Anterior Limb Of The Internal Capsule Research Articles

Erythrocyte membrane fatty acid concentrations and myelin integrity in young people at ultra-high risk of psychosis

Decreased white matter (WM) integrity and disturbance in fatty acid composition have been reported in individuals at ultra-high risk of psychosis (UHR). The current study is the first to investigate both WM integrity and erythrocyte membrane polyunsaturated fatty acid (PUFA) levels as potential risk biomarkers for persistent UHR status, and global functioning in UHR individuals. Forty UHR individuals were analysed at baseline for erythrocyte membrane PUFA concentrates. Tract-based spatial statistics (TBSS) was used to analyse fractional anisotropy (FA) and diffusivity measures. Measures of global functioning and psychiatric symptoms were evaluated at baseline and at 12-months. Fatty acids and WM indices did not predict functional outcomes at baseline or 12-months. Significant differences were found in FA between UHR remitters and non-remitters (individuals who no longer met UHR criteria versus those who continued to meet criteria at 12-months). Docosahexaenoic acid (DHA) was found to be a significant predictor of UHR status at 12-months, as was the interaction between the sum of ώ-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of ώ-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals.

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer

BackgroundPrevious neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. MethodsThirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. ResultsThe voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LimitationsThis study is based on cross-sectional data and the sample size is limited. ConclusionThese findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

Pretreatment Brain White Matter Integrity Associated With Neuropathic Pain Relief and Changes in Temporal Summation of Pain Following Ketamine

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalized treatment strategies, but white matter (WM) properties have been underexplored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex [mPFC], posterior cingulate cortex, and precuneus) and descending pain modulation system (periaqueductal gray [PAG]) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP. We used a fixel-based analysis of diffusion-weighted imaging data to evaluate WM microstructure (fiber density [FD]) and macrostructure (fiber bundle cross-section) within the DMN and mPFC-PAG pathways in 70 individuals who underwent magnetic resonance imaging and TSP testing; 35 with NP who underwent ketamine treatment and 35 age- and sex-matched pain-free individuals. Individuals with NP were assessed before and 1 month after treatment; those with ≥30% pain relief were considered responders (n = 18), or otherwise as nonresponders (n = 17). We found that WM structure within the DMN and mPFC-PAG pathways did not differentiate responders from nonresponders. However, pretreatment FD in the anterior limb of the internal capsule correlated with pain relief (r=.48). Moreover, pretreatment FD in the DMN (left mPFC-precuneus/posterior cingulate cortex; r=.52) and mPFC-PAG (r=.42) negatively correlated with changes in TSP. This suggests that WM microstructure in the DMN and mPFC-PAG pathway is associated with the degree to which ketamine reduces central sensitization. Thus, fixel metrics of WM structure may hold promise to predict ketamine NP treatment outcomes. PerspectiveWe used advanced fixel-based analyses of MRI diffusion-weighted imaging data to identify pretreatment WM microstructure associated with ketamine outcomes, including analgesia and markers of attenuated central sensitization. Exploring associations between brain structure and treatment outcomes could contribute to a personalized approach to treatment for individuals with NP.

Helicobacter pylori, persistent infection burden and structural brain imaging markers.

