Inferior Frontal Gyrus Pars Opercularis Research Articles

Predominant polarity as a neurobiological specifier in bipolar disorder: Evidence from a multimodal neuroimaging study

BackgroundWhile predominant (PP) and onset polarity (OP) have considerable clinical and treatment implications in bipolar disorder (BD), the neurobiological underpinnings of PP and OP from a radiological perspective remain largely unknown. The main objective of this study is to investigate the neuroanatomical profile of polarity subphenotypes (PP and OP) in euthymic BD patients, using a standardized multimodal neuroimaging protocol to evaluate regional gray matter (GM) volumes, cortical thickness, as well as white matter (WM) integrity of major projection, commissural and association tracts. MethodsForty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this computational neuroimaging study to comprehensively characterize gray and white matter alterations. Univariate analyses of covariance (ANCOVAs) were conducted with Bonferroni corrections for each MRI modality and Cohen's d effect sizes were calculated for group comparisons. ResultsPhenotype-associated cortical thickness abnormalities and volumetric alterations were identified, but no WM changes ascertained. Specifically, we found a main effect of OP on GM volume of left middle frontal gyrus and of OP and PP (either or both) on cortical thickness of various regions previously implicated in BD, i.e. inferior frontal gyrus-pars opercularis (left) and pars orbitalis (bilateral), left lateral orbitofrontal gyrus, bilateral medial segment of the superior frontal gyrus, left planum polare, right anterior cingulate gyrus, left anterior and posterior insula, bilateral frontal operculum (both OP and PP); left anterior and posterior orbitofrontal gyrus, left transverse temporal gyrus, right posterior insula (only OP); and right medial frontal cortex (only PP). Based on the magnitude of differences on pairwise comparisons, we found a large effect of OP on cortical thickness in a single region (left anterior orbitofrontal gyrus) (OP-M > OP-D), while PP subgroups showed large or medium effect size differences in cortical thickness (PP-M > PP-D) in a wider array of regions (right medial frontal cortex, left frontal operculum, left inferior frontal gyrus-pars opercularis, bilateral medial segment of the superior frontal gyrus). For most regions, PP-D patients showed the greatest decreases in cortical thickness compared to HC while PP-M showed the smallest, with PP-U showing an “unspecified” pattern mostly lying in-between PP-D and PP-M. ConclusionsOur multimodal imaging findings suggest specific polarity BD subgroups with compromised cortical thickness; we recorded a greater impact of PP on brain structure compared to OP, which provides additional evidence that PP can be considered as a neurobiological specifier in BD.

Start shallow and grow deep: The development of a Hebrew reading brain

Brain plasticity implies that readers of different orthographies can have different reading networks. Theoretical models suggest that reading acquisition in transparent orthographies relies on mapping smaller orthographic units to phonology, than reading opaque orthographies; but what are the neural mechanisms underlying this difference? Hebrew has a transparent (pointed) script used for beginners, and a non-transparent script used for skilled readers. The current study examined the developmental changes in brain regions associated with phonological and orthographic processes during reading pointed and un-pointed words. Our results highlight some changes that are universal in reading development, such as a developmental increase in frontal involvement (in bilateral inferior frontal gyrus (IFG) pars opercularis), and increase in left asymmetry (in IFG pars opercularis and superior temporal gyrus, STG) of the reading network. Our results also showed a developmental increase in activation in STG, which stands in contrast to previous studies in other orthographies. We further found an interaction of word length and diacritics in bilateral STG and the visual word form area (VWFA) across both groups. These findings suggest that children slightly adjust their reading depending on orthographic transparency, relying on smaller units when reading a transparent script and on larger units when reading an opaque script. Our results also showed that phonological abilities across groups correlated with activation in the VWFA, regardless of transparency, supporting the continued role of phonology at all levels of orthographic transparency. Our findings are consistent with multiple route reading models, in which both phonological and orthographic processing of multiple size units continue to play a role in children's reading of transparent and opaque scripts during reading development. The results further demonstrate the importance of taking into account differences between orthographies when constructing neural models of reading acquisition.

