Brodmann Area Research Articles

Correlation of visual area with tremor improvement after MRgFUS thalamotomy in Parkinson's disease.

MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive alternative for medication-refractory tremor in Parkinson's disease (PD). However, the impact of MRgFUS thalamotomy on spontaneous neuronal activity in PD remains unclear. The purpose of the current study was to evaluate the effects of MRgFUS thalamotomy on local fluctuations in neuronal activity as measured by the fractional amplitude of low-frequency fluctuations (fALFF) in patients with PD. Participants with PD undergoing MRgFUS thalamotomy were recruited. Tremor scores were assessed before and 3 and 12 months after treatment using the Clinical Rating Scale for Tremor. MRI data were collected before and 1 day, 1 week, 1 month, 3 months, and 12 months after thalamotomy. The fALFF was calculated. A whole-brain voxel-wise paired t-test was used to identify significant changes in fALFF at 12 months after treatment compared to baseline. Then fALFF in the regions with significant differences were extracted from fALFF maps of patients for further one-way repeated-measures ANOVA to investigate its dynamic alterations. The association between fALFF changes induced by thalamotomy and tremor improvement were evaluated using the nonparametric Spearman rank test. Nine participants with PD (mean age ± SD 64.7 ± 6.1 years, 8 males) were evaluated. Voxel-based analysis showed that fALFF in the left occipital cortex (Brodmann area 17 [BA17]) significantly decreased at 12 months after thalamotomy compared to baseline (voxel p < 0.001, cluster p < 0.05 family-wise error [FWE] corrected). At baseline, fALFF in the left occipital BA17 in patients was elevated compared with that in 9 age- and gender-matched healthy subjects (p < 0.05). Longitudinal analysis displayed the dynamic changes of fALFF in this region (F (5,40) = 3.61, p = 0.009). There was a significant positive correlation between the falling trend in fALFF in the left occipital BA17 and hand tremor improvement after treatment over 3 time points (Spearman's rho = 0.44, p = 0.02). The present study investigated the impact of MRgFUS ventral intermediate nucleus thalamotomy on spontaneous neural activity in medication-refractory tremor-dominant PD. The visual area is, for the first time, reported as relevant to tremor improvement in PD after MRgFUS thalamotomy, suggesting a distant effect of MRgFUS thalamotomy and the involvement of specific visuomotor networks in tremor control in PD.

Abnormalities of Thalamic Functional Connectivity in Patients with Migraine: A Resting-State fMRI Study.

IntroductionMigraine is a common headache disorder. Many studies have used magnetic resonance imaging (MRI) to explore the possible pathogenesis of migraine, but they have not reached consistent conclusions and lack rigorous multiple comparison correction. Thus, this study investigates the mechanisms of migraine development from the perspective of altered functional connectivity (FC) in brain regions by using data-driven and regions of interest (ROI)-based approaches.MethodsResting-state functional MRI data were collected from 30 patients with migraine and 40 healthy controls (HCs) matched for age, gender, and years of education. For the data-driven method, we used a voxel-mirrored homotopic connectivity (VMHC) approach to compare the FC between the patients and HCs. For the ROI-based method, significant differences in VMHC maps between the patients and HCs were defined as ROI. The seed-based approach further revealed significant differences in FC between the seeds and the other brain regions. Furthermore, the correlations between abnormal FC and clinical characteristics of patients were investigated. A rigorous multiple comparison correction was used with false discovery rate and permutation test (5000 times).ResultsIn comparison with the controls group, patients showed enhanced VMHC in the bilateral thalamus. We also observed enhanced FC between the left thalamus and the left superior frontal gyrus, and increased FC between the right thalamus and the left middle frontal gyrus (Brodmann area 45 and Brodmann area 8) in patients. Further analysis showed that the FC values in the left superior frontal gyrus and left middle frontal gyrus were negatively corrected with visual analogue scale scores or attack times for headaches.ConclusionsPatients with migraine showed altered VMHC in the bilateral thalamus, and abnormal FC of bilateral thalamus and other brain regions. The abnormalities in thalamic FC are a likely mechanism for the development of migraine.Trial RegistrationChinese Clinical Trial Registry, ChiCTR2000033995. Registered on 20 June 2020.

