Structural asymmetry of the insula is linked to the lateralization of gesture and language

The control of gesture is one of the most left‐lateralized functions, and the insular cortex is one of the most left‐biased structures in the human brain. Therefore, we investigated whether structural asymmetries of the insula are linked to the organization of functional activity during gesture planning. We reconstructed and parcellated the insular cortex of 27 participants. First, we tested 15 strongly left‐handed individuals because of a higher incidence of atypical organization of functions such as gesture and language in such a population. The inter‐hemispheric structural asymmetries were compared with the lateralization of activity for gesture in the supramarginal gyrus (the hotspot of signal increase regardless of the gesturing hand) and Broca's area (the hotspot of signal increase for language production). The more pronounced leftward structural asymmetries were accompanied by greater left‐hemisphere dominance for both of the studied functions. Conversely, an atypical, bilateral or rightward functional shift of gesture and language was accompanied by an attenuated leftward asymmetry of the insula. These significant relationships were driven primarily by differences in surface area. Subsequently, by adding 12 right‐handed individuals to these analyses we demonstrated that the observed significant associations are generalizable to the population. These results provide the first demonstration of the relationships between structural inter‐hemispheric differences of the insula and the cerebral specialization for gesture. They also corroborate the link between insular asymmetries and language lateralization. As such, these outcomes are relevant to the common cerebral specialization for gesture and language.     

Determining the hemispheric dominance of spatial attention: a comparison between fTCD and fMRI

Human brain mapping allows the systematic assessment of interindividual differences in functional brain anatomy. Functional transcranial Doppler sonography (fTCD) is an imaging tool that allows for fast and mobile assessment of hemispheric lateralization of task-related brain activation. It is ideal to screen large cohorts of subjects. The goal of the present study was to investigate whether fTCD and functional magnetic resonance imaging (fMRI) determine hemispheric lateralization of brain activation related to visuospatial attention concordantly. Used together, fMRI and fTCD may then open up a wide range of potential applications in neuroscience. Fifteen subjects were examined both with fTCD and fMRI while they judged accuracy of line bisections (Landmark task). For fTCD, the maximal mean difference in stimulus-related relative cerebral blood flow velocity changes in the left and right middle cerebral arteries was assessed as the lateralization index LI(fTCD). For fMRI, two approaches were used to determine hemispheric dominance. First, we measured brain activity as the extent of the activated region, i.e., the number of activated voxels above a statistical threshold. Second, we calculated the magnitude of the fMRI signal change between the activation and the control task within a region of interest. Results of fTCD and fMRI were concordant in every single case. Therefore, scanning large cohorts with fTCD for hemispheric dominance during Landmark task will provide results consistent with fMRI. FMRI can then be used for in depth assessment of the specific patterns of activation.     

Functional neuroanatomy of language without speech: An ALE meta‐analysis of sign language

Sign language (SL) conveys linguistic information using gestures instead of sounds. Here, we apply a meta‐analytic estimation approach to neuroimaging studies (N = 23; subjects = 316) and ask whether SL comprehension in deaf signers relies on the same primarily left‐hemispheric cortical network implicated in spoken and written language (SWL) comprehension in hearing speakers. We show that: (a) SL recruits bilateral fronto‐temporo‐occipital regions with strong left‐lateralization in the posterior inferior frontal gyrus known as Broca''s area, mirroring functional asymmetries observed for SWL. (b) Within this SL network, Broca''s area constitutes a hub which attributes abstract linguistic information to gestures. (c) SL‐specific voxels in Broca''s area are also crucially involved in SWL, as confirmed by meta‐analytic connectivity modeling using an independent large‐scale neuroimaging database. This strongly suggests that the human brain evolved a lateralized language network with a supramodal hub in Broca''s area which computes linguistic information independent of speech.     

The influence of tobacco consumption on the relationship between schizotypy and hemispheric asymmetry

Tobacco use is positively associated with severity of symptoms along the schizophrenia spectrum. Accordingly it could be argued that neuropsychological performance, formerly thought to be modulated by schizotypy, is actually modulated by drug use or an interaction of drug use and schizotypy. We tested whether habitual cigarette smokers as compared to non-smokers would show a neuropsychological profile similar to that observed along the schizophrenia spectrum and, if so, whether smoking status or nicotine dependence would be more significant modulators of behavior than schizotypy. Because hemispheric dominance has been found to be attenuated along the schizophrenia spectrum, 40 right-handed male students (20 non-smokers) performed lateralized left- (lexical decisions) and right- (facial decision task) hemisphere dominant tasks. All individuals completed self-report measures of schizotypy and nicotine dependence. Schizotypy predicted laterality in addition to smoking status: While positive schizotypy (Unusual Experiences) was unrelated to hemispheric performance, Cognitive Disorganization predicted reduced left hemisphere dominant language functions. These latter findings suggest that Cognitive Disorganization should be regarded separately as a potentially important mediator of thought disorganization and language processing. Additionally, increasing nicotine dependence among smokers predicted a right hemisphere shift of function in both tasks that supports the role of the right hemisphere in compulsive/impulsive behavior.     