Fibromyalgia impact in the prefrontal cortex subfields: An assessment with MRI

IntroductionPrevious studies have associated brain abnormalities in people with fibromyalgia with accelerated brain ageing. The prefrontal cortex is located in the anterior pole of the mammalian brain. It is defined as the part of the cerebral cortex that receives projections from the mediodorsal nucleus of the thalamus. AimThis study aimed to evaluate the volumetric differences in the prefrontal cortex subfields between healthy women and women with fibromyalgia using magnetic resonance imaging (MRI) and controlling for age, estimated intracranial volume, depression, and cognitive impairment. Material and methodsA total of 47 women with fibromyalgia (recruited from a fibromyalgia local association) and 43 healthy women (retrieved from the Open Access Series of Imaging Studies database) participated in this cross-sectional study. Multiple linear regressions were used to predict the value of the prefrontal cortex subfields as well as to determine if there were volumetric differences between the groups. ResultsVolume of all prefrontal cortex regions decreased with each year of age. Healthy women showed higher volume in all the prefrontal cortex subfields than women with fibromyalgia. Regarding partial correlations performed, no significant relation were found between the fibromyalgia impact and the brain volumes analyzed, controlling for depression. ConclusionsWomen with fibromyalgia showed reduced volume in the right caudal middle frontal gyrus, rostral middle frontal gyrus, left inferior frontal gyrus pars opercularis, inferior frontal gyrus pars triangularis, inferior frontal gyrus pars orbitalis, lateral orbitofrontal cortex, right medial orbitofrontal cortex, right rostral anterior cingulate gyrus subfields of the prefrontal cortex and total gray matter compared to healthy women. Furthermore, through an analysis of multiple linear regressions, the left rostral middle frontal gyrus and left lateral orbitofrontal cortex showed significantly volumetric decreases related to depression levels. The total gray matter also shows a significant decrease related to age observed through the analysis of multiple linear regressions. No significant relation were found between the impact of the disease and the brain volumes analyzed, controlling for depression in women with fibromyalgia.

Physical activity moderates the association between executive function and functional connectivity in older adults.

Recent evidence suggests that physical activity may influence the functional connectivity of the aging brain. The purpose of this study was to examine the influence of physical activity on the association between executive function and functional connectivity of key brain networks and graph theory metrics in community-dwelling older adults. Participants were 47 older adults (M = 73 years; SD = 5.92) who participated in neuropsychological testing, physical activity measurements, and magnetic resonance imaging (MRI). Seed-to-voxel moderation analyses and graph theory analyses were conducted. Physical activity was significantly positively associated with default mode network functional connectivity (DMN FC; Posterior Cingulate Gyrus, p-FDR = 0.005; Frontal Pole (L), p-FDR = 0.005; Posterior Cingulate Gyrus, p-FDR = 0.006; Superior Frontal Gyrus (L), p-FDR = 0.016) and dorsal attention network functional connectivity (DAN FC; Inferior Frontal Gyrus Pars Opercularis (R), p-FDR = 0.044). The interaction between physical activity and executive function on the DMN FC and DAN FC was analyzed. The interaction between executive function and physical activity was significantly associated with DMN FC. When this significant interaction was probed, the association between physical activity and DMN FC differed between levels of high and low executive function such that the association was only significant at levels of high executive function. These results suggest that greater physical activity in later life is associated with greater DMN and DAN FC and provides evidence for the importance of physical activity in cognitively healthy older adults.

Investigating Language and Domain-General Processing in Neurotypicals and Individuals With Aphasia - A Functional Near-Infrared Spectroscopy Pilot Study.

