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Recent work has suggested that variability in levels of neural activation may be related to behavioral and cognitive performance across a number of domains and may offer information that is not captured by more traditional measures that use the average level of brain activation. We examined the relationship between reading skill in school-aged children and neural activation variability during a functional MRI reading task after taking into account average levels of activity. The reading task involved matching printed and spoken words to pictures of items. Single trial activation estimates were used to calculate the mean and standard deviation of children's responses to print and speech stimuli; multiple regression analyses evaluated the relationship between reading skill and trial-by-trial activation variability. The reliability of observed findings from the discovery sample (n = 44; ages 8-11; 18 female) was then confirmed in an independent sample of children (n = 32; ages 8-11; 14 female). Across the two samples, reading skill was positively related to trial-by-trial variability in the activation response to print in the left inferior frontal gyrus pars triangularis. This relationship held even when accounting for mean levels of activation. This finding suggests that intrasubject variability in trial-by-trial fMRI activation responses to printed words accounts for individual differences in human reading ability that are not fully captured by traditional mean levels of brain activity. Furthermore, this positive relationship between trial-by-trial activation variability and reading skill may provide evidence that neural variability plays a beneficial role during early reading development.SIGNIFICANCE STATEMENT Recent work has suggested that neural activation variability, or moment-to-moment changes in the engagement of brain regions, is related to individual differences in behavioral and cognitive performance across multiple domains. However, differences in neural activation variability have not yet been evaluated in relation to reading skill. In the current study, we analyzed data from two independent groups of children who performed an fMRI task involving reading and listening to words. Across both samples, reading skill was positively related to trial-by-trial variability in activation to print stimuli in the left inferior frontal gyrus pars triangularis, even when accounting for the more conventional measure of mean levels of brain activity. This finding suggests that neural variability could be beneficial in developing readers.

Neuroimaging studies of biological motion perception have found a network of coordinated brain areas, the hub of which appears to be the human posterior superior temporal sulcus (STSp). Understanding the functional role of the STSp requires characterizing the response tuning of neuronal populations underlying the BOLD response. Thus far our understanding of these response properties comes from single-unit studies of the monkey anterior STS, which has individual neurons tuned to body actions, with a small population invariant to changes in viewpoint, position and size of the action being viewed. To measure for homologous functional properties on the human STS, we used fMR-adaptation to investigate action, position and size invariance. Observers viewed pairs of point-light animations depicting human actions that were either identical, differed in the action depicted, locally scrambled, or differed in the viewing perspective, the position or the size. While extrastriate hMT+ had neural signals indicative of viewpoint specificity, the human STS adapted for all of these changes, as compared to viewing two different actions. Similar findings were observed in more posterior brain areas also implicated in action recognition. Our findings are evidence for viewpoint invariance in the human STS and related brain areas, with the implication that actions are abstracted into object-centered representations during visual analysis.

In this study, active and arousal elements of emotion associated with acute stress were systematically investigated with respect to the relations between the brain activity and autonomic nervous system. In this regard, we examined the differences in short-term heart rate variability (HRV) with respect to time-frequency domain characteristics, nonlinear features, and heart rhythm patterns, when breathing volitionally in a resonant frequency (RF) respiratory with International Affective Picture Systems (IAPS) triggered negative stimulus. In this regard, a sample-based event-related functional magnetic resonance imaging (efMRI) experiments were performed to verify the dynamic changes in brain lateralisation, and 105 healthy right-handed subjects participated in the HRV study while eight of them were randomly chosen to perform small sample based efMRI test. The experimental results suggest that when experiencing negative emotions, RF-based volitional breathing is sufficient to facilitate coherence of autonomic nervous system (ANS) performance, and shifted the brain activation toward left lateralized neural activity. In combination with the previous research on cerebral correlates of emotion, this study validated the feasibility of applying HRV biofeedback in the regulation of negative emotion in healthcare settings. [ABSTRACT FROM AUTHOR]

Although research on goal-directed, proactive inhibitory control (IC) and stimulus-driven, reactive IC is growing, no previous study has compared proactive IC in conditions of uncertainty with regard to upcoming inhibition to conditions of certain upcoming IC. Therefore, we investigated effects of certainty and uncertainty on behavior and blood oxygen level dependent (BOLD) signal in proactive and reactive IC. In two studies, healthy adults performed saccadic go/no-go and prosaccade/antisaccade tasks. The certainty manipulation had a highly significant behavioral effect in both studies, with inhibitory control being more successful under certain than uncertain conditions on both tasks (p ≤ 0.001). Saccadic go responses were significantly less efficient under conditions of uncertainty than certain responding (p < 0.001). Event-related functional magnetic resonance imaging (fMRI) (one study) revealed a dissociation of certainty- and uncertainty-related proactive inhibitory neural correlates in the go/no-go task, with lateral and medial prefrontal and occipital cortex showing stronger deactivations during uncertainty than during certain upcoming inhibition, and lateral parietal cortex being activated more strongly during certain upcoming inhibition than uncertainty or certain upcoming responding. In the antisaccade task, proactive BOLD effects arose due to stronger deactivations in uncertain response conditions of both tasks and before certain prosaccades than antisaccades. Reactive inhibition-related BOLD increases occurred in inferior parietal cortex and supramarginal gyrus (SMG) in the go/no-go task only. Proactive IC may imply focusing attention on the external environment for encoding salient or alerting events as well as inhibitory mechanisms that reduce potentially distracting neural processes. SMG and inferior parietal cortex may play an important role in both proactive and reactive IC of saccades. [ABSTRACT FROM AUTHOR]

