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Semantic verbal fluency brain network: delineating a physiological basis for the functional hubs using dual-echo ASL and graph theory approach
Journal of Neural Engineering
Abstract
Objective:
Semantic verbal fluency (SFV) is a cognitive process that engages and modulates specific brain areas related to language comprehension and production, decision making, response inhibition, and memory retrieval. The impairment of the brain network responsible for these functions is related to various neurological conditions, and different strategies have been proposed to assess SVF-related deficits in such diseases. In the present study, the concomitant changes of brain perfusion and functional connectivity were investigated during the resting state and SVF task performance.
Approach:
Arterial Spin Labeling, a perfusion-based magnetic resonance imaging (MRI) method, was used with a pseudocontinuous labeling approach and dual-echo readout in twenty-eight healthy right-handed Brazilian Portuguese speakers. The acquisition was performed in a resting state condition and during the performance of a semantic verbal fluency task.
Main results:
During task performance, a significant increase in CBF was observed in language-related regions of the frontal lobe, including Brodmann's areas (BA) 6, 9, 45, and 47, associated with semantic processing, word retrieval, and speech motor programming. Such regions, along with the posterior cingulate, showed a crucial role in the SVF functional network, assessed by seed-to-voxel and graph analysis. Our approach successfully overcame the generalization problem regarding functional MRI (fMRI) graph analysis with cognitive, task-based paradigms. Moreover, the CBF maps enabled the functional assessment of orbital frontal and temporal regions commonly affected by magnetic susceptibility artifacts in conventional T2*-weighted fMRI approaches.
Significance:
Our results demonstrated the capability of ASL to evaluate perfusion alterations and functional patterns simultaneously regarding the SVF network providing a quantitative physiological basis to functional hubs in this network, which may support future clinical studies.
... Changes in brain perfusion and functional MRI connectivity during resting state and the performance of an SVF task were evaluated in healthy controls, showing the involvement of prefrontal cortex regions such as Brodmann's areas 6, 9, 45, and 47, and posterior cingulate, all them shown to have essential roles in the SVF functional network, assessed by seed-to-voxel and graph analysis (Paschoal et al. 2021). In clinical settings, children with high-functioning autism spectrum disorder presented hypoconnectivity in the prefrontal cortex during the performance of a verbal fluency task (Chan et al. 2022). ...
Semantic verbal fluency (SVF) impairment is present in several neurological disorders. Although activation in SVF-related areas has been reported, how these regions are connected and their functional roles in the network remain divergent. We assessed SVF static and dynamic functional connectivity (FC) and effective connectivity in healthy participants using functional magnetic resonance imaging. We observed activation in the inferior frontal (IFG), middle temporal (pMTG) and angular gyri (AG), anterior cingulate (AC), insular cortex, and regions of the superior, middle, and medial frontal gyri (SFG, MFG, MidFG). Our static FC analysis showed a highly interconnected task and resting state network. Increased connectivity of AC with the pMTG and AG was observed for the task. The dynamic FC analysis provided circuits with connections similarly modulated across time and regions related to category identification, language comprehension, word selection and recovery, word generation, inhibition of speaking, speech planning, and articulatory planning of orofacial movements. Finally, the effective connectivity analysis provided a network that best explained our data, starting at the AG and going to the pMTG, from which there was a division between the ventral and dorsal streams. The SFG and MFG regions were connected and modulated by the MidFG, while the inferior regions formed the ventral stream. Therefore, we successfully assessed the SVF network, exploring regions associated with the entire processing, from category identification to word generation. The methodological approach can be helpful for further investigation of the SVF network in neurological disorders.
... Previous studies have found a significant increase in cerebral blood flow of languagerelated areas in the frontal lobe, including the BA 6/9/45/47, which was related to semantic processing, word retrieval, and speech motor programming through task-based functional magnetic resonance imaging and cerebral blood flow monitoring research. 32 The post-processing of episodic For patients with post-stroke aphasia (PSA) before and after treatment, we conducted whole-brain voxel functional connectivity analysis using the left posterior inferior temporal gyrus as the seed. a) Shows the increased area (RCA) connected with the left posterior inferior temporal gyrus (brownish yellow); b) RCA (red), BA 9 (green), BA 46 (blue), and BA 44 (yellow) are highlighted. ...
Objectives:
This study aimed to longitudinally observe the improvement mechanism of semantic fluency in subacute post-stroke aphasia (PSA) patients using resting-state functional magnetic resonance imaging (rs-fMRI).
Methods:
Twelve PSA patients, about one month after onset, were enrolled in this study and received speech-language therapy (SLT) for one month. Auditory comprehension and semantic fluency were evaluated using the Western Aphasia Battery (WAB) and the Animal Fluency Test. Before and after treatment, rs-fMRI data were collected, and the dice similarity coefficient was used to measure the spatial similarity between each patient's lesion and a reference lesion. The left posterior inferior temporal gyrus (pITG) was used as a seed to calculate the normalized functional connectivity in whole-brain voxel analysis using DPABI software for statistical analysis.
Results:
The dice similarity coefficient between each patient's lesion and the reference lesion showed moderate to high intensity (0.57 ± 0.14) in the Montreal Neurological Institute space. After treatment, we found a significant increase in functional connectivity between the left pITG and the right prefrontal lobe convergence area (peak t = 8.219, Gaussian random field multiple comparison correction, voxel p < 0.001, cluster p < 0.05). The increase in functional connectivity was negatively correlated with the improvement in auditory comprehension (r =-0.707, p = 0.033) and positively correlated with the improvement in semantic fluency (r = 0.79, p = 0.02).
Conclusion:
The improvement of semantic fluency in subacute PSA patients may require the participation of the right convergence area of the prefrontal lobe.
... Evidence from functional connectivity studies shows that the semantic VF task involves prefrontal functional connectivity changes. Specifically, a left-lateralized increase in connections accompanied by an increase in cerebral blood flow at superior (BA6), middle (BA6) and inferior (BA9,45,47) frontal gyri has been shown during the semantic VF task when compared to baseline (Paschoal et al., 2021). Multiple lines of evidence from lesion studies show that functional segregation for the medial and lateral prefrontal cortex (PFC) is evident for semantic VF. ...
Children with autism spectrum disorder (ASD) show marked difficulties in reading comprehension, a complex cognitive skill fundamental to successful daily functioning that is associated with core executive functions. However, the neurophysiological mechanisms underlying reading comprehension deficits in these children remain elusive. Twenty-one right-handed males with high-functioning ASD (mean age = 10.24 years) and 23 age-, IQ-, educational level-, sex- and handedness-matched typically developing (TD; mean age = 10.14 years) individuals underwent a reading comprehension test and the semantic verbal fluency test that tapped core executive functions underlying reading comprehension during concurrent prefrontal functional near-infrared spectroscopy (fNIRS) measurement. Participants’ information processing efficiency was also assessed. High-functioning ASD children exhibited general reading comprehension [main effect of group: F(1,40) = 7.58, p = 0.009], selective verbal fluency deficits [Group × category interaction: F(1,42) = 4.90, p = 0.032] and slower processing speed (t42 = 2.36, p = 0.023). Regarding the hemodynamics of the prefrontal cortex (PFC), although ASD individuals showed comparable patterns of PFC brain activation to their healthy counterparts, lower PFC intrahemispheric [main effect of group: F(1,42) = 11.36, p = 0.002] and interhemispheric [main effect of group: F(1,42) = 7.79, p = 0.008] functional connectivity were evident during the semantic verbal fluency test. At the whole-group level, poorer reading comprehension performance was associated with poorer performance in the semantic verbal fluency test (r42 = 0.508, p < 0.001). Moreover, poorer semantic verbal fluency test performance was associated with slower information processing speed (r42 = –0.312, p = 0.044), which is associated with reduced left medial PFC functional connectivity (r42 = –0.319, p = 0.040). Abnormal intrahemispheric and interhemispheric prefrontal hypoconnectivity is associated with deficits in executive processes essential for reading comprehension in ASD. Our study has provided important implications for the neuropsychological and neurophysiological mechanisms underlying reading comprehension deficits in ASD.