Brain reorganization patterns associated with language recovery after stroke have long been debated. Studying mechanisms of spontaneous and treatment-induced language recovery in post-stroke aphasia requires a network-based approach given the potential for recruitment of perilesional left hemisphere language regions, homologous right hemisphere language regions, and/or spared bilateral domain-general regions. Recent hardware, software, and methodological advances in functional near-infrared spectroscopy (fNIRS) make it well-suited to examine this question. fNIRS is cost-effective with minimal contraindications, making it a robust option to monitor treatment-related brain activation changes over time. Establishing clear activation patterns in neurotypical adults during language and domain-general cognitive processes via fNIRS is an important first step. Some fNIRS studies have investigated key language processes in healthy adults, yet findings are challenging to interpret in the context of methodological limitations. This pilot study used fNIRS to capture brain activation during language and domain-general processing in neurotypicals and individuals with aphasia. These findings will serve as a reference when interpreting treatment-related changes in brain activation patterns in post-stroke aphasia in the future. Twenty-four young healthy controls, seventeen older healthy controls, and six individuals with left hemisphere stroke-induced aphasia completed two language tasks (i.e., semantic feature, picture naming) and one domain-general cognitive task (i.e., arithmetic) twice during fNIRS. The probe covered bilateral frontal, parietal, and temporal lobes and included short-separation detectors for scalp signal nuisance regression. Younger and older healthy controls activated core language regions during semantic feature processing (e.g., left inferior frontal gyrus pars opercularis) and lexical retrieval (e.g., left inferior frontal gyrus pars triangularis) and domain-general regions (e.g., bilateral middle frontal gyri) during hard versus easy arithmetic as expected. Consistent with theories of post-stroke language recovery, individuals with aphasia activated areas outside the traditional networks: left superior frontal gyrus and left supramarginal gyrus during semantic feature judgment; left superior frontal gyrus and right precentral gyrus during picture naming; and left inferior frontal gyrus pars opercularis during arithmetic processing. The preliminary findings in the stroke group highlight the utility of using fNIRS to study language and domain-general processing in aphasia.

Indirect White Matter Pathways Are Associated With Treated Naming Improvement in Aphasia

Background White matter disconnection of language-specific brain regions associates with worse aphasia recovery. Despite a loss of direct connections, many stroke survivors may maintain indirect connections between brain regions. Objective To determine (1) whether preserved direct connections between language-specific brain regions relate to better poststroke naming treatment outcomes compared to no direct connections and (2) whether for individuals with a loss of direct connections, preserved indirect connections are associated with better treatment outcomes compared to individuals with no connections. Methods We computed structural whole-brain connectomes from 69 individuals with chronic left-hemisphere stroke and aphasia who completed a 3-week-long language treatment that was supplemented by either anodal transcranial direct current stimulation (A-tDCS) or sham stimulation (S-tDCS). We determined differences in naming improvement between individuals with direct, indirect, and no connections using 1-way analyses of covariance and multivariable linear regressions. Results Independently of tDCS modality, direct or indirect connections between the inferior frontal gyrus pars opercularis and angular gyrus were both associated with a greater increase in correct naming compared to no connections (P = .027 and P = .039, respectively). Participants with direct connections between the inferior frontal gyrus pars opercularis and middle temporal gyrus who received S-tDCS and participants with indirect connections who received A-tDCS significantly improved in naming accuracy. Conclusions Poststroke preservation of indirect white matter connections is associated with better treated naming improvement in aphasia even when direct connections are damaged. This mechanistic information can be used to stratify and predict treated naming recovery in individuals with aphasia.

The effect of bilingualism on brain development from early childhood to young adulthood

Bilingualism affects the structure of the brain in adults, as evidenced by experience-dependent grey and white matter changes in brain structures implicated in language learning, processing, and control. However, limited evidence exists on how bilingualism may influence brain development. We examined the developmental patterns of both grey and white matter structures in a cross-sectional study of a large sample (n = 711 for grey matter, n = 637 for white matter) of bilingual and monolingual participants, aged 3–21 years. Metrics of grey matter (thickness, volume, and surface area) and white matter (fractional anisotropy and mean diffusivity) were examined across 41 cortical and subcortical brain structures and 20 tracts, respectively. We used generalized additive modelling to analyze whether, how, and where the developmental trajectories of bilinguals and monolinguals might differ. Bilingual and monolingual participants manifested distinct developmental trajectories in both grey and white matter structures. As compared to monolinguals, bilinguals showed: (a) more grey matter (less developmental loss) starting during late childhood and adolescence, mainly in frontal and parietal regions (particularly in the inferior frontal gyrus pars opercularis, superior frontal cortex, inferior and superior parietal cortex, and precuneus); and (b) higher white matter integrity (greater developmental increase) starting during mid-late adolescence, specifically in striatal–inferior frontal fibers. The data suggest that there may be a developmental basis to the well-documented structural differences in the brain between bilingual and monolingual adults.

