BOLD fMRI Research Articles

Arousal state transitions occlude sensory-evoked neurovascular coupling in neonatal mice

In the adult sensory cortex, increases in neural activity elicited by sensory stimulation usually drive vasodilation mediated by neurovascular coupling. However, whether neurovascular coupling is the same in neonatal animals as adults is controversial, as both canonical and inverted responses have been observed. We investigated the nature of neurovascular coupling in unanesthetized neonatal mice using optical imaging, electrophysiology, and BOLD fMRI. We find in neonatal (postnatal day 15, P15) mice, sensory stimulation induces a small increase in blood volume/BOLD signal, often followed by a large decrease in blood volume. An examination of arousal state of the mice revealed that neonatal mice were asleep a substantial fraction of the time, and that stimulation caused the animal to awaken. As cortical blood volume is much higher during REM and NREM sleep than the awake state, awakening occludes any sensory-evoked neurovascular coupling. When neonatal mice are stimulated during an awake period, they showed relatively normal (but slowed) neurovascular coupling, showing that that the typically observed constriction is due to arousal state changes. These result show that sleep-related vascular changes dominate over any sensory-evoked changes, and hemodynamic measures need to be considered in the context of arousal state changes.

Multivariate fMRI responses in superior temporal cortex predict visual contributions to, and individual differences in, the intelligibility of noisy speech

Humans have the unique ability to decode the rapid stream of language elements that constitute speech, even when it is contaminated by noise. Two reliable observations about noisy speech perception are that seeing the face of the talker improves intelligibility and the existence of individual differences in the ability to perceive noisy speech. We introduce a multivariate BOLD fMRI measure that explains both observations. In two independent fMRI studies, clear and noisy speech was presented in visual, auditory and audiovisual formats to thirty-seven participants who rated intelligibility. An event-related design was used to sort noisy speech trials by their intelligibility. Individual-differences multidimensional scaling was applied to fMRI response patterns in superior temporal cortex and the dissimilarity between responses to clear speech and noisy (but intelligible) speech was measured. Neural dissimilarity was less for audiovisual speech than auditory-only speech, corresponding to the greater intelligibility of noisy audiovisual speech. Dissimilarity was less in participants with better noisy speech perception, corresponding to individual differences. These relationships held for both single word and entire sentence stimuli, suggesting that they were driven by intelligibility rather than the specific stimuli tested. A neural measure of perceptual intelligibility may aid in the development of strategies for helping those with impaired speech perception.

Co-evolving dynamics and topology in a coupled oscillator model of resting brain function

Dynamic models of ongoing BOLD fMRI brain dynamics and models of communication strategies have been two important approaches to understanding how brain network structure constrains function. However, dynamic models have yet to widely incorporate one of the most important insights from communication models: the brain may not use all of its connections in the same way or at the same time. Here we present a variation of a phase delayed Kuramoto coupled oscillator model that dynamically limits communication between nodes on each time step. An active subgraph of the empirically derived anatomical brain network is chosen in accordance with the local dynamic state on every time step, thus coupling dynamics and network structure in a novel way. We analyze this model with respect to its fit to empirical time-averaged functional connectivity, finding that, with the addition of only one parameter, it significantly outperforms standard Kuramoto models with phase delays. We also perform analyses on the novel time series of active edges it produces, demonstrating a slowly evolving topology moving through intermittent episodes of integration and segregation. We hope to demonstrate that the exploration of novel modeling mechanisms and the investigation of dynamics of networks in addition to dynamics on networks may advance our understanding of the relationship between brain structure and function.

From correlation to communication: Disentangling hidden factors from functional connectivity changes.

While correlations in the BOLD fMRI signal are widely used to capture functional connectivity (FC) and its changes across contexts, its interpretation is often ambiguous. The entanglement of multiple factors including local coupling of two neighbors and nonlocal inputs from the rest of the network (affecting one or both regions) limits the scope of the conclusions that can be drawn from correlation measures alone. Here we present a method of estimating the contribution of nonlocal network input to FC changes across different contexts. To disentangle the effect of task-induced coupling change from the network input change, we propose a new metric, "communication change," utilizing BOLD signal correlation and variance. With a combination of simulation and empirical analysis, we demonstrate that (1) input from the rest of the network accounts for a moderate but significant amount of task-induced FC change and (2) the proposed "communication change" is a promising candidate for tracking the local coupling in task context-induced change. Additionally, when compared to FC change across three different tasks, communication change can better discriminate specific task types. Taken together, this novel index of local coupling may have many applications in improving our understanding of local and widespread interactions across large-scale functional networks.

Dependence of resting-state-based cerebrovascular reactivity (CVR) mapping on spatial resolution.

Cerebrovascular reactivity (CVR) is typically assessed with a carbon dioxide (CO2) stimulus combined with BOLD fMRI. Recently, resting-state (RS) BOLD fMRI has been shown capable of generating CVR maps, providing a potential for broader CVR applications in neuroimaging studies. However, prior RS-CVR studies have primarily been performed at a spatial resolution of 3-4 mm voxel sizes. It remains unknown whether RS-CVR can also be obtained at high-resolution without major degradation in image quality. In this study, we investigated RS-CVR mapping based on resting-state BOLD MRI across a range of spatial resolutions in a group of healthy subjects, in an effort to examine the feasibility of RS-CVR measurement at high resolution. Comparing the results of RS-CVR with the maps obtained by the conventional CO2-inhalation method, our results suggested that good CVR map quality can be obtained at a voxel size as small as 2 mm isotropic. Our results also showed that, RS-CVR maps revealed resolution-dependent sensitivity. However, even at a high resolution of 2 mm isotropic voxel size, the voxel-wise sensitivity is still greater than that of typical task-evoked fMRI. Scan duration affected the sensitivity of RS-CVR mapping, but had no significant effect on its accuracy. These findings suggest that RS-CVR mapping can be applied at a similar resolution as state-of-the-art fMRI studies, which will broaden the use of CVR mapping in basic science and clinical applications including retrospective analysis of previously collected fMRI data.