Persistent infections, whether viral, bacterial or parasitic, including Helicobacter pylori infection, have been implicated in non-communicable diseases, including dementia and other neurodegenerative diseases. In this cross-sectional study, data on 635 cognitively normal participants from the UK Biobank study (2006-21, age range: 40-70 years) were used to examine whether H. pylori seropositivity (e.g. presence of antibodies), serointensities of five H. pylori antigens and a measure of total persistent infection burden were associated with selected brain volumetric structural MRI (total, white, grey matter, frontal grey matter (left/right), white matter hyperintensity as percent intracranial volume and bi-lateral sub-cortical volumes) and diffusion-weighted MRI measures (global and tract-specific bi-lateral fractional anisotropy and mean diffusivity), after an average 9-10 years of lag time. Persistent infection burden was calculated as a cumulative score of seropositivity for over 20 different pathogens. Multivariable-adjusted linear regression analyses were conducted, whereby selected potential confounders (all measures) and intracranial volume (sub-cortical volumes) were adjusted, with stratification by Alzheimer's disease polygenic risk score tertile when exposures were H. pylori antigen serointensities. Type I error was adjusted to 0.007. We report little evidence of an association between H. pylori seropositivity and persistent infection burden with various volumetric outcomes (P > 0.007, from multivariable regression models), unlike previously reported in past research. However, H. pylori antigen serointensities, particularly immunoglobulin G against the vacuolating cytotoxin A, GroEL and outer membrane protein antigens, were associated with poorer tract-specific white matter integrity (P < 0.007), with outer membrane protein serointensity linked to worse outcomes in cognition-related tracts such as the external capsule, the anterior limb of the internal capsule and the cingulum, specifically at low Alzheimer's disease polygenic risk. Vacuolating cytotoxin A serointensity was associated with greater white matter hyperintensity volume among individuals with mid-level Alzheimer's disease polygenic risk, while among individuals with the highest Alzheimer's disease polygenic risk, the urease serointensity was consistently associated with reduced bi-lateral caudate volumes and the vacuolating cytotoxin A serointensity was linked to reduced right putamen volume (P < 0.007). Outer membrane protein and urease were associated with larger sub-cortical volumes (e.g. left putamen and right nucleus accumbens) at middle Alzheimer's disease polygenic risk levels (P < 0.007). Our results shed light on the relationship between H. pylori seropositivity, H. pylori antigen levels and persistent infection burden with brain volumetric structural measures. These data are important given the links between infectious agents and neurodegenerative diseases, including Alzheimer's disease, and can be used for the development of drugs and preventive interventions that would reduce the burden of those diseases.

Topographical anatomy of the subthalamic region with special interest in the human medial forebrain bundle.

The medial forebrain bundle (MFB) is a novel promising deep brain stimulation (DBS) target in severe affective disorders that courses through the subthalamic region according to tractography studies. Its potential therapeutic role arose in connection with the development of hypomania during stimulation of the subthalamic nucleus (STN) in Parkinson's disease, offering an alternative explanation for the occurrence of this side effect. However, until now its course exclusively described by tractography had not yet been confirmed by any anatomical method. The aim of this study was to fill this gap as well as to provide a detailed description of the fiber tracts surrounding the STN to facilitate a better understanding of the background of side effects occurring during STN DBS. Ten human cadaveric brains (20 hemispheres) and 100 healthy subjects (200 hemispheres) from the S500 Release of the Human Connectome Project were involved in this study. Nineteen hemispheres were dissected according to Klingler's method. One additional hemisphere was prepared for histological examinations to validate the macroscopical results and stained with neurofibril silver impregnation according to Krutsay. The authors also aimed to reconstruct the MFB using tractography and correlated the results with their dissections and histological findings. The white matter connections coursing through the subthalamic region were successfully dissected. The ansa lenticularis, lenticular fasciculus, thalamic fasciculus, ipsi- and contralateral cerebellar fibers, and medial lemniscus were revealed as closely related fiber tracts to the STN. However, the existence of a distinct fiber bundle corresponding to the MFB described by tractography could not be identified. Using tractography, the authors showed that the depiction of the streamlines representing the MFB was also strongly dependent on the threshold parameters. According to this study's findings, the streamlines of the MFB described by tractography arise from the limitations of the diffusion-weighted MRI fiber tracking method and actually correspond to subthalamic fiber bundles, especially the ansa lenticularis and lenticular fasciculus, which erroneously continue in the anterior limb of the internal capsule, toward the prefrontal cortex.

Motivation levels and white matter microstructure in children living with HIV

Central nervous system involvement in HIV infection leads to neurobehavioural sequelae. Although apathy is a well-recognised symptom in adults living with HIV linked to alterations in brain structure, there is scarce research examining motivation in children living with HIV (CLWH). We used the Children’s Motivation Scale (CMS; normative mean = 50, SD = 10) to assess motivation levels in 76 CLWH aged 6–16 years (63 on antiretroviral therapy [ART]; 13 ART-naïve slow progressors) in South Africa. Overall, CLWH scored low on the CMS (mean = 35.70 [SD = 5.87]). Motivation levels were significantly reduced in children taking ART compared to ART-naïve slow progressors (p = 0.02), but were not correlated with markers of HIV disease (CD4 + cell count or viral load), or neurocognitive function (p > 0.05). CMS scores were correlated with diffusion tensor imaging metrics of white matter microstructure in specific frontostriatal brain regions (p < 0.05). On multiple regression, associations with the anterior limb of the internal capsule, a subcortical white matter region, remained significant after adjusting for potential confounders. These findings suggest that reduced motivation may be an important neurobehavioural symptom in CLWH and may reflect changes in white matter microstructure of frontostriatal brain regions.