Inflammatory biomarkers and brain health indicators in children with overweight and obesity: The ActiveBrains project

IntroductionChronic inflammation plays an important role on the pathogenesis of several cardiovascular and metabolic diseases, as well as on brain function and behaviour. The aim of the present study was to examine the associations between inflammatory biomarkers and a wide range of brain health indicators (i.e., academic performance, executive function, behavioural and emotional functioning, and brain volume) in children with overweight/obesity. MethodsA total of 107 children (10.0 ± 1.1 years, 41% girls) from the ActiveBrains project were included in the analysis. Five inflammatory biomarkers were analysed in plasma: white blood cell (WBC) count, interleukin-6 (IL-6), interleukin-1β, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Academic performance was assessed by Woodcock-Muñoz Tests of Achievement. Executive function was assessed through the Design Fluency Test for cognitive flexibility, the Stroop test for cognitive inhibition, and the Delayed Non-Match-to-Sample task for working memory. Behavioural and emotional functioning was evaluated through the Behavior Assessment System for Children (BASC) questionnaire. Total and regional brain volume was assessed by magnetic resonance imaging. ResultsIL-6 was inversely associated with adaptive skills (β = −0.228; p = 0.030), while TNF-α was related to mathematics (β = −0.198; p = 0.034). In addition, CRP was positively associated with externalizing (β = 0.246; p = 0.046) and internalizing problems (β = 0.234; p = 0.039), as well as the behavioural symptoms index (β = 0.236; p = 0.047). However, these significant associations disappeared after multiple comparisons correction. Inflammatory biomarkers were not associated with executive function and total brain volumes. Regarding regional brain analyses, WBC was positively associated with gray matter volume in the left middle temporal gyrus (β = 0.387; p < 0.001, k = 44), and CRP was positively associated with gray matter volume in the right superior temporal gyrus (β = 0.439; p < 0.001, k = 29). Additionally, when adjusting by total brain volume, CRP was positively associated with gray matter volume in the right supplementary motor cortex (β = 0.453; p < 0.001, k = 51). Moreover, both, IL-6 (β = 0.366; p < 0.001, k = 81) and TNF-α (β = 0.368; p < 0.001, k = 62) were positively associated with white matter volume around the right inferior frontal gyrus pars opercularis, while CRP was inversely associated with white matter volume around the left superior frontal gyrus (β = -0.482; p < 0.001, k = 82). After adjusting by total brain volume, CRP was also inversely associated with white matter volume in 3 additional clusters (β ranging from −0.473 to −0.404; p < 0.001, k = 87). ConclusionsInflammation was slightly associated with brain health (i.e., academic performance, behavioural and emotional functioning and regional brain volume) in children with overweight or obesity. Further larger longitudinal and interventional studies are warranted to elucidate the short-term and long-term effect of systemic low-grade inflammation on children’s brain health.

Investigation of the Processing of Noun and Verb Words with fMRI in Patients with Schizophrenia.

