Multimodal Neuroimaging Methods Research Articles

Evaluation of consciousness rehabilitation via neuroimaging methods.

Accurate evaluation of patients with disorders of consciousness (DoC) is crucial for personalized treatment. However, misdiagnosis remains a serious issue. Neuroimaging methods could observe the conscious activity in patients who have no evidence of consciousness in behavior, and provide objective and quantitative indexes to assist doctors in their diagnosis. In the review, we discussed the current research based on the evaluation of consciousness rehabilitation after DoC using EEG, fMRI, PET, and fNIRS, as well as the advantages and limitations of each method. Nowadays single-modal neuroimaging can no longer meet the researchers` demand. Considering both spatial and temporal resolution, recent studies have attempted to focus on the multi-modal method which can enhance the capability of neuroimaging methods in the evaluation of DoC. As neuroimaging devices become wireless, integrated, and portable, multi-modal neuroimaging methods will drive new advancements in brain science research.

Investigating Neuroimaging Correlates of Early Frailty in Patients With Behavioral Variant Frontotemporal Dementia: A MRI and FDG-PET Study.

Frailty is a dynamic clinical condition characterized by the reduction of interconnections among different psychobiological domains, which leads to a homeostatic vulnerability. The association between physical frailty and cognitive dysfunctions is a possible predictor of poor prognosis in patients with neurodegenerative disorders. However, this construct has not been fully analyzed by a multidimensional neuropsychogeriatric assessment matched with multimodal neuroimaging methods in patients with behavioral variant frontotemporal dementia (bvFTD). We have investigated cognitive dysfunctions and frailty status, assessed by both a neuropsychological evaluation and the Multidimensional Prognostic Index (MPI), in a sample of 18 bvFTD patients and compared to matched healthy controls. Gray matter (GM) volume (as assessed by voxel-based morphometry) and metabolism (on 18fluorodeoxyglucose positron emission tomography) were first separately compared between groups, then voxelwise compared and correlated to each other within patients. Linear regression of the MPI was performed on those voxels presenting a significant correlation between altered GM volume and metabolism. The neuropsychological assessment reflected the diagnoses and the functional–anatomical alterations documented by neuroimaging analyses. In particular, the majority of patients presented significant executive dysfunction and mood changes in terms of apathy, depression, and anxiety. In the overall MPI score, the patients fell in the lower range (indicating an early frailty status). On imaging, they exhibited a bilateral decrease of GM density and hypometabolism involving the frontal pole, the anterior opercular region, and the anterior cingulate cortex. Greater atrophy than hypometabolism was observed in the bilateral orbitofrontal cortex, the triangular part of the inferior frontal gyrus, and the ventral striatum, whereas the contrary was detected in the bilateral dorsal anterior cingulate cortex and pre-supplementary motor area. MPI scores significantly correlated only with the co-occurrence of a decrease of GM density and hypometabolism in the right anterior insular cortex, but not with the separate pathological phenomena. Our results show a correlation between a specific pattern of co-occurring GM atrophy and hypometabolism with early frailty in bvFTD patients. These aspects, combined with executive dysfunction and mood changes, may lead to an increased risk of poor prognosis, highlighting a potentially critical and precocious role of the insula in the pathogenesis of frailty.

Connectome biomarkers of drug-resistant epilepsy.

Drug-resistant epilepsy (DRE) considerably affects patient health, cognition, and well-being, and disproportionally contributes to the overall burden of epilepsy. The most common DRE syndromes are temporal lobe epilepsy related to mesiotemporal sclerosis and extratemporal epilepsy related to cortical malformations. Both syndromes have been traditionally considered as "focal," and most patients benefit from brain surgery for long-term seizure control. However, increasing evidence indicates that many DRE patients also present with widespread structural and functional network disruptions. These anomalies have been suggested to relate to cognitive impairment and prognosis, highlighting their importance for patient management. The advent of multimodal neuroimaging and formal methods to quantify complex systems has offered unprecedented ability to profile structural and functional brain networks in DRE patients. Here, we performed a systematic review on existing DRE network biomarker candidates and their contribution to three key application areas: (1) modeling of cognitive impairments, (2) localization of the surgical target, and (3) prediction of clinical and cognitive outcomes after surgery. Although network biomarkers hold promise for a range of clinical applications, translation of neuroimaging biomarkers to the patient's bedside has been challenged by a lack of clinical and prospective studies. We therefore close by highlighting conceptual and methodological strategies to improve the evaluation and accessibility of network biomarkers, and ultimately guide clinically actionable decisions.