Fronto-limbic white matter microstructural changes in psychiatrically healthy adults with childhood trauma.

Childhood trauma (CT) may influence brain white matter microstructure; however, few studies have examined the differential impact of distinct CT types on white matter microstructure in psychiatrically healthy adults living in a developing country. In adults without significant medical or psychiatric disorders, we investigated the association(s) between CT, including abuse and neglect, and fractional anisotropy (FA) of limbic tracts previously shown to be associated with CT. Participants underwent diffusion tensor imaging and completed the Childhood Trauma Questionnaire. Multivariate analysis of variance models were used to test the effects of total overall CT, as well as CT subtypes, on FA in six fronto-limbic tracts, adjusting for age, sex, and educational level. The final sample included 69 adults (age 47 ± 17 years; 70% female). Overall, CT had a significant main effect on FA for tracts of interest (p < .001). Greater CT severity was associated with lower FA for the bilateral and left stria terminalis (uncorrected) as well as the bilateral, left, and right anterior limb of the internal capsule (ALIC; corrected). Exposure to total non-violent/deprivational trauma specifically was associated with lower FA of the bilateral, left, and right ALIC, suggesting that distinct types of CT are associated with differential white matter changes in apparently healthy adults. The ALIC predominantly carries fibers connecting the thalamus with prefrontal cortical regions. Microstructural alterations in the ALIC may be associated with functional brain changes, which may be adaptive or increase the risk of accelerated age-related cognitive decline, maladaptive behaviors, and subsyndromal psychiatric symptoms.

Ventral targeted anterior capsulotomy for treatment-resistant depression and obsessive-compulsive disorder: A treatment method with cases

BackgroundAblative surgery using bilateral anterior capsulotomy (BAC) is an option for treatment resistant depression (TRD) and obsessive-compulsive disorder (TROCD). The location and extent of the lesion within anterior limb of the internal capsule (ALIC) remains uncertain. Accumulating evidence has suggested that the lesion should be located ventrally while limiting the dorsal extent. Our center is now targeting specific fiber tracts within the lower half of the ALIC. MethodPresurgical diffusion tensor Magnetic Resonance Imaging (MRI) was used to identify individual fibre tracts within the ventral aspect of the ALIC in the last two patients who underwent BAC at our center. One patient had TRD and the other had both TROCD and TRD. Radiofrequency-induced thermal lesions were created in the identified targets with lesion volumes between 20 and 229 mm3 (average 95 mm3). FindingsBoth patients were responders with neither experiencing significant side effects including compromised executive functions. LimitationsThe generalizability of our findings is limited because the outcome is based on two subjects. ConclusionThis work suggests that BAC can be individually tailored and more limited to the ventral aspect of the ALIC and is effective and safe for TRD and TROCD. Accumulating data also suggests that to be clinically effective the length of the capsulotomy should be about 10mm. BAC’s use may increase with the growing utilization and mastery of magnetic resonance guided focused ultrasound.

Based on white matter microstructure to early identify bipolar disorder from patients with depressive episode

ObjectiveBecause of similar clinical manifestations, bipolar disorder (BD) patients are often misdiagnosed as major depressive disorder (MDD). This study aimed to compare the difference between depressed patients later converting to BD and unipolar depression (UD) according to diffusion tensor imaging (DTI). MethodPatients with MDD (562 participants) in depressive episode states and healthy controls (HCs) (145 participants) were recruited over 10 years. Demographic and magnetic resonance imaging (MRI) data were collected at the time of recruitment. All patients with MDD were followed up for 5 years and classified into the transfer to BD (tBD) group (83 participants) and UD group (160 participants) according to the follow-up results. DTI and functional magnetic resonance imaging at baseline were compared. ResultsCommon abnormalities were found in both tBD and UD groups, including left superior cerebellar peduncle (SCP.L), right anterior limb of the internal capsule (ALIC.R), right superior fronto-occipital fasciculus (SFOF.R), and right inferior fronto-occipital fasciculus (IFOF.R). The tBD showed more extensive abnormalities than the UD in the body of corpus callosum, fornix, left superior corona radiata, left posterior corona radiata, left superior longitudinal fasciculus, and left superior fronto-occipital fasciculus. ConclusionThe study demonstrated the common and distinct abnormalities of tBD and UD when compared to HC. The tBD group showed more extensive disruptions of white matter integrity, which could be a potential biomarker for the early identification of BD.

