Nathalie Tzourio-Mazoyer

Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain

An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463-468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high-resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254-266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps.

Evaluation of the dual route theory of reading: a metanalysis of 35 neuroimaging studies

Numerous studies concerned with cerebral structures underlying word reading have been published during the last decade. A few controversies, however, together with methodological or theoretical discrepancies between laboratories, still contribute to blurring the overall view of advances effected in neuroimaging. Carried out within the dual route of reading framework, the aim of this metanalysis was to provide an objective picture of these advances. To achieve this, we used an automated analysis method based on the inventory of activation peaks issued from word or pseudoword reading contrasts of 35 published neuroimaging studies. A first result of this metanalysis was that no cluster of activations has been found more recruited by word than pseudoword reading, implying that the first steps of word access may be common to word and word-like stimuli and would take place within a left occipitotemporal region (previously referred to as the Visual Word Form Area-VWFA) situated in the ventral route, at the junction between inferior temporal and fusiform gyri. The results also indicated the existence of brain regions predominantly involved in one of the two routes to access word. The graphophonological conversion seems indeed to rely on left lateralized brain structures such as superior temporal areas, supramarginal gyrus, and the opercular part of the inferior frontal gyrus, these last two regions reflecting a greater load in working memory during such an access. The lexicosemantic route is thought to arise from the coactivation of the VWFA and semantic areas. These semantic areas would encompass a basal inferior temporal area, the posterior part of the middle temporal gyrus, and the triangular part of inferior frontal gyrus. These results confirm the suitability of the dual route framework to account for activations observed in nonpathological subjects while they read.

Neural Correlates of Simple and Complex Mental Calculation

Some authors proposed that exact mental calculation is based on linguistic representations and relies on the perisylvian language cortices, while the understanding of proximity relations between numerical quantities implicates the parietal cortex. However, other authors opposed developmental arguments to suggest that number sense emerges from nonspecific visuospatial processing areas in the parietal cortex. Within this debate, the present study aimed at revealing the functional anatomy of the two basic resolution strategies involved in mental calculation, namely arithmetical fact retrieval and actual computation, questioning in particular the respective role of language and/or visuospatial cerebral areas. Regional cerebral blood flow was measured with positron emission tomography while subjects were at rest (Rest), read digits (Read), retrieved simple arithmetic facts from memory (i.e., 2 x 4, Retrieve), and performed mental complex calculation (i.e., 32 x 24, Compute). Compared to Read, Retrieve engaged a left parieto-premotor circuit representing a developmental trace of a finger-counting representation that mediates, by extension, the numerical knowledge in adult. Beside this basic network, Retrieve involved a naming network, including the left anterior insula and the right cerebellar cortex, while it did not engage the perisylvian language areas, which were deactivated as compared to Rest. In addition to this retrieval network, Compute specifically involved two functional networks: a left parieto-frontal network in charge of the holding of the multidigit numbers in visuospatial working memory and a bilateral inferior temporal gyri related to the visual mental imagery resolution strategy. Overall, these results provide strong evidence of the involvement of visuospatial representations in different levels of mental calculation.

Neural correlates of topographic mental exploration: the impact of route versus survey perspective learning.

There are two major sources of information to build a topographic representation of an environment, namely actual navigation within the environment (route perspective) and map learning (survey perspective). The aim of the present work was to use positron emission tomography (PET) to compare the neural substrate of the topographic representation built from these two modes. One group of subjects performed a mental exploration task in an environment learned from actual navigation (mental navigation task). Another group of subjects performed exploration in the same environment learned from a map (mental map task). A right hippocampal activation common to both mental navigation and mental map tasks was evidenced and may correspond the neural substrate of a dual-perspective representation. The parahippocampal gyrus was additionally activated bilaterally during mental navigation only. These results suggest that the right hippocampus involvement would be sufficient when the representation incorporates essentially survey information while the bilateral parahippocampal gyrus would be involved when the environment incorporates route information and includes object landmarks. The activation of a parietofrontal network composed of the intraparietal sulcus, the superior frontal sulcus, the middle frontal gyrus, and the pre-SMA was observed in common for both mental navigation and mental map and is likely to reflect the spatial mental imagery components of the tasks.

Revisiting human hemispheric specialization with neuroimaging

Hemispheric specialization (HS) is a hemisphere-dependent relationship between a cognitive, sensory, or motor function and a set of brain structures. It includes both the hosting by a given hemisphere of specialized networks that have unique functional properties and mechanisms that enable the inter-hemispheric coordination necessary for efficient processing. Long derived from neuropsychological and behavioral observations, knowledge of HS is currently being profoundly modified by cutting-edge neuroimaging research that focuses both on the neural implementation of HS for language, visuospatial functions, and motor control/handedness across development and on the analysis of interactions between brain regions within and across hemispheres. New findings reveal the fundamental role of lateralization in the large-scale architecture of the human brain, whose ontogenesis has begun to be investigated with genetic-heritability brain mapping.

