Anatomical variability of the lateral frontal lobe surface: implication for intersubject variability in language neuroimaging

Recent work in our laboratory has suggested that human caudal lateral frontal cortex contains four interleaved regions in each hemisphere that exhibit strong sensory-specific biases in attention tasks (Michalka et al, 2014). Two visually-biased attention regions, superior and inferior pre-central sulcus (sPCS, iPCS), anatomically alternate with two auditory-biased attention regions, caudal inferior frontal sulcus (cIFS) and the transverse gyrus intersection the precentral sulcus (tgPCS). These small regions were identified in fMRI studies in a small number of individual subjects. Here, we have investigated these regions and their putative networks by mining the WashU-Minn Human Connectome Project (HCP) dataset. We used data from the 482 HCP participants with both diffusion-weighted imaging and resting-state fMRI. We defined seed regions from our individual subject data in a task that contrasted auditory and visual spatial attention. Probabilistic activation maps were constructed and thresholded to generate ROIs. These ROIs served as seed regions for resting state and tractography analyses of the HCP dataset. Stronger functional connectivity was observed for the sPCS and iPCS than for tgPCS and cIFS with superior parietal lobule visual attention regions, and conversely stronger connectivity was observed for the tgPCS and cIFS than for sPCS and iPCS with superior temporal lobe auditory attention regions. A similar pattern was observed with tractography for all ROIs, except for tgPCS. We next analyzed the whole-brain connectivity patterns of these ROIs using a multivariate approach; we found that the modality of sensory-bias can be predicted well above chance in both hemispheres at a voxelwise scale (L:71%, R:80%), using only the connectivity pattern of an individual voxel. A long-term goal of this analysis is to develop reliable methods for identifying fine-scale brain networks in large population datasets, which could have important clinical applications. Our preliminary results reveal both successes and challenges of these efforts. Meeting abstract presented at VSS 2015

BackgroundGestational disruptions are linked to the risk of schizophrenia; but in most cases, there is a lack of a clear history or observable anomaly indicating that the disruptions are likely to be subtle (Murray et al., 2017). The time-locked development of cortical sulci in a human embryo is highly sensitive to developmental disruptions (Chi et al., 1977). We can retrospectively infer the likely timing of embryonic/fetal disruption in schizophrenia by studying the structure of major cortical sulci that represent lobar development in adults with schizophrenia.MethodsAnatomical T1 MRI scans from a publicly available dataset (COBRE) of 68 patients with schizophrenia and 72 controls were used to evaluate the sulcal depth. 5 major primary sulci that are invariable, representing lobar development (calcarine sulcus, superior temporal sulcus, superior frontal sulcus, interparietal sulcus and inferior frontal sulcus) with formation representing distinct developmental periods (16, 23, 25, 26 and 28 weeks respectively (Chi et al., 1977)) were chosen. Sulcal depth was measured using Morphologist interface of BrainVISA 4.5 (http://brainvisa.info/). Following the construction of 3-dimensional models of cortical folds, various sulci were automatically classified using a probabilistic algorithm with maximum depth computed for each identified sulcus. The 5 sulci were consistently labeled automatically across all subjects. The identified sulci were visually inspected to ensure that the boundaries are in accordance with Ono’s Atlas of Cerebral Sulci (Ono et al., 1990).ResultsA repeated measure ANOVA with 5 sulci and 2 hemispheres as within-subject factors and gender, age and intracranial volume as covariates revealed a significant between-subjects effect for diagnosis (F[1,134]=14.8, p=0.0002). Gender (F[1,134]=7.4, p=0.007) and age (F[1,134]=4.5, p=0.035) also had significant effect in the model. Parameter estimates revealed a significant effect of diagnosis (Controls>Patients) for left superior temporal (t=3.2, p=0.002), right superior temporal (t=2.8, p=0.006), right inferior frontal (t=2.7, p=0.007) and left calcarine (t=2.2, p=0.03) sulci. 5 non-collinear factors representing the 5 bilateral sulci were obtained using varimax rotation, and related to overall MATRICS standardized composite score in patients using multiple regression. The depth of the superior frontal sulcus was the only predictor of the variation in the cognitive score (F[1,54]=8.7, p=0.005).DiscussionThe above findings suggest that the gestational cortical disruption underlying schizophrenia is likely to predate, if not, coincide with the appearance of calcarine sulcus (i.e. 16 weeks, early second trimester) and affects frontal, temporal and occipital lobes. Nevertheless, the burden of cognitive deficits may relate specifically to aberrant superior frontal development occurring in late second trimester.