ECHDC3 Variant Regulates the Right Hippocampal Microstructural Integrity and Verbal Memory in Type 2 Diabetes Mellitus

ECHDC3 is a risk gene for white matter (WM) hyperintensity and is associated with insulin resistance. This study aimed to investigate whether ECHDC3 variants selectively regulate brain WM microstructures and episodic memory in patients with type 2 diabetes mellitus (T2DM). We enrolled 106 patients with T2DM and 111 healthy controls. A voxel-wise general linear model was employed to explore the interaction effect between ECHDC3 rs11257311 polymorphism and T2DM diagnosis on fractional anisotropy (FA). A linear modulated mediation analysis was conducted to examine the potential of FA value to mediate the influence of T2DM on episodic memory in an ECHDC3-dependent manner. We observed a noteworthy interaction between genotype and diagnosis on FA in the right inferior temporal WM, right anterior limb of the internal capsule, right frontal WM, and the right hippocampus. Modulated mediation analysis revealed a significant ECHDC3 modulation on the T2DM → right hippocampal FA → short-term memory pathway, with only rs11257311 G risk homozygote demonstrating significant mediation effect. Together, our findings provide evidence of ECHDC3 modulating the effect of T2DM on right hippocampal microstructural impairment and short-term memory decline, which might be a neuro-mechanism for T2DM related episodic memory impairment.

Image Findings as Predictors of Fall Risk in Patients with Cerebrovascular Disease.

This study examined computed tomography findings in patients with cerebrovascular disease and determined predictors for falls. Images of the head were divided into 13 regions, and the relationships between computed tomography findings and the presence or absence of falls were investigated. A total of 138 patients with cerebrovascular disease (66% men, aged 73.8 ± 9.6 years) were included. A comparison between the fall and non-fall groups revealed a significant difference in the total functional independence measure scores and imaging findings at admission. Logistic regression analysis showed that the thalamus (p < 0.001), periventricular lucency (p < 0.001), lateral hemisphere room enlargement (p < 0.05), and age (p < 0.05) were related to the presence or absence of falls. For the 42 patients with cerebral hemorrhage, the thalamus (p < 0.01), periventricular lucency (p < 0.05), lateral ventricle vicinity (p < 0.05), and posterior limb of the internal capsule (p < 0.05) were extracted as factors related to the presence or absence of falls. For the 96 patients with cerebral infarction, the thalamus (p < 0.001), periventricular lucency (p < 0.01), and anterior limb of the internal capsule (p < 0.05) were extracted as factors related to the presence or absence of falls. This study found a relationship between the thalamus, lateral ventricle enlargement, periventricular lucency, and falls. Fall prognosis can potentially be predicted from computed tomography findings at admission.

Deep Brain Stimulation for Obsessive-Compulsive Disorder: Optimal Stimulation Sites

BackgroundDeep brain stimulation (DBS) is a promising treatment option for treatment-refractory obsessive-compulsive disorder (OCD). Several stimulation targets have been used, mostly in and around the anterior limb of the internal capsule and ventral striatum. However, the precise target within this region remains a matter of debate. MethodsHere, we retrospectively studied a multicenter cohort of 82 patients with OCD who underwent DBS of the ventral capsule/ventral striatum and mapped optimal stimulation sites in this region. ResultsDBS sweet-spot mapping performed on a discovery set of 58 patients revealed 2 optimal stimulation sites associated with improvements on the Yale-Brown Obsessive Compulsive Scale, one in the anterior limb of the internal capsule that overlapped with a previously identified OCD–DBS response tract and one in the region of the inferior thalamic peduncle and bed nucleus of the stria terminalis. Critically, the nucleus accumbens proper and anterior commissure were associated with beneficial but suboptimal clinical improvements. Moreover, overlap with the resulting sweet- and sour-spots significantly estimated variance in outcomes in an independent cohort of 22 patients from 2 additional DBS centers. Finally, beyond obsessive-compulsive symptoms, stimulation of the anterior site was associated with optimal outcomes for both depression and anxiety, while the posterior site was only associated with improvements in depression. ConclusionsOur results suggest how to refine targeting of DBS in OCD and may be helpful in guiding DBS programming in existing patients.

