fMRI Protocol Research Articles

Evaluating the Utility of EPIK in a Finger Tapping fMRI Experiment using BOLD Detection and Effective Connectivity

EPI with Keyhole (EPIK) is a hybrid imaging technique that overcomes many of the performance disadvantages associated with EPI. Previously, EPIK was shown to provide a higher temporal resolution and fewer image distortions than EPI whilst maintaining comparable performance for the detection of BOLD-based signals. This work carefully examines the putative enhanced sensitivity of EPIK in a typical fMRI setting by using a robust fMRI paradigm – visually guided finger tapping – to demonstrate the advantages of EPIK for fMRI at 3 T. The data acquired were directly compared to the community standard fMRI protocol using single-shot EPI to ascertain a clear comparison. Each sequence was optimised to offer its highest possible spatial resolution for a given set of imaging conditions, i.e., EPIK and EPI achieved an in-planar resolution of 2.08 × 2.08 mm2 with 32 slices and 3.13 × 3.13 mm2 with 36 slices, respectively. EPIK demonstrated a number of clear improvements, such as superior spatial resolution with favourable robustness against susceptibility artefacts. Both imaging sequences revealed robust activation within primary motor, premotor and visual regions, although significantly higher BOLD amplitudes were detected using EPIK within the primary and supplementary motor areas. Dynamic causal modelling, in combination with Bayesian model selection, identified identical winning models for EPIK and EPI data. Coupling parameters reflecting task-related modulations and the connectivity of fixed connections were comparably robust for both sequences. However, fixed connections from the left motor cortex to the right visual cortex were estimated as being significantly more robust for EPIK data.

The resting-brain of obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) is one of the most debilitating psychiatric conditions, having a dramatic impact on patients’ daily living. In this work, we aimed to explore resting-state functional connectivity in OCD patients, using an independent component analysis. Eighty individuals (40 patients and 40 healthy controls) performed a resting state fMRI protocol. OCD patients displayed reduced functional connectivity (FC) in visual and sensorimotor networks. In addition, patients displayed decreased FC between sensory networks and increased FC between default-mode and cerebellar networks.

Limbic and cortical control of phonation for speech in response to a public speech preparation stressor

Knowledge on brain networks subserving vocalization in vocally healthy individuals under various task conditions is scarce but paramount to understand voice disorders. The aims of our study were to determine (1) the effect of social-evaluative stress on the central neural control of phonation underlying speech production; and (2) the neural signature, personality profile, and aerodynamic vocal function in relation to salivary cortisol responses. Thirteen vocally healthy females underwent an event-related sparse-sampling fMRI protocol consisting of voiced and whispered sentence productions with and without exposure to the social-evaluative stressor public speaking anticipation. Participants completed a personality questionnaire, rating scales of negative emotional state, and provided salivary cortisol samples. In the total sample, the task contrast of voiced productions revealed that stressor exposure resulted in a peak activation in the right caudate with concomitant deactivations in the bilateral pgACC and aMCC, and right IFG, BA 9, BA 10, insula, putamen, and thalamus. There were individual differences in stressor-induced brain activations as a function of stress reactivity with greater cortisol reactivity linked with lower laryngeal motor cortex activity and lower scores on aspects of extraversion. Our data confirm that stress alters the phonatory control for speech production through limbic-motor interactions. The findings support the Trait Theory of Voice Disorders (Roy and Bless 2000) and help provide critical insights to the study of voice disorders such as primary muscle tension dysphonia.

Visual and Auditory fMRI Paradigms for Presurgical Language Mapping: Convergent Validity and Relationship to Individual Variables.