Cerebral metabolic pattern associated with progressive parkinsonism in non-human primates reveals early cortical hypometabolism

Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([11C]-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-[18F]-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.

Decreasing Shortest Path Length of the Sensorimotor Network Induces Frontal Glioma-Related Epilepsy.

BackgroundGlioma-related epilepsy (GRE) is a common symptom in patients with prefrontal glioma. Epilepsy onset is associated with functional network alterations. This study investigated alterations of functional networks in patients with prefrontal glioma and GRE.MethodsSixty-five patients with prefrontal lobe gliomas were retrospectively assessed and classified into GRE and non-GRE groups. Additionally, 25 healthy participants were enrolled after matching for general information. Imaging data were acquired within 72 h in pre-operation. The sensorimotor network was used to delineate alterations in functional connectivity (FC) and topological properties. One-way analysis of variance and post-hoc analysis with Bonferroni correction were used to calculate differences of FC and topological properties.ResultsAll significant alterations were solely found in the sensorimotor network. Irrespective of gliomas located in the left or right prefrontal lobes, the edge between medial Brodmann area 6 and caudal ventrolateral Brodmann area 6 decreased FC in the GRE group compared with the non-GRE group [p < 0.0001 (left glioma), p = 0.0002 (right glioma)]. Moreover, the shortest path length decrease was found in the GRE group compared with the non-GRE group [p = 0.0292 (left glioma) and p = 0.0129 (right glioma)].ConclusionsThe reduction of FC between the medial BA 6 (supplementary motor area) and caudal ventrolateral BA 6 in the ipsilateral hemisphere and the shortening of the path length of the sensorimotor network were characteristics alterations in patients with GRE onset. These findings fill in the gap which is the relationship between GRE onset and the alterations of functional networks in patients with prefrontal glioma.Significance StatementGlioma related epilepsy is the most common symptom of prefrontal glioma. It is important to identify characteristic alterations in functional networks in patients with GRE. We found that all significant alterations occurred in the sensorimotor network. Moreover, a decreased FC in the supplementary motor area and a shortening of the path’s length are additional characteristics of glioma-related epilepsy. We believe that our findings indicate new directions of research that will contribute to future investigations of glioma-related epilepsy onset.

Revealing the Selectivity of Neuroanatomical Alteration in Autism Spectrum Disorder via Reverse Inference

BackgroundAlthough neuroimaging research has identified atypical neuroanatomical substrates in individuals with autism spectrum disorder (ASD), it is at present unclear whether and to what extent disorder-selective gray matter alterations occur in this spectrum of conditions. In fact, a growing body of evidence shows a substantial overlap between the pathomorphological changes across different brain diseases, which may complicate identification of reliable neural markers and differentiation of the anatomical substrates of distinct psychopathologies. MethodsUsing a novel data-driven and Bayesian methodology with published voxel-based morphometry data (849 peer-reviewed experiments and 22,304 clinical subjects), this study performs the first reverse inference investigation to explore the selective structural brain alteration profile of ASD. ResultsWe found that specific brain areas exhibit a >90% probability of gray matter alteration selectivity for ASD: the bilateral precuneus (Brodmann area 7), right inferior occipital gyrus (Brodmann area 18), left cerebellar lobule IX and Crus II, right cerebellar lobule VIIIA, and right Crus I. Of note, many brain voxels that are selective for ASD include areas that are posterior components of the default mode network. ConclusionsThe identification of these spatial gray matter alteration patterns offers new insights into understanding the complex neurobiological underpinnings of ASD and opens attractive prospects for future neuroimaging-based interventions.

A Study of Word Complexity Under Conditions of Non-experimental, Natural Overt Speech Production Using ECoG.