Bilateral basal ganglia hemorrhage in a 2-year-old child

Background: Basal ganglia hemorrhage (BGH) is an intracerebral subtype of hemorrhage located in the caudate nucleus, putamen, globus pallidus, or adjacent structures such as the thalamus or internal capsule. Bilateral involvement of both basal ganglia is exceedingly infrequent. Herein, we report a case of a 2-year-old female who was discovered to have spontaneous bilateral BGH with a unique hemorrhagic extension. Case Description: A 2-year-old female child who presented with a decreased level of consciousness, seizure, and fever was discovered to have bilateral BGH during imaging evaluation that extended from the head of the caudate to involve the putamen, globus pallidus, and anterior limb of the internal capsule. Conclusion: Bilateral BGH is extremely rare, and to the best of our knowledge, this is the first case report in pediatric age groups.

Use of Connectomes in Deep Brain Stimulation for the Treatment of Obsessive-Compulsive Disorder

AbstractObsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by the performance of repetitive behaviors in response to an obsession, which currently ranks as the tenth cause of disability in the world. Patients who are refractory to conventional treatment are candidates for the neurosurgical treatment of deep brain stimulation (DBS). In this procedure, electrodes are implanted in specific anatomical brain targets. The present systematic literature review aimed to describe the main connectomes and associate them with their respective targets involved in DBS for the treatment of OCD, to understand the connectomes related to OCD and their contributions to DBS, and to describe the main targets used in DBS surgery for OCD. Based on the present results, the stimulated targets that showed better clinical outcomes were the anterior limb of the internal capsule, the nucleus accumbens, the subthalamic nucleus, and the ventral capsule/striatal capsule. The target associated with the worst clinical results was the posterior limb of the anterior commissure. The variable stimulation of certain regions of the brain determines different clinical results. However, an individualized investigation of the OCD patient is essential for choosing the best target for DBS.

Anterior Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Tractography and Lesion Geometry study

Introduction: A bilateral anterior capsulotomy effectively treats refractory obsessive-compulsive disorder (OCD). We investigated the geometry of lesions and disruption of white matter pathways within the anterior limb of the internal capsule (ALIC) in patients with different outcomes. Methods: In this retrospective study, we analyzed data from 18 patients with refractory OCD who underwent capsulotomies. Patients were grouped into “responders” and “nonresponders” based on the percentage of decrease in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) after surgery. We investigated neurobehavioral adverse effects and analyzed the overlap between lesions and the ventromedial prefrontal (vmPFC) and dorsolateral prefrontal (dlPFC) pathways. Probabilistic maps were constructed to investigate the relationship between lesion location and clinical outcomes. Results: Of the 18 patients who underwent capsulotomies, 12 were responders (>35% improvement in YBOCS), and six were nonresponders. The vmPFC pathway was more involved than the dlPFC pathway in responders (p = 0.01), but no significant difference was observed in nonresponders (p = 0.10). The probabilistic voxel-wise efficacy map showed a relationship between ventral voxels within the ALIC with symptom improvement. Weight gains occurred in 11/18 (61%) patients and could be associated with medial voxels within the ALIC. Conclusion: The optimal outcome after capsulotomy in refractory OCD is linked to vmPFC disruption in the ALIC. Medial voxels within the ALIC could be associated with weight gains following capsulotomy.

Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder.

Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD. Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAc-ALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG. The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude. These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD. Clinical trial registration no.: NCT02398318 (ClinicalTrials.gov).

Intraoperative valence testing to adjudicate between ventral capsule/ventral striatum and bed nucleus of the stria terminalis target selection in deep brain stimulation for obsessive-compulsive disorder.

