Task-induced Brain Activation Research Articles

Amplitude of low-frequency fluctuation after taste exposure revealed by resting-state fMRI

Taste perception has been deeply explored from the behavioural level to delineating neural mechanisms. However, most previous studies about the neural underpinnings of taste perception have focused on task-related brain activation. Notably, evidence indicates that task-induced brain activation often involves interference from irrelevant task materials and only accounts for a small fraction of the brain's energy consumption. Investigation of the resting-state spontaneous brain activity would bring us a comprehensive understanding of the neural mechanism of taste perception. Here we acquired resting-state functional magnetic resonance imaging (rs-fMRI) data from twenty-two participants immediately after they received sweet, sour and tasteless gustatory stimulation. Our results showed that, in contrast to the tasteless condition, the sour exposure induced decreased amplitude of low-frequency fluctuation (ALFF) in the somatosensory cortex in the left post-central gyrus, and the sweet exposure led to increased ALFF in the bilateral putamen involved in reward processing. Moreover, in contrast to the sweet stimulation condition, the sour stimulation condition showed increased ALFF in the right superior frontal gyrus, which has been linked to functioning in high-order cognitive control. Altogether, our data indicate that taste exposure may affect the spontaneous functional activity in brain regions, including the somatosensory areas, reward processing areas and high-order cognitive functioning areas. Our findings may contribute to a further understanding the neural network and mechanisms after taste exposure.

Brain Activity During Experimental Knee Pain and Its Relationship With Kinesiophobia in Patients With Patellofemoral Pain: A Preliminary Functional Magnetic Resonance Imaging Investigation.

The etiology of patellofemoral pain has remained elusive, potentially due to an incomplete understanding of how pain, motor control, and kinesiophobia disrupt central nervous system functioning. To directly evaluate brain activity during experimental knee pain and its relationship to kinesiophobia in patients with patellofemoral pain. Cross-sectional. Young females clinically diagnosed with patellofemoral pain (n = 14; 14.4 [3.3]y; body mass index = 22.4 [3.8]; height = 1.61 [0.1]m; body mass = 58.4 [12.7]kg). A modified Clarke test (experimental pain condition with noxious induction via patella pressure and quadriceps contraction) was administered to the nondominant knee (to minimize limb dominance confounds) of patients during brain functional magnetic resonance imaging (fMRI) acquisition. Patients also completed a quadriceps contraction without application of external pressure (control contraction). Kinesiophobia was measured using the Tampa Scale of Kinesiophobia. The fMRI analyses assessed brain activation during the modified Clarke test and control contraction and assessed relationships between task-induced brain activity and kinesiophobia. Standard processing for neuroimaging and appropriate cluster-wise statistical thresholds to determine significance were applied to the fMRI data (z > 3.1, P < .05). The fMRI revealed widespread neural activation in the frontal, parietal, and occipital lobes, and cerebellum during the modified Clarke test (all zs > 4.4, all Ps < .04), whereas neural activation was localized primarily to frontal and cerebellar regions during the control contraction test (all zs > 4.4, all Ps < .01). Greater kinesiophobia was positively associated with greater activity in the cerebello-frontal network for the modified Clarke test (all zs > 5.0, all Ps < .01), but no relationships between kinesiophobia and brain activity were observed for the control contraction test (all zs < 3.1, all Ps > .05). Our novel experimental knee pain condition was associated with alterations in central nociceptive processing. These findings may provide novel complementary pathways for targeted restoration of patient function.

Act natural: Functional connectivity from naturalistic stimuli fMRI outperforms resting-state in predicting brain activity

The search for an ‘ideal’ approach to investigate the functional connections in the human brain is an ongoing challenge for the neuroscience community. While resting-state functional magnetic resonance imaging (fMRI) has been widely used to study individual functional connectivity patterns, recent work has highlighted the benefits of collecting functional connectivity data while participants are exposed to naturalistic stimuli, such as watching a movie or listening to a story. For example, functional connectivity data collected during movie-watching were shown to predict cognitive and emotional scores more accurately than resting-state-derived functional connectivity. We have previously reported a tight link between resting-state functional connectivity and task-derived neural activity, such that the former successfully predicts the latter. In the current work we use data from the Human Connectome Project to demonstrate that naturalistic-stimulus-derived functional connectivity predicts task-induced brain activation maps more accurately than resting-state-derived functional connectivity. We then show that activation maps predicted using naturalistic stimuli are better predictors of individual intelligence scores than activation maps predicted using resting-state. We additionally examine the influence of naturalistic-stimulus type on prediction accuracy. Our findings emphasize the potential of naturalistic stimuli as a promising alternative to resting-state fMRI for connectome-based predictive modelling of individual brain activity and cognitive traits.

