlie addictive behaviors, and the anterior limb of the internal capsule (ALIC) is involved in several psychiatric disorders. Our study aimed to explore the functions of NAc and ALIC electrophysiologically.
The local field potentials (LFPs) of the NAc and ALIC were recorded from 7 heroin addicts treated with deep brain stimulation. Correlation analysis was made between LFP powers in various frequency bands and the subjects\' neuropsychological test scores; coherence was calculated for the LFPs in NAc and ALIC.
Both the NAc and ALIC exhibited prominent theta and alpha frequency band activity in the LFP power spectra. Additionally, a distinct beta band peak was detected in the power spectra of ALIC LFPs, which may represent the activity of striatal bridge cells. There was a significant negative correlation between the power of the theta frequency band of ALIC LFPs and visual analogue scale (VAS) scores indicative of cravings (Spearman\'s ρ = -0.758, P = 0.002), and a significant positive correlation was found between the power of the alpha frequency band of NAc LFPs and subjects\' scores on the Hamilton depression inventory (ρ = 0.727, P = 0.005). LFPs of the NAc and ALIC exhibited higher coherence values in the theta and alpha frequency bands.
The results suggest that theta power in the ALIC/dorsal striatum and alpha power in the NAc may be associated with drug cravings and depressive symptoms, respectively, in heroin addicts. For these subjects, the neural activities in the dorsal and ventral striatum were mainly coordinated within the low-frequency band.
The study illustrates the neurophysiologic characteristics of heroin addiction and its comorbidities, providing a potential theoretical basis for optimizing deep brain stimulation (DBS) therapy.

OBJECTIVE: A definition of free will is the ability to select for or against a course of action to fulfill a desire, without extrinsic or intrinsic constraints that compel the choice. Free will has been linked to the evolutionary development of flexible decision making. In order to develop flexibility in thoughts and behavioral responses, learning mechanisms have evolved as a modification of reflexive behavioral strategies. The ultimate goal of the brain is to reduce uncertainty inherently present in a changing environment. A way to reduce the uncertainty, which is encoded by the rostral anterior cingulate, is to make multiple predictions about the environment which are updated in parallel by sensory inputs. The prediction/behavioral strategy that fits the sensory input best is then selected, becomes the next percept/behavioral strategy, and is stored as a basis for future predictions. Acceptance of predictions (positive feedback) is mediated via the accumbens, and switching to other predictions by the dorsal anterior cingulate cortex (ACC) (negative feedback). Maintenance of a prediction is encoded by the pregenual ACC. Different cingulate territories are involved in rejection, acceptance and maintenance of predictions. Free will is known to be decreased in multiple psychopathologies, including obsessive compulsive disorder and addictions.
METHODS: In modern psychosurgery three target structures exist for obsessive compulsive disorder and addiction: the dorsal ACC, the nucleus accumbens, and/or the anterior limb of the internal capsula. Research in all three areas reports favorable results with acceptable side effects. Psychosurgical interventions seem to exert their effect by a common final common pathway mediated via the pregenual ACC.
CONCLUSIONS: Successful neuromodulation increases the capacity to choose from different options for the affected individual, as well as inhibiting unwanted options, therefore increasing free will and free won\'t.