Functional MRI (fMRI) has emerged as a safe alternative to invasive procedures for determining hemispheric language dominance prior to neurosurgery. Despite this, there are currently no standardized fMRI protocols that have been explored in healthy controls to determine the influence of individual patient variables on the results, which poses challenges in clinical interpretation of ambiguous findings in patient populations. In addition, most fMRI protocols are not suitable for individuals with visual or intellectual disabilities (IQ<70). In the current study, 61 healthy adults (ages: 18-74 years) completed two fMRI paradigms for language mapping. One paradigm used visually based stimuli and has shown good face validity to date in our center. The second paradigm used auditory stimuli presented at slowed speed and was designed for individuals with visual or cognitive dysfunction but has not yet been used clinically. The paradigms demonstrated 97% agreement in classifying individuals as left-hemisphere, right-hemisphere, and bilaterally dominant. Cases that were classified differently showed bilateral dominance in response to either paradigm. Dominance classification rates for right- and left-handed individuals were largely in keeping with published data. Within the left-handed group, IQ and education were positively correlated with laterality indices generated by both paradigms (r values range: 0.44-0.95, p<0.01), suggesting that individuals with higher IQ and formal education were more likely to be classified as left-hemisphere dominant in the current sample. This study will help improve clinical interpretation of language fMRI maps by identifying factors that might impact results (like IQ). It also offers an alternative paradigm to make this procedure more accessible to a broader range of patients. Future studies will replicate results with a sample of patients with epilepsy across a broad range of intellectual abilities.

Optimizing BOLD sensitivity in the 7T Human Connectome Project resting-state fMRI protocol using plug-and-play parallel transmission

The Human Connectome Project (HCP) has a 7T component that aims to study the human brain's organization and function with high spatial and temporal resolution fMRI and diffusion-weighted acquisitions. For whole brain applications at 7T, a major weakness however remains the heterogeneity of the radiofrequency transmission field (B1+ ), which prevents from achieving an optimal signal and contrast homogeneously throughout the brain. In this work, we use parallel transmission (pTX) Universal Pulses (UP) to improve the flip angle homogeneity and demonstrate their application to highly accelerated multi-band EPI (MB5 and GRAPPA2, as prescribed in the 7T HCP protocol) sequence, but also to acquire at 7T B1+ -artefact-free T1 - and T2 -weighted anatomical scans used in the pre-processing pipeline of the HCP protocol. As compared to typical implementations of pTX, the proposed solution is fully operator-independent and allows ”plug and play” exploitation of the benefits offered by multi-channel transmission. Validation in five healthy adults shows that the proposed technique achieves a flip angle homogeneity comparable to that of a clinical 3 T system. Compared to standard single-channel transmission, the use of UPs at 7T yielded up to a two-fold increase of the temporal signal-to-noise ratio in the temporal lobes as well as improved detection of functional connectivity in the brain regions most strongly affected by B1+ inhomogeneity.

Accurate autocorrelation modeling substantially improves fMRI reliability

Given the recent controversies in some neuroimaging statistical methods, we compare the most frequently used functional Magnetic Resonance Imaging (fMRI) analysis packages: AFNI, FSL and SPM, with regard to temporal autocorrelation modeling. This process, sometimes known as pre-whitening, is conducted in virtually all task fMRI studies. Here, we employ eleven datasets containing 980 scans corresponding to different fMRI protocols and subject populations. We found that autocorrelation modeling in AFNI, although imperfect, performed much better than the autocorrelation modeling of FSL and SPM. The presence of residual autocorrelated noise in FSL and SPM leads to heavily confounded first level results, particularly for low-frequency experimental designs. SPM’s alternative pre-whitening method, FAST, performed better than SPM’s default. The reliability of task fMRI studies could be improved with more accurate autocorrelation modeling. We recommend that fMRI analysis packages provide diagnostic plots to make users aware of any pre-whitening problems.

Imaging object-scene relations processing in visible and invisible natural scenes

Integrating objects with their context is a key step in interpreting complex visual scenes. Here, we used functional Magnetic Resonance Imaging (fMRI) while participants viewed visual scenes depicting a person performing an action with an object that was either congruent or incongruent with the scene. Univariate and multivariate analyses revealed different activity for congruent vs. incongruent scenes in the lateral occipital complex, inferior temporal cortex, parahippocampal cortex, and prefrontal cortex. Importantly, and in contrast to previous studies, these activations could not be explained by task-induced conflict. A secondary goal of this study was to examine whether processing of object-context relations could occur in the absence of awareness. We found no evidence for brain activity differentiating between congruent and incongruent invisible masked scenes, which might reflect a genuine lack of activation, or stem from the limitations of our study. Overall, our results provide novel support for the roles of parahippocampal cortex and frontal areas in conscious processing of object-context relations, which cannot be explained by either low-level differences or task demands. Yet they further suggest that brain activity is decreased by visual masking to the point of becoming undetectable with our fMRI protocol.