A model-based approach to assess reproducibility for large-scale high-throughput MRI-based studies

Magnetic Resonance Imaging (MRI) technology has been increasingly used in neuroscience studies. Reproducibility of statistically significant findings generated by MRI-based studies, especially association studies (phenotype vs. MRI metric) and task-induced brain activation, has been recently heavily debated. However, most currently available reproducibility measures depend on thresholds for the test statistics and cannot be use to evaluate overall study reproducibility. It is also crucial to elucidate the relationship between overall study reproducibility and sample size in an experimental design. In this study, we proposed a model-based reproducibility index to quantify reproducibility which could be used in large-scale high-throughput MRI-based studies including both association studies and task-induced brain activation. We performed the model-based reproducibility assessments for a few association studies and task-induced brain activation by using several recent large sMRI/fMRI databases. For large sample size association studies between brain structure/function features and some basic physiological phenotypes (i.e. Sex, BMI), we demonstrated that the model-based reproducibility of these studies is more than 0.99. For MID task activation, similar results could be observed. Furthermore, we proposed a model-based analytical tool to evaluate minimal sample size for the purpose of achieving a desirable model-based reproducibility. Additionally, we evaluated the model-based reproducibility of gray matter volume (GMV) changes for UK Biobank (UKB) vs. Parkinson Progression Marker Initiative (PPMI) and UK Biobank (UKB) vs. Human Connectome Project (HCP). We demonstrated that both sample size and study-specific experimental factors play important roles in the model-based reproducibility assessments for different experiments. In summary, a systematic assessment of reproducibility is fundamental and important in the current large-scale high-throughput MRI-based studies.

Predicting individual traits from unperformed tasks

Relating individual differences in cognitive traits to brain functional organization is a long-lasting challenge for the neuroscience community. Individual intelligence scores were previously predicted from whole-brain connectivity patterns, extracted from functional magnetic resonance imaging (fMRI) data acquired at rest. Recently, it was shown that task-induced brain activation maps outperform these resting-state connectivity patterns in predicting individual intelligence, suggesting that a cognitively demanding environment improves prediction of cognitive abilities. Here, we use data from the Human Connectome Project to predict task-induced brain activation maps from resting-state fMRI, and proceed to use these predicted activity maps to further predict individual differences in a variety of traits. While models based on original task activation maps remain the most accurate, models based on predicted maps significantly outperformed those based on the resting-state connectome. Thus, we provide a promising approach for the evaluation of measures of human behavior from brain activation maps, that could be used without having participants actually perform the tasks.

DOES FEAR OF MOVEMENT ALTER BRAIN ACTIVITY? INVESTIGATING THE NEURAL MARKERS OF KINESIOPHOBIA IN PEDIATRIC PATIENTS WITH PATELLOFEMORAL PAIN

