Impaired Arithmetic Fact Retrieval in an Adult with Developmental Dyscalculia: Evidence from Behavioral and Functional Brain Imaging Data.

Developmental dyscalculia (DD) is a developmental disorder characterized by arithmetic difficulties. Recently, it has been suggested that the neural networks supporting procedure-based calculation (e.g., in subtraction) and left-hemispheric verbal arithmetic fact retrieval (e.g., in multiplication) are partially distinct. Here we compared the neurofunctional correlates of subtraction and multiplication in a 19-year-old student (RM) with DD to 18 age-matched controls. Behaviorally, RM performed significantly worse than controls in multiplication, while subtraction was unaffected. Neurofunctional differences were most pronounced regarding multiplication: RM showed significantly stronger activation than controls not only in left angular gyrus but also in a fronto-parietal network (including left intraparietal sulcus and inferior frontal gyrus) typically activated during procedure-based calculation. Region-of-interest analyses indicated group differences in multiplication only, which, however, did not survive correction for multiple comparisons. Our results are consistent with dissociable and processing-specific, but not operation-specific neurofunctional networks. Procedure-based calculation is not only associated with subtraction but also with (untrained) multiplication facts. Only after rote learning, facts can be retrieved quasi automatically from memory. We suggest that this learning process and the associated shift in activation patterns has not fully occurred in RM, as reflected in her need to resort to procedure-based strategies to solve multiplication facts.

Delineating between-subject heterogeneity in alpha networks with Spatio-Spectral Eigenmodes.

Between subject variability in the spatial and spectral structure of oscillatory networks can be highly informative but poses a considerable analytic challenge. Here, we describe a data-driven modal decomposition of a multivariate autoregressive model that simultaneously identifies oscillations by their peak frequency, damping time and network structure. We use this decomposition to define a set of Spatio-Spectral Eigenmodes (SSEs) providing a parsimonious description of oscillatory networks. We show that the multivariate system transfer function can be rewritten in these modal coordinates, and that the full transfer function is a linear superposition of all modes in the decomposition. The modal transfer function is a linear summation and therefore allows for single oscillatory signals to be isolated and analysed in terms of their spectral content, spatial distribution and network structure. We validate the method on simulated data and explore the structure of whole brain oscillatory networks in eyes-open resting state MEG data from the Human Connectome Project. We are able to show a wide between participant variability in peak frequency and network structure of alpha oscillations and show a distinction between occipital 'high-frequency alpha' and parietal 'low-frequency alpha'. The frequency difference between occipital and parietal alpha components is present within individual participants but is partially masked by larger between subject variability; a 10Hz oscillation may represent the high-frequency occipital component in one participant and the low-frequency parietal component in another. This rich characterisation of individual neural phenotypes has the potential to enhance analyses into the relationship between neural dynamics and a person's behavioural, cognitive or clinical state.

A quick and reliable estimate of extended high-frequency hearing.

OBJECTIVE: To encourage researchers to perform high-frequency threshold estimation using a technique outlined by Rieke and colleagues, described as fixed-level frequency threshold estimation. Their method used a Bekesy-style roving tone to estimate the highest audible frequency of a listener. The tone was fixed in its intensity (SPL) and changed in frequency as the participant indicated whether they could perceive the tone, or not. This was developed specifically for ototoxicity monitoring in the extended high-frequency region. Rieke and colleagues established that this approach to measuring hearing thresholds is both fast and reliable. DESIGN: The current article extends this approach to using a simple PC-soundcard-transducer setup and the method of limits to rapidly establish the highest audible frequency of a listener.Study sample: 24 listeners performed standard and fixed-level audiometry in the extended high-frequency range. RESULTS: The method described is rapid and reliable and a single summary metric is obtained for each listener. CONCLUSIONS: The advantage of the described approach over standard pure-tone audiometry in the extended high-frequency range is the time taken, the ability to avoid missing data points and the risk of distortions or electrical noise when close to maximal system output.

Default mode network can support the level of detail in experience during active task states.