Customizing TMS Applications in Traumatic Brain Injury Using Neuroimaging.

Our total sample (N = 97) included 58 individuals with TBI (49 mild, 8 moderate, and 1 severe in a state of disordered consciousness), of which 24 had co-occurring conditions (depression in 14 and alcohol use disorder in 10). Of those without TBI, 6 individuals had alcohol use disorder and 33 were healthy controls. Of our total sample, 54 were veterans and 43 were civilians. Proof-of-concept study incorporating data from 5 analyses/studies that used multimodal approaches to integrate neuroimaging with TMS. Multimodal neuroimaging methods including structural magnetic resonance imaging (MRI), MRI-guided TMS navigation, functional MRI, diffusion MRI, and TMS-induced electric fields. Outcomes included symptom scales, neuropsychological tests, and physiological measures. It is feasible to use multimodal neuroimaging data to customize TMS targets and understand brain-based changes in targeted networks among people with TBI. TBI is an anatomically heterogeneous disorder. Preliminary evidence from the 5 studies suggests that using multimodal neuroimaging approaches to customize TMS treatment is feasible. To test whether this will lead to increased clinical efficacy, studies that integrate neuroimaging and TMS targeting data with outcomes are needed.

Structural and biochemical imaging reveals systemic LPS-induced changes in the rat brain

Despite mounting evidence for the role of inflammation in Major Depressive Disorder (MDD), in vivo preclinical investigations of inflammation-induced negative affect using whole brain imaging modalities are scarce, precluding a valid model within which to evaluate pharmacological interventions. Here we used an E. coli lipopolysaccharide (LPS)-based model of inflammation-induced depressive signs in rats to explore brain changes using multimodal neuroimaging methods. During the acute phase of the LPS response (2 h post injection), prior to the emergence of a task-quantifiable depressive phenotype, striatal glutamine levels and splenial, retrosplenial, and peri-callosal hippocampal cortex volumes were greater than at baseline. LPS-induced depressive behaviors observed at 24 h, however, occurred concurrently with lower than control levels of striatal glutamine and a reversibility of volume expansion (i.e., shrinkage of splenial, retrosplenial, and peri-callosal hippocampal cortex to baseline volumes). In both striatum and hippocampus at 24 h, mRNA expression in LPS relative to control animals demonstrated alterations in enzymes and transporters regulating glutamine homeostasis. Collectively, the observed behavioral, in vivo structural and metabolic, and mRNA expression alterations suggest a critical role for astrocytic regulation of inflammation-induced depressive behaviors.

Robust automated computational approach for classifying frontotemporal neurodegeneration: Multimodal/multicenter neuroimaging

IntroductionTimely diagnosis of behavioral variant frontotemporal dementia (bvFTD) remains challenging because it depends on clinical expertise and potentially ambiguous diagnostic guidelines. Recent recommendations highlight the role of multimodal neuroimaging and machine learning methods as complementary tools to address this problem. MethodsWe developed an automatic, cross-center, multimodal computational approach for robust classification of patients with bvFTD and healthy controls. We analyzed structural magnetic resonance imaging and resting-state functional connectivity from 44 patients with bvFTD and 60 healthy controls (across three imaging centers with different acquisition protocols) using a fully automated processing pipeline, including site normalization, native space feature extraction, and a random forest classifier. ResultsOur method successfully combined multimodal imaging information with high accuracy (91%), sensitivity (83.7%), and specificity (96.6%). DiscussionThis multimodal approach enhanced the system's performance and provided a clinically informative method for neuroimaging analysis. This underscores the relevance of combining multimodal imaging and machine learning as a gold standard for dementia diagnosis.