Action naming is reported to be more damaged in patients with schizophrenia than object naming. Aim of this study is to understand the cortical mechanism underlying the negative symptoms seen in patients with schizophrenia such as inactivity, restricted behavioral repertoire, by using functional MRI (fMRI) to determine whether the action origin words have a different representation in the brain regions of patients with schizophrenia and healthy individuals. Our hypothesis is that restriction in the repertoire of movement and behavior and the failure of words of "action" than words of "object" are interrelated through the same cortical mechanisms. If this hypothesis is correct, the reason for not taking action in patients with schizophrenia may be improper definition of the action (verb). fMRI study was conducted with 12 patients with schizophrenia and 12 healthy individuals. fMRI recording was performed after applying positive and negative syndrome (PANSS) scale, Calgary depression scale, hand preference scale to the participants. During the sessions, "lexical decision task" is applied by showing a total of 240 words (120 words - 60 verbs (words of action) and 60 nouns (words of object) - and 120 non-words) to the subjects. In fMRI findings, in the group main effect, which can also be expressed as the difference of the noun and verb words in the group of schizophrenia from the noun and verb words in the healthy control group, the activation of the anterior prefrontal cortex is found to be lower in patients with schizophrenia than in healthy individuals. When the brain areas which show the difference in verb words in schizophrenia group from both noun words in schizophrenia group and noun and verb words in healthy individuals are examined, inferior frontal gyrus pars triangularis (BA45) showed more activation in patients with schizophrenia than healthy individuals, but again for the same task, inferior frontal gyrus pars opercularis (BA44) and left primary sensory area showed less activation in patients with schizophrenia than healthy individuals. There is no difference between patients with schizophrenia and healthy volunteers in terms of correctly identified words and reaction time. Considering the lack of difference between the groups in terms of number of correctly identified words and reaction time, and BA 44's role in recognition and imitation of action and being a part of the mirror neuron system, the significant inverse correlation between PANSS negative score and BA40 can be seen as an effort to compensate for BA44 inadequate activity through BA40.

Regional Brain Activity During Rest and Gastric Water Load in Subtypes of Functional Dyspepsia: A Preliminary Brain Functional Magnetic Resonance Imaging Study.

Background/AimsFunctional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized.MethodsTwenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging.ResultsFor regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05).ConclusionsCompared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.

Abstract WP420: Lesions Associated With Impaired Expression of Emotion Right Hemisphere Stroke

Introduction: Impaired expression of emotion through tone, loudness, rate, and rhythm of speech (affective prosody) is common after right hemisphere (RH) stroke and impedes all social interactions. Hypothesis: Abnormal patterns of acoustic features correlate with listener judgment of affective prosody and are associated with infarcts of specific RH gray and white matter regions. Methods: Forty acute ischemic RH stroke patients had MRI DWI and described a picture within 48 hours of onset. Affective prosody of picture descriptions was rated by 21 healthy volunteers (1-7 scale). We identified acoustic features that correlated with listener ratings with Spearman correlations and with linear regression to identify independent predictors. A neurologist identified percent damage to each of 9 regions after co-registration of DWI to an atlas. We identified lesions associated with abnormalities in important acoustic features using logistic regression. Results: Listener ratings of prosody correlated with duration of voiced segments divided by total duration of speech segments(DurV/Dur) (rho=0.63; p&lt;0.00001) and Spectral Flatness (SF) (rho= -0.55; p=0.0002). Variability in listener rating was best accounted for by DurV/Dur, SF, pitch range, and fundamental frequency coefficient of variation (CoV) in both women (F (4,12) =6.58; p=0.0048) and men (F(5,18)=5.13; p=0.0056). The only feature independently associated with prosody rating after adjusting for other variables was DurV/Dur (p&lt;0.0001) for women, and SF (p=0.007) for men. Low SF was predicted by sex, age, lesion volume, and percent damage to the 9 RH regions (X 2 =27; p=0.0081). Sex, lesion volume, damage to inferior frontal gyrus pars opercularis, inferior fronto-occipital fasciculus, superior longitudinal fasciculus (SLF), and uncinate were the only independent predictors. The same variables predicted CoV (X 2 =33; p=0.0005); age and damage to supramarginal gyrus and SLF were the only independent predictors. The same variables plus education predicted low DurV/Dur (X 2 =25; p=0.02). Conclusions: Impaired emotional expression after RH stroke is due to changes in specific acoustic features caused by infarct in right pars opercularis or supramarginal gyrus, or associated white matter tracts.

