Insula Gyrus Research Articles

Age-Related Reduction in Cortical Thickness in First-Episode Treatment-Naïve Patients with Schizophrenia.

Substantial evidence supports the neurodevelopmental hypothesis of schizophrenia. Meanwhile, progressive neurodegenerative processes have also been reported, leading to the hypothesis that neurodegeneration is a characteristic component in the neuropathology of schizophrenia. However, a major challenge for the neurodegenerative hypothesis is that antipsychotic drugs used by patients have profound impact on brain structures. To clarify this potential confounding factor, we measured the cortical thickness across the whole brain using high-resolution T1-weighted magnetic resonance imaging in 145 first-episode and treatment-naïve patients with schizophrenia and 147 healthy controls. The results showed that, in the patient group, the frontal, temporal, parietal, and cingulate gyri displayed a significant age-related reduction of cortical thickness. In the control group, age-related cortical thickness reduction was mostly located in the frontal, temporal, and cingulate gyri, albeit to a lesser extent. Importantly, relative to healthy controls, patients exhibited a significantly smaller age-related cortical thickness in the anterior cingulate, inferior temporal, and insular gyri in the right hemisphere. These results provide evidence supporting the existence of neurodegenerative processes in schizophrenia and suggest that these processes already occur in the early stage of the illness.

Bilateral insular functional connectivity in epilepsy patients: A cortico-cortical evoked potential study

Objective To explore bilateral insular functional connectivity in refractory epilepsy patients using electrical cortical stimulation by stereoelectroencephalography (SEEG) electrodes. Methods We retrospectively analyzed the clinical data of 4 patients with insular or insular-related drug resistant epilepsy at Epilepsy Center of Yuquan Hospital of Tsinghua University from January 2014 to August 2016. Four patients were implanted with SEEG electrodes in bilateral insular lobes for cortical electrical stimulation. The evoked potential response of each contact was determined by visual analysis and nonparametric test. The evoked potential response was recorded at the contralateral insular lobe electrode on the stimulating side, and the response rate and anatomical distribution were determined. Results A total of 28 SEEG electrodes (98 contacts) were implanted into the insular lobe in 4 patients, of which 12 electrodes (47 contacts) were implanted into the left insular lobe. Cortical-cortical evoked potential (CCEP) responses were found between bilateral insular lobes in 4 patients, and homotopic bidirectional CCEP connections were found between bilateral insular lobes. The response rate of contralateral insular CCEP was 39.8%, and the peak latency was 15.5-196.0 ms. There were bi-directional CCEP connections between corresponding bilateral insular gyri. Conclusions There are bi-directional functional connections between bilateral insular lobes in patients with insular or insular-related epilepsy, particularly in patients with post-viral encephalitis epilepsy. However, more studies are needed to confirm this result. Key words: Epilepsy; Insular; Stereoelectroencephalography; Electrical cortical stimulation; Cortico-cortical evoked potential

Self-injuring adolescent girls exhibit insular cortex volumetric abnormalities that are similar to those seen in adults with borderline personality disorder.

Self-inflicted injury (SII) in adolescence is a serious public health concern that portends prospective vulnerability to internalizing and externalizing psychopathology, borderline personality development, suicide attempts, and suicide. To date, however, our understanding of neurobiological vulnerabilities to SII is limited. Behaviorally, affect dysregulation is common among those who self-injure. This suggests ineffective cortical modulation of emotion, as observed among adults with borderline personality disorder. In borderline samples, structural and functional abnormalities are observed in several frontal regions that subserve emotion regulation (e.g., anterior cingulate, insula, dorsolateral prefrontal cortex). However, no volumetric analyses of cortical brain regions have been conducted among self-injuring adolescents. We used voxel-based morphometry to compare cortical gray matter volumes between self-injuring adolescent girls, ages 13-19 years (n = 20), and controls (n = 20). Whole-brain analyses revealed reduced gray matter volumes among self-injurers in the insular cortex bilaterally, and in the right inferior frontal gyrus, an adjacent neural structure also implicated in emotion and self-regulation. Insular and inferior frontal gyrus gray matter volumes correlated inversely with self-reported emotion dysregulation, over-and-above effects of psychopathology. Findings are consistent with an emotion dysregulation construal of SII, and indicate structural abnormalities in some but not all cortical brain regions implicated in borderline personality disorder among adults.

