Anterior Limb Of The Internal Capsule Research Articles

Effective deep brain stimulation for obsessive-compulsive disorder after failed anterior capsulotomy: illustrative cases.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by recurrent, unwanted thoughts (obsessions) and repetitive behaviors (compulsions) performed to relieve distress related to the obsessions. For patients with severe illness refractory to first-line pharmacotherapy and psychotherapy, neurosurgical treatments such as deep brain stimulation (DBS) and stereotactic lesioning are an option. The choice between DBS and lesioning is often driven by patient preference, but these options are not mutually exclusive. Here, the authors highlight the success of one surgical therapy (DBS) after the failure of another (lesioning). Two patients with severe, treatment-refractory OCD underwent DBS lead implantation targeting the ventral capsule/ventral striatum after they did not attain any worthwhile benefit from a previous anterior capsulotomy. Both patients showed significant improvement (≥ 35% reduction in Yale-Brown Obsessive-Compulsive Scale [YBOCS] score) of their OCD symptoms at the long-term follow-up after DBS. One patient experienced a 37% reduction in symptom severity as measured by the YBOCS, and the other patient experienced a 47% reduction. DBS and lesioning procedures are both effective surgical options for patients with intractable OCD. In these cases, the authors demonstrate that DBS can be utilized even after a lesioning procedure in nominally the same target (ventral portion of the anterior limb of the internal capsule). https://thejns.org/doi/10.3171/CASE24289.

Involvement of the cerebellum in structural connectivity enhancement in episodic migraine

BackgroundThe pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls.MethodsTo that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM.ResultsWe found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine.ConclusionsA distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.

Long-Term Safety and Efficacy of Focused Ultrasound Capsulotomy for Obsessive-Compulsive Disorder and Major Depressive Disorder

BackgroundMagnetic resonance–guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluated the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). MethodsThis phase 1, single-center, open-label study recruited patients with treatment-resistant OCD and MDD. Outcomes were measured 6 months, 12 months, and 18 to 24 months (long term) after MRgFUS capsulotomy. Neuropsychological testing and neuroimaging were conducted at baseline and 12 months postoperatively. The primary outcome was safety. The secondary outcome was clinical response, defined for OCD as a ≥35% improvement in Yale-Brown Obsessive Compulsive Scale scores and for MDD as a ≥50% reduction in Hamilton Depression Rating Scale scores compared with baseline. ResultsNo serious adverse effects were registered. In patients with OCD (n= 15), baseline Yale-Brown Obsessive Compulsive Scale scores (31.9 ± 1.2) were significantly reduced by 23% (p = .01) at 6 months and 35% (p < .0001) at 12 months. In patients with MDD (n = 12), a 26% and 25% nonsignificant reduction in Hamilton Depression Rating Scale scores (baseline 24.3 ± 1.2) was observed at 6 months and 12 months, respectively. Neuropsychological testing revealed no negative effects of capsulotomy. In the OCD and MDD cohorts, we found a correlation between clinical outcome and lesion laterality, with more medial left–placed lesions (OCD, p = .08) and more lateral right–placed lesions (MDD, p < .05) being respectively associated with a stronger response. In the MDD cohort, more ventral tracts appeared to be associated with a poorer response. ConclusionsMRgFUS capsulotomy is safe in patients with OCD and MDD and particularly effective in the former population.

Therapeutic DBS for OCD Suppresses the Default Mode Network.

Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is an emerging treatment for severe, refractory obsessive-compulsive disorder (OCD). The therapeutic effects of DBS are hypothesized to be mediated by direct modulation of a distributed cortico-striato-thalmo-cortical network underlying OCD symptoms. However, the exact underlying mechanism by which DBS exerts its therapeutic effects still remains unclear. In five participants receiving DBS for severe, refractory OCD (3 responders, 2 non-responders), we conducted a DBS On/Off cycling paradigm during the acquisition of functional MRI to determine the network effects of stimulation across a variety of bipolar configurations. We also performed tractography using diffusion-weighted imaging (DWI) to relate the functional impact of DBS to the underlying structural connectivity between active stimulation contacts and functional brain networks. We found that therapeutic DBS had a distributed effect, suppressing BOLD activity within regions such as the orbitofrontal cortex, dorsomedial prefrontal cortex, and subthalamic nuclei compared to non-therapeutic configurations. Many of the regions suppressed by therapeutic DBS were components of the default mode network (DMN). Moreover, the estimated stimulation field from the therapeutic configurations exhibited significant structural connectivity to core nodes of the DMN. Therapeutic DBS for OCD suppresses BOLD activity within a distributed set of regions within the DMN relative to non-therapeutic configurations. We propose that these effects may be mediated by interruption of communication through structural white matter connections surrounding the DBS active contacts.