Distinct neural processes support post-success and post-error slowing in the stop signal task

Executive control requires behavioral adaptation to environmental contingencies. In the stop signal task (SST), participants exhibit slower go trial reaction time (RT) following a stop trial, whether or not they successfully interrupt the motor response. In previous fMRI studies, we demonstrated activation of the right-hemispheric ventrolateral prefrontal cortex, in the area of inferior frontal gyrus, pars opercularis (IFGpo) and anterior insula (AI), during post-error slowing (PES). However, in similar analyses we were not able to identify regional activities during post-success slowing (PSS). Here, we revisited this issue in a larger sample of participants (n=100) each performing the SST for 40 min during fMRI. We replicated IFGpo/AI activation to PES (p≤0.05, FWE corrected). Further, PSS engages decreased activation in a number of cortical regions including the left inferior frontal cortex (IFC; p≤0.05, FWE corrected). We employed Granger causality mapping to identify areas that provide inputs each to the right IFGpo/AI and left IFC, and computed single-trial amplitude (STA) of stop trials of these input regions as well as the STA of post-stop trials of the right IFGpo/AI and left IFC. The STAs of the right inferior precentral sulcus and supplementary motor area (SMA) and right IFGpo/AI were positively correlated and the STAs of the left SMA and left IFC were positively correlated (slope>0, p’s≤0.01, one-sample t test), linking regional responses during stop success and error trials to those during PSS and PES. These findings suggest distinct neural mechanisms to support PSS and PES.

The canonical semantic network supports residual language function in chronic post-stroke aphasia.

Current theories of language recovery after stroke are limited by a reliance on small studies. Here, we aimed to test predictions of current theory and resolve inconsistencies regarding right hemispheric contributions to long-term recovery. We first defined the canonical semantic network in 43 healthy controls. Then, in a group of 43 patients with chronic post-stroke aphasia, we tested whether activity in this network predicted performance on measures of semantic comprehension, naming, and fluency while controlling for lesion volume effects. Canonical network activation accounted for 22%-33% of the variance in language test scores. Whole-brain analyses corroborated these findings, and revealed a core set of regions showing positive relationships to all language measures. We next evaluated the relationship between activation magnitudes in left and right hemispheric portions of the network, and characterized how right hemispheric activation related to the extent of left hemispheric damage. Activation magnitudes in each hemispheric network were strongly correlated, but four right frontal regions showed heightened activity in patients with large lesions. Activity in two of these regions (inferior frontal gyrus pars opercularis and supplementary motor area) was associated with better language abilities in patients with larger lesions, but poorer language abilities in patients with smaller lesions. Our results indicate that bilateral language networks support language processing after stroke, and that right hemispheric activations related to extensive left hemispheric damage occur outside of the canonical semantic network and differentially relate to behavior depending on the extent of left hemispheric damage. Hum Brain Mapp 38:1636-1658, 2017. © 2016 Wiley Periodicals, Inc.

The Effects of an APOE Promoter Polymorphism on Human White Matter Connectivity during Non-Demented Aging.

Polymorphisms of the apolipoprotein E (APOE) promoter rs405509 are related to Alzheimer's disease (AD). The T/T allele of rs405509 decreases the transcription of the APOE gene and leads to impairments in a specific brain structural network in aged individuals; thus, it is an important risk factor for AD. However, it remains unknown whether rs405509 affects white matter networks during aging. Here, we investigated the effect of the rs405509 genotype (T/T versus G-allele) on age-related brain white matter structural networks via construction of the graph theory-based structural connectome using diffusion MRI data in a large cohort. Network communication efficiency was quantified, along with the network's betweenness centrality (Bc), global efficiency, local efficiency, and shortest path length. Regarding cognition, TT carriers had significant negative correlations between age and memory performance and between age and executive functions. A network analysis showed that TT carriers had an accelerated age-related loss of Bc and that regional Bc decreased in the left inferior frontal gyrus pars opercularis, the left posterior cingulate cortex, the right inferior occipital gyrus (IOG.R), and the left angular gyrus (ANG.L). Additional brain-behavior relationship analyses showed that polymorphism of rs405509 and age have strong interaction effects on the association of nodal Bc and cognition, mainly in the IOG.R and ANG.L. These results demonstrate that the rs405509 T/T allele of APOE causes an age-related cognitive decline in non-demented elderly people, possibly by modulating brain network communication efficiency, which may be beneficial for understanding the neural mechanisms of rs405509-related cognitive aging and AD pathogenesis.