Brain structural changes associated with aberrant functional responses to the Valsalva maneuver in heart failure.

Heart failure (HF) patients show inability to regulate autonomic functions in response to autonomic challenges. The autonomic deficits may stem from brain tissue injury in central autonomic regulatory areas, resulting from ischemic and hypoxic processes accompanying the condition. However, the direct evaluation of correlations between brain structural injury and functional timing and magnitude of neural signal patterns within affected areas, which may lead to impaired autonomic outflow, is unclear. In this study, we evaluate neural responses to the Valsalva maneuver with blood oxygen level-dependent functional magnetic resonance imaging in 29 HF patients and 35 control subjects and brain structural changes using diffusion tensor imaging-based mean diffusivity in a subsample of 19 HF and 24 control subjects. HF showed decreased neural activation in multiple autonomic and motor control areas, including cerebellum cortices, vermis, left insular, left putamen, and bilateral postcentral gyrus. Structural brain changes emerged in similar autonomic, as well as cognitive and mood regulation areas. Functional MRI responses in cerebellum and insula in HF subjects are delayed or decreased in magnitude to the challenge. The impaired functional responses of insular and cerebellar sites are correlated with the severity of tissue changes. These results indicate that the functions of insular and cerebellar regions, sites that are involved in autonomic regulation, are compromised, and that autonomic deficits in these areas have brain structural basis for impaired functions. Our study enhanced our understanding of brain structural and functional alterations underlying impaired autonomic regulations in HF subjects.

F122. Non-lesional eating epilepsy with mesial temporal and inferior insular onset: A stereo-EEG study

Introduction Reflex epilepsy is characterized by seizures that are triggered by internal or external stimuli. Based on the complexity of the trigger, the reflex epilepsies can be subdivided into simple and complex. Eating Epilepsy (EE) is a subtype of the complex reflex epilepsies and represents a heterogeneous electro-clinical syndrome. The body of literature on EE consists mostly of a few case series with variable medical and surgical outcomes. We present a case of non-lesional EE with excellent outcome from resective epilepsy surgery after an extensive pre-surgical investigation to identify of the seizure onset zone (SOZ). Methods We retrospectively evaluated a case of drug-resistant eating-induced seizures referred for pre surgical assessment at London Health Sciences Centre Epilepsy Program, London, Canada. Patient’s data was reviewed including clinical history, neurological exam, imaging (Brain MRI and FDG-PET), neuropsychology assessment, scalp video-EEG, Stereoelectroencephalography (SEEG) and the surgical management. Results A 34-year-old gentleman has a 4-year history of seizures characterized by diffuse tingling sensation followed by loss of awareness with staring and right hand automatisms that lasted 1–2 min. 90% of his seizures were observed to be induced by eating at the beginning of a meal. His neuropsychological testing was essentially normal. Scalp video-EEG showed independent bilateral temporal spikes (R > L). Five eating-induced seizures were recorded immediately after initiation of eating with 2–3 Hz rhythmic activity over the right temporal region with perisylvian spreading. Brain MRI and PET studies were normal. Based on the electro-clinical data, the working hypothesis was right perisylvian onset of the seizures. The patient underwent intracranial recordings with stereo-EEG sampling the right temporal pole, amygdala, hippocampus, parietal operculum, temporal operculum and insula. Five seizures were captured induced by eating with stereotypical electrographic onset involving the right amygdala and hippocampus and inferior insula. Extra operative cortical stimulation (1–3.5 mA) elicited many prolonged after discharges in the same regions but they did not provoke clinical seizures. The patient thus underwent a right anterior temporal lobectomy and partial inferior insulectomy with decortication of the posterior short insular gyrus & the anterior and posterior gyri. Pathology revealed transcortical and hippocampal gliosis. He remained seizure-free (Engel 1) at his 8 months post-surgical follow-up. Conclusion This case of a drug-resistant non-lesional EE illustrates the value of stereo-EEG in the presurgical work-up that led to seizure-freedom following combined right anterior temporal lobectomy and right inferior insula resection. In non-lesional cases of drug-resistant EE, the epileptogenic zone is likely wide and it requires stereo-EEG to determine the SOZ.