Background:Patellofemoral pain (PFP) is a chronic knee condition that inhibits movement quality and can cascade into kinesiophobia (i.e., fear of pain/movement). Despite its high prevalence in adolescent girls, PFP etiology has remained elusive, potentially due to an incomplete understanding of how pain, motor control, and kinesiophobia interact with central nervous system (CNS) functioning. Discovering linkages between motor control, kinesiophobia, and the CNS for patients with PFP could provide novel opportunities to refine neural therapeutic strategies for enhanced, personalized treatment approaches.Hypothesis/Purpose:To identify neural markers of kinesiophobia in pediatric patients with PFP.Methods:Adolescent girls clinically diagnosed with PFP (n = 14; 14.3 ± 3.2 yrs) were positioned supine in a magnetic resonance imaging (MRI) scanner. A modified Clarke’s test (patellofemoral grind test) was administered to the left knee of patients during brain functional MRI (fMRI) acquisition. The experimenter placed a hand at the superior patellar border applying intermittent distal pressure while the patient contracted her quadriceps. Patients also completed a quadriceps contraction test without application of external pressure (control). Kinesiophobia was measured using the Tampa Scale of Kinesiophobia. fMRI analyses compared brain activation between the two tasks, and correlation analyses were performed to assess relationships between task-induced brain activity and kinesiophobia. Statistical corrections were made to account for multiple, voxel-wise comparisons.Results:Evidenced in Table 1 and Figure 1A, neuroimaging analyses revealed distinct bidirectional activation during the Clarke’s test compared to the control (all p corrected < .05, all z max > 3.1). Table 1 and Figure 1B further highlight that greater kinesiophobia was associated with increased brain activity during the Clarke’s test in two clusters (both p corrected < .05, both z max > 3.1), but no relationships between kinesiophobia and brain activity during the control test were observed (all p corrected > .05, all z max < 3.1).Conclusion:The current results indicate that the Clarke’s test induced differential pain-related brain activity relative to the control (e.g., paracingulate gyrus). The patients’ degree of kinesiophobia was also related to brain activity in regions important for sensorimotor control, attention, and pain. Collectively, these data indicate that PFP may be due to alterations in nociceptive processing throughout the CNS, providing novel complementary pathways for targeted restoration of patellofemoral joint dysfunction. Future research should consider combined mechanistic pain profiling, sensorimotor, psychometric, and CNS assessments to identify patients most susceptible to kinesiophobia to refine treatment approaches that work towards a goal of disease prevention.Tables/Figures:Figure 1: A:.Greater activation during the modified Clarke’s test compared to the control test is colored red and less activation during the Clarke’s test compared to the control test colored blue. B: Green indicates regions for which higher kinesiophobia was positively associated with increased activity during the Clarke’s test. All image slices are shown in neurological convention and identified by the respective Z coordinate in Montreal neurological institute space. Cluster and anatomical details are provided in Table 1.

Fear-induced brain activations distinguish anxious and trauma-exposed brains

Translational models of fear conditioning and extinction have elucidated a core neural network involved in the learning, consolidation, and expression of conditioned fear and its extinction. Anxious or trauma-exposed brains are characterized by dysregulated neural activations within regions of this fear network. In this study, we examined how the functional MRI activations of 10 brain regions commonly activated during fear conditioning and extinction might distinguish anxious or trauma-exposed brains from controls. To achieve this, activations during four phases of a fear conditioning and extinction paradigm in 304 participants with or without a psychiatric diagnosis were studied. By training convolutional neural networks (CNNs) using task-specific brain activations, we reliably distinguished the anxious and trauma-exposed brains from controls. The performance of models decreased significantly when we trained our CNN using activations from task-irrelevant brain regions or from a brain network that is irrelevant to fear. Our results suggest that neuroimaging data analytics of task-induced brain activations within the fear network might provide novel prospects for development of brain-based psychiatric diagnosis.

Tracking differential activation of primary and supplementary motor cortex across timing tasks: An fNIRS validation study

Functional near-infrared spectroscopy (fNIRS) provides an alternative to functional magnetic resonance imaging (fMRI) for assessing changes in cortical hemodynamics. To establish the utility of fNIRS for measuring differential recruitment of the motor network during the production of timing-based actions, we measured cortical hemodynamic responses in 10 healthy adults while they performed two versions of a finger-tapping task. The task, used in an earlier fMRI study (Jantzen et al., 2004), was designed to track the neural basis of different timing behaviors. Participants paced their tapping to a metronomic tone, then continued tapping at the established pace without the tone. Initial tapping was either synchronous or syncopated relative to the tone. This produced a 2 × 2 design: synchronous or syncopated tapping and pacing the tapping with or continuing without a tone. Accuracy of the timing of tapping was tracked while cortical hemodynamics were monitored using fNIRS. Hemodynamic responses were computed by canonical statistical analysis across trials in each of the four conditions. Task-induced brain activation resulted in significant increases in oxygenated hemoglobin concentration (oxy-Hb) in a broad region in and around the motor cortex. Overall, syncopated tapping was harder behaviorally and produced more cortical activation than synchronous tapping. Thus, we observed significant changes in oxy-Hb in direct relation to the complexity of the task.