Ultra-high field MRI reveals mood-related circuit disturbances in depression: a comparison between 3-Tesla and 7-Tesla

Ultra-high field 7-Tesla (7 T) MRI has the potential to advance our understanding of neuropsychiatric disorders, including major depressive disorder (MDD). To date, few studies have quantified the advantage of resting state functional MRI (fMRI) at 7 T compared to 3-Tesla (3 T). We conducted a series of experiments that demonstrate the improvement in temporal signal-to-noise ratio (TSNR) of a multi-echo multi-band fMRI protocol with ultra-high field 7 T MRI, compared to a similar protocol using 3 T MRI in healthy controls (HC). We also directly tested the enhancement in ultra-high field 7 T fMRI signal power by examining the ventral tegmental area (VTA), a small midbrain structure that is critical to the expected neuropathology of MDD but difficult to discern with standard 3 T MRI. We demonstrate up to 300% improvement in TSNR and resting state functional connectivity coefficients provided by ultra-high field 7 T fMRI compared to 3 T, indicating enhanced power for detection of functional neural architecture. A multi-echo based acquisition protocol and signal denoising pipeline afforded greater gain in signal power compared to classic acquisition and denoising pipelines. Furthermore, ultra-high field fMRI revealed mood-related neurocircuit disturbances in patients with MDD compared to HC, which were not detectable with 3 T fMRI. Ultra-high field 7 T fMRI may provide an effective tool for studying functional neural architecture relevant to MDD and other neuropsychiatric disorders.

The Superior Colliculus in De Novo Parkinson's Disease: A Prodromal Dysfunction?

Background: The dual hit hypothesis about the pathogenesis of Parkinson's disease (PD) suggests that the brainstem can convey pathological entries to the brain. However, information about the involvement of different brainstem structures are difficult to collect in living PD patients. We have filled this gap by studying with functional brain MRI the superior colliculus (SC), a brainstem sensorimotor structure. Starting with the discovery that the SC shows abnormal visual responses in PD rat models, we aimed at studying the SC also in de novo PD patients. Methods: De novo PD patients and controls were studied using a recently developed fMRI protocol to stimulate and visualize the SC, the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). The visual responses modulation of these structures was studied using luminance contrasts from 1% to 9%. We compared SC, LGN, and V1 BOLD responses of de novo PD patients with matching controls. The effects of dopaminergic treatment in PD patients were further evaluated. Findings: In the 22 enrolled PD patients, there was no modulation of the SC responses to the luminance contrasts, and the LGN was only modulated by 3%-9% luminance contrasts compared to the 22 controls. No major differences were found in V1 between both groups. Moreover, SC lack of modulation was more frequent in less affected de novo PD patients (Hoehn & Yahr stage 1). Dopaminergic treatment had no effect on SC and LGN modulation. Interpretation: De novo PD patients showed pathological responses to the luminance contrasts in the SC, suggesting that SC dysfunction could be diagnostic of PD. Since the SC seems to be more affected at stage 1 of PD, its dysfunction might be detected even earlier, supporting its potential role as a prodromal biomarker of PD. Clinical Trial Number: ClinicalTrial.gov (NCT02488395). Funding Statement: The work was funded by the University Grenoble Alpes, “La Fondation de l’Avenir” and “France Parkinson”. The Grenoble MRI facility IRMaGe was partly funded by the French program ‘Investissement d’Avenir” run by the Agence Nationale pour la Recherche (ANR-11-INBS-0006). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All participants provided written informed consent to the study. The study was approved by the local ethical committee (ID RCB- 2014-A01835-42).