The neurophysiological correlates of religious chanting

Despite extensive research on various types of meditation, research on the neural correlates of religious chanting is in a nascent stage. Using multi-modal electrophysiological and neuroimaging methods, we illustrate that during religious chanting, the posterior cingulate cortex shows the largest decrease in eigenvector centrality, potentially due to regional endogenous generation of delta oscillations. Our data show that these functional effects are not due to peripheral cardiac or respiratory activity, nor due to implicit language processing. Finally, we suggest that the neurophysiological correlates of religious chanting are likely different from those of meditation and prayer, and would possibly induce distinctive psychotherapeutic effects.

Neuroimaging Biomarkers of mTOR Inhibition on Vascular and Metabolic Functions in Aging Brain and Alzheimer's Disease.

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. Specifically, we focus on pharmacological treatment (e.g., rapamycin) for restoring brain functions in animals modeling human AD; nutritional interventions (e.g., CR and ketogenic diet) for enhancing brain vascular and metabolic functions in rodents at young age (5–6 months of age) and preserving those functions in aging (18–20 months of age). Various magnetic resonance (MR) methods [i.e., imaging (MRI), angiography (MRA), and spectroscopy (MRS)], confocal microscopic imaging, and positron emission tomography (PET) provided in vivo metabolic and vascular measures. We also discuss the translational potential of mTOR interventions. Since PET and various MR neuroimaging methods, as well as the different interventions (e.g., rapamycin, CR, and ketogenic diet) are also available for humans, these findings may have tremendous implications in future clinical trials of neurological disorders in aging populations.

Moderating Effect of White Matter Integrity on Brain Activation During Dual-Task Walking in Older Adults.

Using multimodal neuroimaging methods, the current study was designed to examine the relationship between white matter microstructural integrity (WMI) and changes in prefrontal cortex (PFC) oxygenated hemoglobin (HbO2) during active walking in older adults. Consistent with neural inefficiency, we hypothesized that worse WMI would be associated with a greater increase in PFC HbO2 from single to dual-task walking in the context of worse or similar gait performance. Fifty-five cognitively healthy older adults (mean age = 74.76 years, 49% women) underwent diffusion tensor imaging (DTI) to derive a whole-brain measure of fractional anisotropy (FA) and functional Near Infrared Spectroscopy (fNIRS), which measured PFC HbO2 during walking tasks. Gait velocity was assessed using an instrumented walkway. A linear mixed effects model revealed that HbO2 levels increased from single to dual-task walking (P < 0.01) given the greater cognitive demands inherent in the latter condition. Moreover, WMI moderated the effect of dual tasking on PFC HbO2 (P < 0.05). Specifically, worse WMI was associated with a larger increase in PFC HbO2 levels from single to dual-task walking in the context of similar gait velocity. Results suggest that compromised WMI may be a mechanism underlying inefficient brain response to cognitive demands of locomotion.

Cortical thickness and white matter integrity abnormalities in obsessive-compulsive disorder: A combined multimodal surface-based morphometry and tract-based spatial statistics study.

Cerebral morphological abnormalities may play a key role in pathogenesis of obsessive-compulsive disorder (OCD). However, few studies have used multimodal imaging strategies to investigate alterations of cortical morphometry and white matter (WM) integrity. This study aimed to evaluate cortical thickness, cortical and subcortical volume, and WM integrity characteristics in OCD patients comprehensively. We acquired magnetic resonance imaging (MRI) scans from 52 OCD patients and 46 well-matched healthy controls (HCs). Cortical thickness and cortical and subcortical volume were measured using the surface-based morphometry (SBM) approach. We also evaluated fractional anisotropy (FA) and mean diffusivity (MD) derived from diffusion tensor imaging (DTI) using tract-based spatial statistics (TBSS). The disease severity was evaluated by score of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). For those brain regions exhibiting altered structure, correlations between alterations and clinical symptoms severity were analyzed in all patients and medication-naïve patients, respectively. Compared with controls, OCD patients exhibited cortical thinning in right posterior cingulate cortex (PCC), as well as significantly decreased FA values in the genu and body of corpus callosum (CC). In medication-naïve patients group, the total Y-BOCS score and obsession score were significantly negative correlated with right PCC cortical thickness. OCD patients demonstrated symptom-related reduced cortical thickness structural alteration of the right PCC, and altered WM integrity in the genu and body of CC. Medication seems could alleviate the alteration of cortical thickness but not WM integrity. Combined multimodal neuroimaging methods may provide a more comprehensive perspective to clarify the pathological mechanism of OCD.