A Reproducible Pipeline for Parcellation of the Anterior Limb of the Internal Capsule

BackgroundThe anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions. MethodsFollowing algorithm development and refinement, we analyzed 43 control participants, each with 2 sets of 3T magnetic resonance imaging data and a subset of 5 control participants with 7T data from the Human Connectome Project. We generated 22 segmented ALIC fiber bundles (11 per hemisphere) based on PFC regions of interest, and we analyzed the relationships among bundles. ResultsWe successfully reproduced the topographies established by previous anatomical work using images acquired at both 3T and 7T. Quantitative assessment demonstrated significantly smaller intraparticipant variability than interparticipant variability for both test and retest groups across all but one PFC region. We examined the overlap between fibers from different PFC regions and a response tract for obsessive-compulsive disorder deep brain stimulation, and we reconstructed the PFC hyperdirect pathway using a modified version of our pipeline. ConclusionsOur diffusion magnetic resonance imaging algorithm reliably generates biologically validated ALIC white matter reconstructions, thereby allowing for more precise modeling of fibers for neuromodulation therapies.

White matter changes after Gamma Knife Capsulotomy in patients with intractable obsessive-compulsive disorder

BackgroundAnterior capsulotomy is one of the therapeutic options for refractory obsessive–compulsive disorder (OCD). Safety and efficacy of Gamma Knife Capsulotomy (GKC) have been demonstrated in the past. ObjectiveTo characterize changes induced by GKC using a fixel-based analysis (FBA) and possible predictors of efficacy. MethodsPatients with OCD refractory to other therapies underwent bilateral GKC with 120 Gy as a maximum dose on the anterior limb of the internal capsule (ALIC). The clinical outcome was percent reduction in Yale- Brown Obsessive–Compulsive Scale (Y-BOCS). White Matter changes were analyzed using fixel-based analysis (FBA) for fibre density (FD), fibre-bundle cross-section (FC) and the combination of the two (FDC). ResultsSeven patients underwent GKC. Median follow-up was 13 months (range 12–58 months). Mean (±SD) decrease in Y-BOCS score at last follow-up was 61 % ± 35 % with five patients considered as responders. FBA showed a symmetric FD reduction in the ALIC with extension to the anterior fronto-thalamic radiation; a reduction of FC along the superior longitudinal fasciculus (SLF) in both hemispheres with a predominance in the left one. Reductions in FDC were detected predominantly in the right hemisphere, with a similar pattern to FD reductions and associated with a positive correlation (p < 0.05) between Y-BOCS reduction and fibres passing in the ventral part. ConclusionsGKC is safe and efficient in reducing OCD severity in selected patients. Changes induced in white matter by GKC extend over the ALIC. Reduction of fibres passing the ventral part of the right sided ALIC correlates with better results.

IMG-04. ASSOCIATION BETWEEN MICROSTRUCTURAL INTEGRITY OF BRAIN SUBSTRUCTURES AND NEUROCOGNITIVE OUTCOMES: A MULTI-TRAJECTORY ANALYSIS IN CHILDHOOD BRAIN TUMOR SURVIVORS

Abstract BACKGROUND The relationship between the brain’s microstructural integrity and neurocognitive outcomes is not well characterized in childhood brain tumor survivors. In healthy children, mean diffusivity (MD) generally decreases and fractional anisotropy (FA) increases with age as the brain progressively myelinates and develops. Increasing MD and decreasing FA is suggestive of microstructural injury. We investigate the association between longitudinal neurocognitive outcomes and change in MD and FA in childhood brain tumor survivors. METHODS Patients diagnosed with a brain tumor at &amp;lt; 20 years of age with ≥ 2 neurocognitive assessments and paired DTI at each neurocognitive timepoint were retrospectively identified and eligible for inclusion. Multi-trajectory modeling was applied to cluster patients into distinct neurocognitive trajectories based on intelligent quotient, processing speed and working memory. Linear mixed models were used to determine whether the clusters were associated with change in MD and FA over time. RESULTS A total of 61 patients were eligible with 151 neurocognitive assessments paired with DTI. Mean follow-up was 4.8 years. Multi-trajectory modeling identified two clusters of patients with distinct neurocognitive trajectories. Compared to the low-performance group, the high-performance group (45.5%) had higher baseline neurocognitive scores with less decline in all neurocognitive outcomes. The high-performance group was also associated with a greater decrease in MD and greater increase in FA of the hippocampus and several white matter tracts such as the corpus callosum, pontine crossing tract, anterior limb of the internal capsule and inferior cerebellar peduncle, after adjusting for age and sex (all p&amp;lt;0.05). Additionally, the high-performance group was associated with a greater increase in FA in the superior, middle and inferior frontal gyri (all p&amp;lt;0.05). CONCLUSIONS The high-performance neurocognitive group was associated with greater microstructural integrity over time in multiple brain substructures compared to the low-performance group, as measured by change in fractional anisotropy and mean diffusivity.