Regions of transmodal cortex, in particular the default mode network (DMN), have historically been argued to serve functions unrelated to task performance, in part because of associations with naturally occurring periods of off-task thought. In contrast, contemporary views of the DMN suggest it plays an integrative role in cognition that emerges from its location at the top of a cortical hierarchy and its relative isolation from systems directly involved in perception and action. The combination of these topographical features may allow the DMN to support abstract representations derived from lower levels in the hierarchy and so reflect the broader cognitive landscape. To investigate these contrasting views of DMN function, we sampled experience as participants performed tasks varying in their working-memory load while inside an fMRI scanner. We used self-report data to establish dimensions of thought that describe levels of detail, the relationship to a task, the modality of thought, and its emotional qualities. We used representational similarity analysis to examine correspondences between patterns of neural activity and each dimension of thought. Our results were inconsistent with a task-negative view of DMN function. Distinctions between on- and off-task thought were associated with patterns of consistent neural activity in regions adjacent to unimodal cortex, including motor and premotor cortex. Detail in ongoing thought was associated with patterns of activity within the DMN during periods of working-memory maintenance. These results demonstrate a contribution of the DMN to ongoing cognition extending beyond task-unrelated processing that can include detailed experiences occurring under active task conditions.

Anterior paracingulate and cingulate cortex mediates the effects of cognitive load on speech sound discrimination.

Perceiving speech while performing another task is a common challenge in everyday life. How the brain controls resource allocation during speech perception remains poorly understood. Using functional magnetic resonance imaging (fMRI), we investigated the effect of cognitive load on speech perception by examining brain responses of participants performing a phoneme discrimination task and a visual working memory task simultaneously. The visual task involved holding either a single meaningless image in working memory (low cognitive load) or four different images (high cognitive load). Performing the speech task under high load, compared to low load, resulted in decreased activity in pSTG/pMTG and increased activity in visual occipital cortex and two regions known to contribute to visual attention regulation-the superior parietal lobule (SPL) and the paracingulate and anterior cingulate gyrus (PaCG, ACG). Critically, activity in PaCG/ACG was correlated with performance in the visual task and with activity in pSTG/pMTG: Increased activity in PaCG/ACG was observed for individuals with poorer visual performance and with decreased activity in pSTG/pMTG. Moreover, activity in a pSTG/pMTG seed region showed psychophysiological interactions with areas of the PaCG/ACG, with stronger interaction in the high-load than the low-load condition. These findings show that the acoustic analysis of speech is affected by the demands of a concurrent visual task and that the PaCG/ACG plays a role in allocating cognitive resources to concurrent auditory and visual information.

Task-based and resting-state fMRI reveal compensatory network changes following damage to left inferior frontal gyrus.

Damage to left inferior prefrontal cortex in stroke aphasia is associated with semantic deficits reflecting poor control over conceptual retrieval, as opposed to loss of knowledge. However, little is known about how functional recruitment within the semantic network changes in patients with executive-semantic deficits. The current study acquired functional magnetic resonance imaging (fMRI) data from 14 patients with semantic aphasia, who had difficulty with flexible semantic retrieval following left prefrontal damage, and 16 healthy age-matched controls, allowing us to examine activation and connectivity in the semantic network. We examined neural activity while participants listened to spoken sentences that varied in their levels of lexical ambiguity and during rest. We found group differences in two regions thought to be good candidates for functional compensation: ventral anterior temporal lobe (vATL), which is strongly implicated in comprehension, and posterior middle temporal gyrus (pMTG), which is hypothesized to work together with left inferior prefrontal cortex to support controlled aspects of semantic retrieval. The patients recruited both of these sites more than controls in response to meaningful sentences. Subsequent analysis identified that, in control participants, the recruitment of pMTG to ambiguous sentences was inversely related to functional coupling between pMTG and anterior superior temporal gyrus (aSTG) at rest, while the patients showed the opposite pattern. Moreover, stronger connectivity between pMTG and aSTG in patients was associated with better performance on a test of verbal semantic association, suggesting that this temporal lobe connection supports comprehension in the face of damage to left inferior prefrontal cortex. These results characterize network changes in patients with executive-semantic deficits and converge with studies of healthy participants in providing evidence for a distributed system underpinning semantic control that includes pMTG in addition to left inferior prefrontal cortex.

Charting the effects of TMS with fMRI: Modulation of cortical recruitment within the distributed network supporting semantic control.