MRI-compatible pneumatic stimulator for sensorimotor mapping

BackgroundTwo major concerns with respect to task-based motor functional magnetic resonance imaging (fMRI) are inadequate participants’ performance as well as intra- and inter-subject variability in execution of the motor action. New methodThis study validates the use of an MRI-compatible stimulator based on a pneumatic artificial muscle (PAM) for block-design fMRI mapping of the primary sensorimotor (SM1) cortex in a series of fifteen right-handed healthy subjects. The PAM stimulator elicits computer-controlled timely and reproducible passive movements of fingers/toes. Participants performed comparable active and passive PAM-induced flexion-extensions of the index fingers. ResultsPassive movement of the right index finger and passive alternating right and left index finger movement resulted in a significant increase in blood-oxygen-level-dependent (BOLD) signal in contralateral SM1 cortex in 14/15 and 15/15 subjects respectively. Similar networks were recruited by active and passive index finger movements. However, at the group level, active movement induced significantly higher increases in BOLD signal than passive movement in contralateral SM1 cortex (p < 0.05 Family Wise Error [FWE] corrected), supplementary motor area (p < 0.001 uncorrected), ipsilateral cerebellum (p < 0.001 uncorrected), and bilateral putamina (p < 0.001 uncorrected). Comparison with existing method(s)As compared to the several MRI-compatible robotic devices for computer-controlled passive movement of the fingers that were introduced in the past decades, the proposed PAM-based stimulator is smaller, handier, and easier to use in the MRI setting. ConclusionsPAM-based stimulators can be reliably used for passive sensorimotor fMRI mapping in healthy subjects. Using this approach, bilateral SM1 cortices can be mapped accurately during a single 6-min block-design fMRI protocol.

Functional MRI connectivity of children with autism and low verbal and cognitive performance

BackgroundFunctional neuroimaging research in autism spectrum disorder has reported patterns of decreased long-range, within-network, and interhemispheric connectivity. Research has also reported increased corticostriatal connectivity and between-network connectivity for default and attentional networks. Past studies have excluded individuals with autism and low verbal and cognitive performance (LVCP), so connectivity in individuals more significantly affected with autism has not yet been studied. This represents a critical gap in our understanding of brain function across the autism spectrum.MethodsUsing behavioral support procedures adapted from Nordahl, et al. (J Neurodev Disord 8:20–20, 2016), we completed non-sedated structural and functional MRI scans of 56 children ages 7–17, including LVCP children (n = 17, mean IQ = 54), children with autism and higher performance (HVCP, n = 20, mean IQ = 106), and neurotypical children (NT, n = 19, mean IQ = 111). Preparation included detailed intake questionnaires, video modeling, behavioral and anxiety reduction techniques, active noise-canceling headphones, and in-scan presentation of the Inscapes movie paradigm from Vanderwal et al. (Neuroimage 122:222–32, 2015). A high temporal resolution multiband echoplanar fMRI protocol analyzed motion-free time series data, extracted from concatenated volumes to mitigate the influence of motion artifact. All participants had > 200 volumes of motion-free fMRI scanning. Analyses were corrected for multiple comparisons.ResultsLVCP showed decreased within-network connectivity in default, salience, auditory, and frontoparietal networks (LVCP < HVCP) and decreased interhemispheric connectivity (LVCP < HVCP=NT). Between-network connectivity was higher for LVCP than NT between default and dorsal attention and frontoparietal networks. Lower IQ was associated with decreased connectivity within the default network and increased connectivity between default and dorsal attention networks.ConclusionsThis study demonstrates that with moderate levels of support, including readily available techniques, information about brain similarities and differences in LVCP individuals can be further studied. This initial study suggested decreased network segmentation and integration in LVCP individuals. Further imaging studies of LVCP individuals with larger samples will add to understanding of origins and effects of autism on brain function and behavior.

Melody Processing Characterizes Functional Neuroanatomy in the Aging Brain.

The functional neuroanatomical mechanisms underpinning cognition in the normal older brain remain poorly defined, but have important implications for understanding the neurobiology of aging and the impact of neurodegenerative diseases. Auditory processing is an attractive model system for addressing these issues. Here, we used fMRI of melody processing to investigate auditory pattern processing in normal older individuals. We manipulated the temporal (rhythmic) structure and familiarity of melodies in a passive listening, ‘sparse’ fMRI protocol. A distributed cortico-subcortical network was activated by auditory stimulation compared with silence; and within this network, we identified separable signatures of anisochrony processing in bilateral posterior superior temporal lobes; melodic familiarity in bilateral anterior temporal and inferior frontal cortices; and melodic novelty in bilateral temporal and left parietal cortices. Left planum temporale emerged as a ‘hub’ region functionally partitioned for processing different melody dimensions. Activation of Heschl’s gyrus by auditory stimulation correlated with the integrity of underlying cortical tissue architecture, measured using multi-parameter mapping. Our findings delineate neural substrates for analyzing perceptual and semantic properties of melodies in normal aging. Melody (auditory pattern) processing may be a useful candidate paradigm for assessing cerebral networks in the older brain and potentially, in neurodegenerative diseases of later life.