Age-related differences in task-induced brain activation is not task specific: Multivariate pattern generalization between metacognition, cognition and perception

Adolescence is associated with widespread maturation of brain structures and functional connectivity profiles that shift from local to more distributed and better integrated networks, which are active during a variety of cognitive tasks. Nevertheless, the approach to examine task-induced developmental brain changes is function-specific, leaving the question open whether functional maturation is specific to the particular cognitive demands of the task used, or generalizes across different tasks. In the present study we examine the hypothesis that functional brain maturation is driven by global changes in how the brain handles cognitive demands. Multivariate pattern classification analysis (MVPA) was used to examine whether age discriminative task-induced activation patterns generalize across a wide range of information processing levels. 25 young (13-years old) and 22 old (17-years old) adolescents performed three conceptually different tasks of metacognition, cognition and visual processing. MVPA applied within each task indicated that task-induced brain activation is consistent and reliably different between ages 13 and 17. These age-discriminative activation patterns proved to be common across the different tasks used, despite the differences in cognitive demands and brain structures engaged by each of the three tasks. MVP classifiers trained to detect age-discriminative patterns in brain activation during one task were significantly able to decode age from brain activation maps during execution of other tasks with accuracies between 63 and 75%. The results emphasize that age-specific characteristics of task-induced brain activation have to be understood at the level of brain-wide networks that show maturational changes in their organization and processing efficacy during adolescence.

Brain structural basis of individual variability in dream recall frequency.

Recent neuroimaging studies have indicated that inter-individual variability in dream recall frequency (DRF) is associated with both resting-state regional cerebral blood flow and task-induced brain activations. However, the brain structure underpinning this inter-individual variability in DRF remains unclear. The aim of the current study is to investigate the relationship between brain structural characteristics and DRF. We collected both T1-weighted and diffusion tensor magnetic resonance imaging data from 43 healthy volunteers. DRF was obtained from a two-week sleep diary with a subjective report of dream recall upon waking every morning. General linear model analysis was used to evaluate the relationship between brain structural characteristics (cortical volume and white matter integrity) and DRF. Not only the cortical volume of the medial portion of the right fusiform gyrus and parahippocampal gyrus but also the fractional anisotropy of white matter fibers connected to these regions were significantly negatively correlated with DRF, and these relationships were not modulated by a regular sleep. These findings provide direct evidence that brain structural characteristics are associated with inter-individual variability in DRF and may help us to better understand the structural mechanisms in the brain underlying dream recall.

Effects of visual information regarding tactile stimulation on the somatosensory cortical activation: a functional MRI study.

Many studies have investigated the evidence for tactile and visual interactive responses to activation of various brain regions. However, few studies have reported on the effects of visuo-tactile multisensory integration on the amount of brain activation on the somatosensory cortical regions. The aim of this study was to examine whether coincidental information obtained by tactile stimulation can affect the somatosensory cortical activation using functional MRI. Ten right-handed healthy subjects were recruited for this study. Two tasks (tactile stimulation and visuotactile stimulation) were performed using a block paradigm during fMRI scanning. In the tactile stimulation task, in subjects with eyes closed, tactile stimulation was applied on the dorsum of the right hand, corresponding to the proximal to distal directions, using a rubber brush. In the visuotactile stimulation task, tactile stimulation was applied to observe the attached mirror in the MRI chamber reflecting their hands being touched with the brush. In the result of SPM group analysis, we found brain activation on the somatosensory cortical area. Tactile stimulation task induced brain activations in the left primary sensory-motor cortex (SM1) and secondary somatosensory cortex (S2). In the visuo-tactile stimulation task, brain activations were observed in the both SM1, both S2, and right posterior parietal cortex. In all tasks, the peak activation was detected in the contralateral SM1. We examined the effects of visuo-tactile multisensory integration on the SM1 and found that visual information during tactile stimulation could enhance activations on SM1 compared to the tactile unisensory stimulation.