Background:
The brain activation patterns of mild cognitive impairment (MCI) are still unclear and they involve multiple brain regions. Most previous studies have focused on abnormal activation in the frontal and temporal lobes, with few investigating the entire brain.
Objective:
To identify and compare the changes in cerebral hemodynamics and abnormal activation patterns in the entire brain of MCI patients and healthy older adults.
Methods:
Patients with MCI (n = 22) and healthy controls (HC, n = 34) matched by age, education levels, sex, and mental state were enrolled. They performed the same letter and category verbal fluency test (VFT) tasks while their behavioral performance and global cerebral hemodynamics were analyzed.
Results:
The performance during the category VFT task was significantly better than that during the letter VFT task across all participants (HC: correct: p < 0.001; intrusions: p < 0.001; MCI: correct: p < 0.001; intrusions: p < 0.001). The number of correct words during the letter and category VFT tasks was significantly higher in the HC group than in the MCI group (p < 0.001). The deoxygenated-hemoglobin (HbR) concentrations in the left parietal lobule (p = 0.0352) and left inferior parietal lobule (p = 0.0314) were significantly different during the category VFT task.
Conclusion:
The differences between HC and MCI groups were greater in the category task. The HbR concentration was more sensitive for the category VFT task and concentration changes in the left parietal lobule and left inferior parietal lobule may be useful for clinical screening and application; thus, they deserve more attention.
Arterial Spin Labeling (ASL) is a noninvasive MRI-based method to measure cerebral blood flow (CBF). Recently, the study of ASL as a functional tool has emerged once CBF fluctuation comes from capillaries in brain tissue, giving a more spatially specific response when compared to the standard functional MRI method, based on the blood oxygenation level-dependent (BOLD) contrast. Although the BOLD effect could be desirable to study brain function, if one aims to quantify CBF, such effect is considered contamination that can be more attenuated if short TE value is used in the image acquisition. An approach that provides both CBF and function information in a simultaneous acquisition is the use of a dual-echo ASL (DE-ASL) readout. Our purpose was to evaluate the information provided by DE-ASL regarding CBF quantification and functional connectivity with a motor task. Pseudocontinuous ASL of twenty healthy subjects (age: 32.4 ± 10.2 years, 13 male) was acquired at a 3T scanner. We analyzed the influence of TE on CBF values and brain connectivity provided by CBF and concurrent BOLD (cc-BOLD) time series. Brain networks were obtained by the general linear model and independent component analysis. Connectivity matrices were generated using a bivariate correlation (Fisher Z values). No effect of the sequence readout, but significant effect of the TE value, was observed on gray matter CBF values. Motor networks with reduced extension and more connections with important regions for brain integration were observed for CBF data acquired with short TE, proving its higher spatial specificity. Therefore, it was possible to use a dual-echo readout provided by a standard commercial ASL pulse sequence to obtain reliable quantitative CBF values and functional information simultaneously.
We describe frontal language reorganization in a 50–60 year-old right-handed patient with a low-grade left frontotemporal insular glioma. Pre-operative fMRI revealed robust activation in the left superior temporal gyrus (Wernicke Area, WA) and in the right inferior frontal gyrus (right anatomical homolog of Broca Area, BA). Intra-operative cortical stimulation of the left inferior frontal gyrus and adjacent cortices elicited no speech deficits, and gross total resection including the expected location of BA resulted in no speech impairment. We employed statistical inference methods to reconstruct the functional brain network and determined how different brain areas connect with one another. We found that the right homolog of the BA in this patient functionally connected to the same areas as the left BA in a typical healthy control. As opposed to the functional connection of the left BA in a healthy brain, the right BA did not connect directly with the left WA, but connected indirectly, mediated by the pre-Supplementary Motor Area and the Middle Frontal Gyrus. This case illustrates that pre-surgical fMRI may be used to identify atypical hemispheric language reorganization in the presence of brain tumor and that network theory opens the possibility for future insight into the neural mechanism underlying the language reorganization.
Verbal and figural fluency are related to executive functions (EFs), but the extent to which they benefit from executive resources and their respective cortical representations is not clear. Moreover, different brain areas and cognitive functions are involved in fluency processing. This study investigated effects of modulation of cortical excitability in the left dorsolateral prefrontal cortex (l-DLPFC), left temporal area and right posterior parietal cortex (r-PPC) with transcranial direct current stimulation (tDCS), on verbal and figural fluency. Fifteen healthy adult participants received anodal l-DLPFC (F3), anodal left temporal (T3), anodal r-PPC (P4) and sham tDCS (15 min, 1.5 mA). After five minutes of stimulation, participants underwent the verbal fluency (i.e., semantic and phonemic fluency tasks) and figural fluency tasks. Participants significantly generated more words with phonemic cues during anodal l-DLPFC tDCS and more words with semantic cues during both anodal left temporal and anodal l-DLPFC tDCS. In contrast, they generated more unique figures under anodal r-PPC and anodal l-DLPFC tDCS. Our results implicate that prefrontal regions and EFs are shared anatomical correlates and cognitive processes relevant for both, verbal and figural fluency (supramodal contribution of DLPFC activation), whereas r-PPC and left temporal cortex are more specifically involved in figural and semantic fluency (modality-specific contribution).
In this study, we examine the development of orthographic networks in the mental lexicon using graph theory. According to this view, words are represented by nodes in a network and connected as a function of their orthographic similarity. With a sampling approach based on a language corpus for German school children, we were able to simulate lexical development for children from Grade 1–8. By sampling different lexicon sizes from the corpus, we were able to analyze the content of the orthographic lexicon at different time points and examined network characteristics using graph theory. Results show that, similar to semantic and phonological networks, orthographic networks possess small-word characteristics defined by short average path lengths between nodes and strong local clustering. Moreover, the interconnectivity of the network decreases with growth. Implications for the study of the effect of network measures on language processing are discussed.
Typical simultaneous blood oxygenation-level dependent (BOLD) and arterial spin labeling (ASL) sequences acquire two echoes, one perfusion-sensitive and one BOLD-sensitive. However, for ASL, spatial resolution and brain coverage are limited due to the T1 decay of the labeled blood. This study applies a sequence combining a multiband acquisition with four echoes for simultaneous BOLD and pseudo-continuous ASL (pCASL) echo planar imaging (MBME ASL/BOLD) for block-design task-fMRI. A multiband acceleration of four was employed to increase brain coverage and reduce slice-timing effects on the ASL signal. Multi-echo independent component analysis (MEICA) was implemented to automatically denoise the BOLD signal by regressing non-BOLD components. This technique led to increased temporal signal-to-noise ratio (tSNR) and BOLD sensitivity. The MEICA technique was also modified to denoise the ASL signal by regressing artifact and BOLD signals from the first echo time-series. The MBME ASL/BOLD sequence was applied to a finger-tapping task functional MRI (fMRI) experiment. Signal characteristics and activation were evaluated using single echo BOLD, combined ME BOLD, combined ME BOLD after MEICA denoising, perfusion-weighted (PW), and perfusion-weighted after MEICA denoising time-series. The PW data was extracted using both surround subtraction and high-pass filtering followed by demodulation. In addition, the CBF/BOLD response ratio and CBF/BOLD coupling were analyzed. Results showed that the MEICA denoising procedure significantly improved the BOLD signal, leading to increased BOLD sensitivity, tSNR, and activation statistics compared to conventional single echo BOLD data. At the same time, the denoised PW data showed increased tSNR and activation statistics compared to the non-denoised PW data. CBF/BOLD coupling was also increased using the denoised ASL and BOLD data. Our preliminary data suggest that the MBME ASL/BOLD sequence can be employed to collect whole-brain task-fMRI with improved data quality for both BOLD and PW time series, thus improving the results of block-design task fMRI.
