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Functional neuroimaging techniques (i.e. single photon emission computed tomography, positron emission tomography, and functional magnetic resonance imaging) have been used to assess the neural correlates of anosognosia in mild cognitive impairment (MCI) and Alzheimer's disease (AD). A systematic review of this literature was performed, following the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement, on PubMed, EMBASE, and PsycINFO databases. Twenty-five articles met all inclusion criteria. Specifically, four brain connectivity and 21 brain perfusion, metabolism, and activation articles. Anosognosia is associated in MCI with frontal lobe and cortical midline regional dysfunction (reduced perfusion and activation), and with reduced parietotemporal metabolism. Reduced within and between network connectivity is observed in the default mode network regions of AD patients with anosognosia compared to AD patients without anosognosia and controls. During initial stages of cognitive decline in anosognosia, reduced indirect neural activity (i.e. perfusion, metabolism, and activation) is associated with the cortical midline regions, followed by the parietotemporal structures in later stages and culminating in frontotemporal dysfunction. Although the current evidence suggests differences in activation between AD or MCI patients with anosognosia and healthy controls, more evidence is needed exploring the differences between MCI and AD patients with and without anosognosia using resting state and task related paradigms.

Aging affects functional connectivity between brain areas, however, a complete picture of how aging affects integration of information within and between functional networks is missing. We used complex network measures, derived from a brain-wide graph, to provide a comprehensive overview of age-related changes in functional connectivity. Functional connectivity in young and older participants was assessed during resting-state fMRI. The results show that aging has a large impact, not only on connectivity within functional networks but also on connectivity between the different functional networks in the brain. Brain networks in the elderly showed decreased modularity (less distinct functional networks) and decreased local efficiency. Connectivity decreased with age within networks supporting higher level cognitive functions, that is, within the default mode, cingulo-opercular and fronto-parietal control networks. Conversely, no changes in connectivity within the somatomotor and visual networks, networks implicated in primary information processing, were observed. Connectivity between these networks even increased with age. A brain-wide analysis approach of functional connectivity in the aging brain thus seems fundamental in understanding how age affects integration of information., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The primary somatosensory cortex (SI) plays a critical role in somatosensation as well as in action performance and social cognition. Although the SI has been a major target of experimental and clinical research using non-invasive transcranial magnetic stimulation (TMS), to date information on the effect of TMS over the SI on its resting-state functional connectivity is very scant. Here, we explored whether continuous theta burst stimulation (cTBS), a repetitive TMS protocol, administered over the SI can change the functional connectivity of the brain at rest, as measured using resting-state functional magnetic resonance imaging (rs-fMRI). In a randomized order on two different days we administered active TMS or sham TMS over the left SI. TMS was delivered off-line before scanning by means of cTBS. The target area was selected previously and individually for each subject as the part of the SI activated both when the participant executes and observes actions. Three analytical approaches, both theory driven (partial correlations and seed based whole brain regression) and more data driven (Independent Component Analysis), indicated a reduction in functional connectivity between the stimulated part of the SI and several brain regions functionally associated with the SI including the dorsal premotor cortex, the cerebellum, basal ganglia, and anterior cingulate cortex. These findings highlight the impact of cTBS delivered over the SI on its functional connectivity at rest. Our data may have implications for experimental and therapeutic applications of cTBS over the SI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Recent studies have shown that aging has a large impact on connectivity within and between functional networks. An open question is whether elderly still have the flexibility to adapt functional network connectivity (FNC) to the demands of the task at hand. To study this, we collected fMRI data in younger and older participants during resting state, a selective attention (SA) task and an n-back working memory task with varying levels of difficulty. Spatial independent component (IC) analysis was used to identify functional networks over all participants and all conditions. Dual regression was used to obtain participant and task specific time-courses per IC. Subsequently, functional connectivity was computed between all ICs in each of the tasks. Based on these functional connectivity matrices, a scaled version of the eigenvector centrality (SEC) was used to measure the total influence of each IC in the complete graph of ICs. The results demonstrated that elderly remain able to adapt FNC to task demands. However, there was an age-related shift in the impetus for FNC change. Older participants showed the maximal change in SEC patterns between resting state and the SA task. Young participants, showed the largest shift in SEC patterns between the less demanding SA task and the more demanding 2-back task. Our results suggest that increased FNC changes from resting state to low demanding tasks in elderly reflect recruitment of additional resources, compared with young adults. The lack of change between the low and high demanding tasks suggests that elderly reach a resource ceiling., (Copyright © 2013 Wiley Periodicals, Inc.)