Differences in functional brain network connectivity during stories presented in audio, illustrated, and animated format in preschool-age children.

The American Academy of Pediatrics (AAP) recommends that parents begin reading to their children soon after birth, and limits on screen-based media. Benefits of traditional book-sharing are well documented in children, while cited deleterious effects of animated content on narrative processing are controversial. The influence of story format on underlying functional brain networks has not previously been studied. Thirty-three healthy children were recruited for this study via advertisement at an academic medical center, which involved functional magnetic resonance imaging (fMRI) at a single visit. Twenty-seven of them completed fMRI (82%; 15 boys, 12 girls; mean 58 ± 8months old). The fMRI protocol involved the presentation of 3 similar, unrhymed stories by the same author lasting 5min each in audio, illustrated, and animated format during separate runs, followed by a test of factual recall. Within- and between-network functional connectivity (FC) was compared across formats involving five functional networks, which were defined via literature review and refined via a data-driven parcellation method: visual perception, visual imagery, language, Default Mode (DMN), and cerebellar association. For illustration relative to audio, FC was decreased within the language network and increased between visual, DMN, and cerebellar networks, suggesting decreased strain on the language network afforded by pictures and visual imagery. Between-network connectivity was decreased for all networks for animation relative to the other formats, particularly illustration, suggesting a bias towards visual perception at the expense of network integration. These findings suggest substantial differences in functional brain network connectivity for animated and more traditional story formats in preschool-age children, reinforcing the appeal of illustrated storybooks at this age to provide efficient scaffolding for language, and suggesting novel neurobiological correlates of how functional networks may contribute to this process.

Functional MRI and delay discounting in patients infected with hepatitis C.

Hepatitis C virus-infected (HCV+) adults evidence increased rates of psychiatric and cognitive difficulties. This is the first study to use functional magnetic resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. To determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit differences in brain activation during a delay discounting task (DDT), a measure of one's tendency to choose smaller immediate rewards over larger delayed rewards-one aspect of impulsivity. Twenty adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. Mixed effects regression analyses of hard versus easy trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less activation in the left lateral occipital gyrus, precuneus, and superior frontal gyrus. There were also significant interactive effects for hard-easy contrasts in the bilateral medial frontal gyrus, left insula, left precuneus, left inferior parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a positive relationship between impulsivity and activation, while the HCV+ group exhibited a negative relationship. Within the HCV+ group, those with high viral load chose immediate rewards more often than those with low viral load, regardless of choice difficulty; those with low viral load chose immediate rewards more often on hard choices relative to easy choices. Results show that HCV+ patients exhibit greater impulsive behavior when presented with difficult choices, and impulsivity is negatively related to activation in regions important for cognitive control. Thus, interventions that decrease impulsive choice may be warranted with some HCV+ patients.

Prominent Changes in Cerebro-Cerebellar Functional Connectivity During Continuous Cognitive Processing.

While task-dependent responses of specific brain areas during cognitive tasks are well established, much less is known about the changes occurring in resting state networks (RSNs) in relation to continuous cognitive processing. In particular, the functional involvement of cerebro-cerebellar loops connecting the posterior cerebellum to associative cortices, remains unclear. In this study, 22 healthy volunteers underwent a multi-session functional magnetic resonance imaging (fMRI) protocol composed of four consecutive 8-min resting state fMRI (rs-fMRI) scans. After a first control scan, participants listened to a narrated story for the entire duration of the second rs-fMRI scan; two further rs-fMRI scans followed the end of story listening. The story plot was purposely designed to stimulate specific cognitive processes that are known to involve the cerebro-cerebellar loops. Almost all of the identified 15 RSNs showed changes in functional connectivity (FC) during and for several minutes after the story. The FC changes mainly occurred in the frontal and prefrontal cortices and in the posterior cerebellum, especially in Crus I-II and lobule VI. The FC changes occurred in cerebellar clusters belonging to different RSNs, including the cerebellar network (CBLN), sensory networks (lateral visual network, LVN; medial visual network, MVN) and cognitive networks (default mode network, DMN; executive control network, ECN; right and left ventral attention networks, RVAN and LVAN; salience network, SN; language network, LN; and working memory network, WMN). Interestingly, a k-means analysis of FC changes revealed clustering of FCN, ECN, and WMN, which are all involved in working memory functions, CBLN, DMN, and SN, which play a key-role in attention switching, and RSNs involved in visual imagery. These results show that the cerebellum is deeply entrained in well-structured network clusters, which reflect multiple aspects of cognitive processing, during and beyond the conclusion of auditory stimulation.