Central sensitization is a driving mechanism in many chronic pain patients, and manifests as hyperalgesia and allodynia beyond any apparent injury. Recent studies have demonstrated analgesic effects of motor cortex (M1) stimulation in several chronic pain disorders, yet its neural mechanisms remain uncertain. We evaluated whether anodal M1 transcranial direct current stimulation (tDCS) would mitigate central sensitization as measured by indices of secondary hyperalgesia. We used a capsaicin-heat pain model to elicit secondary mechanical hyperalgesia in 27 healthy subjects. In an assessor and subject-blind randomized, sham-controlled, crossover trial, anodal M1 tDCS decreased the intensity of pinprick hyperalgesia more than cathodal or sham tDCS. To elucidate the mechanism driving analgesia, subjects underwent fMRI of painful mechanical stimuli prior to and following induction of the pain model, after receiving M1 tDCS. We hypothesized that anodal M1 tDCS would enhance engagement of a descending pain modulatory (DPM) network in response to mechanical stimuli. Anodal tDCS normalized the effects of central sensitization on neurophysiological responses to mechanical pain in the medial prefrontal cortex, pregenual anterior cingulate cortex, and periaqueductal gray, important regions in the DPM network. Taken together, these results provide support for the hypothesis that anodal M1-tDCS reduces central sensitization-induced hyperalgesia through the DPM network in humans.

Central sensitization is a driving mechanism in many chronic pain patients, and manifests as hyperalgesia and allodynia beyond any apparent injury. Recent studies have demonstrated analgesic effects of motor cortex (M1) stimulation in several chronic pain disorders, yet its neural mechanisms remain uncertain. We evaluated whether anodal M1 transcranial direct current stimulation (tDCS) would mitigate central sensitization as measured by indices of secondary hyperalgesia. We used a capsaicin-heat pain model to elicit secondary mechanical hyperalgesia in 27 healthy subjects. In an assessor and subject-blind randomized, sham-controlled, crossover trial, anodal M1 tDCS decreased the intensity of pinprick hyperalgesia more than cathodal or sham tDCS. To elucidate the mechanism driving analgesia, subjects underwent fMRI of painful mechanical stimuli prior to and following induction of the pain model, after receiving M1 tDCS. We hypothesized that anodal M1 tDCS would enhance engagement of a descending pain modulatory (DPM) network in response to mechanical stimuli. Anodal tDCS normalized the effects of central sensitization on neurophysiological responses to mechanical pain in the medial prefrontal cortex, pregenual anterior cingulate cortex, and periaqueductal gray, important regions in the DPM network. Taken together, these results provide support for the hypothesis that anodal M1-tDCS reduces central sensitization-induced hyperalgesia through the DPM network in humans. [ABSTRACT FROM AUTHOR]

Abstract Perception is a highly active process relying on the continuous formulation of predictive inferences using short-term sensory memory templates, which are recursively adjusted based on new input. According to this idea, earlier studies have shown that novel stimuli preceded by a higher number of repetitions yield greater novelty responses, indexed by larger mismatch negativity (MMN). However, it is not clear whether this MMN memory trace effect is driven by more adapted responses to prior stimulation or rather by a heightened processing of the unexpected deviant, and only few studies have so far attempted to characterize the functional neuroanatomy of these effects. Here we implemented a modified version of the auditory frequency oddball paradigm that enables modeling the responses to both repeated standard and deviant stimuli. Fifteen subjects underwent functional magnetic resonance imaging (fMRI) while their attention was diverted from auditory stimulation. We found that deviants with longer stimulus history of standard repetitions yielded a more robust and widespread activation in the bilateral auditory cortex. Standard tones repetition yielded a pattern of response entangling both suppression and enhancement effects depending on the predictability of upcoming stimuli. We also observed that regularity encoding and deviance detection mapped onto spatially segregated cortical subfields. Our data provide a better understanding of the neural representations underlying auditory repetition and deviance detection effects, and further support that perception operates through the principles of Bayesian predictive coding. Highlights • We have implemented a frequency roving standard paradigm while recording hemodynamic responses • Deviant tones preceded by a higher number of standard stimuli elicited larger auditory responses • Deviant tone predictability modulated the encoding of statistical auditory regularities • Stimulus repetition differentially modulated the hemodynamic response to standard and deviant tones [ABSTRACT FROM AUTHOR]

Developmental dyslexia is a specific deficit in reading and spelling that often persists into adulthood. In the present study, we used slow event-related fMRI and independent component analysis to identify brain networks involved in perception of audio-visual speech in a group of adult readers with dyslexia (RD) and a group of fluent readers (FR). Participants saw a video of a female speaker saying a disyllabic word. In the congruent condition, audio and video input were identical whereas in the incongruent condition, the two inputs differed. Participants had to respond to occasionally occurring animal names. The independent components analysis (ICA) identified several components that were differently modulated in FR and RD. Two of these components including fusiform gyrus and occipital gyrus showed less activation in RD compared to FR possibly indicating a deficit to extract face information that is needed to integrate auditory and visual information in natural speech perception. A further component centered on the superior temporal sulcus (STS) also exhibited less activation in RD compared to FR. This finding is corroborated in the univariate analysis that shows less activation in STS for RD compared to FR. These findings suggest a general impairment in recruitment of audiovisual processing areas in dyslexia during the perception of natural speech. [ABSTRACT FROM AUTHOR]