Subtle semantic deficits can be observed in Alzheimer's disease (AD) patients even in the early stages of the illness. In this work, we tested the hypothesis that the semantic control network is deregulated in mild AD patients. We assessed the integrity of the semantic control system using resting-state functional magnetic resonance imaging in a cohort of patients with mild AD (n = 38; mean Mini-Mental State Examination=20.5) and in a group of age-matched healthy controls (n = 19). Voxel-wise analysis spatially constrained in the left fronto-temporal semantic control network identified two regions with altered functional connectivity in AD patients, specifically in the pars opercularis (POp, BA44) and in the posterior middle temporal gyrus (pMTG, BA21). Using whole-brain seed-based analysis, we demonstrated that these two regions have altered functional connectivity even beyond the semantic control network. In particular, the pMTG displayed a wide-distributed pattern of lower connectivity to several brain regions involved in language-semantic processing, along with a possibly compensatory higher connectivity to the Wernicke's area. We conclude that in mild AD brain regions belonging to the semantic control network are abnormally connected not only within the network, but also to other areas known to be critical for language processing.
The brain is constantly monitoring and integrating both cues from the external world and signals generated intrinsically. These extrinsically and intrinsically-driven neural processes are thought to engage anatomically distinct regions, which are thought to constitute the extrinsic and intrinsic systems of the brain. While the specialization of extrinsic and intrinsic system is evident in primary and secondary sensory cortices, a systematic mapping of the whole brain remains elusive. Here, we characterized the extrinsic and intrinsic functional activities in the brain during naturalistic movie-viewing. Using a novel inter-subject functional correlation (ISFC) analysis, we found that the strength of ISFC shifts along the hierarchical organization of the brain. Primary sensory cortices appear to have strong inter-subject functional correlation, consistent with their role in processing exogenous information, while heteromodal regions that attend to endogenous processes have low inter-subject functional correlation. Those brain systems with higher intrinsic tendency show greater inter-individual variability, likely reflecting the aspects of brain connectivity architecture unique to individuals. Our study presents a novel framework for dissecting extrinsically- and intrinsically-driven processes, as well as examining individual differences in brain function during naturalistic stimulation.
Semantic cognition, i.e. processing of meaning is based on semantic representations and their controlled retrieval. Semantic control has been shown to be implemented in a network that consists of left inferior frontal (IFG), and anterior and posterior middle temporal gyri (a/pMTG). We aimed to disrupt semantic control processes with continuous theta burst stimulation (cTBS) over left IFG and pMTG and to study whether behavioral effects are moderated by induced alterations in resting-state functional connectivity. To this end, we applied real cTBS over left IFG and left pMTG as well as sham stimulation on 20 healthy participants in a within-subject design. Stimulation was followed by resting-state functional magnetic resonance imaging and a semantic priming paradigm. Resting-state functional connectivity of regions of interest in left IFG, pMTG and aMTG revealed highly interconnected left-lateralized fronto-temporal networks representing the semantic system. We did not find any significant direct modulation of either task performance or resting-state functional connectivity by effective cTBS. However, after sham cTBS, functional connectivity between IFG and pMTG correlated with task performance under high semantic control demands in the semantic priming paradigm. These findings provide evidence for the functional relevance of interactions between IFG and pMTG for semantic control processes. This interaction was functionally less relevant after cTBS over aIFG which might be interpretable in terms of an indirect disruptive effect of cTBS.
A comprehensive literature review was performed on Intravoxel incoherent motion (IVIM) magnetic resonance imaging technique and its application for liver. Heterogeneous data have been reported. IVIM parameters are magnetic field strength dependent to a mild extent. A lower Dslow (D) value at 3T than at 1.5T and higher PF (F) value at 3T than at 1.5T was noted. An increased number of b values are associated with increased IVIM parameter measurement accuracy. With the current status of art, IVIM technique is not yet capable of detecting early stage liver fibrosis and diagnosing liver fibrosis grades, nor can it differentiate liver tumors. Though IVIM parameters show promise for tumor treatment monitoring, till now how parameters of PF and Dfast(D*) add diagnostic value to Dslow or ADC (apparent diffusion coefficient) remains unclear. More works to improve the measurement robustness are warranted as they are essential to justify follow-up clinical studies on patients.
Until now, several branches of research have fundamentally contributed to a better understanding of the ramifications of bilingualism, multilingualism, and language expertise on psycholinguistic-, cognitive-, and neural implications. In this context, it is noteworthy to mention that from a cognitive perspective, there is a strong convergence of data pointing to an influence of multilingual speech competence on a variety of cognitive functions, including attention, short-term- and working memory, set shifting, switching, and inhibition. In addition, complementary neuroimaging findings have highlighted a specific set of cortical and subcortical brain regions which fundamentally contribute to administrate cognitive control in the multilingual brain, namely Broca's area, the middle-anterior cingulate cortex, the inferior parietal lobe, and the basal ganglia. However, a disadvantage of focusing on group analyses is that this procedure only enables an approximation of the neural networks shared within a population while at the same time smoothing inter-individual differences. In order to address both commonalities (i.e., within group analyses) and inter-individual variability (i.e., single-subject analyses) in language control mechanisms, here I measured five professional simultaneous interpreters while the participants overtly translated or repeated sentences with a simple subject-verb-object structure. Results demonstrated that pars triangularis was commonly activated across participants during backward translation (i.e., from L2 to L1), whereas the other brain regions of the “control network” showed a strong inter-individual variability during both backward and forward (i.e., from L1 to L2) translation. Thus, I propose that pars triangularis plays a crucial role within the language-control network and behaves as a fundamental processing entity supporting simultaneous language translation.
Previous studies showed that the anterior cingulate cortex (ACC) plays a role in selective visual attention. The current study further examined the role of the ACC in attention using a visual cuing task with task-relevant and task-irrelevant stimuli. On every trial, 2 stimuli were presented on the touchscreen; 1 was task-relevant and the other was task-irrelevant. Rats were trained to attend to the task-relevant stimulus over the task-irrelevant stimulus to determine which side of the touchscreen should be selected for reward. After the rats were well-trained, cannulas targeting the ACC were implanted bilaterally for infusions of PBS or muscimol. When the ACC was functionally intact, high task performance was correlated with the anticipatory touches toward the reward; rats touched the stimulus proximal to the correct side more often, regardless of its task-relevancy. Analysis of the presurgery training data showed that rats developed anticipatory touches during training. Linear discriminant analyses of the touches also showed that the touches predict rats' choices in trials. With muscimol infusions, choice accuracy was impaired and the anticipatory touches toward the correct response location were less frequent. A control experiment, in which there were no irrelevant stimuli, showed no effects of ACC inactivation on choice accuracy or anticipatory touches. These results indicate that the rat ACC plays a critical role in reducing distraction from irrelevant stimuli as well as in guiding attention toward the goal locations. (PsycINFO Database Record
Background:
The ability to recognize, understand and interpret other's actions and emotions has been linked to the mirror system or action-observation-network (AON). Although variations in these abilities are prevalent in the neuro-typical population, persons diagnosed with autism spectrum disorders (ASD) have deficits in the social domain and exhibit alterations in this neural network.
Method:
Here, we examined functional network properties of the AON using graph theory measures and region-to-region functional connectivity analyses of resting-state fMRI-data from adolescents and young adults with ASD and typical controls (TC).
Results:
Overall, our graph theory analyses provided convergent evidence that the network integrity of the AON is altered in ASD, and that reductions in network efficiency relate to reductions in overall network density (i.e., decreased overall connection strength). Compared to TC, individuals with ASD showed significant reductions in network efficiency and increased shortest path lengths and centrality. Importantly, when adjusting for overall differences in network density between ASD and TC groups, participants with ASD continued to display reductions in network integrity, suggesting that also network-level organizational properties of the AON are altered in ASD.