Flat panel detector-based CBCT can provide CT-like images of the brain without transferring patients from the angiography suite to a conventional CT facility. Conventional brain CT after uneventful endovascular treatment sometimes shows focal subarachnoid hyperattenuation with contrast leakage, mimicking SAH. Differentiating this finding from SAH is important for immediate postprocedural medical management. We investigated CBCT for detecting subarachnoid hyperattenuation immediately after coil embolization of unruptured cerebral aneurysms. Thirty-six patients with unruptured cerebral aneurysms undergoing CBCT immediately after uncomplicated coil embolization were included. The relationship between the presence of subarachnoid hyperattenuation and total volume of contrast medium injected, aneurysm size and location, and balloon and stent assistance during embolization was investigated. Statistical analyses were performed with the χ(2) test (P < .05). Nine of the 36 patients (25.0%) showed focal subarachnoid hyperattenuation within the relevant parent artery territory harboring the aneurysm. Subarachnoid hyperattenuation locations included the ipsilateral superior frontal sulcus (n = 5), the bilateral superior frontal sulcus (n = 1), and the ipsilateral superior frontal and precentral sulci (n = 3). Statistically significant differences were observed between the presence of a subarachnoid hyperattenuation and the total volume of contrast medium injected (P < .001) and aneurysm size (P < .05). Subarachnoid hyperattenuation can be detected by CBCT immediately after coil embolization for unruptured aneurysms. The increased amounts of contrast medium to be given before CBCT and the specific location of the hyperattenuation may help differentiate benign subarachnoid contrast leakage from SAH.

Identification of degenerate neuronal systems based on intersubject variability

Deep cavernomas of eloquent areas, located in the region of the basal nuclei and thalamus, account for 9 to 36% of these encephalic vascular malformations. Internal capsule cavernomas are particularly challenging, as they are surrounded by important projection fibers and their manipulation can lead to permanent deficits. To demonstrate through surgical cases that cavernomas of the internal capsule can be approached by frontal craniotomy, via the superior frontal sulcus, in a curative manner and with low morbidity. We presented two cases of cavernomas of the internal capsule operated, whose treatment was microsurgical resection via frontal craniotomy and access to the lesion via the superior frontal sulcus, described step-by-step. To elucidate the rationale behind the decision, we used preoperative images with an emphasis on the patients' tractography and the importance of comparing these images with anatomical specimens dissected in the neuroanatomy and microsurgery laboratory. The two cases of internal capsule cavernomas, one in the anterior limb and the other in the posterior limb, were treated surgically via the superior frontal sulcus. Both patients showed radiological cure and clinical improvement in the post-operative segment. The patient consented to the procedure and to the publication of his/her image. Treatment of internal capsule cavernomas via the superior frontal sulcus has proven to be a safe and effective option.

Selectivity for sensory modality characterizes distinct subregions of the human brain, well beyond the primary sensory cortices. We previously identified frontal and posterior cortical regions that are preferentially recruited for visual vs. auditory attention and working memory (WM). Here, we extend our approach to include tactile cognition and to characterize cortical regions recruited by WM in each of three sensory modalities. The joint organization of visual-selective, auditory-selective, tactile-selective, and supramodal WM recruitment within individual subjects has not been fully investigated previously. Male and female human subjects participated in a blocked fMRI task requiring them to perform N-back WM judgements in auditory, visual, or tactile (haptic) modalities. We confirmed our prior reports of multiple visual-biased and auditory-biased frontal lobe regions. We also observed several bilateral tactile-selective regions abutting previously described visual- and auditory-selective regions, including dorsal and ventral precentral sulcus, the postcentral sulcus, and the anterior intraparietal sulcus. Several cortical regions were recruited by WM in all three sensory modalities in individual subjects, including precentral sulcus, inferior frontal sulcus, intraparietal sulcus, anterior insula and pre-supplementary motor area. Supramodal regions exhibited substantial overlap with visual-biased regions in frontal and parietal cortex and comparatively little overlap with tactile- or auditory-biased regions. Lastly, resting-state analyses revealed that auditory-, visual- and tactile-selective WM regions segregate into modality-specific networks that span frontal and posterior cortex. Together, these results shed light on the functional organization of sensory-selective and supramodal regions supporting higher-order cognition.