The Neural Basis of Vocal Pitch Imitation in Humans.

Vocal imitation is a phenotype that is unique to humans among all primate species, and so an understanding of its neural basis is critical in explaining the emergence of both speech and song in human evolution. Two principal neural models of vocal imitation have emerged from a consideration of nonhuman animals. One hypothesis suggests that putative mirror neurons in the inferior frontal gyrus pars opercularis of Broca's area may be important for imitation. An alternative hypothesis derived from the study of songbirds suggests that the corticostriate motor pathway performs sensorimotor processes that are specific to vocal imitation. Using fMRI with a sparse event-related sampling design, we investigated the neural basis of vocal imitation in humans by comparing imitative vocal production of pitch sequences with both nonimitative vocal production and pitch discrimination. The strongest difference between these tasks was found in the putamen bilaterally, providing a striking parallel to the role of the analogous region in songbirds. Other areas preferentially activated during imitation included the orofacial motor cortex, Rolandic operculum, and SMA, which together outline the corticostriate motor loop. No differences were seen in the inferior frontal gyrus. The corticostriate system thus appears to be the central pathway for vocal imitation in humans, as predicted from an analogy with songbirds.

Dysfunction of the Human Mirror Neuron System in Ideomotor Apraxia: Evidence from Mu Suppression.

Stroke patients with ideomotor apraxia (IMA) have difficulties controlling voluntary motor actions, as clearly seen when asked to imitate simple gestures performed by the examiner. Despite extensive research, the neurophysiological mechanisms underlying failure to imitate gestures in IMA remain controversial. The aim of the current study was to explore the relationship between imitation failure in IMA and mirror neuron system (MNS) functioning. Mirror neurons were found to play a crucial role in movement imitation and in imitation-based motor learning. Their recruitment during movement observation and execution is signaled in EEG recordings by suppression of the lower (8-10 Hz) mu range. We examined the modulation of EEG in this range in stroke patients with left (n = 21) and right (n = 15) hemisphere damage during observation of video clips showing different manual movements. IMA severity was assessed by the DeRenzi standardized diagnostic test. Results showed that failure to imitate observed manual movements correlated with diminished mu suppression in patients with damage to the right inferior parietal lobule and in patients with damage to the right inferior frontal gyrus pars opercularis-areas where major components of the human MNS are assumed to reside. Voxel-based lesion symptom mapping revealed a significant impact on imitation capacity for the left inferior and superior parietal lobules and the left post central gyrus. Both left and right hemisphere damages were associated with imitation failure typical of IMA, yet a clear demonstration of relationship to the MNS was obtained only in the right hemisphere damage group. Suppression of the 8-10 Hz range was stronger in central compared with occipital sites, pointing to a dominant implication of mu rather than alpha rhythms. However, the suppression correlated with De Renzi's apraxia test scores not only in central but also in occipital sites, suggesting a multifactorial mechanism for IMA, with a possible impact for deranged visual attention (alpha suppression) beyond the effect of MNS damage (mu suppression).

Cognitive training can reduce the rate of cognitive aging: a neuroimaging cohort study.