The linguistic complexity of words has largely been studied on the behavioral level and in experimental settings. Only little is known about the neural processes underlying it in uninstructed, spontaneous conversations. We built up a multimodal neurolinguistic corpus composed of synchronized audio, video, and electrocorticographic (ECoG) recordings from the fronto-temporo-parietal cortex to address this phenomenon based on uninstructed, spontaneous speech production. We performed extensive linguistic annotations of the language material and calculated word complexity using several numeric parameters. We orthogonalized the parameters with the help of a linear regression model. Then, we correlated the spectral components of neural activity with the individual linguistic parameters and with the residuals of the linear regression model, and compared the results. The proportional relation between the number of consonants and vowels, which was the most informative parameter with regard to the neural representation of word complexity, showed effects in two areas: the frontal one was at the junction of the premotor cortex, the prefrontal cortex, and Brodmann area 44. The postcentral one lay directly above the lateral sulcus and comprised the ventral central sulcus, the parietal operculum and the adjacent inferior parietal cortex. Beyond the physiological findings summarized here, our methods may be useful for those interested in ways of studying neural effects related to natural language production and in surmounting the intrinsic problem of collinearity between multiple features of spontaneously spoken material.

Chronic Behavioral Manipulation via Orally Delivered Chemogenetic Actuator in Macaques.

The chemogenetic technology referred to as designer receptors exclusively activated by designer drugs (DREADDs) offers reversible means to control neuronal activity for investigating its functional correlation with behavioral action. Deschloroclozapine (DCZ), a recently developed highly potent and selective DREADD actuator, displays a capacity to expand the utility of DREADDs for chronic manipulation without side effects in nonhuman primates, which has not yet been validated. Here we investigated the pharmacokinetics and behavioral effects of orally administered DCZ in female and male macaque monkeys. Pharmacokinetic analysis and PET occupancy examination demonstrated that oral administration of DCZ yielded slower and prolonged kinetics, and that its bioavailability was 10%-20% of that in the case of systemic injection. Oral DCZ (300-1000 μg/kg) induced significant working memory impairments for at least 4 h in monkeys with hM4Di expressed in the dorsolateral prefrontal cortex (Brodmann's area 46). Repeated daily oral doses of DCZ consistently caused similar impairments over two weeks without discernible desensitization. Our results indicate that orally delivered DCZ affords a less invasive strategy for chronic but reversible chemogenetic manipulation of neuronal activity in nonhuman primates, and this has potential for clinical application.SIGNIFICANCE STATEMENT The use of designer receptors exclusively activated by designer drugs (DREADDs) for chronic manipulation of neuronal activity for days to weeks may be feasible for investigating brain functions and behavior on a long time-scale, and thereby for developing therapeutics for brain disorders, such as epilepsy. Here we performed pharmacokinetics and in vivo occupancy study of orally administered deschloroclozapine to determine a dose range suitable for DREADDs studies. In monkeys expressing hM4Di in the prefrontal cortex, single and repeated daily doses significantly induced working-memory impairments for hours and over two weeks, respectively, without discernible desensitization. These results indicate that orally delivered deschloroclozapine produces long-term stable chemogenetic effects, and holds great promise for the translational use of DREADDs technology.

Correlation between noise pareidolia test scores for visual hallucinations and regional cerebral blood flow in dementia with Lewy bodies.