Semantic memory comprises our knowledge of the meanings of words and objects but only some of this knowledge is relevant at any given time. Thus, semantic control processes are needed to focus retrieval on relevant information. Research on the neural basis of semantic control has strongly implicated left inferior frontal gyrus (LIFG) but recent work suggests that a wider network supports semantic control, including left posterior middle temporal gyrus (pMTG), right inferior frontal gyrus (RIFG) and pre-supplementary motor area (pre-SMA). In the current study, we used repetitive transcranial magnetic stimulation (1Hz offline TMS) over LIFG, immediately followed by fMRI, to examine modulation of the semantic network. We compared the effect of stimulation on judgements about strongly-associated words (dog-bone) and weaker associations (dog-beach), since previous studies have found that dominant links can be recovered largely automatically with little engagement of LIFG, while more distant connections require greater control. Even though behavioural performance was maintained in response to TMS, LIFG stimulation increased the effect of semantic control demands in pMTG and pre-SMA, relative to stimulation of a control site (occipital pole). These changes were accompanied by reduced recruitment of both the stimulated region (LIFG) and its right hemisphere homologue (RIFG), particularly for strong associations with low control requirements. Thus repetitive TMS to LIFG modulated the contribution of distributed regions to semantic judgements in two distinct ways.

Patterns of neural response in scene-selective regions of the human brain are affected by low-level manipulations of spatial frequency.

Neuroimaging studies have found distinct patterns of response to different categories of scenes. However, the relative importance of low-level image properties in generating these response patterns is not fully understood. To address this issue, we directly manipulated the low level properties of scenes in a way that preserved the ability to perceive the category. We then measured the effect of these manipulations on category-selective patterns of fMRI response in the PPA, RSC and OPA. In Experiment 1, a horizontal-pass or vertical-pass orientation filter was applied to images of indoor and natural scenes. The image filter did not have a large effect on the patterns of response. For example, vertical- and horizontal-pass filtered indoor images generated similar patterns of response. Similarly, vertical- and horizontal-pass filtered natural scenes generated similar patterns of response. In Experiment 2, low-pass or high-pass spatial frequency filters were applied to the images. We found that image filter had a marked effect on the patterns of response in scene-selective regions. For example, low-pass indoor images generated similar patterns of response to low-pass natural images. The effect of filter varied across different scene-selective regions, suggesting differences in the way that scenes are represented in these regions. These results indicate that patterns of response in scene-selective regions are sensitive to the low-level properties of the image, particularly the spatial frequency content.

Responses in the right posterior superior temporal sulcus show a feature-based response to facial expression.

The face-selective region of the right posterior superior temporal sulcus (pSTS) plays an important role in analysing facial expressions. However, it is less clear how facial expressions are represented in this region. In this study, we used the face composite effect to explore whether the pSTS contains a holistic or feature-based representation of facial expression. Aligned and misaligned composite images were created from the top and bottom halves of faces posing different expressions. In Experiment 1, participants performed a behavioural matching task in which they judged whether the top half of two images was the same or different. The ability to discriminate the top half of the face was affected by changes in the bottom half of the face when the images were aligned, but not when they were misaligned. This shows a holistic behavioural response to expression. In Experiment 2, we used fMR-adaptation to ask whether the pSTS has a corresponding holistic neural representation of expression. Aligned or misaligned images were presented in blocks that involved repeating the same image or in which the top or bottom half of the images changed. Increased neural responses were found in the right pSTS regardless of whether the change occurred in the top or bottom of the image, showing that changes in expression were detected across all parts of the face. However, in contrast to the behavioural data, the pattern did not differ between aligned and misaligned stimuli. This suggests that the pSTS does not encode facial expressions holistically. In contrast to the pSTS, a holistic pattern of response to facial expression was found in the right inferior frontal gyrus (IFG). Together, these results suggest that pSTS reflects an early stage in the processing of facial expression in which facial features are represented independently.

The neural correlates of semantic richness: evidence from an fMRI study of word learning.

We investigated the neural correlates of concrete nouns with either many or few semantic features. A group of 21 participants underwent two days of training and were then asked to categorize 40 newly learned words and a set of matched familiar words as living or nonliving in an MRI scanner. Our results showed that the most reliable effects of semantic richness were located in the left angular gyrus (AG) and middle temporal gyrus (MTG), where activation was higher for semantically rich than poor words. Other areas showing the same pattern included bilateral precuneus and posterior cingulate gyrus. Our findings support the view that AG and anterior MTG, as part of the multimodal network, play a significant role in representing and integrating semantic features from different input modalities. We propose that activation in bilateral precuneus and posterior cingulate gyrus reflects interplay between AG and episodic memory systems during semantic retrieval.

Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex.

Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings - as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is better specified by their visible features - however, not all of these features will be relevant to uncovering a given association, tapping selection/inhibition processes. To explore potential differences across modalities, we took a commonly-used manipulation of controlled retrieval demands, namely the identification of weak vs. strong associations, and compared word and picture versions. There were 4 key findings: (1) Regions of interest (ROIs) in posterior IFG (BA44) showed graded effects of modality (e.g., words>pictures in left BA44; pictures>words in right BA44). (2) An equivalent response was observed in left mid-IFG (BA45) across modalities, consistent with the multimodal semantic control deficits that typically follow LIFG lesions. (3) The anterior IFG (BA47) ROI showed a stronger response to verbal than pictorial associations, potentially reflecting a role for this region in establishing a meaningful context that can be used to direct semantic retrieval. (4) The left pMTG ROI also responded to difficulty across modalities yet showed a stronger response overall to verbal stimuli, helping to reconcile two distinct literatures that have implicated this site in semantic control and lexical-semantic access respectively. We propose that left anterior IFG and pMTG work together to maintain a meaningful context that shapes ongoing semantic processing, and that this process is more strongly taxed by word than picture associations.

Neural mechanisms underlying song and speech perception can be differentiated using an illusory percept.

The issue of whether human perception of speech and song recruits integrated or dissociated neural systems is contentious. This issue is difficult to address directly since these stimulus classes differ in their physical attributes. We therefore used a compelling illusion (Deutsch et al. 2011) in which acoustically identical auditory stimuli are perceived as either speech or song. Deutsch's illusion was used in a functional MRI experiment to provide a direct, within-subject investigation of the brain regions involved in the perceptual transformation from speech into song, independent of the physical characteristics of the presented stimuli. An overall differential effect resulting from the perception of song compared with that of speech was revealed in right midposterior superior temporal sulcus/right middle temporal gyrus. A left frontotemporal network, previously implicated in higher-level cognitive analyses of music and speech, was found to co-vary with a behavioural measure of the subjective vividness of the illusion, and this effect was driven by the illusory transformation. These findings provide evidence that illusory song perception is instantiated by a network of brain regions that are predominantly shared with the speech perception network.

Specialized and independent processing of orientation and shape in visual field maps LO1 and LO2.

We identified human visual field maps, LO1 and LO2, in object-selective lateral occipital cortex. Using transcranial magnetic stimulation (TMS), we assessed the functions of these maps in the perception of orientation and shape. TMS of LO1 disrupted orientation, but not shape, discrimination, whereas TMS of LO2 disrupted shape, but not orientation, discrimination. This double dissociation suggests that specialized and independent processing of different visual attributes occurs in LO1 and LO2.

Representations of the temporal envelope of sounds in human auditory cortex: can the results from invasive intracortical "depth" electrode recordings be replicated using non-invasive MEG "virtual electrodes"?

Magnetoencephalography (MEG) beamformer analyses use spatial filters to estimate neuronal activity underlying the magnetic fields measured by the MEG sensors. MEG "virtual electrodes" are the outputs of beamformer spatial filters. The present study aimed to test the hypothesis that MEG virtual electrodes can replicate the findings from intracortical "depth" electrode studies relevant to the processing of the temporal envelopes of sounds [e.g. Nourski et al. (2009) "Temporal envelope of time-compressed speech represented in the human auditory cortex," J. Neurosci. 29:15564-15574]. Specifically we aimed to determine whether it is possible to use non-invasive MEG virtual electrodes to characterise the representation of temporal envelopes of 6-Hz sinusoidal amplitude modulation (SAM) and speech using both auditory evoked fields (AEFs) and patterns of power changes in high-frequency (>70 Hz) bands. MEG signals were analysed using a location of interest (LOI) approach by seeding virtual electrodes in the left and right posteromedial Heschl's gyri. AEFs showed phase-locking to the temporal envelope of SAM and speech stimuli. Time-frequency analyses revealed no clear differences in high gamma power between the pre-stimulus baseline and the post-stimulus presentation periods. Nevertheless the patterns of changes in high gamma power were significantly correlated with the temporal envelopes of 6-Hz SAM and speech in the majority of participants. The present study reveals difficulties in replicating clear augmentations in high gamma power changes using MEG virtual electrodes cf. intracortical "depth" electrode studies (Nourski et al., 2009).