The resting state questionnaire: An introspective questionnaire for evaluation of inner experience during the conscious resting state

We designed a semi-structured questionnaire for the introspective evaluation of inner experience of participants undergoing functional magnetic resonance imaging (fMRI) in the resting state. This resting state questionnaire (ReSQ) consists of 62 items organized by five main types of mental activity: visual mental imagery (IMAG); inner language (LANG), split into two subtypes, inner speech (SPEE) and auditory mental imagery (AUDI); somatosensory awareness (SOMA); inner musical experience (MUSI); and mental manipulation of numbers (NUMB). For IMAG and LANG, additional questions estimated association of such activities with ongoing learning, retrospective memories, or prospective thoughts. Using a 0-100% scale, the participant quantitatively rated the proportion of time spent in each mental activity during the resting state fMRI acquisition. A total of 180 healthy volunteers completed the ReSQ immediately after being scanned with fMRI while at rest. Of these, 66% exhibited dominance of a type of mental activity at rest (IMAG: 35%; LANG: 17%; SOMA: 7%; MUSI: 6%; NUMB: 1%). A majority of participants reported either retrospective memories (82%) or prospective thoughts (78%), with 58% of participants reporting both in at least one type of mental activity. Thoughts related to ongoing learning were low (37% of participants). The present results are consistent with those of previous studies investigating inner experience in a natural environment. In conclusion, we provide a robust and easy-to-implement tool for the exploration of mental activities during rest of healthy participants undergoing fMRI. This tool relies on normative data acquired from a 180-participant sample balanced for sex and handedness.

How verbal and spatial manipulation networks contribute to calculation: An fMRI study

The manipulation of numbers required during calculation is known to rely on working memory (WM) resources. Here, we investigated the respective contributions of verbal and/or spatial WM manipulation brain networks during the addition of four numbers performed by adults, using functional magnetic resonance imaging (fMRI). Both manipulation and maintenance tasks were proposed with syllables, locations, or two-digit numbers. As compared to their maintenance, numbers manipulation (addition) elicited increased activation within a widespread cortical network including inferior temporal, parietal, and prefrontal regions. Our results demonstrate that mastery of arithmetic calculation requires the cooperation of three WM manipulation systems: an executive manipulation system conjointly recruited by the three manipulation tasks, including the anterior cingulate cortex (ACC), the orbital part of the inferior frontal gyrus, and the caudate nuclei; a left-lateralized, language-related, inferior fronto-temporal system elicited by numbers and syllables manipulation tasks required for retrieval, selection, and association of symbolic information; and a right superior and posterior fronto-parietal system elicited by numbers and locations manipulation tasks for spatial WM and attentional processes. Our results provide new information that the anterior intraparietal sulcus (IPS) is involved in tasks requiring a magnitude processing with symbolic (numbers) and nonsymbolic (locations) stimuli. Furthermore, the specificity of arithmetic processing is mediated by a left-hemispheric specialization of the anterior and posterior parts of the IPS as compared to a spatial task involving magnitude processing with nonsymbolic material.

Distinguishing visuospatial working memory and complex mental calculation areas within the parietal lobes.

The present study was aimed at differentiate, within the parietal cortex, the areas underlying visuospatial working memory/attentionnal processes and those devoted to arithmetic processing. We compared, using positron emission tomography, the cerebral networks activated in two groups of subjects, one solving two-by-two digit numbers multiplications and the other performing a visuospatial non-numerical N-Back task. Both tasks were compared to a resting state and a control condition. During both tasks, activation was observed, bilaterally, in superior parietal areas reflecting visuospatial working memory and attentionnal processes shared by both tasks. The calculation task elicited more activation in the left inferior parietal lobule and the left precuneus. These areas could subtend numerical representation, numbers storage and retrieval processes. These results added some strong support for a special role of the left inferior parietal areas in arithmetic processing.

Access to deductive logic depends on a right ventromedial prefrontal area devoted to emotion and feeling: evidence from a training paradigm.

Does the human capacity for access to deductive logic depend on emotion and feeling? With positron emission tomography, we compared the brain networks recruited by two groups of subjects who were either able or not able to shift from errors to logical responses in a deductive reasoning task. They were scanned twice while performing the same task, before and after a training session. The error-to-logical shift occurred in a group that underwent logicoemotional training but not in the other group, trained in logic only-a cold kind of training. The intergroup comparison pointed out that access to deductive logic involved a right ventromedial prefrontal area known to be devoted to emotion and feeling.

Effects of ApoE-ɛ4 allele load and age on the rates of grey matter and hippocampal volumes loss in a longitudinal cohort of 1186 healthy elderly persons

In a sample of 1186 healthy subjects aged 65 to 89 years who were scanned twice with MRI 3.6 years apart, we studied the effects of age and ApoE-epsilon4 allele load on the rate of atrophy of grey matter and hippocampus. Rates of grey matter and hippocampal volumes loss were computed from T1-weighted magnetic resonance images using voxel-based morphometry and region of interest analysis. Longitudinal analysis showed that an age-related annual rate of grey matter volume loss was only seen in epsilon4 homozygotes only (n=14) whereas no age effect was seen epsilon4 heterozygotes (n=239) and in noncarriers (n=933). ApoE-epsilon4 homozygotes also had a significantly larger rate of hippocampal volume loss than heterozygotes or noncarriers. During the same period, no effect or interaction of ApoE genotype and age was observed on cognitive decline, as assessed by the Mini Mental State Examination (MMSE). These data do not suggest an epsilon4 gene dose effect on the rate of hippocampal volume loss in healthy elderly subjects as most of the effect was limited to homozygotes. Hippocampal volume loss may not be a good imaging marker to understand the effect of the ApoE-epsilon4 allele on the risk of dementia in a population-based setting. It could be hypothesized that the impact of a single ApoE-epsilon4 allele on brain structures is largely delayed in time.