This study aimed at investigating the correlation between recurrent visual hallucinations (VHs) and regional cerebral blood flow (rCBF) in patients with dementia with Lewy bodies (DLB). In 147 DLB patients, the correlation between noise pareidolia scores and rCBF in brain perfusion single photon emission computed tomography (SPECT) was evaluated. The 147 subjects comprised 52 probable and 95 possible DLB patients, of whom 107 did not have visual hallucinations and 40 had visual hallucinations. Brain perfusion SPECT was then performed, and memory impairment was assessed using the Mini-Mental State Examination (MMSE), while the optical illusion "pareidolia" (the tendency to see a specific image in a random visual pattern) was evaluated using noise pareidolia test. The correlations between rCBF and MMSE or noise pareidolia scores were then analyzed. The rCBF and MMSE scores were positively correlated, and rCBF was correlated with MMSE scores in a region that was consistent with a previously reported memory-related site. There was no correlation between noise pareidolia scores and occipital CBF, but there were weak correlations between noise pareidolia scores and rCBF in the bilateral frontal lobes (Brodmann area [BA]8 and BA9), left cingulate cortex (BA31), and left angular and supramarginal gyri (BA39 and BA40) in DLB patients. Weak correlation was found between noise pareidolia scores and rCBF in several sites (BA8, BA9, BA31, BA39 and BA40) other than in occipital lobe. These findings suggest that DLB hallucinations may be manifested by more complex brain network disorders, rather than by primary visual cortex disorders alone.

Notched Sound Alleviates Tinnitus by Reorganization Emotional Center.

BackgroundTinnitus is a common disease, and sound therapy is an effective method to alleviate it. Previous studies have shown that notched sound not only changes levels of cortical blood oxygen, but affects blood oxygen in specific cerebral cortical areas, such as Brodmann area 46 (BA46), which is associated with emotion. Extensive evidence has confirmed that tinnitus is closely related to emotion. Whether notched sound plays a role in regulating the emotional center is still unclear.MethodsThis study included 29 patients with newly diagnosed chronic tinnitus who were treated with notched sound. Functional near-infrared spectroscopy (fNIRS) was conducted before and after treatment to observe bilateral changes in cortical blood oxygen in the cerebral hemispheres. We compared the changes in connectivity between the two regions of interest (the superior temporal gyrus and BA46), as wells as other cortical regions before and after treatment.ResultsThe results showed (1) That global connectivity between the bilateral auditory cortex of the superior temporal sulcus and the ipsilateral cortex did not change significantly between baseline and the completion of treatment, and (2) That the connectivity between channel 14 and the right superior temporal sulcus decreased after treatment. The overall connectivity between the right BA46 region and the right cortex decreased after treatment, and decreases in connectivity after treatment were specifically found for channels 10 and 14 in the right parietal lobe and channels 16, 20, 21, and 22 in the frontal lobe, while there was no significant change on the left side. There were no significant changes in the questionnaire measures of tinnitus, anxiety, or depression before and after treatment.ConclusionThe results of the study indicate that cerebral cortex reorganization occurs in tinnitus patients after submitted to treatment with notched sound for 1 month, and that notched sound decreases the connectivity between the auditory cortex and specific brain regions.SignificanceNotched sound not only regulates the auditory center through lateral inhibition, but also alleviates tinnitus by reorganizing the emotional control center.

Effective connectivity of the human mirror neuron system during social cognition.

The human mirror neuron system (MNS) can be considered the neural basis of social cognition. Identifying the global network structure of this system can provide significant progress in the field. In this study, we use dynamic causal modeling (DCM) to determine the effective connectivity between central regions of the MNS for the first time during different social cognition tasks. Sixty-seven healthy participants completed fMRI scanning while performing social cognition tasks, including imitation, empathy and theory of mind. Superior temporal sulcus (STS), inferior parietal lobule (IPL) and Brodmann area 44 (BA44) formed the regions of interest for DCM. Varying connectivity patterns, 540 models were built and fitted for each participant. By applying group-level analysis, Bayesian model selection and Bayesian model averaging, the optimal family and model for all experimental tasks were found. For all social-cognitive processes, effective connectivity from STS to IPL and from STS to BA44 was found. For imitation, additional mutual connections occurred between STS and BA44, as well as BA44 and IPL. The results suggest inverse models in which the motor regions BA44 and IPL receive sensory information from the STS. In contrast, for imitation, a sensory loop with an exchange of motor-to-sensory and sensory-to-motor information seems to exist.

Medial Temporal Lobe Networks in Alzheimer's Disease: Structural and Molecular Vulnerabilities.