Cognitive Function and Prognosis of Multimodal Neuroimage-Guided Thrombectomy on Mild to Moderate Anterior Circulation Infarction Patients with Broadened Therapeutic Window: A Prospective Study

Background and Objectives: Endovascular mechanical thrombectomy is an important approach for acute ischemic stroke (AIS) treatment. Multimodal neuroimaging methods ideally provide the exact localization, extent, and metabolic activity of target tissues. Post-stroke cognitive impairment has recently been realized to be another major concern except for neurological function impairment. The aim of our study was to carry out a prospective study to compare neurological and cognitive functions after thrombectomy in mild to moderate anterior circulation infarction patients selected by multimodal neuroimaging. Methods: Ninety patients were recruited from January 2016 to March 2017 consecutively. Neurological function was assessed by NIHSS before thrombectomy, and 6 h, 24 h, 7 days, 90 days after mechanical thrombectomy. Cognitive functions were evaluated by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Hachinski Ischemic Scale. Results: Patients who received mechanical thrombectomy had significantly better neurological functions at 6 h (p < 0.001), 24 h (p < 0.001), 7 days (p < 0.001), and 90 days (p < 0.001), as well as cognitive functions evaluated by MoCA (26.23 ± 3.85 vs. 24.62 ± 2.25, p = 0.022, n = 85) and MMSE (26.65 ± 2.77 vs. 25.10 ± 2.36, p = 0.023, n = 85) compared to the standard therapy group. Conclusions: The current prospective study demonstrated that mechanical thrombectomy can significantly improve neurological and cognitive functions in patients with mild to moderate AIS at broadened therapeutic window under multimodal CT and multimodal MRI imaging.

Reversing the Atypical Valuation of Drug and Nondrug Rewards in Smokers Using Multimodal Neuroimaging

BackgroundChronic substance use can disrupt the reward function of the anterior cingulate cortex (ACC), biasing the ACC to favor goal-directed behaviors that converge on drug use. Here we used multimodal neuroimaging methods to ask whether modulating reward-related signaling in the ACC can reverse the atypical valuation of nondrug and drug rewards in abstinent smokers. MethodsWe first recorded functional magnetic resonance imaging data from 20 moderately dependent cigarette smokers (mean age = 25 years; no history of neuropsychiatric disorders), following an overnight period of abstinence, to identify regions of the left dorsal lateral prefrontal cortex associated with the anticipation of drug-related rewards (cigarette puff). Next, we recorded the reward positivity—an electrophysiological signal believed to index sensitivity of the ACC to rewards—while participants engaged in two feedback tasks to gain either monetary or cigarette rewards. Lastly, guided by functional magnetic resonance imaging data, a robotic arm positioned a repetitive transcranial magnetic stimulation coil over a subject-specific dorsal lateral prefrontal cortex target, and 50 repetitive transcranial magnetic stimulation pulses were delivered at 10 Hz (excitatory stimulation) immediately before each block of 10 trials of the money condition and at 1 Hz (inhibitory stimulation) before each block of 10 trials of the cigarette condition. ResultsOur findings show that abstained smokers exhibited a heightened reward positivity to cigarette rewards relative to monetary rewards, and by applying excitatory or inhibitory repetitive transcranial magnetic stimulation to a subject-specific frontal-cingulate reward pathway, this pattern of results was reversed. ConclusionsBy modulating how the brain links value to drug and nondrug rewards, novel brain-based treatments may finally be on the horizon.

Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury.

Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork suggests that mTBI can be conceptualized as a dysconnection syndrome. It remains unclear whether reduced WM integrity is the trigger for changes in cortical surface area or whether tissue deformations are the direct result of mechanical forces acting on the brain. The findings suggest that rapid identification of high-risk patients with the use of clinical scales should be assessed acutely as part of the mTBI protocol.

Trimodal approach (PET/MR/EEG) of response inhibition as a possible biomarker for schizophrenia

IntroductionThe aim of the FP7-European funded project TRIMAGE is to create a trimodal, cost-effective imaging tool consisting of PET/MR/EEG to enable effective early diagnosis of schizophrenia.ObjectiveIn the scope of this project we are interested in the multimodal assessment of response inhibition. The loudness dependence of auditory evoked potential (LDAEP) is a suitable biomarker of inhibitory action in signal processing. Variations in response inhibition can have great impact on different aspects of life. Individuals with reduced capability of inhibitory control have a tendency to impulsive behavior. Studies showed that they have stronger LDAEP values. Patients with schizophrenia may exhibit alterations in the responsiveness to sensory stimuli. Thus, a reduced LDAEP was found in these patients. However, these deviances differed in clinical features of the disorder. Therefore, we would like to further elucidate the relationship between multimodal neuroimaging methods and dimensions of symptoms, observable behavior, personality traits and general psychopathological dysfunction.MethodsA sample of 20 healthy controls and 20 patients with manifest schizophrenia will be examined with the LDAEP paradigm in a trimodal approach with customary imaging tools. PET measurements with the radiotracer [11C]-flumazenil will be used to assess the binding potentials of GABA-A receptors. MRS will provide data about GABA concentrations. Simultaneously recorded EEG-fMRI data will permit new insight in the relationship between LDAEP and impulsivity.DiscussionThe project will use alternative approaches to psychiatric classification. Response inhibition in sensory processing will be investigated from different angles (biochemical, neurophysiological, and neuroanatomical) and combined with psychological characteristic values.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Editorial: Principles Underlying Post-Stroke Recovery of Upper Extremity Sensorimotor Function – A Neuroimaging Perspective

Editorial: Principles Underlying Post-Stroke Recovery of Upper Extremity Sensorimotor Function – A Neuroimaging Perspective

The Structural Connectivity Pattern of the Default Mode Network and Its Association with Memory and Anxiety.

The default mode network (DMN) is one of the most widely studied resting state functional networks. The structural basis for the DMN is of particular interest and has been studied by several researchers using diffusion tensor imaging (DTI). Most of these previous studies focused on a few regions or white matter tracts of the DMN so that the global structural connectivity pattern and network properties of the DMN remain unclear. Moreover, evidences indicate that the DMN is involved in both memory and emotion, but how the DMN regulates memory and anxiety from the perspective of the whole DMN structural network remains unknown. We used multimodal neuroimaging methods to investigate the structural connectivity pattern of the DMN and the association of its network properties with memory and anxiety in 205 young healthy subjects with age ranging from 18 to 29 years old. The Group ICA method was used to extract the DMN component from functional magnetic resonance imaging (fMRI) data and a probabilistic fiber tractography technique based on DTI data was applied to construct the global structural connectivity pattern of the DMN. Then we used the graph theory method to analyze the DMN structural network and found that memory quotient (MQ) score was significantly positively correlated with the global and local efficiency of the DMN whereas anxiety was found to be negatively correlated with the efficiency. The strong structural connectivity between multiple brain regions within DMN may reflect that the DMN has certain structural basis. Meanwhile, the results we found that the network efficiency of the DMN were related to memory and anxiety measures, indicated that the DMN may play a role in the memory and anxiety.

A Review of Transcranial Magnetic Stimulation and Multimodal Neuroimaging to Characterize Post-Stroke Neuroplasticity.