Gait Characteristic in a Stroke Patient with an Intact Corticospinal Tract and Corticoreticular Pathway: A Case Study

Purpose: The prefrontal lobe, supplementary motor area, cerebellum, and basal ganglia are activated during gait. In addition, gait is controlled by nerves, such as the corticospinal tract (CST) and corticoreticular pathway (CRP). In this study, the presence of an injury to the CST and CRP was identified by diffusion tensor imaging and the characteristics of the gait pattern were investigated according to inferior cerebral artery infarction. Methods: One patient and six control subjects of a similar age participated. A 69-year-old female patient had an injury to the left basal ganglia, insular gyrus, corona radiata, dorsolateral prefrontal cortex, and postcentral gyrus due to an inferior cerebral artery infarction. Diffusion tensor imaging (DTI) data was acquired 4 weeks after the stroke. The kinematic and spatio-temporal parameters of gait were collected using a three-dimensional gait analysis system. Results: On 4 weeks DTI, the CST and CRP in the affected hemisphere did not show injury to the affected and unaffected hemisphere. Gait analysis showed that the cadence of spatio-temporal parameter was decreased significantly in the patient. The angle of the knee joint was decreased significantly in the affected and unaffected sides compared to the control group. Conclusion: The results of diffusion tensor imaging showed that although the patient was evaluated to be capable of an independent gait, the quality and quantity of gait might be reduced. This study could help better understand the gait ability analysis of stroke patients and the abnormal gait pattern of patients with a brain injury.

A Brainnetome Atlas Based Mild Cognitive Impairment Identification Using Hurst Exponent.

Mild cognitive impairment (MCI), which generally represents the transition state between normal aging and the early changes related to Alzheimer’s disease (AD), has drawn increasing attention from neuroscientists due that efficient AD treatments need early initiation ahead of irreversible brain tissue damage. Thus effective MCI identification methods are desperately needed, which may be of great importance for the clinical intervention of AD. In this article, the range scaled analysis, which could effectively detect the temporal complexity of a time series, was utilized to calculate the Hurst exponent (HE) of functional magnetic resonance imaging (fMRI) data at a voxel level from 64 MCI patients and 60 healthy controls (HCs). Then the average HE values of each region of interest (ROI) in brainnetome atlas were extracted and compared between MCI and HC. At last, the abnormal average HE values were adopted as the classification features for a proposed support vector machine (SVM) based identification algorithm, and the classification performance was estimated with leave-one-out cross-validation (LOOCV). Our results indicated 83.1% accuracy, 82.8% sensitivity and 83.3% specificity, and an area under curve of 0.88, suggesting that the HE index could serve as an effective feature for the MCI identification. Furthermore, the abnormal HE brain regions in MCI were predominately involved in left middle frontal gyrus, right hippocampus, bilateral parahippocampal gyrus, bilateral amygdala, left cingulate gyrus, left insular gyrus, left fusiform gyrus, left superior parietal gyrus, left orbital gyrus and left basal ganglia.

Gustatory and olfactory responses to stimulation of the human insula.

Despite numerous studies suggesting the role of insular cortex in the processing of gustatory and olfactory inputs, the exact location of olfactogustatory representation in the insula remains controversial. Here we provide a functional mapping of olfactory-gustatory responses to stimulation of the human insular cortex. We reviewed 651 electrical stimulations of the insula that were performed in 221 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory epilepsy. Gustatory sensations were evoked in 15 (2.7%) of the 550 stimulations that elicited a clinical response. They were exclusively obtained after stimulation of a relatively delimited zone of insula, located in its mid-dorsal part (posterior short gyrus). Six olfactory sensations (1.1%) could be obtained during stimulations of an insular region that partially overlapped with the gustatory representation. Our study provides a functional mapping of gustatory representation in the insular posterior short gyrus and the first detailed description of olfactory sensations obtained by direct stimulation of mid-dorsal insula. Our data also show a spatial overlap between gustatory, olfactory, and oral somatosensory representation in the mid-dorsal insula, and suggest that this part of the insula may be an integrated oral sensory region that plays a key role in flavor perception. It also indicates that dysfunction in this region should be considered during the evaluation of gustatory and olfactory epileptic seizures. Ann Neurol 2017;82:360-370.