Ten Key Insights into the Use of Spinal Cord fMRI.

A comprehensive review of the literature-to-date on functional magnetic resonance imaging (fMRI) of the spinal cord is presented. Spinal fMRI has been shown, over more than two decades of work, to be a reliable tool for detecting neural activity. We discuss 10 key points regarding the history, development, methods, and applications of spinal fMRI. Animal models have served a key purpose for the development of spinal fMRI protocols and for experimental spinal cord injury studies. Applications of spinal fMRI span from animal models across healthy and patient populations in humans using both task-based and resting-state paradigms. The literature also demonstrates clear trends in study design and acquisition methods, as the majority of studies follow a task-based, block design paradigm, and utilize variations of single-shot fast spin-echo imaging methods. We, therefore, discuss the similarities and differences of these to resting-state fMRI and gradient-echo EPI protocols. Although it is newly emerging, complex connectivity and network analysis is not only possible, but has also been shown to be reliable and reproducible in the spinal cord for both task-based and resting-state studies. Despite the technical challenges associated with spinal fMRI, this review identifies reliable solutions that have been developed to overcome these challenges.

Trajectories of Alcohol Initiation and Use During Adolescence: The Role of Stress and Amygdala Reactivity

Early alcohol use initiation predicts onset of alcohol use disorders in adulthood. However, little is known about developmental trajectories of alcohol use initiation and their putative biological and environmental correlates. Adolescents (N= 330) with high or low familial loading for depression were assessed annually for up to 6 years. Data were collected assessing affective symptoms, alcohol use, and stress at each assessment. Adolescents also participated in a functional magnetic resonance imaging protocol that included measurement of threat-related amygdala and reward-related ventral striatum activity. Latent class analyses identified 2 trajectories of alcohol use initiation. Early initiators (n= 32) reported greater baseline alcohol use and rate of change of use compared with late initiators and/or current abstainers (n= 298). Early initiators reported higher baseline levels of stressful life events (p= .001) and exhibited higher amygdala (p= .001) but not ventral striatum activity compared with late initiators. Early initiators were 15.3 times more likely to have a full drink (p< .0001), 9.1 times more likely to experience intoxication (p< .0001), and 6.7 times more likely to develop an alcohol use disorder by 19 years of age compared with late initiators (p= .003). Adolescents on a trajectory of early alcohol use initiation have higher levels of stress, have increased threat-related amygdala activity, are more likely to consume a full standard alcoholic drink, are more likely to experience early intoxication, and are at a heightened risk for the onset of an alcohol use disorder.

Mouse fMRI under ketamine and xylazine anesthesia: Robust contralateral somatosensory cortex activation in response to forepaw stimulation

Mouse fMRI is critically useful to investigate functions of mouse models. Until now, the somatosensory-evoked responses in anesthetized mice are often widespread and inconsistent across reports. Here, we adopted a ketamine and xylazine mixture for mouse fMRI, which is relatively new anesthetics in fMRI experiments. Forepaw stimulation frequency was optimized using cerebral blood volume (CBV)-weighted optical imaging (n = 11) and blood-oxygenation-level dependent (BOLD) fMRI with a gradient-echo time of 16 ms at 9.4 T, and 4 Hz stimulation with 0.5 ms and 0.5 mA pulses induced the highest hemodynamic response. For 20-s 4-Hz unilateral forepaw stimulation, localized BOLD activity was consistently found in the contralateral primary forelimb somatosensory cortex (S1FL), while no significant change was observed in the ipsilateral S1FL. The mean magnitude was 1.44 ± 0.20% SEM (n = 9) in the contralateral S1FL and 0.69 ± 0.10% in the contralateral thalamus. The variability of evoked fMRI responses across sessions was investigated by comparing with resting state fMRI (rsfMRI) functional connectivity (FC). Evoked responses in S1FL were correlated positively with rsfMRI FC between bilateral S1FL (r = 0.63 to 0.69) and negatively with FC between S1FL and the anterior cingulate cortex (r = −0.50 to −0.57), suggesting that rsfMRI FC is a good index of the evoked fMRI response and anesthetized animal condition. Finally, three weekly fMRI scans were performed in 5 mice, and localized activity was reproducibly observed in S1FL, with a success rate of 70–95%. In summary, our developed fMRI protocol can be used for mapping functions of mouse models.