Deep brain stimulation (DBS) is an accepted therapy for severe, treatment-refractory obsessive-compulsive disorder (trOCD). The optimal DBS target location within the anterior limb of the internal capsule, particularly along the anterior-posterior axis, remains elusive. Empirical evidence from several studies in the past decade has suggested that the ideal target lies in the vicinity of the anterior commissure (AC), either just anterior to the AC, above the ventral striatum (VS), or just posterior to the AC, above the bed nucleus of the stria terminalis (BNST). Various methods have been utilized to optimize target selection for trOCD DBS. The authors describe their practice of planning trajectories to both the VS and BNST and adjudicating between them with awake intraoperative valence testing to individualize permanent target selection. Eight patients with trOCD underwent awake DBS with trajectories planned for both VS and BNST targets bilaterally. The authors intraoperatively assessed the acute effects of stimulation on mood, energy, and anxiety and implanted the trajectory with the most reliable positive valence responses and least stimulation-induced side effects. The method of intraoperative target adjudication is described, and the OCD outcome at last follow-up is reported. The mean patient age at surgery was 41.25 ± 15.1 years, and the mean disease duration was 22.75 ± 10.2 years. The median preoperative Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score was 39 (range 34-40). Two patients had previously undergone capsulotomy, with insufficient response. Seven (44%) of 16 leads were moved to the second target based on intraoperative stimulation findings, 4 of them to avoid strong negative valence effects. Three patients had an asymmetric implant (1 lead in each target). All 8 patients (100%) met full response criteria, and the mean Y-BOCS score reduction across the full cohort was 51.2% ± 12.8%. Planning and intraoperatively testing trajectories flanking the AC-superjacent to the VS anteriorly and to the BNST posteriorly-allowed identification of positive valence responses and acute adverse effects. Awake testing helped to select between possible trajectories and identify individually optimized targets in DBS for trOCD.

Sleep disorders and white matter integrity in patients with sporadic amyotrophic lateral sclerosis

This study aimed to explore the characteristics of sleep disorders and their relationship with abnormal white-matter integrity in patients with sporadic amyotrophic lateral sclerosis. One hundred and thirty-six patients and 80 healthy controls were screened consecutively, and 56 patients and 43 healthy controls were ultimately analyzed. Sleep disorders were confirmed using the Pittsburgh sleep quality index, the Epworth sleepiness scale, and polysomnography; patients were classified into those with poor and good sleep quality. White-matter integrity was assessed using diffusion tensor imaging and compared between groups to identify the white-matter tracts associated with sleep disorders. The relationship between scores on the Pittsburgh sleep quality index and impaired white-matter tracts was analyzed using multiple regression. Poor sleep quality was more common in patients (adjusted odds ratio, 4.26; p = 0.005). Compared to patients with good sleep quality (n = 30), patients with poor sleep quality (n = 26; 46.4%) showed decreased fractional anisotropy, increased mean diffusivity, and increased radial diffusivity of projection and commissural fibers, and increased radial diffusivity of the right thalamus. The Pittsburgh score showed the best fit with the mean fractional anisotropy of the right anterior limb of the internal capsule (r = - 0.355, p = 0.011) and the mean radial diffusivity of the right thalamus (r = 0.309, p = 0.028). We conclude that sleep disorders are common in patients with sporadic amyotrophic lateral sclerosis and are associated with reduced white-matter integrity. The pathophysiology of amyotrophic lateral sclerosis may contribute directly to sleep disorders.

Deep brain stimulation for autism spectrum disorder.

Deep brain stimulation (DBS) is a medical treatment that aims to obtain therapeutic effects by applying chronic electrical impulses in specific brain structures and neurological circuits. Over the years, DBS has been studied for the treatment of many psychiatric disorders. Scientific research on the use of DBS in people with autism has focused this interest mainly on treatment-resistant obsessive-compulsive disorder, drug-resistant epilepsy, self-injurious behaviors (SIB), and aggressive behaviors toward the self. Autism spectrum disorder (ASD) includes a group of developmental disabilities characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills and the presence of repetitive and stereotyped behaviors as well as restricted interests. People with autism often have numerous medical and psychiatric comorbidities that worsen the quality of life of patients and their caregivers. Obsessive-compulsive symptoms can be found in up to 81.3% of people with autism. They are often severe, refractory to treatment, and particularly difficult to treat. SIB has a high prevalence in severely retarded individuals and is often associated with autism. Drug treatment of both autism and SIB presents a therapeutic challenge. To describe the current state of the art regarding the efficacy of DBS in people with ASD, a literature search was conducted for relevant studies using the PubMed database. Thirteen studies have been considered in this paper. Up to date, DBS has been used for the stimulation of the nucleus accumbens, globus pallidus internus, anterior limb of the internal capsule, ventral anterior limb of the internal capsule, basolateral amygdala, ventral capsule and ventral striatum, medial forebrain bundle, and posterior hypothalamus. In the total sample of 16 patients, 4 were adolescents, and 12 were adults. All patients had symptoms resistant to multiple drug therapy. Many patients taken into consideration by the studies showed clinical improvements as evidenced by the scores of the psychopathological scales used. In some cases, clinical improvements have varied over time, which may require further investigation. Among the new therapeutic perspectives, DBS could be a valid option. However, further, and more in-depth research is needed in this field.