The medial temporal lobe (MTL) is connected to the rest of the brain through two main networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. Given the crucial role of the MTL and networks in the physiopathology of Alzheimer's disease (AD), the present study aimed at (1) investigating whether MTL atrophy propagates specifically within the AT and PM networks, and (2) evaluating the vulnerability of these networks to AD proteinopathies. To do that, we used neuroimaging data acquired in human male and female in three distinct cohorts: (1) resting-state functional MRI (rs-fMRI) from the aging brain cohort (ABC) to define the AT and PM networks (n = 68); (2) longitudinal structural MRI from Alzheimer's disease neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns (n = 349); and (3) positron emission tomography (PET) data from ADNI3 to evaluate the networks' vulnerability to amyloid and tau (n = 186). Our results suggest that the atrophy of distinct MTL subregions propagates within the AT and PM networks in a dissociable manner. Brodmann area (BA)35 structurally covaried within the AT network while the parahippocampal cortex (PHC) covaried within the PM network. In addition, these networks are differentially associated with relative tau and amyloid burden, with higher tau levels in AT than in PM and higher amyloid levels in PM than in AT. Our results also suggest differences in the relative burden of tau species. The current results provide further support for the notion that two distinct MTL networks display differential alterations in the context of AD. These findings have important implications for disease spread and the cognitive manifestations of AD.SIGNIFICANCE STATEMENT The current study provides further support for the notion that two distinct medial temporal lobe (MTL) networks, i.e., anterior-temporal (AT) and the posterior-medial (PM), display differential alterations in the context of Alzheimer's disease (AD). Importantly, neurodegeneration appears to occur within these networks in a dissociable manner marked by their covariance patterns. In addition, the AT and PM networks are also differentially associated with relative tau and amyloid burden, and perhaps differences in the relative burden of tau species [e.g., neurofibriliary tangles (NFTs) vs tau in neuritic plaques]. These findings, in the context of a growing literature consistent with the present results, have important implications for disease spread and the cognitive manifestations of AD in light of the differential cognitive processes ascribed to them.

Sacral Neuromodulation Improves Abnormal Prefrontal Brain Activity in Patients with Overactive Bladder: A Possible Central Mechanism.

We explored the central pathogenesis of overactive bladder (OAB) and the central mechanism of action of sacral neuromodulation (SNM). We prospectively enrolled patients with OAB who chose SNM and healthy controls (HCs). At baseline, all subjects completed a 72-hour voiding diary, OAB symptom score and prefrontal cortex functional near-infrared spectroscopy scan synchronous urodynamic monitoring. All OAB patients were tested after implantation of the SNM electrode, and both success and failure groups were reevaluated. NIRS_KIT software was used to analyze prefrontal activity (p <0.05 and corrected by false discovery rate). SPSS® 22.0 was used to analyze clinical parameters, and p <0.05 was considered statistically significant. A total of 16 HC and 20 OAB patients were enrolled. SNM treatment was successful in 18 OAB patients and failed in 2. The parameters of the voiding diary, OAB symptom score and urodynamic monitoring of OAB group were significantly improved after SNM treatment in success group, not in the failure group. Compared with HCs, Brodmann's area 9 (left dorsolateral prefrontal cortex [DLPFC]) was significantly deactivated in the preoperative OAB success group and significantly activated after SNM treatment. Before surgery, compared with the success group, the failure group showed significantly deactivated Brodmann's area 9 (left DLPFC). Our study provides novel neuroimaging evidence for the possible central pathogenesis of OAB (ie abnormal deactivation of the left DLPFC) and the possible central mechanism of action of SNM (ie restore activation of the left DLPFC).

Co-expression network analysis of frontal cortex during the progression of Alzheimer's disease.