Invasive Investigation of Insular Cortex Epilepsy.

Invasive long-term EEG investigations of the insula have been performed since the mid-nineties in an expanding range of focal epilepsies suspected to involve the insular cortex. The various clinical forms of insular epilepsies were delineated during the last 2 decades, and include the following presentations: perisylvian epilepsy, temporal plus epilepsy, sleep hypermotor epilepsy, MRI-negative frontal and parietal lobe epilepsies, and insular lesions. In fact, a majority of complex stereoelectroencephalography procedures will include at least one electrode targeting the insula. Stereoelectroencephalography is currently the preferred method to investigate the insula, using orthogonal, oblique, or a combination of both trajectories, with no evidence of higher risk of intracranial bleeding than in other brain regions. Orthogonal trajectories allow to sample the overlaying opercula, while oblique trajectories offer a better sampling of the insular cortex. Intrainsular ictal EEG pattern are often characterized by a prolonged focal discharge restricted to one of the five insular gyri, militating for a dense enough sampling of the insular cortex in suspected insular epilepsies. Stereoelectroencephalography offers the potential to perform thermolesion of insular epileptogenic zones which, together with MRI-guided laser ablation, represent a possibly safer alternative treatment to open-skull surgical resection of the insula.

Sex differences in insular cortex gyri responses to a brief static handgrip challenge

BackgroundCardiovascular disease varies between sexes, suggesting male-female autonomic control differences. Insular gyri help coordinate autonomic regulation and show a sex-dependent response to a sympathetic challenge.MethodsWe examined sex-related insular gyral responses to a short static handgrip exercise challenge eliciting parasympathetic withdrawal with functional magnetic resonance imaging (fMRI) during four 16-s challenges (80% maximum strength) in 23 healthy females (age; mean ± std 50 ± 8 years) and 40 males (46 ± 9 years). Heart rate (HR) and fMRI signals were compared with repeated measures ANOVA (P < 0.05). Additional analyses were performed with age and age interactions, as well as right-handed only subjects.ResultsFemales showed higher resting HR than males, but smaller percent HR change increases to the challenges. All gyri showed fMRI patterns concurrent with an HR peak and decline to baseline. fMRI signals followed an anterior-posterior organization in both sexes, but lateralization varied by gyri and sex. All subjects showed greater signals in the anterior vs. posterior gyri (females 0.3%, males 0.15%). The middle gyri showed no lateralization in females but left-sided dominance in males (0.1%). The posterior gyri showed greater left than right activation in both sexes. The anterior-most gyri exhibited a prominent sex difference, with females showing a greater right-sided activation (0.2%) vs. males displaying a greater left-sided activation (0.15%). Age and handedness affected a minority of findings but did not alter the overall pattern of results.ConclusionsThe anterior insula plays a greater role in cardiovascular regulation than posterior areas during a predominantly parasympathetic withdrawal challenge, with opposite lateralization between sexes. In females, the left anterior-most gyrus responded distinctly from other regions than males. Those sex-specific structural and functional brain patterns may contribute over time to variations in cardiovascular disease between the sexes.

Age-related connectivity differences between attention deficit and hyperactivity disorder patients and typically developing subjects: a resting-state functional MRI study.

Attention deficit and hyperactivity disorder (ADHD) is a disorder characterized by behavioral symptoms including hyperactivity/impulsivity among children, adolescents, and adults. These ADHD related symptoms are influenced by the complex interaction of brain networks which were under explored. We explored age-related brain network differences between ADHD patients and typically developing (TD) subjects using resting state fMRI (rs-fMRI) for three age groups of children, adolescents, and adults. We collected rs-fMRI data from 184 individuals (27 ADHD children and 31 TD children; 32 ADHD adolescents and 32 TD adolescents; and 31 ADHD adults and 31 TD adults). The Brainnetome Atlas was used to define nodes in the network analysis. We compared three age groups of ADHD and TD subjects to identify the distinct regions that could explain age-related brain network differences based on degree centrality, a well-known measure of nodal centrality. The left middle temporal gyrus showed significant interaction effects between disease status (i.e., ADHD or TD) and age (i.e., child, adolescent, or adult) (P < 0.001). Additional regions were identified at a relaxed threshold (P < 0.05). Many of the identified regions (the left inferior frontal gyrus, the left middle temporal gyrus, and the left insular gyrus) were related to cognitive function. The results of our study suggest that aberrant development in cognitive brain regions might be associated with age-related brain network changes in ADHD patients. These findings contribute to better understand how brain function influences the symptoms of ADHD.