Recent work has suggested that variability in levels of neural activation may be related to behavioral and cognitive performance across a number of domains and may offer information that is not captured by more traditional measures that use the average level of brain activation. We examined the relationship between reading skill in school-aged children and neural activation variability during a functional MRI reading task after taking into account average levels of activity. The reading task involved matching printed and spoken words to pictures of items. Single trial activation estimates were used to calculate the mean and standard deviation of children's responses to print and speech stimuli; multiple regression analyses evaluated the relationship between reading skill and trial-by-trial activation variability. The reliability of observed findings from the discovery sample (n = 44; ages 8-11; 18 female) was then confirmed in an independent sample of children (n = 32; ages 8-11; 14 female). Across the two samples, reading skill was positively related to trial-by-trial variability in the activation response to print in the left inferior frontal gyrus pars triangularis. This relationship held even when accounting for mean levels of activation. This finding suggests that intrasubject variability in trial-by-trial fMRI activation responses to printed words accounts for individual differences in human reading ability that are not fully captured by traditional mean levels of brain activity. Furthermore, this positive relationship between trial-by-trial activation variability and reading skill may provide evidence that neural variability plays a beneficial role during early reading development. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) causes neural dysfunction associated with cognitive deficit and emotional dysregulation. This study assessed the associations of the neurofunctional changes, gray matter (GM) and white matter (WM) volume alterations in conjunction with in vivo metabolic changes on the working memory tasks in patients with OCD.Methods: Eighteen patients with OCD and 18 healthy controls matched for age, sex, and educational levels underwent high-resolution T1-weighted magnetic resonance imaging (MRI), event-related functional MRI (fMRI), and proton magnetic resonance spectroscopy (1H-MRS) at 3T.Results: In fMRI, patients with OCD showed lower activities in the cerebellum, inferior temporal gyrus, orbitofrontal gyrus, dorsolateral prefrontal cortex and calcarine gyrus compared to the controls. In VBM, the patients showed significantly reduced GM volumes, especially in the cerebellum, hippocampus, and superior temporal gyrus, together with significantly reduced WM volumes in the retrolenticular part of the internal capsule, dorsolateral prefrontal cortex (DLPFC) and orbitofrontal gyrus. In 1H-MRS, the ratios of N-acetylaspartate/creatine and choline/creatine were significantly lower in the DLPFC of the patients than in the controls, whereas the ratio of β∙γ-glutamine-glutamate/creatine was significantly higher in the patients than in the controls.Limitations: This study examined small numbers of subjects in each one of the groups.Conclusions: The findings will be helpful to aid us in understanding of neurocognitive impairment in OCD, and thus, enhancing the diagnostic accuracy for OCD by additional information on the associated brain functional deficit, cerebral volume change and metabolic abnormality. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) can generate brain images that show neuronal activity due to sensory, cognitive or motor tasks. Haemodynamic response function (HRF) may be considered as a biomarker to discriminate the Alzheimer disease (AD) from healthy ageing. As blood-oxygenation-level-dependent fMRI signal is much weak and noisy, particularly for the elderly subjects, a robust method is necessary for HRF estimation to efficiently differentiate the AD. After applying minimum description length wavelet as an extra denoising step, deconvolution algorithm is here employed for HRF estimation, substituting the averaging method used in the previous works. The HRF amplitude peaks are compared for three groups HRF of young, non-demented and demented elderly groups for both vision and motor regions. Prior works often reported significant differences in the HRF peak amplitude between the young and the elderly. The authors’ experimentations show that the HRF peaks are not significantly different comparing the young adults with the elderly (either demented or non-demented). It is here demonstrated that the contradictory findings of the previous studies on the HRF peaks for the elderly compared with the young are originated from the noise contribution in fMRI data.

Purpose To assess the impact of colored noise on statistics in event-related functional MRI (fMRI) (visual stimulation using checkerboards) acquired by simultaneous multislice imaging enabling repetition times (TRs) between 2.64 to 0.26 s. Methods T-values within the visual cortex obtained with analysis tools that assume a first-order autoregressive plus white noise process (AR(1)+w) with a fixed AR coefficient versus higher-order AR models with spatially varying AR coefficients were compared. In addition, dependency of T-values on correction of physiological noise (respiration, heart rate) was evaluated. Results Optimal statistical power was obtained for a TR of 0.33 s, but T-values as obtained by AR(1)+w models were strongly dependent on the predefined AR coefficients in fMRI with short TRs which required higher-order AR models to achieve stable statistics. Direct estimation of AR coefficients revealed the highest values within the default mode network while physiological noise had little influence on statistics in cortical structures. Conclusion Colored noise in event-related fMRI obtained at short TRs originates mainly from neural sources and calls for more sophisticated correction of serial autocorrelations which cannot be achieved with standard methods relying on AR(1)+w models with globally fixed AR coefficients. Magn Reson Med 76:1805-1813, 2016. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]

It is predicted that bilinguals rely on their first language (L1) to process the second language (L2). However, it remains largely unknown as to how the brain processes unique grammatical features of L2. To answer this question, we explored how Chinese-English bilinguals recognized English inflected verbs that are lacking in Chinese. By using a semantic consistency judgment task, we found that highly proficient late bilinguals processed dichotomic regular and irregular inflections the way English monolinguals did. Behaviorally, regular past tense verbs significantly primed recognition of verb stems, but irregulars did not enhance recognition of their simple forms. Brain imaging results showed that, in contrast to irregulars, late bilinguals additionally employed the procedural memory system of the inferior frontal gyrus (IFG), superior temporal gyrus (STG), middle temporal gyrus (MTG), supramarginal gyrus (SMG), cerebellum, and basal ganglia (BG) to process regulars. Such a differential brain activity pattern elicited by L2 syntax and semantics was distinctive from the way Chinese-English bilinguals processed their L1 syntax and semantics, which supported Ullman's declarative/procedural model. Native-like brain activity elicited by L2 grammatical features suggested that unique language features were processed through specialized neural substrates by late bilinguals either. Meanwhile, we also found that late bilingual learners with a high L2 proficiency still employed the cognitive control system (the BA47 and dorsal lateral prefrontal cortex, DLPFC) more heavily to process L2 syntax than L2 semantics. It supported the sensorimotor/emergentist (S/E) model which emphasized that cognitive control must be involved in L2 processing, and ran contrary to the fade-away prediction of the cognitive control process of the Convergent Hypothesis. [ABSTRACT FROM AUTHOR]