Conclusion:
While differences in empirical connectivity contributed to reductions in network integrity, graph theoretical analyses provided indications that also changes in the high-level network organization reduced integrity of the AON.
Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients.
This review paper provides analyses confirming correlation between various brain regions activity, particularly its prefrontal portions, and schizophrenia patients’ performance in verbal fluency tests. Various factors modifying patients’ performance in the aforementioned tasks were singled out and discussed. Systematically we have reviewed the results of non-verbal fluency tests conducted in the schizophrenic patients. The authors also summarizes findings of earlier studies stressing the role of semantic fluency as a predictor of first-episode psychosis.Verbal and non-verbal fluency tests engage complex cognitive processes and executive functions in patients. As a result, the interpretation of their results is often complicated and requires special competences. The tests are popular neuropsychological tools used for assessment of verbal memory, executive functions, visual-spatial abilities and psychomotor speed in patients with mental and neurological disorders. The aim of this paper is to discuss diagnostic tools used for measuring both types of fluency (verbal and non-verbal), test interpretation methods, as well as their usefulness in clinical diagnostics and scientific research.
Semantic verbal fluency test is an important cognitive measure, broadly used in the neuropsychological assessment of the elderly, however its standards scores are less informative than what this task can provide. Graph theory represents a promising tool to understand a variety of neuropsychological states and this study presents a graph analysis of data generated by the semantic verbal fluency test in cognitive health elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic (aMCI) and amnestic multiple domain (a+mdMCI) - and Alzheimer’s disease (AD). The groups were compared when divided in three (NC – MCI – AD) and four groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, in the graph measures of diameter, the average shortest path, and on the density of the network. The graph measures also sorted the elderly in their groups with good specificity and sensitivity. When the four groups were compared the graph measures revealed significant difference between the groups in the density of the network, except between the two MCI subtypes and NC and aMCI. The diameter of the network and average shortest path were significant different between the NC and AD an aMCI and AD. Again the graph analysis sorted the elderly in their groups with good specificity and sensitivity, being better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of the semantic memory through the verbal fluency task, amplifying the predictive power of this test. The clinical use of graph analysis may likely give an important contribution to the differential diagnosis on elderly, helping in precocious diagnosis, and, consequently, improving prognosis.
In humans, the most obvious functional lateralization is the specialization of the left hemisphere for language. Therefore, the involvement of the right hemisphere in language is one of the most remarkable findings during the last two decades of fMRI research. However, the importance of this finding continues to be underestimated. We examined the interaction between the two hemispheres and also the role of the right hemisphere in language. From two seeds representing Broca's area, we conducted a seed correlation analysis (SCA) of resting state fMRI data and could identify a resting state network (RSN) overlapping to significant extent with a language network that was generated by an automated meta-analysis tool. To elucidate the relationship between the clusters of this RSN, we then performed graph theoretical analyses (GTA) using the same resting state dataset. We show that the right hemisphere is clearly involved in language. A modularity analysis revealed that the interaction between the two hemispheres is mediated by three partitions: A bilateral frontal partition consists of nodes representing the classical left sided language regions as well as two right-sided homologs. The second bilateral partition consists of nodes from the right frontal, the left inferior parietal cortex as well as of two nodes within the posterior cerebellum. The third partition is also bilateral and comprises five regions from the posterior midline parts of the brain to the temporal and frontal cortex, two of the nodes are prominent default mode nodes. The involvement of this last partition in a language relevant function is a novel finding.
Testing of verbal fluency is currently part of standard presurgical neuropsychological assessment for patients with focal epilepsy. However, to date no systematic review has been conducted on semantic (SVF) and phonemic verbal fluency (PVF) in this patient group. The present review compares verbal fluency between healthy control subjects and subgroups of adult presurgical patients with focal epilepsy according to lateralisation and localisation of the dysfunction. PubMed was searched with a comprehensive search string. Abstracts of all studies and full-texts of potentially relevant studies were screened. Study quality was assessed by independent raters according to predefined criteria. 39 studies were included. Meta-analyses were performed to compare SVF and PVF across groups of patients with temporal (TLE) and frontal lobe epilepsy (FLE) as well as healthy controls (HC). Both patients with left- and right sided TLE were impaired on SVF and PVF compared to HC. Patients with left-sided TLE were slightly more impaired than patients with right-sided TLE. Patients with FLE showed a larger impairment in PVF than patients with TLE, whereas on SVF there was no difference between FLE and TLE. For TLE comparisons the study pool seems to have been sufficient, whereas more studies are needed to verify results for FLE. Semantic verbal fluency might not differentiate between FLE and TLE. While verbal fluency impairment was anticipated, especially in left-sided TLE and FLE patients, the impairment in patients with right-sided TLE was larger than expected. Results are discussed with regard to neuropsychological theory and practice.
The processing of verbal fluency tasks relies on the coordinated activity of a number of brain areas, particularly in the frontal and temporal lobes of the left hemisphere. Recent studies using functional magnetic resonance imaging (fMRI) to study the neural networks subserving verbal fluency functions have yielded divergent results especially with respect to a parcellation of the inferior frontal gyrus for phonemic and semantic verbal fluency. We conducted a coordinate-based activation likelihood estimation (ALE) meta-analysis on brain activation during the processing of phonemic and semantic verbal fluency tasks involving 28 individual studies with 490 healthy volunteers.
For phonemic as well as for semantic verbal fluency, the most prominent clusters of brain activation were found in the left inferior/middle frontal gyrus (LIFG/MIFG) and the anterior cingulate gyrus. BA 44 was only involved in the processing of phonemic verbal fluency tasks, BA 45 and 47 in the processing of phonemic and semantic fluency tasks.
Our comparison of brain activation during the execution of either phonemic or semantic verbal fluency tasks revealed evidence for spatially different activation in BA 44, but not other regions of the LIFG/LMFG (BA 9, 45, 47) during phonemic and semantic verbal fluency processing.
It has been increasingly believed that attention-deficit hyperactivity disorder (ADHD) is a disorder with lifelong course associated with cognitive difficulties including among others, language production, verbal learning, and verbal fluency. However, research is limited to children and adolescents, and very few researchers have examined the impact of ADHD in adulthood on the cognitive domain. The aim of the present study is to examine the performance of adults, diagnosed with ADHD in childhood, on semantic and phonemic verbal fluency tasks. It is hypothesized that adults with ADHD will perform worse on both tasks than matched controls. Sixty university students (30 diagnosed with ADHD in childhood and 30 matched controls) of mean age 20.5 participated in the study. They all completed two verbal fluency tasks. The ADHD group had statistically significant lower scores than the non-ADHD group on the phonemic, but not the semantic task. The study provides some evidence that ADHD in childhood has a negative impact on adults' phonemic verbal fluency. This finding could be probably explained by the fact that phonemic fluency is considered more cognitively demanding and impacting more on the frontal lobe functions, known to be impaired in ADHD, than semantic fluency.
The verbal fluency test (VFT) can be dissociated into "clustering" (generating words within subcategories) and "switching" (shifting between clusters), which may be valuable in differential diagnosis. In the current study, we investigated the validity of VFT in the differential diagnosis of Alzheimer's disease (AD, n = 65), vascular dementia (VaD, n = 65), mild cognitive impairment (MCI, n = 92), and vascular cognitive impairment without dementia (VCIND, n = 76) relative to cognitively normal senior controls (NC, n = 374). We found that in the NC group, the total correct score was significantly correlated with age and education; males generated more subcategories; cluster size increased with education, and subcategory and switching decreased with age. A significantly progressive advantage was observed in VFT scores in the sequence NC > MCI/VCIND > AD/VaD, and this significantly discriminated dementia patients from the other groups. AD patients performed better in all four VFT scores than VaD patients. Subcategory and switching scores significantly distinguished AD from VaD patients (AD > VaD; mean difference, 0.50 for subcategory, P <0.05; 0.71 for switching, P <0.05). MCI patients scored higher than VCIND patients, but the difference did not reach statistical significance. These results suggest that semantic VFT is useful for the detection of MCI and VCIND, and in the differential diagnosis of cognitive impairment.