Divergence between functional magnetic resonance imaging and clinical indicators of language dominance in preoperative language mapping

Accurate determination of hemispheric language dominance prior to epilepsy surgery is critically important to minimize cognitive morbidity. Functional MRI (fMRI) is a noninvasive method that is highly concordant with other clinical indicators of language laterality, and is now commonly used to confirm language dominance. However, there is also a high frequency of divergence between fMRI findings and other clinical indices that complicate determination of dominance and surgical decision‐making in individual patients. Despite this, divergent cases are rarely published or discussed. This article provides three illustrative examples to demonstrate common scenarios where fMRI may produce conflicting or otherwise difficult‐to‐interpret findings. We will also discuss potential reasons for divergence and propose a flow‐chart to aid clinical decision making in such situations.     

Increased prefrontal volume in PD with levodopa‐induced dyskinesias: A voxel‐based morphometry study

Levodopa‐induced dyskinesias represent disabling complications from long‐term therapy with dopaminergic drugs for treating Parkinson's disease (PD). Although several neuroimaging studies have reported altered striatofrontal function that contributes to the emergence of these motor complications, the neuroanatomical correlates of this disorder are still unknown. Optimized voxel‐based morphometry (VBM) was applied to the MRI brain images of 36 PD patients with levodopa‐induced dyskinesias, 36 PD patients without levodopa‐induced dyskinesias, and 32 age‐ and sex‐matched controls. The VBM analysis comparing dyskinetic and nondyskinetic groups provided evidence of increased gray matter volume of the bilateral inferior frontal gyrus in dyskinetic patients, a finding that was more evident in patients with early‐onset PD. No significant differences were detected in the dyskinetic and nondyskinetic groups when compared with the controls. Our findings suggest that the presence of dyskinesias in patients with PD is characterized by an aberrant neural plasticity that could play a role in the pathophysiology of these motor complications. © 2011 Movement Disorder Society     

Neuroanatomical correlates of apathy in Parkinson's disease: A magnetic resonance imaging study using voxel‐based morphometry

Apathy is generally defined as a disorder of motivation and is considered one of the most common neuropsychiatric disturbances in Parkinson's disease (PD). Only few studies addressed the neuroanatomical correlates of apathy in PD. The aim of this article was to determine the structural correlates of apathy in PD patients. Fifty‐five PD patients underwent a neuropsychiatric and neuropsychological examination, and a 3 T magnetic resonance imaging scan was acquired. A voxel‐based multiple regression analysis was used to calculate correlation between gray matter density and severity measures of apathy. Apathy correlates with decreased cognitive functioning and more depressive symptoms but not with more severe motor symptoms. High apathy scores were correlated with low gray matter density values in a number of cortical brain areas: the bilateral precentral gyrus (BA 4, 6), the bilateral inferior parietal gyrus (BA 40), the bilateral inferior frontal gyrus (BA 44, 47), the bilateral insula (BA 13), the right (posterior) cingulate gyrus (BA 24, 30, 31), and the right precuneus (BA 31). Apathy in PD correlates with reduced gray matter density in a number of brain regions. The involvement of the cingulate gyrus and inferior frontal gyrus is in line with the results of earlier studies addressing apathy in patients with Alzheimer's disease or depressive disorder. Further studies addressing the pathogenesis of apathy are needed. © 2010 Movement Disorder Society.     

Altered anterior‐posterior connectivity through the arcuate fasciculus in temporal lobe epilepsy

How the interactions between cortices through a specific white matter pathway change during cognitive processing in patients with epilepsy remains unclear. Here, we used surface‐based structural connectivity analysis to examine the change in structural connectivity with Broca's area/the right Broca's homologue in the lateral temporal and inferior parietal cortices through the arcuate fasciculus (AF) in 17 patients with left temporal lobe epilepsy (TLE) compared with 17 healthy controls. Then, we investigated its functional relevance to the changes in task‐related responses and task‐modulated functional connectivity with Broca's area/the right Broca's homologue during a semantic classification task of a single word. The structural connectivity through the AF pathway and task‐modulated functional connectivity with Broca's area decreased in the left midtemporal cortex. Furthermore, task‐related response decreased in the left mid temporal cortex that overlapped with the region showing a decrease in the structural connectivity. In contrast, the region showing an increase in the structural connectivity through the AF overlapped with the regions showing an increase in task‐modulated functional connectivity in the left inferior parietal cortex. These structural and functional changes in the overlapping regions were correlated. The results suggest that the change in the structural connectivity through the left frontal–temporal AF pathway underlies the altered functional networks between the frontal and temporal cortices during the language‐related processing in patients with left TLE. The left frontal–parietal AF pathway might be employed to connect anterior and posterior brain regions during language processing and compensate for the compromised left frontal–temporal AF pathway. Hum Brain Mapp 37:4425–4438, 2016. © 2016 Wiley Periodicals, Inc.     