Many studies have proven transcranial alternating current stimulation (tACS) to manipulate brain activity. Until now it is not known, however, how these manipulations in brain activity are represented in brain metabolism or how spatially specific these changes are. Alpha-tACS has been shown to enhance the amplitude of the individual alpha frequency (IAF) and a negative correlation between alpha amplitude and occipital BOLD signal was reported in numerous EEG/fMRI experiments. Thus, alpha-tACS was chosen to test the effects of tACS on the BOLD signal. A reduction thereof was expected during alpha-tACS which shows the spatial extent of tACS effects beyond modeling studies. Three groups of subjects were measured in an MRI scanner, receiving tACS at either their IAF (N = 11), 1 Hz (control; N = 12) or sham (i.e., no stimulation — a second control; N = 11) while responding to a visual vigilance task. Stimulation was administered in an interleaved pattern of tACS-on runs and tACS-free baseline periods. The BOLD signal was analyzed in response to tACS-onset during resting state and in response to seldom target stimuli. Alpha-tACS at 1.0 mA reduced the task-related BOLD response to visual targets in the occipital cortex as compared to tACS-free baseline periods. The deactivation was strongest in an area where the BOLD signal was shown to correlate negatively with alpha amplitude. A direct effect of tACS on resting state BOLD signal levels could not be shown. Our findings suggest that tACS-related changes in BOLD activity occur only as a modulation of an existing BOLD response. [ABSTRACT FROM AUTHOR]

Background Recently, Bastiaanse et al. (2011) identified past time-reference morphology as a particular source of the prominent verb inflection problems in agrammatism. Using a verb form with past time-reference requires additional processing, because a link has to be made to the event in discourse—this in contrast to non-past time-reference. Discourse-related electrophysiological processing differences were demonstrated in non-brain-damaged speakers earlier (Bos et al., 2013). As tense is not equivalent to time-reference, this theory applies to all discourse-linked verb forms, regardless of tense. For example, reference to the past can be made by simple past (‘V-ed’), or by an auxiliary in present tense plus a participle, the periphrastic past (‘has+V-ed’). For Dutch aphasic speakers both types of past time-reference are more difficult than simple present (Bos & Bastiaanse, 2014). Sahin et al. (2006) found left inferior frontal gyrus (IFG) and supplementary motor area (SMA) involvement in processing grammatical morphology for simple past versus simple present tense. We investigated if and where discourse-linked past time-reference is reflected in additional brain activation for periphrastic verbs forms that differ in time reference, but not in tense of the auxiliary. Methods We carried out an event related fMRI-study with 20 healthy Dutch speakers (mean age 24). They were presented with a picture denoting the target verb action. Subsequently, a written sentence had to be completed with non-past or past time-reference. One or two series of dots indicated single or periphrastic target verb forms, respectively. Contrasts were (1) simple past versus simple present tense (skated–skates) and (2) periphrastic past versus future time-reference (has skated–will skate). We analysed DARTEL-normalised functional scans of response preparation from picture offset to response onset in SPM8 with a factorial design (time-reference x simple/periphrastic). Results/discussion Analysis (see Figure 1) showed greater BOLD signal change for both types of past over non-past time-reference bilaterally frontal—the SMA and frontal superior medial gyrus. We ascribe this to increased difficulty in selecting past time-reference inflection, hence, discourse linking. We found significantly increased LIFG activation for simple past over simple present, but not for periphrastic past over future (see Figure 1C). LIFG might be taxed for past tense inflection, but not past time-reference specifically. Although periphrastic past and future differ in time-reference, both verb clusters have a present tense auxiliary. Our results align with a fundamental difference between past and non-past time-reference, and are in accordance with past time-reference processing difficulties of aphasic individuals.

Functional Magnetic Resonance Imaging (fMRI) was used to investigate the brain activity associated with response change in a belief bias paradigm before and after logic training. Participants completed two sets of belief biased reasoning tasks. In the first set they were instructed to respond based on their empirical beliefs, and in the second – following logic training – they were instructed to respond logically. The comparison between conflict problems in the second scan versus in the first scan revealed differing activation for the left inferior frontal gyrus, left middle frontal gyrus, cerebellum, and precuneus. The scan was time locked to the presentation of the minor premise, and thus demonstrated effects of belief–logic conflict on neural activation earlier in the time course than has previously been shown in fMRI. These data, moreover, indicated that logical training results in changes in brain activity associated with cognitive control processing. [ABSTRACT FROM AUTHOR]

Highlights: [•] Event-related fMRI investigated the contribution of the right hemisphere in linguistic tasks. [•] Bilateral involvement of the pars opercularis (Brodmann’s area 44). [•] Bilateral involvement of the supramarginal gyrus of the inferior parietal lobule. [•] Strong connections between areas 44 and 40 through SLF III. [•] Delineate anterior-posterior language processing system bilaterally. [•] Increased right hemisphere involvement during metaphorical interpretations. [ABSTRACT FROM AUTHOR]