Short- and long-term reliability of language fMRI

When using functional magnetic resonance imaging (fMRI) for mapping important language functions, a high test-retest reliability is mandatory, both in basic scientific research and for clinical applications. We, therefore, systematically tested the short- and long-term reliability of fMRI in a group of healthy subjects using a picture naming task and a sparse-sampling fMRI protocol. We hypothesized that test-retest reliability might be higher for (i) speech-related motor areas than for other language areas and for (ii) the short as compared to the long intersession interval.16 right-handed subjects (mean age: 29 years) participated in three sessions separated by 2–6 (session 1 and 2, short-term) and 21–34 days (session 1 and 3, long-term). Subjects were asked to perform the same overt picture naming task in each fMRI session (50 black-white images per session). Reliability was tested using the following measures: (i) Euclidean distances (ED) between local activation maxima and Centers of Gravity (CoGs), (ii) overlap volumes and (iii) voxel-wise intraclass correlation coefficients (ICCs). Analyses were performed for three regions of interest which were chosen based on whole-brain group data: primary motor cortex (M1), superior temporal gyrus (STG) and inferior frontal gyrus (IFG).Our results revealed that the activation centers were highly reliable, independent of the time interval, ROI or hemisphere with significantly smaller ED for the local activation maxima (6.45 ± 1.36 mm) as compared to the CoGs (8.03 ± 2.01 mm). In contrast, the extent of activation revealed rather low reliability values with overlaps ranging from 24% (IFG) to 56% (STG). Here, the left hemisphere showed significantly higher overlap volumes than the right hemisphere. Although mean ICCs ranged between poor (ICC<0.5) and moderate (ICC 0.5–0.74) reliability, highly reliable voxels (ICC>0.75) were found for all ROIs. Voxel-wise reliability of the different ROIs was influenced by the intersession interval.Taken together, we could show that, despite of considerable ROI-dependent variations of the extent of activation over time, highly reliable centers of activation can be identified using an overt picture naming paradigm.

From percept to concept in the ventral temporal lobes: Graded hemispheric specialisation based on stimulus and task

The left and right ventral anterior temporal lobes (vATL) have been implicated as key regions for the representation of conceptual knowledge. However, the nature and degree of hemispheric specialisation in their function is unclear. To address this issue, we investigated hemispheric specialisation in the ventral temporal lobes using a distortion-corrected spin-echo fMRI protocol that enhanced signal in vATL. We employed an orthogonal manipulation of stimulus (written words vs pictured objects) and task (naming vs recognition). Words elicited left-lateralised vATL activation while objects elicited bilateral activation with no hemispheric bias. In contrast, posterior ventral temporal cortex exhibited a rightward bias for objects as well as a leftward bias for words. Naming tasks produced left-lateralised activation in vATL while activity for recognition was equal in left and right vATLs. These findings are incompatible with proposals that left and right ATLs are strongly modular in function, since these predict rightward as well as leftward biases. Instead, they support an alternative model in which (a) left and right ATL together form a bilateral, integrated system for the representation of concepts and (b) within this system, graded hemispheric specialisation emerges as a consequence of differential connectivity with other neural systems. On this view, greater left vATL activation for written word processing develops as a consequence of the inputs this region receives from left-lateralised visual word processing system in posterior temporal cortex. Greater left vATL activation during naming tasks is most likely due to connectivity with left-lateralised speech output systems in prefrontal and motor cortices.