A robust implementation of a kurtosis beamformer for the accurate identification of epileptogenic foci.

OBJECTIVE: To improve the accuracy and reliability of the localisation of epileptogenic activity using spatially filtered MEG data. METHODS: A synthetic epileptic source was embedded in healthy brain activity in different orientations in order to estimate how reliably this signal containing high levels of kurtosis can be localised. An existing approach (SAM(g2)) was compared to a new implementation of the methodology. RESULTS: The results confirm that a kurtosis beamformer is an effective tool with which to localise spontaneous epileptiform activity. However, it is crucial that the orientation of source reconstruction matches that of the true source otherwise the epileptic activity is either mis-localised or completely missed. Therefore as the original SAM(g2) implementation is restricted to the tangential plane, in certain circumstances it will perform poorly compared to the approach described here. CONCLUSIONS: A kurtosis beamformer is made more accurate and more robust if the analysis is not restricted to the tangential plane and if the optimisation routine for selecting the source orientation is performed using kurtosis rather than power. SIGNIFICANCE: MEG is increasingly being used for the non-invasive localisation of epileptic biomagnetic signals and the implementation described in this paper increases the clinical utility of the technique.

Examining the effects of one- and three-dimensional spatial filtering analyses in magnetoencephalography.

Spatial filtering, or beamforming, is a commonly used data-driven analysis technique in the field of Magnetoencephalography (MEG). Although routinely referred to as a single technique, beamforming in fact encompasses several different methods, both with regard to defining the spatial filters used to reconstruct source-space time series and in terms of the analysis of these time series. This paper evaluates two alternative methods of spatial filter construction and application. It demonstrates how encoding different requirements into the design of these filters has an effect on the results obtained. The analyses presented demonstrate the potential value of implementations which examine the timeseries projections in multiple orientations at a single location by showing that beamforming can reconstruct predominantly radial sources in the case of a multiple-spheres forward model. The accuracy of source reconstruction appears to be more related to depth than source orientation. Furthermore, it is shown that using three 1-dimensional spatial filters can result in inaccurate source-space time series reconstruction. The paper concludes with brief recommendations regarding reporting beamforming methodologies in order to help remove ambiguity about the specifics of the techniques which have been used.

Non-parametric statistical thresholding of baseline free MEG beamformer images.

Magnetoencephalography (MEG) provides excellent temporal resolution when examining cortical activity in humans. Inverse methods such as beamforming (a spatial filtering approach) provide the means by which activity at cortical locations can be estimated. To date, the majority of work in this field has been based upon power changes between active and baseline conditions. Recent work, however, has focused upon other properties of the time series data reconstructed by these methods. One such metric, the Source Stability Index (SSI), relates to the consistency of the time series calculated only over an active period without the use of a baseline condition. In this paper we apply non-parametric statistics to SSI volumetric maps of simulation, auditory and somatosensory data in order to provide a robust and principled method of statistical inference in the absence of a baseline condition.

Source stability index: a novel beamforming based localisation metric.

Many experimental studies into human brain function now use magnetoencephalography (MEG) to non-invasively investigate human neuronal activity. A number of different analysis techniques use the observed magnetic fields outside of the head to estimate the location and strength of the underlying neural generators. One such technique, a spatial filtering method known as Beamforming, produces whole-head volumetric images of activation. Typically, a differential power map throughout the head is generated between a time window containing the response to a stimulus of interest and a window containing background brain activity. A statistical test is normally performed to reveal locations which show a significantly different response in the presence of the stimulus. Despite this being a widely used measure, for both phase-locked and non-phase-locked information, it requires a number of assumptions; namely that the baseline activity defined is stable and also that a change in total power is the most effective way of revealing the neuronal sources required for the task. This paper introduces a metric which evaluates the consistency of the response at each location within a cortical volume. Such a method of localisation negates the need for a baseline period of activity to be defined and also moves away from simply considering the energy content of brain activity. The paper presents both simulated and real data. It demonstrates that this new metric of stability is able to more accurately and, crucially, more reliably draw inferences about neuronal sources of interest.