Mechanisms of Alzheimer's disease (AD) and its putative prodromal stage, amnestic mild cognitive impairment (aMCI), involve the dysregulation of multiple candidate molecular pathways that drive selective cellular vulnerability in cognitive brain regions. However, the spatiotemporal overlap of markers for pathway dysregulation in different brain regions and cell types presents a challenge for pinpointing causal versus epiphenomenal changes characterizing disease progression. To approach this problem, we performed Weighted Gene Co-expression Network Analysis and STRING interactome analysis of gene expression patterns quantified in frontal cortex samples (Brodmann area 10) from subjects who died with a clinical diagnosis of no cognitive impairment, aMCI, or mild/moderate AD. Frontal cortex was chosen due to the relatively protracted involvement of this region in AD, which might reveal pathways associated with disease onset. A co-expressed network correlating with clinical diagnosis was functionally associated with insulin signaling, with insulin (INS) being the most highly connected gene within the network. Co-expressed networks correlating with neuropathological diagnostic criteria (e.g., NIA-Reagan Likelihood of AD) were associated with platelet-endothelium-leucocyte cell adhesion pathways and hypoxia-oxidative stress. Dysregulation of these functional pathways may represent incipient alterations impacting disease progression and the clinical presentation of aMCI and AD.

Altered functional connectivity of primary visual cortex in adults with strabismus and amblyopia: a resting-state fMRI study.

Functional connectivity of the primary visual cortex was explored with resting functional magnetic resonance imaging among adults with strabismus and amblyopia and healthy controls. We used the two-sample test and receiver operating characteristic curves to investigate the differences in mean functional connectivity values between the groups with strabismus and amblyopia and healthy controls. Compared with healthy controls, functional connectivity values in the left Brodmann areas 17, including bilateral lingual/angular gyri, were reduced in groups with strabismus and amblyopia. Moreover, functional connectivity values in the right Brodmann area 17, including left cuneus, right inferior occipital gyrus, and left inferior parietal lobule, were reduced in adults with strabismus and amblyopia. Our findings indicate that functional connectivity abnormalities exist between the primary visual cortex and other regions. This may be the basis of the pathological mechanism of visual dysfunction and stereovision disorders in adults with strabismus and amblyopia.

Effective connectivity and criminal sentencing decisions: dynamic causal models in laypersons and legal experts.

This magnetic resonance imaging study is designed to obtain relevant implications for criminal justice and explores the effective connectivity underlying expertise. Laypersons and experts considered sentences for remorseful and remorseless defendants, respectively, with and without mitigation, in hypothetical murder cases. Two groups revealed no differential activation. However, dynamic causal modeling analysis found distinct patterns of connectivity associated with subjects’ expertise and mitigating factors. In sentencing for remorseful defendants, laypersons showed increased strength in all bidirectional connections among activated regions of Brodmann area (BA) 32, BA23, the right posterior insula, and the precuneus. In contrast, legal experts sentenced based on mitigation reasoning, showed increased strength only in the bidirectional connection between the insula and the precuneus. When sentencing for remorseless ones without mitigation, both laypersons and experts increased the connection strength, but with reverse directionality, between regions; legal experts strengthened connectivity from BA10 to other regions, that is, the right anterior insula and BA23, but the directionality was reversed in laypersons. In addition, the strength of connection to BA32 and BA10 was correlated with changes in punishments by mitigating factors. This is a crucial result that establishes the validity of the connectivity estimates, which were uninformed by the independent (behavioral) differences in the severity of punishment.

Changes in sensory-related brain networks of patients with moyamoya disease with limb paresthesia: A resting-state fMRI-based functional connectivity analysis