Human brain functional networks contain a few densely connected hubs that play a vital role in transferring information across regions during resting and task states. However, the relationship of these functional hubs to measures of brain physiology, such as regional cerebral blood flow (rCBF), remains incompletely understood. Here, we used functional MRI data of blood-oxygenation-level-dependent and arterial-spin-labeling perfusion contrasts to investigate the relationship between functional connectivity strength (FCS) and rCBF during resting and an N-back working-memory task. During resting state, functional brain hubs with higher FCS were identified, primarily in the default-mode, insula, and visual regions. The FCS showed a striking spatial correlation with rCBF, and the correlation was stronger in the default-mode network (DMN; including medial frontal-parietal cortices) and executive control network (ECN; including lateral frontal-parietal cortices) compared with visual and sensorimotor networks. Moreover, the relationship was connection-distance dependent; i.e., rCBF correlated stronger with long-range hubs than short-range ones. It is notable that several DMN and ECN regions exhibited higher rCBF per unit connectivity strength (rCBF/FCS ratio); whereas, this index was lower in posterior visual areas. During the working-memory experiment, both FCS-rCBF coupling and rCBF/FCS ratio were modulated by task load in the ECN and/or DMN regions. Finally, task-induced changes of FCS and rCBF in the lateral-parietal lobe positively correlated with behavioral performance. Together, our results indicate a tight coupling between blood supply and brain functional topology during rest and its modulation in response to task demands, which may shed light on the physiological basis of human brain functional connectome.
Resting state functional connectivity reveals intrinsic, spontaneous networks that elucidate the functional architecture of the human brain. However, valid statistical analysis used to identify such networks must address sources of noise in order to avoid possible confounds such as spurious correlations based on non-neuronal sources. We have developed a functional connectivity toolbox Conn ( www.nitrc.org/projects/conn ) that implements the component-based noise correction method (CompCor) strategy for physiological and other noise source reduction, additional removal of movement, and temporal covariates, temporal filtering and windowing of the residual blood oxygen level-dependent (BOLD) contrast signal, first-level estimation of multiple standard functional connectivity magnetic resonance imaging (fcMRI) measures, and second-level random-effect analysis for resting state as well as task-related data. Compared to methods that rely on global signal regression, the CompCor noise reduction method allows for interpretation of anticorrelations as there is no regression of the global signal. The toolbox implements fcMRI measures, such as estimation of seed-to-voxel and region of interest (ROI)-to-ROI functional correlations, as well as semipartial correlation and bivariate/multivariate regression analysis for multiple ROI sources, graph theoretical analysis, and novel voxel-to-voxel analysis of functional connectivity. We describe the methods implemented in the Conn toolbox for the analysis of fcMRI data, together with examples of use and interscan reliability estimates of all the implemented fcMRI measures. The results indicate that the CompCor method increases the sensitivity and selectivity of fcMRI analysis, and show a high degree of interscan reliability for many fcMRI measures.
Modern anatomical tracing and imaging techniques are beginning to reveal the structural anatomy of neural circuits at small and large scales in unprecedented detail. When examined with analytic tools from graph theory and network science, neural connectivity exhibits highly non-random features, including high clustering and short path length, as well as modules and highly central hub nodes. These characteristic topological features of neural connections shape non-random dynamic interactions that occur during spontaneous activity or in response to external stimulation. Disturbances of connectivity and thus of neural dynamics are thought to underlie a number of disease states of the brain, and some evidence suggests that degraded functional performance of brain networks may be the outcome of a process of randomization affecting their nodes and edges. This article provides a survey of the non-random structure of neural connectivity, primarily at the large scale of regions and pathways in the mammalian cerebral cortex. In addition, we will discuss how non-random connections can give rise to differentiated and complex patterns of dynamics and information flow. Finally, we will explore the idea that at least some disorders of the nervous system are associated with increased randomness of neural connections.
Arterial spin labeling (ASL) is a magnetic resonance imaging technique for measuring tissue perfusion using a freely diffusible intrinsic tracer. As compared with other perfusion techniques, ASL offers several advantages and is now available for routine clinical practice in many institutions. Its noninvasive nature and ability to quantitatively measure tissue perfusion make ASL ideal for research and clinical studies. Recent technical advances have increased its sensitivity and also extended its potential applications. This review focuses on some basic knowledge of ASL perfusion, emerging techniques and clinical applications in neuroimaging.
In the past decade, resting-state functional MRI (R-fMRI) measures of brain activity have attracted considerable attention. Based on changes in the blood oxygen level-dependent signal, R-fMRI offers a novel way to assess the brain's spontaneous or intrinsic (i.e., task-free) activity with both high spatial and temporal resolutions. The properties of both the intra- and inter-regional connectivity of resting-state brain activity have been well documented, promoting our understanding of the brain as a complex network. Specifically, the topological organization of brain networks has been recently studied with graph theory. In this review, we will summarize the recent advances in graph-based brain network analyses of R-fMRI signals, both in typical and atypical populations. Application of these approaches to R-fMRI data has demonstrated non-trivial topological properties of functional networks in the human brain. Among these is the knowledge that the brain's intrinsic activity is organized as a small-world, highly efficient network, with significant modularity and highly connected hub regions. These network properties have also been found to change throughout normal development, aging, and in various pathological conditions. The literature reviewed here suggests that graph-based network analyses are capable of uncovering system-level changes associated with different processes in the resting brain, which could provide novel insights into the understanding of the underlying physiological mechanisms of brain function. We also highlight several potential research topics in the future.
The medial temporal lobe (MTL) contains subregions that are subject to severe distortion and signal loss in functional MRI. Air/tissue and bone/tissue interfaces in the vicinity of the MTL distort the local magnetic field due to differences in magnetic susceptibility. Fast image acquisition and thin slices can reduce the amount of distortion and signal loss, but at the cost of image signal-to-noise ratio (SNR).
In this paper, we quantify the severity of distortion and signal loss in MTL subregions for three different echo planar imaging (EPI) acquisitions at 3 Tesla: a conventional moderate-resolution EPI (3x3x3 mm), a conventional high-resolution EPI (1.5x1.5x2 mm), and a zoomed high-resolution EPI. We also demonstrate the advantage of reversing the phase encode direction to control the direction of distortion and to maximize efficacy of distortion compensation during data post-processing. With the high-resolution zoomed acquisition, distortion is not significant and signal loss is present only in the most anterior regions of the parahippocampal gyrus. Furthermore, we find that the severity of signal loss is variable across subjects, with some subjects showing negligible loss and others showing more dramatic loss.
Although both distortion and signal loss are minimized in a zoomed field of view acquisition with thin slices, this improvement in accuracy comes at the cost of reduced SNR. We quantify this trade-off between distortion and SNR in order to provide a decision tree for design of high-resolution experiments investigating the function of subregions in MTL.
The role of the anterior temporal lobes (ATLs) in semantic cognition is not clear from the current literature. Semantic dementia patients show a progressive and a specific semantic impairment, following bilateral atrophy of the ATLs. Neuroimaging studies of healthy participants, however, do not consistently show ATL activation during semantic tasks. Consequently, several influential theories of semantic memory do not ascribe a central role to the ATLs. We conducted a meta-analysis of 164 functional neuroimaging studies of semantic processing to investigate factors that might contribute to the inconsistency in previous results. Four factors influenced the likelihood of finding ATL activation: (1) the use of PET versus fMRI, reflecting the fact that fMRI but not PET is sensitive to distortion artifacts caused by large variations in magnetic susceptibility in the area of the ATL; (2) a field of view (FOV) of more than 15 cm, thereby ensuring whole-brain coverage; (3) the use of a high baseline task to prevent subtraction of otherwise uncontrolled semantic activation; (4) the inclusion of the ATL as an ROI. The type of stimuli or task did not influence the likelihood of ATL activation, consistent with the view that this region underpins an amodal semantic system. Spoken words, written words, and picture stimuli produced overlapping ATL peaks. On average, these were more inferior for picture-based tasks. We suggest that the specific pattern of ATL activation may be influenced by stimulus type due to variations across this region in the degree of connectivity with modality-specific areas in posterior temporal cortex.