Abstract: The current study investigated neuropsychological and underlying structural and functional brain alterations in long-term adequately treated patients with Hashimoto's thyroiditis in order to examine much discussed residual complaints in patients in relation to possible long-term neural alterations with a specific interest in the underlying autoimmune process. Eighteen patients with treated hypothyroidism due to Hashimoto's thyroiditis (mean age 32, range 18–54 years; two males; mean treatment duration 4.4 years) and 18 healthy matched control subjects underwent 3-Tesla magnetic resonance imaging (MRI). Voxel-based morphometry was used to investigate grey matter density, resting-state functional MRI to analyse the brain connectivity of areas known to be altered in hypothyroidism and event-related functional MRI to examine brain activity during associative memory encoding. Neuropsychological assessment included memory, working memory, psychomotor speed and attention. We previously reported subclinically reduced mood in this study population and investigated its neural correlates here. Thyroid stimulating hormone, free triiodthyronine, free thyroxine and thyroid peroxidase antibodies were measured in serum. We did not find cognitive deficits or alterations in grey matter density, functional connectivity or associative memory-related brain activity in comparison to the control group and cognition was unrelated to thyroid serum measures in the patient group. Thyroid peroxidase antibodies in the patient group correlated with increased grey matter density in right amygdala and enhanced connectivity between subcallosal and parahippocampal areas. Treatment duration was associated with brain structure in frontal and occipital cortex and connectivity between left amygdala and frontal cortex. Mood correlated with brain areas associated with distinct functional networks, but not with those most prominently affected in depression. In conclusion, no cognitive or neural alterations were detected in this young and otherwise healthy cohort of patients in comparison to a healthy control group and current mood status could not be related to depression-related networks. However, autoimmune activity and treatment duration showed a relationship with depression and hypothyroidism-related brain structure and function. They are thus promising factors to further investigate residual complaints despite biochemically adequate treatment in patients with Hashimoto's thyroiditis. Given the small sample size, all findings require replication. [Copyright &y& Elsevier]

Abstract: Understanding the intentions and desires of those around us is vital for adapting to a dynamic social environment. In this paper, a novel event-related functional Magnetic Resonance Imaging (fMRI) paradigm with dynamic and natural stimuli (2s video clips) was developed to directly examine the neural networks associated with processing of gestures with social intent as compared to nonsocial intent. When comparing social to nonsocial gestures, increased activation in both the mentalizing (or theory of mind) and amygdala networks was found. As a secondary aim, a factor of actor-orientation was included in the paradigm to examine how the neural mechanisms differ with respect to personal engagement during a social interaction versus passively observing an interaction. Activity in the lateral occipital cortex and precentral gyrus was found sensitive to actor-orientation during social interactions. Lastly, by manipulating face-visibility we tested whether facial information alone is the primary driver of neural activation differences observed between social and nonsocial gestures. We discovered that activity in the posterior superior temporal sulcus (pSTS) and fusiform gyrus (FFG) was partially driven by observing facial expressions during social gestures. Altogether, using multiple factors associated with processing of natural social interaction, we conceptually advance our understanding of how social stimuli is processed in the brain and discuss the application of this paradigm to clinical populations where atypical social cognition is manifested as a key symptom. [Copyright &y& Elsevier]

Highlights: [•] Functional magnetic resonance imaging, real-life scientific innovation problem materials and experimental paradigm were used. [•] The left DLPFC might be responsible for the automatic retrieval of technical problems. [•] The left AG might be involved in forming novel associations between technical problems and related prototypes. [Copyright &y& Elsevier]

Heuristics through the application of heuristic knowledge to the creation of imitation devices may be one of the most common processes in scientific innovation. In particular, heuristics suggests that innovation includes the automatic activation of heuristic knowledge and formation of novel associations between heuristic knowledge and problem situations. In this study, 76 scientific innovation problem situations were selected as materials. Among these, 36 contain related heuristic knowledge and 40 have no such information. Through functional magnetic resonance imaging, the learning-testing paradigm was used to explore the brain mechanisms of scientific problem finding inspired by heuristic knowledge. Participants were asked to find a problem on the basis of a given innovation problem situation. Two scenarios were presented: finding scientific problems with related heuristic knowledge and finding conventional problems without related heuristic knowledge. The authors assumed that the regions in the brain significantly activated by the finding scientific problems with related heuristic knowledge condition compared with the finding normal problems without related heuristic knowledge condition are relevant to the brain mechanisms of scientific problem finding inspired by heuristic knowledge. The first scenario more significantly activated the left precuneus and left angular gyrus than did the second scenario. These findings suggest that the precuneus is relevant to the successful storage and retrieval of heuristic knowledge and that the left angular gyrus is involved in the formation of novel associations between heuristic knowledge and problem situations for finding scientific problems. [ABSTRACT FROM AUTHOR]

Abstract: Technical developments in MRI have improved signal to noise, allowing use of analysis methods such as Finite impulse response (FIR) of rapid event related functional MRI (er-fMRI). FIR is one of the most informative analysis methods as it determines onset and full shape of the hemodynamic response function (HRF) without any a priori assumptions. FIR is however vulnerable to multicollinearity, which is directly related to the distribution of stimuli over time. Efficiency can be optimized by simplifying a design, and restricting stimuli distribution to specific sequences, while more design flexibility necessarily reduces efficiency. However, the actual effect of efficiency on fMRI results has never been tested in vivo. Thus, it is currently difficult to make an informed choice between protocol flexibility and statistical efficiency. The main goal of this study was to assign concrete fMRI signal to noise values to the abstract scale of FIR statistical efficiency. Ten subjects repeated a perception task with five random and m-sequence based protocol, with varying but, according to literature, acceptable levels of multicollinearity. Results indicated substantial differences in signal standard deviation, while the level was a function of multicollinearity. Experiment protocols varied up to 55.4% in standard deviation. Results confirm that quality of fMRI in an FIR analysis can significantly and substantially vary with statistical efficiency. Our in vivo measurements can be used to aid in making an informed decision between freedom in protocol design and statistical efficiency. [Copyright &y& Elsevier]

Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g., stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to nonincentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to nonincentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered. Hum Brain Mapp , 2013. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Neural correlates of Braille reading have been widely studied with different neuroimaging techniques. Nevertheless, the exact brain processes underlying this unique activity are still unknown, due to suboptimal accuracy of imaging and/or stimuli delivery methods. To study somatosensory perception effectively, the stimulation must reflect parameters of the natural stimulus and must be applied with precise timing. In functional magnetic resonance imaging (fMRI) providing these characteristics requires technologically advanced solutions and there have been several successful direct tactile stimulation devices designed that allow investigation of somatotopic organization of brain sensory areas. They may, however, be of limited applicability in studying brain mechanisms related to such distinctive tactile activity as Braille reading. In this paper we describe the design and experimental evaluation of an innovative MRI-compatible Braille Character Stimulator (BCS) enabling precise and stable delivery of standardized Braille characters with high temporal resolution. Our device is fully programmable, flexible in stimuli delivery and can be easily implemented in any research unit. The Braille Character Stimulator was tested with a same-different discrimination task on Braille characters during an event-related fMRI experiment in eleven right-handed sighted adult subjects. The results show significant activations in several cortical areas, including bilateral primary (SI) and secondary somatosensory (SII) cortices, bilateral premotor and supplementary motor areas, inferior frontal gyri, inferior temporal gyri and precuneus, as well as contralateral (to the stimulated hand) thalamus. The results validate the use of the BCS as a method of effective stimuli application in fMRI studies, in both sighted and visually impaired subjects. [Copyright &y& Elsevier]

Abstract: Functional magnetic resonance imaging (fMRI) exploits the blood oxygenation level dependent (BOLD) effect to detect neuronal activation related to various experimental paradigms. Some of these, such as reversal learning, involve the orbitofrontal cortex and its interaction with other brain regions like the amygdala, striatum or dorsolateral prefrontal cortex. These paradigms are commonly investigated with event-related methods and gradient echo-planar imaging (EPI) with short echo time of 27 ms. However, susceptibility-induced signal losses and image distortions in the orbitofrontal cortex are still a problem for this optimized sequence as this brain region consists of several slices with different optimal echo times. An EPI sequence with slice-dependent echo times is suitable to maximize BOLD sensitivity in all slices and might thus improve signal detection in the orbitofrontal cortex. To test this hypothesis, we first optimized echo times via BOLD sensitivity simulation. Second, we measured 12 healthy volunteers using a standard EPI sequence with an echo time of 27 ms and a modified EPI sequence with echo times ranging from 22 ms to 47 ms. In the orbitofrontal cortex, the number of activated voxels increased from 87±44 to 549±83 and the maximal t-value increased from 4.4±0.3 to 5.4±0.3 when the modified EPI was used. We conclude that an EPI with slice-dependent echo times may be a valuable tool to mitigate susceptibility artifacts in event-related whole-brain fMRI studies with a focus on the orbitofrontal cortex. [Copyright &y& Elsevier]

Abstract: Despite vast knowledge on the behavioral processes mediating the development of episodic memory, little is known about the neural mechanisms underlying these changes. We used event-related fMRI to examine the neural correlates of both encoding and recall processes during an episodic memory task in two different groups of school age children (8–9 and 12–13 years). The memory task was composed of an encoding phase in which children were presented with a series of unrelated pictorial pairs, and a retrieval phase during which one of these items acted as a cue to prompt recall of the paired item. Age-related differences in activations were observed for both encoding and recall. Younger children recruited additional regions in the right dorsolateral prefrontal and right temporal cortex compared to older children during successful encoding of the pairs. During successful recall, older children recruited additional regions in the left ventrolateral prefrontal and left inferior parietal cortex compared to younger children. The results suggest that the prefrontal cortex contributes to not only the formation of memories but also access to them, and this contribution changes with development. The protracted development of the prefrontal cortex has implications for our understanding of the development of episodic memory. [Copyright &y& Elsevier]

Background & Aims: Patients with irritable bowel syndrome (IBS) have increased activity in the insula and reduced activation of the dorsolateral prefrontal cortex (DLPFC) in response to visceral stimulation. We investigated whether they have latent impairments in cognitive flexibility because of dysfunction in the DLPFC and insula and altered connectivity between brain regions. Methods: We analyzed data from 30 individuals with IBS (15 men; age, 21.7 ± 3.0 y) diagnosed based on Rome III criteria, along with 30 individuals matched for age, sex, and education level (controls). Event-related functional magnetic resonance imaging of the brain was performed to evaluate cognitive flexibility and was assessed by the Wisconsin Card Sorting Test, in which subjects are allowed to change choice criteria, defined as set-shifting in response to error feedback. Brain images were analyzed with statistical parametric mapping 5 and 8 software and dynamic causal modeling. Results: Subjects with IBS had significantly more Nelson perseverative errors (P < .05) and set-maintenance difficulties (P < .05) than controls. They also showed significantly decreased activity of the right DLPFC (Brodmann''s area 9; P < .001) and right hippocampus (P < .001), and significantly increased activity of the left posterior insula (P < .001) at error feedback during set-shifting. Dynamic causal modeling analysis during set-shifting revealed significantly less connectivity from the DLPFC to pre–supplementary motor area in subjects with IBS, compared with controls (P = .012). Conclusions: Individuals with IBS have latent impairments in cognitive flexibility as a result of altered activity of the DLPFC, insula, and hippocampus, and impaired connectivity between the DLPFC and pre–supplementary motor area. [Copyright &y& Elsevier]

A quantitative approach to virtual-lesion physiology is presented which integrates event-related fMRI, image-guided, repetitive, transcranial magnetic stimulation (irTMS), and simultaneous recording of 3-D movement kinematics. By linking motor neuroscience with clinical disorders of motor function, our method allows development of a healthy, human system model of disorders of skilled action. [ABSTRACT FROM AUTHOR]