Background: MR imaging of the spinal cord (SC) gray matter (GM) at the cervical and lumbar enlargements' level may be particularly informative in lower motor neuron disorders, e. g., spinal muscular atrophy, but also in other neurodegenerative or autoimmune diseases affecting the SC. Radially sampled averaged magnetization inversion recovery acquisition (rAMIRA) is a novel approach to perform SC imaging in clinical settings with favorable contrast and is well-suited for SC GM quantitation. However, before applying rAMIRA in clinical studies, it is important to understand (i) the sources of inter-subject variability of total SC cross-sectional areas (TCA) and GM area (GMA) measurements in healthy subjects and (ii) their relation to age and sex to facilitate the detection of pathology-associated changes. In this study, we aimed to develop normalization strategies for rAMIRA-derived SC metrics using skull and spine-based metrics to reduce anatomical variability.Methods: Sixty-one healthy subjects (age range 11–93 years, 37.7% women) were investigated with axial two-dimensional rAMIRA imaging at 3T MRI. Cervical and thoracic levels including the level of the cervical (C4/C5) and lumbar enlargements (Tmax) were examined. SC T2-weighted sagittal images and high-resolution 3D whole-brain T1-weighted images were acquired. TCA and GMAs were quantified. Anatomical variables with associations of |r| > 0.30 in univariate association with SC areas, and age and sex were used to construct normalization models using backward selection with TCAC4/C5 as outcome. The effect of the normalization was assessed by % relative standard deviation (RSD) reductions.Results: Mean inter-individual variability and the SD of the SC area metrics were considerable: TCAC4/5: 8.1%/9.0; TCATmax: 8.9%/6.5; GMAC4/C5: 8.6%/2.2; GMATmax: 12.2%/3.8. Normalization based on sex, brain WM volume, and spinal canal area resulted in RSD reductions of 23.7% for TCAs and 12.0% for GM areas at C4/C5. Normalizations based on the area of spinal canal alone resulted in RSD reductions of 10.2% for TCAs and 9.6% for GM areas at C4/C5, respectively.Discussion: Anatomic inter-individual variability of SC areas is substantial. This study identified effective normalization models for inter-subject variability reduction in TCA and SC GMA in healthy subjects based on rAMIRA imaging.

Laminar distribution of nicotinic receptor subtypes in human cerebral cortex as determined by [ 3H](-)nicotine, [ 3H]cytisine and [ 3H]epibatidine in vitro autoradiography

In developed countries, the number of traffic accidents caused by older drivers is increasing. Approximately half of the older drivers who cause fatal accidents are cognitively normal. Thus, it is important to identify older drivers who are cognitively normal but at high risk of causing fatal traffic accidents. However, no standardized method for assessing the driving ability of older drivers has been established. We aimed to establish an objective assessment of driving ability and to clarify the neural basis of unsafe driving in healthy older people. We enrolled 32 healthy older individuals aged over 65 years and classified unsafe drivers using an on-road driving test. We then utilized a machine learning approach to distinguish unsafe drivers from safe drivers based on clinical features and gray matter volume data. Twenty-one participants were classified as safe drivers and 11 participants as unsafe drivers. A linear support vector machine classifier successfully distinguished unsafe drivers from safe drivers with 87.5% accuracy (sensitivity of 63.6% and specificity of 100%). Five parameters (age and gray matter volume in four cortical regions, including the left superior part of the precentral sulcus, the left sulcus intermedius primus [of Jensen], the right orbital part of the inferior frontal gyrus, and the right superior frontal sulcus), were consistently selected as features for the final classification model. Our findings indicate that the cortical regions implicated in voluntary orienting of attention, decision making, and working memory may constitute the essential neural basis of driving behavior.