Morphometric changes of gray matter in Parkinson's disease with depression: A voxel‐based morphometry study

The origin of the high rate of depression in idiopathic Parkinson's disease (PD) is unknown. We applied voxel‐based morphometry (VBM), as a sensitive tool in detection of gray matter MR density alterations, to find differences in depressed and nondepressed PD patients. Patients with idiopathic PD were classified into depressed (DPD) and nondepressed (NDPD) groups based on the Montgomery‐Åsberg Depression Rating Scale (MADRS). Subsequently, a group comparisons were performed between depressed PD (n = 23), nondepressed PD (n = 27) and normal healthy controls (NC, n = 16). There was no difference in gray matter density comparing healthy controls to any PD groups. However, when NDPD and DPD cohorts were compared, density alteration of the bilateral orbitofrontal, bilateral rectal gyrus, and also the right superior temporal pole was detected in the depressed subgroup. Exploratory analyses revealed an inverse correlation of MADRS scores and severity of VBM alteration in these regions beside the right medial temporal gyrus, anterior and medial cingular gyrus, and parahippocampal gyrus. These results suggest that depression in PD is related to gray matter decrease in the bilateral orbitofrontal and right temporal regions as well as the limbic system. © 2007 Movement Disorder Society     

The differential effect of right versus left hemispheric cerebral infarction on catecholamines and behavior in the rat

Following right middle cerebral artery ligation in rats, there is a 2–3 week period of spontaneous hyperactivity. Concomitant with this hyperactivity catecholamine concentrations decrease in several areas of the brain including both cortical and subcortical regions. In marked contrast, there are no demonstrable effects of left hemispheric infarction on either spontaneous activity or brain catecholamine concentrations. This asymmetry of behavioral and biochemical response to cerebral infarction cannot be attributed to differences in the lesion size produced in either hemisphere. Feeding and drinking are not affected but the asymmetrical effect on activity can be demonstrated in either a home cage running wheel or an open field environment. It is uncertain whether these findings are the result of hemispheric asymmetries in either catecholaminergic or non-catecholaminergic neurons.     

Contribution of insula in Parkinson's disease: A quantitative meta‐analysis study

The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson's disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate‐based quantitative meta‐analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect. Hum Brain Mapp 37:1375‐1392, 2016. © 2016 Wiley Periodicals, Inc.     

Resting‐state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post‐surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting‐state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting‐state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left‐hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. Hum Brain Mapp, 36:288–303, 2015. © 2014 Wiley Periodicals, Inc.     

Structural abnormalities in the dyslexic brain: A meta‐analysis of voxel‐based morphometry studies

We used coordinate‐based meta‐analysis in order to objectively quantify gray matter abnormalities reported in nine Voxel‐Based Morphometry studies of developmental dyslexia. Consistently across studies, reduced gray matter volume in dyslexic readers was found in the right superior temporal gyrus and left superior temporal sulcus. These results were related to findings from previous meta‐analyses on functional brain abnormalities in dyslexic readers. Convergence of gray matter reduction and reading‐related underactivation was found for the left superior temporal sulcus. Recent studies point to the presence of both functional and structural abnormalities in left temporal and occipito‐temporal brain regions before reading onset. Hum Brain Mapp 34:3055–3065, 2013. © 2012 Wiley Periodicals, Inc.     

Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases

The Wada test is an invasive procedure used to determine cerebral memory and language dominance as well as risk of cognitive deficits following neurosurgery. However, the potential risks of Wada testing have led some to consider foregoing Wada testing in candidates for resective epilepsy surgery with right hemispheric seizure onset. We present two atypical cases in which the Wada test showed unexpected memory and language lateralization. These cases underscore the importance of functional magnetic resonance in which imaging and Wada examination in right-handed individuals even when the lesion would not suggest atypical language representation.     