Built on an analogy between the visual and auditory systems, the following dual stream model for language processing was suggested recently: a dorsal stream is involved in mapping sound to articulation, and a ventral stream in mapping sound to meaning. The goal of the study presented here was to test the neuroanatomical basis of this model. Combining functional magnetic resonance imaging (fMRI) with a novel diffusion tensor imaging (DTI)-based tractography method we were able to identify the most probable anatomical pathways connecting brain regions activated during two prototypical language tasks. Sublexical repetition of speech is subserved by a dorsal pathway, connecting the superior temporal lobe and premotor cortices in the frontal lobe via the arcuate and superior longitudinal fascicle. In contrast, higher-level language comprehension is mediated by a ventral pathway connecting the middle temporal lobe and the ventrolateral prefrontal cortex via the extreme capsule. Thus, according to our findings, the function of the dorsal route, traditionally considered to be the major language pathway, is mainly restricted to sensory-motor mapping of sound to articulation, whereas linguistic processing of sound to meaning requires temporofrontal interaction transmitted via the ventral route.
• DTI
• extreme capsule
• fMRI
• language networks
• arcuate fascicle
• extreme capsule
Background:
Arterial spin labeling (ASL) is an established magnetic resonance imaging (MRI) technique that is finding broader applications in functional studies of the healthy and diseased brain. To promote improvement in cerebral blood flow (CBF) signal specificity, many algorithms and imaging procedures, such as subtraction methods, were proposed to eliminate or, at least, minimize noise sources. Therefore, this study addressed the main considerations of how CBF functional connectivity (FC) is changed, regarding resting brain network (RBN) identification and correlations between regions of interest (ROI), by different subtraction methods and removal of residual motion artifacts and global signal fluctuations (RMAGSF).
Methods:
Twenty young healthy participants (13 M/7F, mean age = 25 ± 3 years) underwent an MRI protocol with a pseudo-continuous ASL (pCASL) sequence. Perfusion-based images were obtained using simple, sinc and running subtraction. RMAGSF removal was applied to all CBF time series. Independent Component Analysis (ICA) was used for RBN identification, while Pearson' correlation was performed for ROI-based FC analysis.
Results:
Temporal signal-to-noise ratio (tSNR) was higher in CBF maps obtained by sinc subtraction, although RMAGSF removal had a significant effect on maps obtained with simple and running subtractions. Neither the subtraction method nor the RMAGSF removal directly affected the identification of RBNs. However, the number of correlated and anti-correlated voxels varied for different subtraction and filtering methods. In an ROI-to-ROI level, changes were prominent in FC values and their statistical significance.
Conclusions:
Our study showed that both RMAGSF filtering and subtraction method might influence resting-state FC results, especially in an ROI level, consequently affecting FC analysis and its interpretation. Taking our results and the whole discussion together, we understand that for an exploratory assessment of the brain, one could avoid removing RMAGSF to not bias FC measures, but could use sinc subtraction to minimize low-frequency contamination. However, CBF signal specificity and frequency range for filtering purposes still need to be assessed in future studies.
Schizophrenia is a severe mental disorder that affects the anatomy and function of the brain, with an impact on one's thoughts, feelings, and behavior. The purpose of the study was to investigate cerebral blood flow (CBF) and brain connectivity in a group of patients with schizophrenia. Pseudo-continuous arterial spin labeling (pCASL) images were acquired from 28 patients in treatment and 28 age-matched healthy controls. Mean CBF and connectivity patterns were assessed. Schizophrenia patients had decreased CBF in the bilateral frontal pole and superior frontal gyrus, right medial frontal gyrus, triangular and opercular parts of the inferior frontal gyrus, posterior division of the left supramarginal gyrus, superior and inferior divisions of the left lateral occipital cortex, and bilateral occipital pole. Moreover, through different methods to assess connectivity, our results showed abnormal connectivity patterns in regions involved in motor, sensorial, and cognitive functions. Using pCASL, a non-invasive technique, we found CBF deficits and altered functional organization of the brain in schizophrenia patients that are associated with the symptoms and characteristics of the disorder.
Arterial spin labeling (ASL) MRI with a dual-echo readout module (DE-ASL) enables noninvasive simultaneous acquisition of cerebral blood flow (CBF)-weighted images and blood oxygenation level dependent (BOLD) contrast. Up to date, resting-state functional connectivity (FC) studies based on CBF fluctuations have been very limited, while the BOLD is still the method most frequently used. The purposes of this technical report were (i) to assess the potentiality of the DE-ASL sequence for the quantification of resting-state FC and brain organization, with respect to the conventional BOLD (cvBOLD) and (ii) to investigate the relationship between a series of complex network measures and the CBF information. Thirteen volunteers were scanned on a 3 T scanner acquiring a pseudocontinuous multislice DE-ASL sequence, from which the concomitant BOLD (ccBOLD) simultaneously to the ASL can be extracted. In the proposed comparison, the brain FC and graph-theoretical analysis were used for quantifying the connectivity strength between pairs of regions and for assessing the network model properties in all the sequences. The main finding was that the ccBOLD part of the DE-ASL sequence provided highly comparable connectivity results compared to cvBOLD. As expected, because of its different nature, ASL sequence showed different patterns of brain connectivity and graph indices compared to BOLD sequences. To conclude, the resting-state FC can be reliably detected using DE-ASL, simultaneously to CBF quantifications, whereas a single fMRI experiment precludes the quantitative measurement of BOLD signal changes. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
Objective:
Dual-echo arterial spin labeling (DE-ASL) techniques have been recently proposed for the simultaneous acquisition of ASL and blood-oxygenation-level-dependent (BOLD)-functional magnetic resonance imaging (fMRI) data. The assessment of this technique in detecting functional connectivity at rest or during motor and motor imagery tasks is still unexplored both per-se and in comparison with conventional methods. The purpose is to quantify the sensitivity of the DE-ASL sequence with respect to the conventional fMRI sequence (cvBOLD) in detecting brain activations, and to assess and compare the relevance of node features in decoding the network structure.
Approach:
Thirteen volunteers were scanned acquiring a pseudo-continuous DE-ASL sequence from which the concomitant BOLD (ccBOLD) simultaneously to the ASL can be extracted. The approach consists of two steps: (i) model-based analyses for assessing brain activations at individual and group levels, followed by statistical analysis for comparing the activation elicited by the three sequences under two conditions (motor and motor imagery), respectively; (ii) brain connectivity graph-theoretical analysis for assessing and comparing the networks model properties.
Main results:
Our results suggest that cvBOLD and ccBOLD have comparable sensitivity in detecting the regions involved in the active task, whereas ASL offers a higher degree of co-localization with smaller activation volumes. The connectivity results and the comparative analysis of node features across sequences revealed that there are no strong changes between rest and tasks and that the differences between the sequences are limited to few connections.
Significance:
Considering the comparable sensitivity of the ccBOLD and cvBOLD sequences in detecting activated brain regions, the results demonstrate that DE-ASL can be successfully applied in functional studies allowing to obtain both ASL and BOLD information within a single sequence. Further, DE-ASL is a powerful technique for research and clinical applications allowing to perform quantitative comparisons as well as to characterize functional connectivity.