Default mode network and frontolimbic gray matter abnormalities in patients with borderline personality disorder: A voxel-based meta-analysis.

Specific frontolimbic abnormalities are hypothesized to underlie the etiology of borderline personality disorder (BPD). However, findings from neuroimaging studies were inconsistent. In the current study, we aimed to provide a complete overview of cerebral microstructural alterations in gray matter (GM) of BPD patients. A total of 11 studies were enrolled, comprising 275 BPD patients and 290 healthy controls (HCs). A meta-analysis was conduct to quantitatively estimate regional GM abnormalities in BPD patients using the seed-based d mapping (SDM). Meta-regression was also conducted. Compared with HCs, the BPD patients exhibited increased GM mainly in bilateral supplementary motor area extending to right posterior cingulated cortex (PCC) and bilateral primary motor cortex, right middle frontal gyrus (MFG), and the bilateral precuneus extending to bilateral PCC. Decreased GM was identified in bilateral middle temporal gyri, right inferior frontal gyrus extending to right insular, left hippocampus and left superior frontal gyrus extending to left medial orbitofrontal cortex. The mean age of BPD patients were found nagativly associated with GM alterations in right MFG. Our findings suggested that BPD patients have significantly GM abnormalities in the default mode network and frontolimbic circuit. Our results provided further evidences in elucidating the underline neural mechanisms of BPD.

Topographical APOE ɛ4 Genotype Influence on Cerebral Metabolism in the Continuum of Alzheimer's Disease: Amyloid Burden Adjusted Analysis.

APOE ɛ4 contributes to Alzheimer's disease (AD) pathogenesis by amyloid-beta (Aβ)-dependent and Aβ-independent processes. We investigated the APOE ɛ4 influence on regional cerebral glucose metabolism (rCMglc) in the continuum of AD after Aβ adjustment. We included 318 cognitively normal (CN) elderly, 498 mild cognitive impairment (MCI), and 178 AD from the Alzheimer's Disease Neuroimaging Initiative database. They had [18F] florbetapir positron emission tomography (PET) and [18F] fluorodeoxyglucose (FDG)-PET conducted within 3 months of a clinical and cognitive assessment visit and APOE genotype. At first, the rCMglc differences between APOE ɛ4 carriers (ɛ4+) and non-carriers (ɛ4-) were estimated on a voxel-based analysis using a 'two-sample t-test' design. In the second analysis, Aβ was added as covariate. In CN, ɛ4+ showed reduced rCMglc compared to ɛ4-in the bilateral frontal, temporal, and the left parietal regions. In MCI, ɛ4+ showed reduced rCMglc compared to ɛ4- in the bilateral posterior parietal, temporal, and left frontal regions. In AD, ɛ4+ showed reduced rCMglc in the left hippocampus, right insular, and right temporal gyrus. However, after Aβ adjustment, the significant differences in the temporal regions were absent in CN and MCI, and none of the areas detected as significant in the first analysis were statistically significant in AD. Our study demonstrated that Aβ-independent APOE ɛ4 influence on rCMglc is limited to the parietal and frontal, but not temporal lobes. These results suggest that APOE ɛ4 may predispose for regional vulnerability according to Aβ-independent and Aβ-dependent processes.