This study’s aim was to investigate functional brain connectivity changes among patients with moyamoya disease (MMD) with limb paresthesia, using functional connectivity analysis based on resting-state functional magnetic resonance imaging (rs-fMRI). A total of 181 patients with MMD were enrolled, including 57 with left limb paresthesia (MLP group), 61 with right limb paresthesia (MRP group), and 63 without paresthesia (MWP group). Encephaloduroarteriosynangiosis (EDAS) was performed in 20 of the 57 patients with left limb paresthesia and 15 of the 61 patients with right limb paresthesia. Twenty-nine age- and sex-matched healthy controls (HC group) were recruited during the same period. All participants underwent rs-fMRI examination, and the patients treated with EDAS were re-examined 3–4 months after the surgery. After data preprocessing, we selected Brodmann area 3 on each side of the brain as the seed region to construct a functional connectivity network of the whole brain, and then we analyzed the differences in functional connectivity between the HC group, MWP group, MLP group, and MRP group. The functional connectivity of Brodmann area 3 (on either side) with the ipsilateral frontal (superior frontal gyrus, middle frontal gyrus, and inferior frontal gyrus) and parietal (supramarginal gyrus, angular gyrus, and superior parietal lobule) cortices was increased among patients with MMD. The functional connectivity enhancement in these brain regions was broader and greater in patients with contralateral limb paresthesia than in patients without paresthesia, and the regions with functional connectivity changes were roughly distributed symmetrically among the MLP group and the MRP group. There were no changes 3–4 months after EDAS in the increased functional connectivity between the frontal and parietal cortices and Brodmann area 3. Limb paresthesia in patients with MMD may be driven by abnormal functional connectivity in the frontal and parietal cortices. Functional changes in associated brain regions may be a target for evaluating the severity of MMD and its response to treatment.

Lesion location and outcome following cingulotomy for obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is among the most debilitating and medically refractory psychiatric disorders. While cingulotomy is an anatomically targeted neurosurgical treatment that has shown significant promise in treating OCD-related symptoms, the precise underlying neuroanatomical basis for its beneficial effects has remained poorly understood. Therefore, the authors sought to determine whether lesion location is related to responder status following cingulotomy. The authors reviewed the records of 18 patients who had undergone cingulotomy. Responders were defined as patients who had at least a 35% improvement in the Yale-Brown Obsessive Compulsive Scale (YBOCS) score. The authors traced the lesion sites on T1-weighted MRI scans and used an anatomical registration matrix generated by the imaging software FreeSurfer to superimpose these lesions onto a template brain. Lesion placement was compared between responders and nonresponders. The placement of lesions relative to various anatomical regions was also compared. A decrease in postoperative YBOCS score was significantly correlated with more superiorly placed lesions (decrease -0.52, p = 0.0012). While all lesions were centered within 6 mm of the cingulate sulcus, responder lesions were placed more superiorly and posteriorly along the cingulate sulcus (1-way ANOVA, p = 0.003). The proportions of the cingulum bundle, cingulate gyrus, and paracingulate cortex affected by the lesions were the same between responders and nonresponders. However, all responders had lesions covering a larger subregion of Brodmann area (BA) 32. In particular, responder lesions covered a significantly greater proportion of the posterior BA32 (1-way ANOVA, p = 0.0064). Lesions in patients responsive to cingulotomy tended to be located more superiorly and posteriorly and share greater coverage of a posterior subregion of BA32 than lesions in patients not responsive to this treatment.

Distinguishing transient from persistent tactile agnosia after partial anterior circulation infarcts – Behavioral and neuroimaging evidence for white matter disconnection

From a cohort of 36 patients presenting apperceptive tactile agnosia after first cortical ischemic stroke, 14 showed temporary impairment at admission. A previous multi-voxel analysis of the cortical lesions, using as explanatory variable the course of tactile object recognition performance over the recovery period of 9 months, partitioned the cohort into three subgroups. Of the 14 patients constituting two of the subgroups, 7 recovered from their impairment whereas 7 did not. These two subgroups could not be distinguished at admission. The primary aim of the present study is to present two assessments that can do so.The first assessment comprises a pattern of behavioral measures, determined via principal component analysis, encoded in three tests: picking small objects, macrogeometrical discrimination and tactile object recognition. The receiver operating characteristic curve derived from permutation of the behavioral test scores yielded an 80% probability of correct identification of the patient subgroup and an 8% probability for false identification. As done with the permuted scores, the pattern could predict the persistence of affliction of new stroke patients with tactile agnosia.The second predictive assessment extends our previous evaluation of cortical MRI lesion maps to include subcortical regions. Confirming our previous study, the lesions of the persistently impaired subgroup disrupted significantly the anterior arcuatus fasciculus and associated superior longitudinal fasciculus III in the ipsilesional hemisphere, impeding reciprocal information transfer between supramarginal gyrus and both the ventral premotor cortex and Brodmann area 44. Due to the importance of interhemispheric information transfer in tactile agnosia, we performed a supplementary analysis of tactile object recognition scores. It showed that haptic information transfer from the non-affected to the affected hands in the persistent cases partly restored function during the nine months, possibly following restoration of functional interhemispheric haptic information transfer at the border of posterior corpus callosum and splenium.In conclusion, the combined findings of the cortical lesion at subarea PFt of the inferior parietal lobule and the associated subcortical tract lesions permit almost perfect prediction of persistent impairment of tactile object recognition. The study substantiates the need for combined analysis of both cortical lesions and white matter tract disconnections.