Following stroke, the brain undergoes various stages of recovery where the central nervous system can reorganize neural circuitry (neuroplasticity) both spontaneously and with the aid of behavioral rehabilitation and non-invasive brain stimulation. Multiple neuroimaging techniques can characterize common structural and functional stroke-related deficits, and importantly, help predict recovery of function. Diffusion tensor imaging (DTI) typically reveals increased overall diffusivity throughout the brain following stroke, and is capable of indexing the extent of white matter damage. Magnetic resonance spectroscopy (MRS) provides an index of metabolic changes in surviving neural tissue after stroke, serving as a marker of brain function. The neural correlates of altered brain activity after stroke have been demonstrated by abnormal activation of sensorimotor cortices during task performance, and at rest, using functional magnetic resonance imaging (fMRI). Electroencephalography (EEG) has been used to characterize motor dysfunction in terms of increased cortical amplitude in the sensorimotor regions when performing upper limb movement, indicating abnormally increased cognitive effort and planning in individuals with stroke. Transcranial magnetic stimulation (TMS) work reveals changes in ipsilesional and contralesional cortical excitability in the sensorimotor cortices. The severity of motor deficits indexed using TMS has been linked to the magnitude of activity imbalance between the sensorimotor cortices. In this paper, we will provide a narrative review of data from studies utilizing DTI, MRS, fMRI, EEG, and brain stimulation techniques focusing on TMS and its combination with uni- and multimodal neuroimaging methods to assess recovery after stroke. Approaches that delineate the best measures with which to predict or positively alter outcomes will be highlighted.

Perceived illusory orientation from the flash grab effect induces the Tilt Aftereffect

PURPOSE: Tilt aftereffect (TAE) is the phenomenon that the perceived orientation of a test stimulus is altered after prolonged exposure to an oriented adaptor. This phenomenon has been widely considered to result from adaptation of orientation-selective neurons in the early visual cortex. In this study, we investigated whether the TAE could be induced from a perceived illusory orientation of adapting stimulus dissociated from its physical orientation, by taking advantage of a new illusion— the flash grab effect. METHODS: Subjects viewed a physically vertical line that was repeatedly and briefly flashed on top of a patterned disk that oscillated clockwise and counterclockwise, with the flashed line presented at the moment of the rotation reversals. Importantly the adapting line was perceived as tilted away from vertical. Following adaptation to 11 cycles of the flashed line, a test line was briefly presented near vertical orientation at the corresponding location without the background disk. RESULTS: Results showed that a significant TAE was induced by the perceived orientation. In contrast, when the physical orientation of the titled adapting line was adjust by each individual subject so that the adapting line was perceived to be vertical, no TAE was observed. Thus when perceived and physical orientations of the adapting lines are pitted against each other, the TAE is dependent on the perceived rather than the physical orientation. In separate experiments using multimodal neuroimaging methods, we have shown that the perceived tilt from flash grab effect is primarily due to feedback processing in the brain. CONCLUSIONS: Our results suggest that higher-level processes and feedback signals play an important role in the TAE.

Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy.

Integration of multimodal neuroimaging methods: a rationale for clinical applications of simultaneous EEG-fMRI

Functional magnetic resonance imaging (fMRI), which has high spatial resolution, is increasingly used to evaluate cerebral functions in neurological and psychiatric diseases. The main limitation of fMRI is that it detects neural activity indirectly, through the associated slow hemodynamic variations. Because neurovascular coupling can be regionally altered by pathological conditions or drugs, fMRI responses may not truly reflect neural activity. Electroencephalography (EEG) recordings, which directly detect neural activity with optimal temporal resolution, can now be obtained during fMRI data acquisition. Therefore, there is a growing interest in combining the techniques to obtain simultaneous EEG-fMRI recordings. The EEG-fMRI approach has several promising clinical applications. The first is the detection of cortical areas involved in interictal and ictal epileptic activity. Second, combining evoked potentials with fMRI could be an accurate way to study eloquent cortical areas for the planning of neurosurgery or rehabilitation, circumventing the above-mentioned limitation of fMRI. Finally, the use of this approach to evaluate the functional connectivity of resting-state networks would extend the applications of EEG-fMRI to uncooperative or unconscious patients. Integration of multimodal neuroimaging methods: a rationale for clinical applications of simultaneous EEG-fMRI.