Functional mapping of the insular and opercular cortex: A study using SEEG electrical stimulation in epileptic patients

Insular and opercular cortex is involved in complicated physiological function.Insular seizures involve extensive epileptic network, which results in the complex and diverse semiology.Electrical cortical stimulation(ECS) can explore the functional mapping and symptomatogenic zone. The clinical presurgical evaluation and ECS data of 20 patients whose electrode contacts were located in the insular and opercular were analyzed retrospectively.CT scan/3D MRI data fusion was performed in order to accurately identify and locate each contact and check the electrode trajectory by the MRI images performed after the electrodes were removed.ECS was applied between two contiguous contacts.Stimulation usually lasted for 5 s at 50 Hz(pulse width=0.3 ms). Depending on the area of stimulated cortex, the stimulation intensities ranged from 0.2 to 3.0 mA.The classification of the insular were anterior short gyrus, middle short gyrus, precentral gyrus, postcentral gyrus, posterior long gyrus and insular pole.The classification of the opercular were orbital, frontal, precentral, central, parietal and temporal opercular. One hundred and six contacts were located in the insular and 51 responses were evoked (48.11%). Four hundred eighteen contacts were located in the insular and 132 responses were evoked (31.58%). We classified the principal responses as somatosensory, pain, auditory, oropharyngeal, speech disturbances and neurovegetative response.Somatosensory responses were mainly evoked in parietal opercular and postcentral gyrus, while pain response distributed sporadically.Auditory were only evoked in temporal opercular(transverse temporal gyri) and posterior long gyrus.Oropharyngeal symptoms were only evoked in central opercular.Speech disturbances were located in precentral and central opercular and neurovegetative responses were mainly evoked in insular pole and middle short gyrus. These findings may indicate a functional specificity for the insular gyrus and opercular, which contribute to the understanding of anatomo-functional organization and the role in insular and opercular epileptic network.Moreover, it could optimize the implantation strategy for exploring these structures.

Middle short gyrus of the insula implicated in speech production: Intracerebral electric stimulation of patients with epilepsy by an oblique approach using a robotized arm

Introduction Few data exist about of the role of the insula in the processing of speech. The data of this study suggests the involvement of the upper middle short gyrus in speech production. Materials and methods For this study, we included 25 patients suffering from severe drug refractory partial epilepsy were investigated by stereo-electroencephalography (SEEG). At least one electrode was used to explore the insular cortex using an oblique approach (trans-frontal or trans-parietal) and who had a normal insular region. In total, 313 stimulations were performed in 27 insula. Eighty-three responses induced by insular electrical stimulation (ES), eight (9.6%) were reported by five patients as speech arrest (5 responses) and a lowering of voice intensity (3 responses). The stereotactic approach allows us to identify the stimulation sites within the insular cortex in terms of its gyri and sulci. Also, the stimulation sites were anatomically localized via image fusion between pre-implantation 3D MRI and post-implantation 3D CT scans revealing the electrode contacts. Results Eight responses were reported as speech disturbances. 7 among them were evoked in 4 patients by stimulation in the middle short gyrus (8.4% of total responses, and 25.9% of responses evoked in the middle short gyrus). The site of the 8th response was in the post-central insular gyrus in the same insular region where the oropharyngeal responses induced by other ES (pharyngeal construction) in this study. The data suggest the involvement of the middle short gyrus of the insula in the procedures of language. These responses were evoked in the non-dominant side four times out of five. This study provides evidence that the middle short gyrus of the insula in both hemispheres responds to ES producing speech disturbances. Conclusion The results of this study are the first to report language disorders in humans evoked by electrical stimulation of the insular cortex during SEEG explorations by electrodes implanted by oblique approach in terms of gyral and sulcal anatomy.

Abnormal activation of the social brain network in children with autism spectrum disorder: an FMRI study.

ObjectiveThe aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC).MethodsFunctional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC.ResultsWhen emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation.ConclusionThese findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion.

Vestibular responses to direct stimulation of the human insular cortex.

The present study provides a functional mapping of vestibular responses in the human insular cortex. A total of 642 electrical stimulations of the insula were performed in 219 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory partial epilepsy. We retrospectively identified 41 contacts where stimulation elicited vestibular sensations (VSs) and analyzed their location with respect to (1) their stereotactic coordinates (for all contacts), (2) the anatomy of insula gyri (for 20 vestibular sites), and (3) the probabilistic cytoarchitectonic maps of the insula (for 9 vestibular sites). VSs occurred in 7.6% of the 541 evoked sensations after electrical stimulations of the insula. VSs were mostly obtained after stimulation of the posterior insula, that is, in the granular insular cortex and the postcentral insular gyrus. The data also suggest a spatial segregation of the responses in the insula, with the rotatory and translational VSs being evoked at more posterior stimulation sites than other less definable VSs. No left-right differences were observed. These results demonstrate vestibular sensory processing in the insula that is centered on its posterior part. The present data add to the understanding of the multiple sensory functions of the insular cortex and of the cortical processing of vestibular signals. The data also indicate that lesion or dysfunction in the posterior insula should be considered during the evaluation of vestibular epileptic seizures.