Treating Obsessive-Compulsive Disorder by Invasively Modulating Thoughts, Feelings, or Both

The defining characteristic of pathological compulsions is that they are carried out to reduce momentary distress, even though performing the compulsive act or thought is rationally not in the individual’s true best interest. This inability to flexibly adapt is a prominent component of obsessive-compulsive disorder (OCD) and closely related illnesses such as Tourette syndrome and is also observed in substance use disorders ( 1 Figee M. Pattij T. Willuhn I. Luigjes J. van den Brink W. Goudriaan A. et al. Compulsivity in obsessive-compulsive disorder and addictions. Eur Neuropsychopharmacol. 2016; 26: 856-868 Crossref PubMed Scopus (111) Google Scholar ). Following the 20th century experience with ablative procedures such as capsulotomy, deep brain stimulation (DBS) was applied to the treatment of OCD. Electrodes are most commonly placed within the anterior limb of the internal capsule (ALIC), modulating cortico-basal ganglia-thalamo-cortical parallel white matter loops relevant to limbic, associative, and motor functions, respectively. ALIC stimulation has proven to be a highly effective treatment for severe OCD ( 2 Smith AH, Mayberg HS, Figee M (in press): Neuromodulation and psychiatric disorders. In: Nestler EJ, Charney DS, editors. Neurobiology of Mental Illness, 6th ed. New York: Oxford University Press. Google Scholar ). DBS to a different anatomical location, the subthalamic nucleus (STN), was initially developed for Parkinson’s disease, but positive early experience in patients with comorbid Parkinson’s disease and OCD led to research establishing high-frequency stimulation straight to the STN as clinically efficacious for OCD ( 3 Mallet L. Polosan M. Jaafari N. Baup N. Welter M.L. Fontaine D. et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008; 359: 2121-2134 Crossref PubMed Scopus (687) Google Scholar ). In a similar manner, promising early pilot studies led to further exploration of other targets. These include the bed nucleus of the stria terminalis, the “extended amygdala” located between the ALIC and STN targets ( 4 Mosley P.E. Windels F. Morris J. Coyne T. Marsh R. Giorni A. et al. A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder. Transl Psychiatry. 2021; 11: 190 Crossref PubMed Scopus (38) Google Scholar ). More recently, evidence has emerged for the effectiveness of stimulation delivered deeper in the midbrain than the STN, adjacent to the ventral tegmental area (VTA)—a source of dopaminergic projections to the cortex (via the medial forebrain bundle [MFB]) and a recipient of proposed regulatory projections back from the cortex (via the “supralateral MFB”) ( 5 Meyer D.M. Spanier S. Kilian H.M. Reisert M. Urbach H. Sajonz B.E. et al. Efficacy of superolateral medial forebrain bundle deep brain stimulation in obsessive-compulsive disorder. Brain Stimul. 2022; 15: 582-585 Abstract Full Text Full Text PDF Scopus (3) Google Scholar ). SEE CORRESPONDING ARTICLE ON PAGE 1010 SEE CORRESPONDING ARTICLE ON PAGE 1010 The Rostral Zona Incerta: A Subcortical Integrative Hub and Potential Deep Brain Stimulation Target for Obsessive-Compulsive DisorderBiological PsychiatryVol. 93Issue 11PreviewThe zona incerta (ZI) is involved in mediating survival behaviors and is connected to a wide range of cortical and subcortical structures, including key basal ganglia nuclei. Based on these connections and their links to behavioral modulation, we propose that the ZI is a connectional hub for mediating between top-down and bottom-up control and a possible target for deep brain stimulation for obsessive-compulsive disorder. Full-Text PDF