BackgroundThe neural mechanisms underlying the restorative effects of cognitive training on aging brains remain unclear. To address this issue, we examined the relationship between changes in spontaneous brain activity and cognitive performance that occur after cognitive training.MethodsParticipants were older adults who were part of a randomized control trial within a larger longitudinal cognitive training study. We conducted single-domain and multi-domain cognitive training in two respective intervention groups. Participants were trained for 1 h, twice a week, for 12 weeks. Cognition was assessed in all participants and magnetic resonance images were obtained at baseline and 1 year after training. To assess spontaneous fluctuations in brain activity, we acquired resting-state fMRI data. Two indices—functional entropy and time-domain entropy—were used to measure the effects of training. Functional entropy increases with aging, and indicates disruptions in functional conectivity. Time-domain entropy decreases with aging, and indicates structural alterations in the brain and blood-flow reduction.ResultsSeventy participants completed the study: 26 in the multi-domain cognitive training group (70.38 ± 3.30 yrs), 27 in single-domain group (70.48 ± 3.93 yrs), and 17 in a control group (68.59 ± 3.24 yrs). Functional entropy increased significantly less in the multi-domain (p = 0.047) and single-domain groups (p = 9.51 × 10−4) compared with the control group. In the multi-domain group, this was true in the paracentral lobule (p = 0.004, Bonferroni corrected p < 0.05). Time-domain entropy also improved with training. Compared with controls, time-domain entropy in the multi-domain group decreased less in the inferior frontal gyrus pars opercularis (p = 3.59 × 10−4), the medial part of superior frontal gyrus (p = 1.17 × 10−5), and the thalamus (p = 4.72 × 10−5), while that in the single-domain group decreased less in the cuneus (p = 2.58 × 10−4, Bonferroni corrected p < 0.05). Additionally, changes in regional entropy for some regions such as hippocampus significantly correlated with improvements in cognitive performance.ConclusionsCognitive training can induce plastic changes in neural functional connectivity of healthy older people, and these changes may underlie the positive effect of cognitive training.Trial registrationChiCTR-TRC-08000732 (Date of registration: 5th November, 2008).Electronic supplementary materialThe online version of this article (doi:10.1186/s12877-016-0194-5) contains supplementary material, which is available to authorized users.

The relationships between the amount of spared tissue, percent signal change, and accuracy in semantic processing in aphasia

Recovery from aphasia, loss of language following a cerebrovascular incident (stroke), is a complex process involving both left and right hemispheric regions. In our study, we analyzed the relationships between semantic processing behavioral data, lesion size and location, and percent signal change from functional magnetic resonance imaging (fMRI) data. This study included 14 persons with aphasia in the chronic stage of recovery (six or more months post stroke), along with normal controls, who performed semantic processing tasks of determining whether a written semantic feature matched a picture or whether two written words were related. Using region of interest (ROI) analysis, we found that left inferior frontal gyrus pars opercularis and pars triangularis, despite significant damage, were the only regions to correlate with behavioral accuracy. Additionally, bilateral frontal regions including superior frontal gyrus, middle frontal gyrus, and anterior cingulate appear to serve as an assistive network in the case of damage to traditional language regions that include inferior frontal gyrus, middle temporal gyrus, supramarginal gyrus, and angular gyrus. Right hemisphere posterior regions including right middle temporal gyrus, right supramarginal gyrus, and right angular gyrus are engaged in the case of extensive damage to left hemisphere language regions. Additionally, right inferior frontal gyrus pars orbitalis is presumed to serve a monitoring function. These results reinforce the importance of the left hemisphere in language processing in aphasia, and provide a framework for the relative importance of left and right language regions in the brain.

Developmental changes in brain activation involved in the production of novel speech sounds in children

Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6-18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech.

Early Activity in Broca's Area During Reading Reflects Fast Access to Articulatory Codes From Print

Prior evidence for early activity in Broca's area during reading may reflect fast access to articulatory codes in left inferior frontal gyrus pars opercularis (LIFGpo). We put this hypothesis to test using a benchmark for articulatory involvement in reading known as the masked onset priming effect (MOPE). In masked onset priming, briefly presented pronounceable strings of letters that share an initial phoneme with subsequently presented target words (e.g., gilp-GAME) facilitate word naming responses compared with unrelated primes (dilp-GAME). Crucially, these priming effects only occur when the task requires articulation (naming), and not when it requires lexical decisions. A standard explanation of masked onset priming is that it reflects fast computation of articulatory output codes from letter representations. We therefore predicted 1) that activity in left IFG pars opercularis would be modulated by masked onset priming, 2) that priming-related modulation in LIFGpo would immediately follow activity in occipital cortex, and 3) that this modulation would be greater for naming than for lexical decision. These predictions were confirmed in a magnetoencephalography (MEG) priming study. MOPEs emerged in left IFG at ∼100 ms posttarget onset, and the priming effects were more sustained when the task involved articulation.