Microanatomical study of the insular perforating arteries.

The insular perforating arteries originate from the middle cerebral artery. They have only been very partially described up to now. In the literature, they come from the M2 segment and three types are listed: the short, medium and long perforators. The first two types supply the claustrum as well as the external and extreme capsules. We describe the anatomy of long perforating insular arteries and their arterial contribution to the main white matter bundles of the oval center of Vieussens. Twenty adult cadaveric hemispheres were studied after perfusion of the arteries and veins with colored latex. The arteries were dissected and photographed under an operating microscope. The long insular perforating arteries come from the M2 segment or from the junction of the M2 and M3 segments and sometimes from the M3 segment. They often perforate the insular cortex on the top of the posterior short insular gyrus and the insular long gyri, or in the superior peri-insular sulcus, before coming together in the oval center. At this level, they give arterial contribution to the main white matter bundles such as corticospinal and corticonuclear tracts for motricity, and the arcuate fasciculus and the occipitofrontal tract for language in the dominant hemisphere. These perforating arteries have to be carefully respected during insular surgery to avoid neurologic weakness.

Functional connectivity of insular efferences.

The aim of our study was to explore the functional connectivity between the insula and other cortical regions, in human, using cortico-cortical evoked potentials (CCEPs) We performed intra-cerebral electrical stimulation in eleven patients with refractory epilepsy investigated with depth electrodes, including 39 targeting the insula. Electrical stimulation consisted of two series of 20 pulses of 1-ms duration, 0.2-Hz frequency, and 1-mA intensity delivered at each of the 39 insular bipoles. Rates of connectivity were reported whenever a noninsular cortical region was tested by at least ten stimulating/recording electrode pairs in three or more patients Significant CCEPs were elicited in 193 of the 578 (33%) tested connections, with an average latency of 33 ± 5 ms. The highest connectivity rates were observed with the nearby perisylvian structures (59%), followed by the pericentral cortex (38%), the temporal neocortex (28%), the lateral parietal cortex (26%), the orbitofrontal cortex (25%), the mesial temporal structures (24%), the dorsolateral frontal cortex (15%), the temporal pole (14%), and the mesial parietal cortex (11%). No connectivity was detected in the mesial frontal cortex or cingulate gyrus. The pattern of connectivity also differed between the five insular gyri, with greater connectivity rate for the posterior short gyrus (49%), than for the middle short (29%), and two long gyri (28 and 33%) The human insula is characterized by a rich and complex connectivity that varies as a function of the insular gyrus and appears to partly differ from the efferences described in nonhuman primates.

A novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology

We describe the clinical, neuropathological, and genetic features of a Finnish patient with a novel α-synuclein (SNCA) mutation A53E. The patient was clinically diagnosed with atypical Parkinson's disease (PD) with age of onset at 36 years. In the neuropathological analysis performed at the age of 60 years, highly abundant SNCA pathology was observed throughout the brain and spinal cord showing features of multiple system atrophy and PD. Neuronal and glial (including oligodendroglial) SNCA inclusions and neurites were found to be particularly prominent in the putamen, caudatus, amygdala, temporal and insular cortices, gyrus cinguli, and hippocampus CA2-3 region. These areas as well as the substantia nigra and locus coeruleus showed neuronal loss and gliosis. We also found TDP-43 positive but mostly SNCA negative perinuclear inclusions in the dentate fascia of the hippocampus. The A53E mutation was found in 2 other relatives who had parkinsonism. Our results suggest that the novel SNCA A53E substitution is a causative mutation resulting clinically in parkinsonism and pathologically in severe multiple system atrophy- and PD-type phenotype.