To investigate which neural correlates are associated with successful working memory performance, fMRI was recorded in healthy younger and older adults during performance on an n-back task with varying task demands. To identify functional networks supporting working memory processes, we used independent component analysis (ICA) decomposition of the fMRI data. Compared to younger adults, older adults showed a larger neural (BOLD) response in the more complex (2-back) than in the baseline (0-back) task condition, in the ventral lateral prefrontal cortex (VLPFC) and in the right fronto-parietal network (FPN). Our results indicated that a higher BOLD response in the VLPFC was associated with increased performance accuracy in older adults, in the more complex task condition. This 'BOLD-performance' relationship suggests that the neural correlates linked with successful performance in the older adults are related to specific working memory processes present in the complex but not in the baseline task condition [corrected].Furthermore, the selective presence of this relationship in older but not in younger adults suggests that increased neural activity in the VLPFC serves a compensatory role in the aging brain which benefits task performance in the elderly.

The ability to suppress irrelevant information declines with age, while the ability to enhance relevant information remains largely intact. We examined mechanisms behind this dissociation in an fMRI study, using a selective attention task in which relevant and irrelevant information appeared simultaneously. Slowing of response times due to distraction by irrelevant targets was larger in older than younger participants. Increased distraction was related to larger increases in activity and connectivity in areas of the dorsal attention network, indicating a more pronounced (re-)orientation of attention. The decreases in accuracy in target compared to nontarget trials were smaller in older compared to younger participants. In older adults we found increased recruitment of areas in the fronto-parietal control network (FPCN) during target detection. Moreover, older adults showed increased connectivity between the FPCN, supporting cognitive control, and somatomotor areas implicated in response selection and execution. This connectivity increase was related to improved target detection, suggesting that older adults engage additional cognitive control, which might enable the observed intact performance in detecting and responding to target stimuli., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The importance of studying connectivity in the aging brain is increasingly recognized. Recent studies have shown that connectivity within the default mode network is reduced with age and have demonstrated a clear relation of these changes with cognitive functioning. However, research on age-related changes in other functional networks is sparse and mainly focused on prespecified functional networks. Using functional magnetic resonance imaging, we investigated age-related changes in functional connectivity during a visual oddball task in a range of functional networks. It was found that compared with young participants, elderly showed a decrease in connectivity between areas belonging to the same functional network. This was found in the default mode network and the somatomotor network. Moreover, in all identified networks, elderly showed increased connectivity between areas within these networks and areas belonging to different functional networks. Decreased connectivity within functional networks was related to poorer cognitive functioning in elderly. The results were interpreted as a decrease in the specificity of functional networks in older participants., (Copyright © 2012 Wiley Periodicals, Inc.)

Dyslexia is heritable and associated with auditory processing deficits. We investigate whether temporal auditory processing is compromised in young children at-risk for dyslexia and whether it is associated with later language and reading skills. We recorded EEG from 17 months-old children with or without familial risk for dyslexia to investigate whether their auditory system was able to detect a temporal change in a tone pattern. The children were followed longitudinally and performed an intelligence- and language development test at ages 4 and 4.5 years. Literacy related skills were measured at the beginning of second grade, and word- and pseudo-word reading fluency were measured at the end of second grade. The EEG responses showed that control children could detect the temporal change as indicated by a mismatch response (MMR). The MMR was not observed in at-risk children. Furthermore, the fronto-central MMR amplitude correlated with preliterate language comprehension and with later word reading fluency, but not with phonological awareness. We conclude that temporal auditory processing differentiates young children at risk for dyslexia from controls and is a precursor of preliterate language comprehension and reading fluency., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To assess whether proton MR spectroscopy of the brain in children with developmental delay reveals a consistent pattern of abnormalities., Materials and Methods: Eighty-eight patients (median age, 4.6 years; interquartile range, 3.1-8.1 years) with unexplained developmental delay, were compared with 48 normally developing age-matched controls. Patients and controls were assigned to five age-groups. Multivoxel MR spectroscopy was performed on a volume of interest superior to the lateral ventricles. The relative levels of choline, creatine, N-acetyl aspartate, and glutamate/glutamine in 24 voxels containing white matter and 12 voxels containing gray matter were quantified in an operator-independent manner and expressed in proportion to the total metabolite peak area in the volume of interest., Results: White matter choline in DD showed less decrease with age. Mean choline levels, compared with mean control levels, increased from 99 to 111% with increasing age. This was statistically significant in the highest age groups (P = 0.015 [7 < yr