Abstract: It has previously been shown that task performance and frontal cortical activation increase after cognitive conflict. This has been argued to support a model of attention where the level of conflict automatically adjusts the amount of cognitive control applied. Conceivably, conflict could also modulate lower-level processing pathways, which would be evident as trial-to-trial changes in domain specific activation. The present fMRI experiment used a syllable identification task where conflict is manipulated by presenting recently ignored syllables. Results showed that on trials following a high conflict trial, activation increased primarily in the planum temporale region of the left temporal cortex, an area believed to be involved in syllable discrimination. The experiment thus showed a transient, domain specific attention effect that was modulated on a trial-to-trial basis. We argue that this indicates a self-regulating system where increased levels of conflict directs resources in order to improve performance. [Copyright &y& Elsevier]

Abstract: A recent breakthrough in understanding brain–language mechanisms is the discovery of local motor cortex activations that index specific meaning features of words, phrases and sentences. The words “talk” and “walk” activate different parts of the motor cortex, reflecting the body part relationship of actions the linguistic items are typically used to speak about. It has been suggested that such semantic motor mapping can be explained by behaviorist theories, based on conditioning mechanisms also effective in Pavlov''s dog when it salivates to bell sounds. In contrast, a neurobiological approach to language predicts modulation of semantic activation by grammatical, including inflectional–morphological, information. Here, we test these competing predictions by putting action words into different phrasal contexts invoking morphosyntactic and morphophonological processes and demonstrate that semantic motor mappings are modulated by grammatical sentence properties, especially the presence of overtly realized inflectional affixes on nouns or verbs embedded in grammatical phrases. Mechanistic neuroscience theories taking into account both meaning and grammar, including morphology and syntax, are required to explain these observations. A direct comparison between phrases containing nouns and verbs revealed a tendency towards greater activation to noun phrases in left-inferior premotor cortex and posterior Broca''s region (BA 44), thus questioning previous suggestions that left inferiorfrontal areas might be dedicated to verb processing per se. [Copyright &y& Elsevier]

Background: There is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation. Results: Examination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes. Conclusions: Overall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T. [ABSTRACT FROM AUTHOR]

Abstract: Older adults often exhibit greater brain activation in prefrontal cortex compared to younger adults, and there is some evidence that this increased activation compensates for age-related neural degradation that would otherwise adversely affect cognitive performance. Less is known about aging and compensatory recruitment in the parietal cortex. In this event-related functional magnetic resonance imaging study, we presented healthy young and old participants with two Stroop-like tasks (number magnitude and physical size). In young, the number magnitude task activated right parietal cortex and the physical size task activated left parietal cortex. In older adults, we observed contralateral parietal recruitment that depended on the task: in the number magnitude task older participants recruited left posterior parietal cortex (in addition to the right parietal activity observed in young) while in the physical size task they recruited right (in addition to left) posterior parietal cortex. In both cases, the additional parietal activity was associated with better performance suggesting that it played a compensatory role. Older adults also recruited left prefrontal cortex during both tasks and this common activation was also associated with better performance. The results provide evidence for task-specific compensatory recruitment in parietal cortex as well as task-independent compensatory recruitment in prefrontal cortex in normal aging. [Copyright &y& Elsevier]

Objectives. Functional imaging studies in major depressive disorder (MDD) indicate abnormal resting state neural activity and negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network (DMN). Methods. Since activity in DMN regions has been associated with self-relatedness, we investigated neural activity in these regions during self-related emotional judgement and passive picture viewing in 25 patients with MDD and 25 healthy controls in an event-related fMRI design. Results. Behaviourally, MDD subjects showed significantly higher ratings of self-relatedness that also correlated with depression symptoms such as hopelessness. Neuroimaging results in MDD patients showed significantly lower negative BOLD responses (NBRs) in anterior medial cortical regions during judgement of self-relatedness while posterior medial regions showed increased NBRs. Unlike in healthy subjects, the anterior medial cortical NBRs were no longer parametrically modulated by the degree of self-relatedness in MDD patients. Conclusions. Our findings suggest that reduced NBRs in the anterior regions of the default-mode network may signify decoupling from self-relatedness in MDD patients with the consecutive abnormal increase of self-focus. [ABSTRACT FROM AUTHOR]

Abstract: Major depressive disorder (MDD) is characterized by the presence of disturbances in emotional processing. However, the neural correlates of these alterations, and how they may be affected by therapeutic interventions, remain unclear. The present study addressed these issues in a preliminary investigation using functional magnetic resonance imaging (fMRI) to examine neural responses to positive, negative, and neutral pictures in unmedicated MDD patients (N = 22) versus controls (N = 14). After this initial scan, MDD patients were treated with cognitive behavioral therapy (CBT) and scanned again after treatment. Within regions that showed pre-treatment differences between patients and controls, we tested the association between pre-treatment activity and subsequent treatment response as well as activity changes from pre- to post-treatment. This study yielded three main findings. First, prior to treatment and relative to controls, patients exhibited overall reduced activity in the ventromedial prefrontal cortex (PFC), diminished discrimination between emotional and neutral items in the amygdala, caudate, and hippocampus, and enhanced responses to negative versus positive stimuli in the left anterior temporal lobe (ATL) and right dorsolateral PFC. Second, CBT-related symptom improvement in MDD patients was predicted by increased activity at baseline in ventromedial PFC as well as the valence effects in the ATL and dorsolateral PFC. Third, from pre- to post-treatment, MDD patients exhibited overall increases in ventromedial PFC activation, enhanced arousal responses in the amygdala, caudate, and hippocampus, and a reversal of valence effects in the ATL. The study was limited by the relatively small sample that was able to complete both scan sessions, as well as an inability to determine the influence of comorbid disorders within the current sample. Nevertheless, components of the neural networks corresponding to emotion processing disturbances in MDD appear to resolve following treatment and are predictive of treatment response, possibly reflecting improvements in emotion regulation processes in response to CBT. [Copyright &y& Elsevier]