Developmental and Condition-Related Changes in the Prefrontal Cortex Activity during Rest

The prefrontal cortex (PFC) plays an important role in cognitive process related to executive function, but is also active during resting states. Quantifying prefrontal cortex activity during resting states provides a baseline for interpreting task-induced brain activity. Researchers commonly use resting conditions where participants are prompted to stare at a screen (eyes open) or close their eyes (eyes closed). Are these two conditions equivalent representations of a baseline resting state? Further, does prefrontal cortex activity during these conditions change as a function of development? The aim of this study was to examine differences in prefrontal cortex activity between eyes open and eyes closed conditions during resting states in children and adults to provide a rationale of proper selection of baseline condition in future research. Thirty-six participants in 3 age groups were recruited in this study including twenty-four adults, five 12 - 15 years old children, and seven 8 - 11 years old children. Relative changes in concentrations of oxygenated hemoglobin (Δoxy-Hb) and deoxygenated hemoglobin (Δdeoxy-Hb) were obtained by using functional Near-Infrared Spectroscopy (fNIRS) in eyes closed (EC) and eyes open (EO) conditions, 3 minutes each. Contrasts were tested to compare the differences of Δoxy-Hb and Δdeoxy-Hb between eyes open and eyes closed conditions. The EC condition had significantly higher Δoxy-Hb than EO when all groups were combined (t (17.268) = 3.021, p = .008, Cohen’s d = –0.72). When comparing Δoxy-Hb between eyes conditions within each group, the younger group had significantly higher Δoxy-Hb in EC than EO (t (9.459) = 2.734, p = 0.022, Cohen’s d = –1.46). Based on these results, the EO condition may be a better baseline condition, particularly in studies with younger children, since it has less activity in the PFC that could interfere with interpretations of task-induced activity.

Resting-state brain activity in the motor cortex reflects task-induced activity: A multi-voxel pattern analysis.

It has been suggested that resting-state brain activity reflects task-induced brain activity patterns. In this study, we examined whether neural representations of specific movements can be observed in the resting-state brain activity patterns of motor areas. First, we defined two regions of interest (ROIs) to examine brain activity associated with two different behavioral tasks. Using multi-voxel pattern analysis with regularized logistic regression, we designed a decoder to detect voxel-level neural representations corresponding to the tasks in each ROI. Next, we applied the decoder to resting-state brain activity. We found that the decoder discriminated resting-state neural activity with accuracy comparable to that associated with task-induced neural activity. The distribution of learned weighted parameters for each ROI was similar for resting-state and task-induced activities. Large weighted parameters were mainly located on conjunctive areas. Moreover, the accuracy of detection was higher than that for a decoder whose weights were randomly shuffled, indicating that the resting-state brain activity includes multi-voxel patterns similar to the neural representation for the tasks. Therefore, these results suggest that the neural representation of resting-state brain activity is more finely organized and more complex than conventionally considered.

Event-related dynamics of glutamate and BOLD effects measured using functional magnetic resonance spectroscopy (fMRS) at 3 T in a repetition suppression paradigm

Proton MR spectroscopy (1H-MRS) complements other brain research methods by providing measures of neurometabolites noninvasively in a localized brain area. Improvements in MR scanner technologies, and data acquisition and analysis methods should allow functional 1H-MRS (fMRS) to measure neurometabolite concentration changes during task-induced brain activation. The aim of the current study was to further develop event-related fMRS at 3T to investigate glutamate dynamics in response to repetition suppression. A secondary aim was to investigate the relationship between blood-oxygen-level-dependent (BOLD) responses and glutamate dynamics in the same paradigm at the same time. A novel approach of interleaved water-suppressed (metabolite) and unsuppressed (water) fMRS was used to simultaneously detect the event-related dynamics of glutamate and BOLD signal to repetition suppression in the lateral occipital cortex of thirteen (N=13) volunteers. On average, 1H-MRS-visible glutamate increased after novel visual stimuli presentations by 12% and decreased by 11–13% on repeated compared to novel presentations. The BOLD signal, as measured by water peak amplitude changes, showed significant difference between Task and Rest trials, and, on a GLM based analysis of the time series, demonstrated a significant difference between the novel and repeated trials, however appeared to be decoupled from the glutamate response as no correlation was found between the two. These results are the first demonstration that reductions in neuronal activity typical of repetition suppression effects are reflected by reduced glutamatergic and BOLD measures, that glutamate and BOLD responses may not be coupled as previously thought, and that these changes and relationships can be measured simultaneously using event-related fMRS at 3T.