Motor fatigue is an exercise-induced reduction in the force-generating capacity. The underlying mechanisms can be separated into factors residing in the periphery or in the central nervous system. We designed an experiment in which we investigated central processes underlying motor fatigue by means of magnetic resonance imaging in combination with the twitch interpolation technique. Subjects performed a sustained maximal abduction (2 min) with the right index finger. Brain activation was recorded with an MR scanner, together with index finger abduction force, EMG of several hand muscles and interpolated twitches. Mean activity per volume was calculated for the primary motor cortex and the secondary motor areas (supplementary motor, premotor, and cingulate areas) as well as mean force and mean rectified EMG amplitude. Results showed a progressive decline in maximal index finger abduction force and EMG of the target muscles combined with an increase in brain activity in the contralateral primary motor cortex and secondary motor areas. Analysis of the twitches superimposed on the sustained contraction revealed that during the contraction the voluntary drive decreased significantly. In conclusion, our data showed that despite an increase in brain activity the voluntary activation decreased. This suggests that, although the CNS increased its input to the relevant motor areas, this increase was insufficient to overcome fatigue-related changes in the voluntary drive.

Objective: To apply and validate the use of electromyogram (EMG) recorded during functional magnetic resonance imaging (fMRI) in patients with movement disorders, to directly relate involuntary movements to brain activity., Methods: Eight "familial cortical myoclonic tremor with epilepsy" (FCMTE) patients, with tremor-like cortical myoclonus and cerebellar Purkinje cell degeneration, and nine healthy controls performed hand posture and movement in an on/off fashion (block design). Superfluous movements were quantified as deviations in EMG power, positive and negative, with respect to the average EMG per session. This measure, "residual EMG" (r-EMG), was derived by Gram-Schmidt orthogonalization. Activation maps resulting from conventional block regressors and novel r-EMG regressors were compared., Results: In healthy participants, the block posture regressor identified mainly cerebellar activity and some activity in other areas belonging to motor circuitry. In FCMTE patients, no cerebellar activity was seen with the block posture regressor, compatible with cerebellar Purkinje cell changes in FCMTE. EMG power showed little variation during posture in healthy controls. Therefore, the r-EMG regressor was almost constant and revealed no brain activity as expected. In contrast, in FCMTE patients the r-EMG posture regressor was highly variable due to continuous myoclonic jerks. It identified sensorimotor cortical areas, compatible with cortical hyperexcitability in FCMTE patients., Conclusion: Conventional block regressors can be used to identify neuronal circuitry associated with a specific motor task, whereas r-EMG regressors can help identify brain activation directly related to involuntary movements. Simultaneous EMG-fMRI is complementary to conventional fMRI and will facilitate studies of hyperkinetic movement disorders., (Copyright 2007 Wiley-Liss, Inc.)