Verbal fluency tasks are typically used in neuropsychological practice for assessment of language function in a variety of neurological disorders. Recently, it has been shown that the hippocampus, a region thought to be exclusive to the domain of memory, is also involved in tests of semantic fluency. The present study further explores hippocampal contribution to verbal fluency using functional Magnetic Resonance Imaging (fMRI) and examining mean activity and inter-regional functional connectivity with known task-related brain regions. Given the clear lateralization of brain areas involved in language, lateralization of hippocampal involvement in semantic and phonemic word fluency was also investigated. Different hippocampal recruitment during semantic and phonemic fluency was found: greater change in activity was seen during semantic fluency, as compared with phonemic fluency. This pattern was obtained in the right and the left hippocampus, with no lateralization effects. Functional connectivity analyses corroborate the notion of selective contribution of the hippocampus to semantic fluency. During the semantic fluency task, connectivity levels between the hippocampi and components of the semantic network did not differ from connectivity levels within the semantic network. In contrast, during the phonemic fluency task, the hippocampi were less correlated with components of the phonemic network, as compared to the within phonemic network connectivity. Importantly, hippocampal connectivity with the semantic network was task-dependent and restricted to periods of semantic fluency performance. Altogether, results suggest that the right and the left hippocampus are integral components of the brain network that selectively supports verbal semantic fluency, but not phonemic fluency.
The posterior medial cortex (PMC) is particularly poorly understood. Its neural activity changes have been related to highly disparate mental processes. We therefore investigated PMC properties with a data-driven exploratory approach. First, we subdivided the PMC by whole-brain coactivation profiles. Second, functional connectivity of the ensuing PMC regions was compared by task-constrained meta-analytic coactivation mapping (MACM) and task-unconstrained resting-state correlations (RSFC). Third, PMC regions were functionally described by forward/reverse functional inference. A precuneal cluster was mostly connected to the intraparietal sulcus, frontal eye fields, and right temporo-parietal junction; associated with attention and motor tasks. A ventral posterior cingulate cortex (PCC) cluster was mostly connected to the ventromedial prefrontal cortex and middle left inferior parietal cortex (IPC); associated with facial appraisal and language tasks. A dorsal PCC cluster was mostly connected to the dorsomedial prefrontal cortex, anterior/posterior IPC, posterior midcingulate cortex, and left dorsolateral prefrontal cortex; associated with delay discounting. A cluster in the retrosplenial cortex was mostly connected to the anterior thalamus and hippocampus. Furthermore, all PMC clusters were congruently coupled with the default mode network according to task-constrained but not task-unconstrained connectivity. We thus identified regions in the PMC and characterized their neural networks and functional implications.
Purpose:
To assess the applicability of arterial spin labeling (ASL) in comparison to blood-oxygenation-level-dependent (BOLD) contrast fMRI in detecting brain activations elicited by active and passive hand movements.
Materials and methods:
A block design for ASL and BOLD fMRI was applied in 8 healthy subjects using active and passive hand tasks. Data analyses were performed at individual and group level, comparing both the different movements and the performance of the two techniques.
Results:
Group analyses showed involvement of the same areas during both tasks, as the contralateral sensorimotor cortex, supplementary motor area, cerebellum, inferior parietal lobes, thalamus. ASL detected smaller activation volumes than BOLD, but the areas had a high degree of colocalization. Few significant differences (P < 0.05) were found when the two tasks were compared for the number of activated voxels, coordinates of center of mass, and CBF estimates. Considering together all the areas, the mean %BOLD change was 0.79 ± 0.27 and 0.73 ± 0.24 for the active and passive movements respectively, while the mean %CBF changes were 34.1 ± 8.9 and 27.1 ± 14.8.
Conclusion:
Our findings confirm passive and active tasks are strongly coupled, supporting the importance of passive tasks as a diagnostic tool in the clinical setting. ASL fMRI proved suitable for functional mapping and quantifying CBF changes, making it a promising technique for patient cohort applications.
Taking notes on laptops rather than in longhand is increasingly common. Many researchers have suggested that laptop note taking is less effective than longhand note taking for learning. Prior studies have primarily focused on students' capacity for multitasking and distraction when using laptops. The present research suggests that even when laptops are used solely to take notes, they may still be impairing learning because their use results in shallower processing. In three studies, we found that students who took notes on laptops performed worse on conceptual questions than students who took notes longhand. We show that whereas taking more notes can be beneficial, laptop note takers' tendency to transcribe lectures verbatim rather than processing information and reframing it in their own words is detrimental to learning.
La perfusion par marquage de spins artériels ou arterial spin labeling (ASL) est une technique IRM de quantification du débit sanguin tissulaire. L’ASL est une technique non invasive qui marque les protons du sang artériel par une impulsion de radiofréquence, sans injection de produit de contraste exogène. Les objectifs de cet article sont triples : présenter les principes de la perfusion par ASL, les types de marquage et les modalités d’obtention des cartographies ; préciser les modalités de sa mise en œuvre sur les IRM cliniques et les critères qualité des cartographies obtenues, en insistant sur les artefacts ; décrire les principales applications encéphaliques et rénales.
Letter fluency deficits are commonly detected in non-demented Parkinson's disease (PD) patients but the underlying cause remains uncertain. We investigated the role of slowed processing speed and executive dysfunction. Eighteen non-demented PD participants and nineteen controls were compared on letter fluency using a fluency index (Fi); the average time to "think" of each word, a measure independent of motor speed. Video analyses produced thinking times to switch between word clusters and generate a word within a cluster. Correlational and regression analyses were undertaken with tests of processing speed and executive functioning. The PD group exhibited significantly longer fluency indices than controls across all components. Performance on tests of executive functioning explained a significant proportion of variance whereas performance in processing speed tests did not. Moreover, PD participants with an executive functioning impairment showed significantly worse switching fluency indices only compared with Controls and PD participants without executive dysfunction. PD participants with executive dysfunction exhibited a disproportionate impairment in the time taken to switch between clusters than to think of words within clusters. Executive functioning contributed to fluency performance more than processing speed. Cognitive heterogeneity and motor slowing, may mask the profile of cognitive dysfunction in neurodegenerative disease. (JINS, 2013, 19, 1-9).
Verbal fluency tests (VFT) have established position in methodology of cognitive functions research. They are used in neuropsychological assessment of neurological and psychiatric diseases. This article's aim is to present current knowledge of the VFT both to clinicians and researchers. It describes models of cognitive processes involved in task performance mainly: semantic memory access and executive functions and. It describes studies on verbal fluency both in healthy and impaired subjects involving neuroimaging discussing neuroanatomical structures involved in task performance. Authors are quite unanimous as to connection between frontal and temporal lobes condition and task performance, but also other cortical and subcortical structures seem to be involved. Methods of qualitative performance analysis and studies applying them are further described. This article brings up also important questions of psychometric and demographic characteristics of the task and limitations arising from the lack of Polish norms of the tool.
Numerous neuroimaging studies have implicated default mode network (DMN) involvement in both internally driven processes and memory. Nevertheless, it is unclear whether memory operations reflect a particular case of internally driven processing or alternatively involve the DMN in a distinct manner, possibly depending on memory type. This question is critical for refining neurocognitive memory theorem in the context of other endogenic processes and elucidating the functional significance of this key network. We used functional MRI to examine DMN activity and connectivity patterns while participants overtly generated words according to nonmnemonic (phonemic) or mnemonic (semantic or episodic) cues. Overall, mnemonic word fluency was found to elicit greater DMN activity and stronger within-network functional connectivity compared with nonmnemonic fluency. Furthermore, two levels of functional organization of memory retrieval were shown. First, across both mnemonic tasks, activity was greater mainly in the posterior cingulate cortex, implying selective contribution to generic aspects of memory beyond its general involvement in endogenous processes. Second, parts of the DMN showed distinct selectivity for each of the mnemonic conditions; greater recruitment of the anterior prefrontal cortex, retroesplenial cortex, and hippocampi and elevated connectivity between anterior and posterior medial DMN nodes characterized the semantic condition, whereas increased recruitment of posterior DMN components and elevated connectivity between them characterized the episodic condition. This finding emphasizes the involvement of DMN elements in discrete aspects of memory retrieval. Altogether, our results show a specific contribution of the DMN to memory processes, corresponding to the specific type of memory retrieval.