Abstracts: A distinct type of mental preparation (activity in medial frontal and temporal areas) had been found to facilitate insight problem solving independent of specific problems . In order to explore whether neural activity during a preparatory interval (mental preparation) is associated with which insight problems would be solved or not, we developed a task that uses Chinese logogriphs (riddles) as materials. Blood oxygenation level-dependent fMRI contrasts between Successful and Unsuccessful mental preparation were measured. Results showed that mental preparation leading to successful problem solving involves heightened activity in the left middle/medial frontal gyrus, the left middle/superior temporal gyrus, the right cerebellum, the bilateral claustrum and the left postcentral gyrus. We discussed the role of these areas in mental preparation for successful insight problem solving. [Copyright &y& Elsevier]

Sörqvist, P. & Sætrevik, B. (2010). The neural basis of updating: Distinguishing substitution processes from other concurrent processes. Scandinavian Journal of Psychology, 51, 357–362. Most previous studies of updating processes have not been able to contrast processes of substituting items in memory with other concurrent processes. In the present investigation, we used a new task called “number updating” and an fMRI protocol to contrast the activation of trials that require item substitution (adding a new item to the working memory representation and suppressing an old item) with trials that involve no substitution (discarding the new item). Trials that require item substitution activated the dorsolateral prefrontal cortex, the posterior medial frontal cortex and the parietal lobes, areas typically seen activated for working memory tasks in general. Trials that do not require substitution activated the anterior medial frontal cortex. Studies examining executive functions have associated this area with cognitive conflict, and may represent suppression of the substitution processes [ABSTRACT FROM AUTHOR]

Abstract: Valence and arousal are thought to be the primary dimensions of human emotion. However, the degree to which valence and arousal interact in determining brain responses to emotional pictures is still elusive. This functional MRI study aimed to delineate neural systems responding to valence and arousal, and their interaction. We measured neural activation in healthy females (N =23) to affective pictures using a 2 (Valence)×2 (Arousal) design. Results show that arousal was preferentially processed by middle temporal gyrus, hippocampus and ventrolateral prefrontal cortex. Regions responding to negative valence included visual and lateral prefrontal regions, positive valence activated middle temporal and orbitofrontal areas. Importantly, distinct arousal-by-valence interactions were present in anterior insula (negative pictures), and in occipital cortex, parahippocampal gyrus and posterior cingulate (positive pictures). These data demonstrate that the brain not only differentiates between valence and arousal but also responds to specific combinations of these two, thereby highlighting the sophisticated nature of emotion processing in (female) human subjects. [Copyright &y& Elsevier]

Abstract: In previous behavioral studies, a prime syllable was presented just prior to a dichotic syllable pair, with instructions to ignore the prime and report one syllable from the dichotic pair. When the prime matched one of the syllables in the dichotic pair, response selection was biased towards selecting the unprimed target. The suggested mechanism was that the prime was inhibited to reduce conflict between task-irrelevant prime processing and task-relevant dichotic target processing, and a residual effect of the prime inhibition biased the resolution of the conflict between the two targets. The current experiment repeated the primed dichotic listening task in an event-related fMRI setting. The fMRI data showed that when the task-irrelevant prime matched the task-relevant targets, activations in posterior medial frontal cortex (pMFC) and in right inferior frontal gyrus (IFG) increased, which was considered to represent conflict and inhibition, respectively. Further, matching trials where the unprimed target was selected showed activation in right IFG, while matching trials where the primed target was selected showed activations in pMFC and left IFG, indicating the difference between inhibition-biased selection and unbiased selection. [Copyright &y& Elsevier]

A major challenge in research on executive control is to reveal its functional decomposition into underlying neural mechanisms. A typical assumption is that this decomposition occurs solely through anatomically based dissociations. Here we tested an alternative hypothesis that different cognitive control processes may be implemented within the same brain regions, with fractionation and dissociation occurring on the basis of temporal dynamics. Regions within lateral prefrontal cortex (PFC) were examined that, in a prior study, exhibited contrasting temporal dynamics between older and younger adults during performance of the AX-CPT cognitive control task. The temporal dynamics in younger adults fit a proactive control pattern (primarily cue-based activation), whereas in older adults a reactive control pattern was found (primarily probebased activation). In the current study, we found that following a period of task-strategy training, these older adults exhibited a proactive shift within a subset of the PFC regions, normalizing their activity dynamics toward young adult patterns. Conversely, under conditions of penalty-based monetary incentives, the younger adults exhibited a reactive shift some of the same regions, altering their temporal dynamics toward the older adult baseline pattern. These experimentally induced crossover patterns of temporal dynamics provide strong support for dual modes of cognitive control that can be flexibly shifted within PFC regions, via modulation of neural responses to changing task conditions or behavioral goals. [ABSTRACT FROM AUTHOR]

Studies using functional magnetic resonance imaging (fMRI) show predominant negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network such as the pregenual anterior cingulate cortex, the ventromedial prefrontal cortex, and the posterior cingulate cortex. Patients with major depressive disorder (MDD) show emotional–cognitive disturbances, which have been associated with alterations within the default-mode network. However, it remains unclear whether these default-mode network alterations are related to abnormalities in NBRs. We therefore investigated neural activity in the default-mode network during different emotional tasks in patients with MDD in an event-related fMRI design. MDD patients showed significantly reduced NBRs in several regions of the default-mode network. Decreased NBRs in MDD patients correlated with depression severity and feelings of hopelessness. In sum, our findings demonstrate that default-mode network NBRs are reduced in MDD and modulate these patients' abnormally negative emotions.Neuropsychopharmacology (2009) 34, 932–943; doi:10.1038/npp.2008.81; published online 4 June 2008 [ABSTRACT FROM AUTHOR]