The association between frontotemporal connecting fibers and seizure severity in patients with temporal lobe epilepsy

The patients with temporal lobe epilepsy (TLE) admitted in the Department of Neurology, Zhongshan Hospital, Fudan University from June 2009 to February 2012 were prospectively enrolled. The diffusion tensor imaing was performed on the patients at the time of enrollment and 3 years later. The fractional anisotropy (FA) values of the white matter connecting fibers(bilateral hooked, arcuate, cingulate, and superior longitudinal tracts), the connecting fibers of both hemispheres(anterior union, anterior callosal forceps, posterior forceps, and bilateral fornix), and fibers of perirhinal cortices system(bilateral radiating crown and anterior limb of the internal capsule) were measured by the region of interest method. The severity of epilepsy was evaluated using the Veterans Administration Seizure Type and Frequency Rating Scale(VA-2) and National Hospital Seizure Severity Scale (NHS3). A total of 51 patients with TLE were screened, with 27 patients completing the 3-year follow-up. There were 13 males and 14 females with an age of (32±11) years and a follow-up duration of (39.1±1.1) months. During the follow-up, 6 patients had increased/unchanged NHS3 or VA-2 scores, while 21 patients had decreased scores. Three years later, the FA values of the bilateral arcuate fasciculus, the right superior longitudinal fasciculus, the right radial coronal and corpus callosum anterior forceps in TLE patients decreased compared to baseline(P<0.05). However, compared to the patients with decreased VA-2 scores during the follow-up, the degree of increase in FA values (ΔFA, follow-up FA value-baseline FA value) of the ipsilateral hook bundle caused by epilepsy was more significant in the group with increased/unchanged VA-2 scores (decreased score group vs increased/unchanged score group:-0.032±0.063 vs 0.018±0.043, t=2.305, P=0.035). The value of ΔFA in epileptic patients with increased/unchanged NHS3 scores (0.075±0.113) was higher compared to those with decreased scores (-0.079±0.099, t=2.804, P=0.010). Correlation analysis also showed the changes in FA values of epileptic lateral fasciculus (r=0.503, P=0.009) and arcuate fasciculus (r=0.602, P=0.001)were positively correlated with the changes in VA-2 and HNS3 scores, respectively. The seizure severity in patients with TLE was closely associated with the microstructure changes in the frontal and temporal white matter, especially the arcuate and uncinate tracts, on the same side that caused seizures, which may indicate the white matter remodeling and abnormal network reformation associated with seizures.

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.

Deep Brain Stimulation for Primary Refractory Tinnitus: A Systematic Review.

tinnitus is a common and often debilitating condition with limited evidence-based treatment options. Deep brain stimulation (DBS) is an approved treatment modality for certain neurological conditions; its experimental use as a treatment modality for severe tinnitus is novel and beginning to show promise. This systematic review focuses on the current evidence for the safety and efficacy of DBS for treatment of refractory tinnitus. a systematic search in PubMed and EMBASE was performed to identify peer-reviewed studies on DBS of non-cortical structures for the primary indication of tinnitus treatment. Three studies were identified as meeting these criteria, one of which had two related sub-studies. seven patients with available data who underwent DBS for tinnitus were identified. DBS targets included nucleus accumbens (NAc), ventral anterior limb of the internal capsule (vALIC), caudate nucleus, and the medial geniculate body (MGB) of the thalamus. All studies used the Tinnitus Functional Index (TFI) as a primary outcome measure. DBS of the caudate was most commonly reported (n = 5), with a mean TFI improvement of 23.3 points. Only one subject underwent DBS targeting the NAc/vALIC (extrapolated TFI improvement 46.8) and one subject underwent DBS targeting the MGB (TFI improvement 59 points). DBS is a promising treatment option for refractory subjective tinnitus, with early data, from small patient cohorts in multiple studies, suggesting its safety and efficacy. Further studies with a larger patient population are needed to support this safety and efficacy before implementing this treatment to daily practice.

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.

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.

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.

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.

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.

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.