Using diffusion tensor imaging to effectively target TMS to deep brain structures

TMS has become a powerful tool to explore cortical function, and in parallel has proven promising in the development of therapies for various psychiatric and neurological disorders. Unfortunately, much of the inference of the direct effects of TMS has been assumed to be limited to the area a few centimeters beneath the scalp, though clearly more distant regions are likely to be influenced by structurally connected stimulation sites. In this study, we sought to develop a novel paradigm to individualize TMS coil placement to non-invasively achieve activation of specific deep brain targets of relevance to the treatment of psychiatric disorders. In ten subjects, structural diffusion imaging tractography data were used to identify an accessible cortical target in the right frontal pole that demonstrated both anatomic and functional connectivity to right Brodmann area 25 (BA25). Concurrent TMS-fMRI interleaving was used with a series of single, interleaved TMS pulses applied to the right frontal pole at four intensity levels ranging from 80% to 140% of motor threshold. In nine of ten subjects, TMS to the individualized frontal pole sites resulted in significant linear increase in BOLD activation of BA25 with increasing TMS intensity. The reliable activation of BA25 in a dosage-dependent manner suggests the possibility that the careful combination of imaging with TMS can make use of network properties to help overcome depth limitations and allow noninvasive brain stimulation to influence deep brain structures.

Possible Contribution of Altered Cholinergic Activity in the Visual Cortex in Visual Hallucinations in Parkinson's Disease.

Up to one-third of patients with Parkinson's disease (PD) experience visual hallucinations (VHs). Lewy bodies are sparse in the visual cortices and seem unlikely to explain the hallucinations. Some neuroimaging studies have found that perfusion is reduced in the occipital lobe in individuals with VHs. Recent work has suggested that decreased cholinergic input may directly lead to the decreased perfusion. The investigators hypothesized that individuals with PD and VHs would have biochemical evidence of reduced microvascular perfusion and reduced cholinergic activity in areas of the brain that process visual images. Tissue from Brodmann's area (BA) 18 and BA 19 was obtained from a well-characterized cohort matched for age, gender, and postmortem interval in 69 individuals (PD without VHs, N=11; PD without dementia plus VHs N=10, N=10; PD with dementia plus VHs, N=16; and control subjects, N=32). Von Willebrand factor, vascular endothelial growth factor A, and myelin-associated glycoprotein:proteolipid protein-1 (MAG:PLP1) ratio-a measure of tissue oxygenation relative to metabolic demand, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), choline acetyltransferase, and α-synuclein-were quantified by enzyme-linked immunosorbent assay. The primary outcome was the MAG:PLP1 ratio. There was no biochemical evidence of chronic hypoperfusion in PD, although microvessel density was decreased in ventral BA 18 and BA 19. There was no between-group difference in BChE in either dorsal BA 18 or BA 19. AChE concentration was reduced in individuals with PD compared with control subjects in dorsal and ventral BA 18 and dorsal BA 19, and it was increased in ventral BA 19. These changes were most marked in the PD plus VHs group. These results suggest that changes in cholinergic activity rather than chronic hypoperfusion may underlie VHs in PD.