The lateral‐occipital and the inferior‐frontal cortex play different roles during the naming of visually presented objects

We reasoned that if an area is devoted to processing only the visual features of objects, then transcranial magnetic stimulation (TMS) applied to this area in either hemisphere would affect the naming of objects presented in contralateral but not ipsilateral space. In contrast, if an area is involved in language, then one might expect to see effects of TMS when applied over the left but not the right hemisphere, regardless whether objects are in contralateral or ipsilateral space. Our experiments reveal two important findings. First, TMS delivered to the lateral‐occipital complex (LOC), a visual‐form area, affected the naming of objects presented in contralateral but not ipsilateral space, independent of which hemisphere was stimulated. In two additional experiments, when participants named the color of objects or made judgments about the size of stimuli as shown physically on a computer screen, TMS over the contralateral LOC did not affect color naming but did affect the participants' ability to make size judgments. Second, TMS delivered to the left but not the right posterior inferior‐frontal gyrus (pIFG) affected the naming of objects irrespective of whether objects were presented in contralateral or ipsilateral space. In a separate experiment, when participants were asked to either read or categorize words, TMS over the left but not the right pIFG affected word categorization but not word reading. On the basis of these findings, we propose that when people name visually‐presented objects, LOC processes the visual form of objects while the left pIFG processes the semantics of objects. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Right‐hemispheric language reorganization in patients with brain arteriovenous malformations: A functional magnetic resonance imaging study

Brain arteriovenous malformation (AVM), a presumed congenital lesion, may involve traditional language areas but usually does not lead to language dysfunction unless it ruptures. The objective of this research was to study right‐hemispheric language reorganization patterns in patients with brain AVMs using functional magnetic resonance imaging (fMRI). We prospectively enrolled 30 AVM patients with lesions involving language areas and 32 age‐ and sex‐matched healthy controls. Each subject underwent fMRI during three language tasks: visual synonym judgment, oral word reading, and auditory sentence comprehension. The activation differences between the AVM and control groups were investigated by voxelwise analysis. Lateralization indices (LIs) for the frontal lobe, temporal lobe, and cerebellum were compared between the two groups, respectively. Results suggested that the language functions of AVM patients and controls were all normal. Voxelwise analysis showed no significantly different activations between the two groups in visual synonym judgment and oral word reading tasks. In auditory sentence comprehension task, AVM patients had significantly more activations in the right precentral gyrus (BA 6) and right cerebellar lobule VI (AAL 9042). According to the LI results, the frontal lobe in oral word reading task and the temporal lobe in auditory sentence comprehension task were significantly more right‐lateralized in the AVM group. These findings suggest that for patients with AVMs involving language cortex, different language reorganization patterns may develop for different language functions. The recruitment of brain areas in the right cerebral and cerebellar hemispheres may play a compensatory role in the reorganized language network of AVM patients.     

The relationship between individual differences in gray matter volume and religiosity and mystical experiences: A preregistered voxel‐based morphometry study

The neural substrates of religious belief and experience are an intriguing though contentious topic. Here, we had the unique opportunity to establish the relation between validated measures of religiosity and gray matter volume in a large sample of participants (N = 211). In this registered report, we conducted a confirmatory voxel‐based morphometry analysis to test three central hypotheses regarding the relationship between religiosity and mystical experiences and gray matter volume. The preregisterered hypotheses, analysis plan, preprocessing and analysis code and statistical brain maps are all available from online repositories. By using a region‐of‐interest analysis, we found no evidence that religiosity is associated with a reduced volume of the orbito‐frontal cortex and changes in the structure of the bilateral inferior parietal lobes. Neither did we find support for the notion that mystical experiences are associated with a reduced volume of the hippocampus, the right middle temporal gyrus or with the inferior parietal lobes. A whole‐brain analysis furthermore indicated that no structural brain differences were found in association with religiosity and mystical experiences. We believe that the search for the neural correlates of religious beliefs and experiences should therefore shift focus from studying structural brain differences to a functional and multivariate approach.     

A comparison of gray and white matter density in patients with Parkinson's disease dementia and dementia with Lewy bodies using voxel‐based morphometry

Despite clinical and neuropsychological similarities between Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD. We used voxel‐based morphometry using a 3‐T MRI scanner to compare gray and white matter densities in 20 patients with probable PDD and 18 patients with probable DLB, who had similar overall severity of dementia and similar demographic characteristics. The gray matter density was significantly decreased in the left occipital, parietal, and striatal areas in patients with DLB compared with patients with PDD. The white matter density was significantly decreased in bilateral occipital and left occipito‐parietal areas in patients with DLB compared with those with PDD. The degree of white and gray matter atrophy was similar in patients with DLB; in contrast, there was markedly less atrophy in the white matter than in the gray matter in patients with PDD. On analyzing the change of WM density relative to that of GM density in patients with DLB compared to those with PDD, the area of WM atrophy in the occipital areas was more extensive than that of GM atrophy. Our data demonstrate that atrophy of both gray and white matter was more severe in patients with DLB and that white matter atrophy relative to gray matter atrophy was less severe in patients with PDD. These data may reflect a difference in the underlying nature of PDD and DLB. © 2009 Movement Disorder Society