We studied the relationship between muscle activity (electromyography, EMG), force, and brain activity during isometric contractions of the index finger, on a group and individual level. Ten subjects contracted their right or left index finger at 5, 15, 30, 50, and 70% of their maximal force. Subjects received visual feedback of the produced force. We focused our analysis on brain activation that correlated with EMG. Brain activity of specific anatomical areas (region-of-interest analysis, ROI) was quantified and correlated with EMG activity. Furthermore, we tried to distinguish between brain areas in which activity was modulated by the amount of EMG and areas that were active during the task but in which the activity was not modulated. Therefore, we used two regressors simultaneously: (1) the produced EMG and (2) the task (a categorical regressor). As expected, activity in the motor areas (contralateral sensorimotor cortex, premotor areas, and ipsilateral cerebellum) strongly correlated with the amount of EMG. In contrast, activity in frontal and parietal areas (inferior part of the right precentral sulcus, ipsilateral supramarginal gyrus, bilateral inferior parietal lobule, bilateral putamen, and insular cortex) correlated with activation per se, independently of the amount of EMG. Activity in these areas was equal during contractions of the right or left index finger. We suppose that these areas are more involved in higher order motor processes during the preparatory phase or monitoring feedback mechanisms. Furthermore, our ROI analysis showed that muscle and brain activity strongly correlate in traditional motor areas, both at group and at subject level.

The goal of the present validation study is to show that continuous surface EMG recorded simultaneously with 3T fMRI can be used to identify local brain activity related to (1) motor tasks, and to (2) muscle activity independently of a specific motor task, i.e. spontaneous (abnormal) movements. Five healthy participants performed a motor task, consisting of posture (low EMG power), and slow (medium EMG power) and fast (high EMG power) wrist flexion-extension movements. Brain activation maps derived from a conventional block design analysis (block-only design) were compared with brain activation maps derived using EMG-based regressors: (1) using the continuous EMG power as a single regressor of interest (EMG-only design) to relate motor performance and brain activity, and (2) using EMG power variability as an additional regressor in the fMRI block design analysis to relate movement variability and brain activity (mathematically) independent of the motor task. The agreement between the identified brain areas for the block-only design and the EMG-only design was excellent for all participants. Additionally, we showed that EMG power variability correlated well with activity in brain areas known to be involved in movement modulation. These innovative EMG-fMRI analysis techniques will allow the application of novel motor paradigms. This is an important step forward in the study of both the normally functioning motor system and the pathophysiological mechanisms in movement disorders., (Copyright 2007 Wiley-Liss, Inc.)

Dyslexia is heritable and associated with phonological processing deficits that can be reflected in the event-related potentials (ERPs). Here, we recorded ERPs from 2-month-old infants at risk of dyslexia and from a control group to investigate whether their auditory system processes /bAk/ and /dAk/ changes differently. The speech sounds were presented in an oddball paradigm. The children were followed longitudinally and performed a word reading fluency test in second grade. The infant ERPs were subsequently analyzed according to high or low reading fluency in order to find a neurophysiological precursor of poor reading fluency. The results show that the fluent reading children (from both the at-risk and the control group) processed the speech sound changes differentially in infancy as indicated by a mismatch response (MMR). In the control group the MMR was frontally positive and in the fluent at-risk group the MMR was parietally positive. The non-fluent at-risk group did not show an MMR. We conclude that at-risk children who became fluent readers were better at speech processing in infancy than those who became non-fluent readers. This indicates a very early speech processing deficit in the group of later non-fluent readers. (Contains 1 figure and 1 table.)

A child’s school achievement is influenced by environmental factors. The environmental factors, when represented by socio-economic status (SES) of the family, have been demonstrated to be related to the reading skills of a child. The neural correlates of the relation between SES and reading have been less thoroughly investigated. The present study expands current research by exploring the relation between SES, quantified by paternal educational level, reading of the offspring and the structure of white matter pathways in the left hemisphere as derived from DTI-based tractography analyses. Therefore, three dorsal white matter pathways, i.e. the long, anterior and posterior segments of the arcuate fasciculus (AF), and three ventral white matter pathways, i.e. the inferior fronto-occipital fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the uncinate fasciculus (UF), were manually dissected in the left hemisphere of 34 adolescents with a wide range of reading skills. The results demonstrated a relation between word reading, SES quantified by paternal educational level, and fractional anisotropy (FA) within the left dorsal AF segment and the left ventral UF. Thus, the present study proposes a relationship between paternal educational level and a specific white matter pathway that is important for reading, aiming to guide future research that can determine processes underlying this relationship. [ABSTRACT FROM AUTHOR]