Polarity-specific transcranial direct current stimulation disrupts auditory pitch learning

Transcranial direct current stimulation (tDCS) is attracting increasing interest because of its potential for therapeutic use. While its effects have been investigated mainly with motor and visual tasks, less is known in the auditory domain. Past tDCS studies with auditory tasks demonstrated various behavioral outcomes, possibly due to differences in stimulation parameters, task-induced brain activity, or task measurements used in each study. Further research, using well-validated tasks is therefore required for clarification of behavioral effects of tDCS on the auditory system. Here, we took advantage of findings from a prior functional magnetic resonance imaging study, which demonstrated that the right auditory cortex is modulated during fine-grained pitch learning of microtonal melodic patterns. Targeting the right auditory cortex with tDCS using this same task thus allowed us to test the hypothesis that this region is causally involved in pitch learning. Participants in the current study were trained for 3 days while we measured pitch discrimination thresholds using microtonal melodies on each day using a psychophysical staircase procedure. We administered anodal, cathodal, or sham tDCS to three groups of participants over the right auditory cortex on the second day of training during performance of the task. Both the sham and the cathodal groups showed the expected significant learning effect (decreased pitch threshold) over the 3 days of training; in contrast we observed a blocking effect of anodal tDCS on auditory pitch learning, such that this group showed no significant change in thresholds over the 3 days. The results support a causal role for the right auditory cortex in pitch discrimination learning.

N-Back task performance and corresponding brain-activation patterns in women with restrictive and bulimic eating-disorder variants: Preliminary findings

Eating disorder (ED) variants characterized by “binge-eating/purging” symptoms differ from “restricting-only” variants along diverse clinical dimensions, but few studies have compared people with these different eating-disorder phenotypes on measures of neurocognitive function and brain activation. We tested the performances of 19 women with “restricting-only” eating syndromes and 27 with “binge-eating/purging” variants on a modified n-back task, and used functional magnetic resonance imaging (fMRI) to examine task-induced brain activations in frontal regions of interest. When compared with “binge-eating/purging” participants, “restricting-only” participants showed superior performance. Furthermore, in an intermediate-demand condition, “binge-eating/purging” participants showed significantly less event-related activation than did “restricting-only” participants in a right posterior prefrontal region spanning Brodmann areas 6–8—a region that has been linked to planning of motor responses, working memory for sequential information, and management of uncertainty. Our findings suggest that working memory is poorer in eating-disordered individuals with binge-eating/purging behaviors than in those who solely restrict food intake, and that observed performance differences coincide with interpretable group-based activation differences in a frontal region thought to subserve planning and decision making.

Task-Induced Brain Activity Patterns in Type 2 Diabetes: A Potential Biomarker for Cognitive Decline

Patients with type 2 diabetes demonstrate reduced functional connectivity within the resting state default mode network (DMN), which may signal heightened risk for cognitive decline. In other populations at risk for cognitive decline, additional magnetic resonance imaging abnormalities are evident during task performance, including impaired deactivation of the DMN and reduced activation of task-relevant regions. We investigated whether middle-aged type 2 diabetic patients show these brain activity patterns during encoding and recognition tasks. Compared with control participants, we observed both reduced 1) activation of the dorsolateral prefrontal cortex during encoding and 2) deactivation of the DMN during recognition in type 2 diabetic patients, despite normal cognition. During recognition, activation in several task-relevant regions, including the dorsolateral prefrontal cortex and DMN regions, was positively correlated with HbA1c and insulin resistance, suggesting that these important markers of glucose metabolism impact the brain’s response to a cognitive challenge. Plasma glucose ≥11 mmol/L was associated with impaired deactivation of the DMN, suggesting that acute hyperglycemia contributes to brain abnormalities. Since elderly type 2 diabetic patients often demonstrate cognitive impairments, it is possible that these task-induced brain activity patterns observed in middle age may signal impending cognitive decline.