Denoising is critical to improving the quality and stability of cerebral blood flow (CBF) quantification in arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) due to the intrinsic low signal-to-noise-ratio (SNR) of ASL data. Previous studies have been focused on reducing the spatial or temporal noise using standard filtering techniques, and less attention has been paid to two global nuisance effects, the residual motion artifacts and the global signal fluctuations. Since both nuisances affect the whole brain, removing them in advance should enhance the CBF quantification quality for ASL MRI. The purpose of this paper was to assess this potential benefit. Three methods were proposed to suppress each or both of the two global nuisances. Their performances for CBF quantification were validated using ASL data acquired from 13 subjects. Evaluation results showed that covarying out both global nuisances significantly improved temporal SNR and test-retest stability of CBF measurement. Although the concept of removing both nuisances is not technically novel per se, this paper clearly showed the benefits for ASL CBF quantification. Dissemination of the proposed methods in a free ASL data processing toolbox should be of interest to a broad range of ASL users.
The left inferior frontal gyrus (LIFG) has consistently been associated with both phonologic and semantic operations in functional neuroimaging studies. Two main theories have proposed a different functional organization in the LIFG for these processes. One theory suggests an anatomic parcellation of phonologic and semantic operations within the LIFG. An alternative theory proposes that both processes are encompassed within a supramodal executive function in a single region in the LIFG. To test these theories, we carried out a systematic review of functional magnetic resonance imaging studies employing phonologic and semantic verbal fluency tasks. Seventeen articles meeting our pre-established criteria were found, consisting of 22 relevant experiments with 197 healthy subjects and a total of 41 peak activations in the LIFG. We determined 95% confidence intervals of the mean location (x, y, and z coordinates) of peaks of blood oxygenation level-dependent (BOLD) responses from published phonologic and semantic verbal fluency studies using the nonparametric technique of bootstrap analysis. Significant differences were revealed in dorsal–ventral (z-coordinate) localizations of the peak BOLD response: phonologic verbal fluency peak BOLD response was significantly more dorsal to the peak associated with semantic verbal fluency (confidence interval of difference: 1.9–17.4 mm). No significant differences were evident in antero–posterior (x-coordinate) or medial–lateral (y-coordinate) positions. The results support distinct dorsal–ventral locations for phonologic and semantic processes within the LIFG. Current limitations to meta-analytic integration of published functional neuroimaging studies are discussed. Hum Brain Mapp, 2006. © 2006 Wiley-Liss, Inc.
Measurement of tissue perfusion is important for the functional assessment of organs in vivo. Here we report the use of 1H NMR imaging to generate perfusion maps in the rat brain at 4.7 T. Blood water flowing to the brain is saturated in the neck region with a sliceselective saturation imaging sequence, creating an endogenous tracer in the form of proximally saturated spins. Because proton T1 times are relatively long, particularly at high field strengths, saturated spins exchange with bulk water in the brain and a steady state is created where the regional concentration of saturated spins is determined by the regional blood flow and regional T1. Distal saturation applied equidistantly outside the brain serves as a control for effects of the saturation pulses. Average cerebral blood flow in normocapnic rat brain under halothane anesthesia was determined to be 105 ± 16 cc. 100 g−1. min−1 (mean ± SEM, n = 3), in good agreement with values reported in the literature, and was sensitive to increases in arterial pCO2. This technique allows regional perfusion maps to be measured noninvasively, with the resolution of 1H MRI, and should be readily applicable to human studies. © 1992 Academic Press, Inc.
The new clinically available arterial spin labeling (ASL) perfusion imaging sequences present some advantages relatively to the commonly used blood oxygen level-dependent (BOLD) method for functional brain studies using magnetic resonance imaging (MRI). In particular, regional cerebral blood flow (CBF) changes are thought to be more directly related with neuronal activation. In this study, we aimed to investigate the accuracy of the functional localization of the hand motor area obtained by simultaneous CBF and BOLD contrasts provided by ASL functional MRI (fMRI) and compare it with a standard BOLD fMRI protocol. For this purpose, we measured the distance between the center of gravity of the activation clusters obtained with each contrast (CBF, BOLD(ASL) , and Standard BOLD) and 11 positions defined on a well-established anatomical landmark of the hand motor area (the omega in the axial plane of the precentral gyrus). We found that CBF measurements were significantly closer to the anatomical landmark than the ones obtained using either simultaneous BOLD(ASL) or standard BOLD contrasts. Moreover, we also observed reduced intersubject variability of the functional localization, as well as percent signal change, for CBF relative to both BOLD contrast measurements. In conclusion, our results add further evidence in support to the notion that CBF provides a more accurate localization of motor activation than BOLD contrast, indicating that ASL may be an appropriate technique for clinical fMRI studies. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.
In this review of 100 fMRI studies of speech comprehension and production, published in 2009, activation is reported for: prelexical speech perception in bilateral superior temporal gyri; meaningful speech in middle and inferior temporal cortex; semantic retrieval in the left angular gyrus and pars orbitalis; and sentence comprehension in bilateral superior temporal sulci. For incomprehensible sentences, activation increases in four inferior frontal regions, posterior planum temporale, and ventral supramarginal gyrus. These effects are associated with the use of prior knowledge of semantic associations, word sequences, and articulation that predict the content of the sentence. Speech production activates the same set of regions as speech comprehension but in addition, activation is reported for: word retrieval in left middle frontal cortex; articulatory planning in the left anterior insula; the initiation and execution of speech in left putamen, pre-SMA, SMA, and motor cortex; and for suppressing unintended responses in the anterior cingulate and bilateral head of caudate nuclei. Anatomical and functional connectivity studies are now required to identify the processing pathways that integrate these areas to support language.
Brain connectivity datasets comprise networks of brain regions connected by anatomical tracts or by functional associations. Complex network analysis-a new multidisciplinary approach to the study of complex systems-aims to characterize these brain networks with a small number of neurobiologically meaningful and easily computable measures. In this article, we discuss construction of brain networks from connectivity data and describe the most commonly used network measures of structural and functional connectivity. We describe measures that variously detect functional integration and segregation, quantify centrality of individual brain regions or pathways, characterize patterns of local anatomical circuitry, and test resilience of networks to insult. We discuss the issues surrounding comparison of structural and functional network connectivity, as well as comparison of networks across subjects. Finally, we describe a Matlab toolbox (http://www.brain-connectivity-toolbox.net) accompanying this article and containing a collection of complex network measures and large-scale neuroanatomical connectivity datasets.
Quantitative magnetic resonance measurements of regional tissue perfusion can be obtained using magnetically labeled arterial water as a diffusable tracer. Continuous labeling is achieved in flowing spins using adiabatic inversion. The effects of continuous labeling of proximal arterial spins and T1 relaxation in distal tissue magnetization result in a steady-state change in tissue magnetization which is tissue specific, i.e., it can be quantified in units of blood flow per gram of tissue per unit time. This magnetization is sampled using standard imaging sequences. The theoretical basis for this method, including the effects of macromolecular spin saturation, is reviewed. Recent results demonstrating the successful implementation of this technique in vitro and in vivo in rat brain, heart, and kidney, and in human brain and kidney are presented, as well as the use of a separate RF coil for arterial labeling to produce selective perfusion images in rat brain. This approach allows quantitative perfusion images to be obtained completely non-invasively at the resolution of 1H MRI, and is useful in the clinical and investigational evaluation of organ physiology.