Neuronavigation is used in neurosurgical practice to locate the cortical structures. If this tool is unavailable, basic anatomical knowledge should be used. Craniometry has been rarely detailed in recent literature, systematically using bony landmarks. The aim of this study is to describe skin landmarks for neurosurgical practice. Dissection of 10 hemispheres with insertion of radio-opaque markers within the limits of lateral sulcus, central and pre-central sulci, and preoccipital notch. Computed tomography was performed in all cases and multiplanar reconstructions were performed. Maximal intensity projection (MIP) fusion images were used for measurements between known skin landmarks and sulci of interests. The Anterior Sylvian Point is measured 31.8 ± 2.8mm behind the orbital wall, 36.9 ± 3mm above the zygomatic arch. The horizontal part of the lateral sulcus is measured 59 ± 6mm above the tragus. The Superior Rolandic Point is measured 190.7 ± 4.5mm behind the nasion. The Pre-occipital Notch is measured 37.0 ± 6.9mm above the tragus and 67.1 ± 6.4mm behind. The Ideal Entry Points (IEP) for ventricular punctures are measured 120.2 ± 7mm behind the nasion and 33.8 ± 3mm laterally for the frontal IEP, and 61.3mm ± 2.5mm above and 64.7 ± 6.8mm behind the tragus for the parieto-occipital IEP. In this study, we described simple skin landmarks for lateral sulcus, central sulcus, preoccipital notch, and an IEP for ventricular drainage. Precise knowledge of brain sulcal anatomy will guide patient's positioning, skin incision, and craniotomies; and permits checking of imaging data provided by neuronavigation systems.

A model for visual naming based on spatiotemporal dynamics of ECoG high-gamma modulation

Differential Neural Activation for Updating Rule versus Stimulus Information in Working Memory

in a patient with frontal lobe epilepsy www.

The primary purpose of these studies was to link together concepts related to attention/working memory and feedforward/feedback activity using MEG response profiles obtained in humans. Similar to recent studies of attention in monkeys, we show early "spike-like" activity (<200 ms poststimulus), most likely reflecting an early transient excitatory response mixed with feedback influences, followed by "slow-wave" activity (>200 ms poststimulus) in MEG cortical response profiles evoked by a visual working memory task. We experimentally dissociated the early transient activity from the later sustained activity (predominantly feedback) by conducting an auditory size classification task. Words, representing common objects, evoked activity in occipital cortex (presumably due to imagery) even though visual stimuli were not present in this task. The initial "spike" was absent from the response profile obtained from occipital cortex, leaving only "slow-wave" activity, thereby allowing us to characterize or profile feedback activity in this situation. Attention or task relevance enhanced the initial "spike" and "slow-wave" activity in visually responsive areas. Prefrontal activity, along the superior frontal sulcus, evoked by the working memory task, was active later in time than initial activity in visual cortex and later than the earliest effect of attention modulation in visual cortex.

Human and nonhuman primate visual systems are divided into object and spatial information processing pathways. In the macaque, it has been shown that these pathways project to separate areas in the frontal lobe and that the ventral and dorsal frontal areas are, respectively, involved in working memory for objects and spatial locations. A positron emission tomography (PET) study was done to determine if a similar anatomical segregation exists in humans for object and spatial visual working memory. Face working memory demonstrated significant increases in regional cerebral blood flow (rCBF), relative to location working memory, in fusiform, parahippocampal, inferior frontal, and anterior cingulate cortices, and in right thalamus and midline cerebellum. Location working memory demonstrated significant increases in cRBF, relative to face working memory, in superior and inferior parietal cortex, and in the superior frontal sulcus. Our results show that the neural systems involved in working memory for faces and for spatial location are functionally segregated, with different areas recruited in both extrastriate and frontal cortices for processing the two types of visual information.