Task-induced brain activity in aphasic stroke patients: what is driving recovery?

The estimated prevalence of aphasia in the UK and the USA is 250 000 and 1 000 000, respectively. The commonest aetiology is stroke. The impairment may improve with behavioural therapy, and trials using cortical stimulation or pharmacotherapy are undergoing proof-of-principle investigation, but with mixed results. Aphasia is a heterogeneous syndrome, and the simple classifications according to the Broca-Wernicke-Lichtheim model inadequately describe the diverse communication difficulties with which patients may present. Greater knowledge of how intact neural networks promote recovery after aphasic stroke, either spontaneously or in response to interventions, will result in clearer hypotheses about how to improve the treatment of aphasia. Twenty-five years ago, a pioneering study on healthy participants heralded the introduction of functional neuroimaging to the study of mechanisms of recovery from aphasia. Over the ensuing decades, such studies have been interpreted as supporting one of three hypotheses, which are not mutually exclusive. The first two predate the introduction of functional neuroimaging: that recovery is the consequence of the reconstitution of domain-specific language systems in tissue around the lesion (the 'perilesional' hypothesis), or by homotopic cortex in the contralateral hemisphere (the 'laterality-shift' hypothesis). The third is that loss of transcallosal inhibition to contralateral homotopic cortex hinders recovery (the 'disinhibition' hypothesis). These different hypotheses at times give conflicting views about rehabilitative intervention; for example, should one attempt to activate or inhibit a contralateral homotopic region with cortical stimulation techniques to promote recovery? This review proposes that although the functional imaging data are statistically valid in most cases, their interpretation has often favoured one explanation while ignoring plausible alternatives. In our view, this is particularly evident when recovery is attributed to activity in 'language networks' occupying sites not observed in healthy participants. In this review we will argue that much of the distribution of what has often been interpreted as language-specific activity, particularly in midline and contralateral cortical regions, is an upregulation of activity in intact domain-general systems for cognitive control and attention, responding in a task-dependent manner to the increased 'effort' when damaged downstream domain-specific language networks are impaired. We further propose that it is an inability fully to activate these systems that may result in sub optimal recovery in some patients. Interpretation of the data in terms of activity in domain-general networks affords insights into novel approaches to rehabilitation.

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double-blind, randomized, placebo-controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH-induced connectivity increase to sensory-motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor cortex areas showed the opposite pattern with MPH-induced connectivity increase to CST components and connectivity decrease to sensory-motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico-cortical and cortico-subcortical connectivity of many other cognitive and sensory-motor RSN.

Fractional amplitude of low-frequency fluctuation changes in monkeys with spinal cord injury: A resting-state fMRI study

PurposeAlthough functional magnetic resonance imaging (fMRI) has revealed that spinal cord injury (SCI) causes anomalous changes in task-induced brain activation, its effect during the resting state remains unclear. The aim of this study is to explore the changes of the brain resting-state function in non-human primates with unilateral SCI. Materials and methodsEleven adult female rhesus monkeys were subjected to resting-state fMRI: five with unilateral thoracic SCI and six healthy monkeys, to obtain the fractional amplitude of low-frequency fluctuations (fALFF) of the blood oxygenation level-dependent (BOLD) contrast signal to determine the influence of SCI on the cerebral resting-state function. ResultsThe SCI-induced fALFF vary significantly in several encephalic regions, including the left cerebellum, the left thalamus, the right lateral geniculate nucleus, the right superior parietal lobule, and the posterior cingulate gyrus. ConclusionAnalysis of the resting-state fMRI provides evidence of abnormal spontaneous brain activations in primates with SCI, which may help us understand the pathophysiologic mechanisms underlying the changes in neural plasticity in the central nervous system after SCI.