Task-evoked metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks.

External tasks evoke characteristic fMRI BOLD signal deactivations in the default mode network (DMN). However, for the corresponding metabolic glucose demands both decreases and increases have been reported. To resolve this discrepancy, functional PET/MRI data from 50 healthy subjects performing Tetris were combined with previously published data sets of working memory, visual and motor stimulation. We show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive networks. Specifically, the dorsal attention and frontoparietal network shape the glucose metabolism of the posteromedial DMN in opposing directions. While tasks that mainly require an external focus of attention lead to a consistent downregulation of both metabolism and the BOLD signal in the posteromedial DMN, cognitive control during working memory requires a metabolically expensive BOLD suppression. This indicates that two types of BOLD deactivations with different oxygen-to-glucose index may occur in this region. We further speculate that consistent downregulation of the two signals is mediated by decreased glutamate signaling, while divergence may be subject to active GABAergic inhibition. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation.

Role of Advanced MR Imaging in Diagnosis of Neurological Malignancies: Current Status and Future Perspective.

Lesions of the central nervous system (CNS) can present with numerous and overlapping radiographical and clinical features that make diagnosis difficult based exclusively on history, physical examination, and traditional imaging modalities. Given that there are significant differences in optimal treatment protocols for these various CNS lesions, rapid and non-invasive diagnosis could lead to improved patient care. Recently, various advanced magnetic resonance imaging (MRI) techniques showed promising methods to differentiate between various tumors and lesions that conventional MRI cannot define by comparing their physiologic characteristics, such as vascularity, permeability, oxygenation, and metabolism. These advanced MRI techniques include dynamic susceptibility contrast MRI (DSC), diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, Golden-Angle Radial Sparse Parallel imaging (GRASP), Blood oxygen level-dependent functional MRI (BOLD fMRI), and arterial spin labeling (ASL) MRI. In this article, a narrative review is used to discuss the current trends in advanced MRI techniques and potential future applications in identifying difficult-to-distinguish CNS lesions. Advanced MRI techniques were found to be promising non-invasive modalities to differentiate between paraganglioma, schwannoma, and meningioma. They are also considered promising methods to differentiate gliomas from lymphoma, post-radiation changes, pseudoprogression, demyelination, and metastasis. Advanced MRI techniques allow clinicians to take advantage of intrinsic biological differences in CNS lesions to better identify the etiology of these lesions, potentially leading to more effective patient care and a decrease in unnecessary invasive procedures. More clinical studies with larger sample sizes should be encouraged to assess the significance of each advanced MRI technique and the specificity and sensitivity of each radiologic parameter.

The effect of different brain lesions on the reorganization of language functions within the dominant hemisphere assessed with task-based BOLD-fMRI.

Language reorganization has been described in brain lesions with respect to their location and timing, but little is known with respect to their etiology. We used fMRI to investigate the effects of different types of left hemisphere lesions (GL = gliomas, TLE = temporal lobe epilepsy and CA = cavernous angioma) on the topographic intra-hemispheric language plasticity, also considering their location. Forty-seven right-handed patients with 3 different left hemisphere lesions (16 GL, 15 TLE and 16 CA) and 17 healthy controls underwent BOLD fMRI with a verb-generation task. Euclidean distance was used to measure activation peak shifts among groups with respect to reference Tailarach coordinates of Inferior Frontal Gyrus, Superior Temporal Sulcus and Temporo-Parietal Junction. Mixed-model ANOVAs were used to test for differences in activation peak shifts. Significant activation peak shifts were found in GL patients with respect both to HC and other groups (TLA and CA). In addition, in the same group of patients a significant effect of tumor location (anterior or posterior) was detected. We demonstrated that intra-hemispheric language plasticity is influenced by the type of lesion affecting the left hemisphere and that fMRI is especially valuable in the preoperative assessment of such reorganization in glioma patients.

Identifying the neural correlates of anticipatory postural control: A novel fMRI paradigm.

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the thigh remains supported. For the unsupported leg raise (ULR) the leg is raised from the hip, requiring postural muscle activation in the abdominal/hip extensor musculature. Significant brain activation during the SLR task occurred predominantly in the right primary and secondary sensorimotor cortical regions. Brain activation during the ULR task occurred bilaterally in the primary and secondary sensorimotor cortical regions, as well as cerebellum and putamen. In comparison with the SLR, the ULR was associated with significantly greater activation in the right premotor/SMA, left primary motor and cingulate cortices, primary somatosensory cortex, supramarginal gyrus/parietal operculum, superior parietal lobule, cerebellar vermis, and cerebellar hemispheres. Cortical and subcortical regions activated during the ULR, but not during the SLR, were consistent with the planning, and execution of a task involving multisegmental, bilateral postural control. Future studies using this paradigm will determine mechanisms underlying impaired postural control in patients with neurological and musculoskeletal dysfunction.

Correspondence between BOLD fMRI task response and cerebrovascular reactivity across the cerebral cortex.

BOLD sensitivity to baseline perfusion and blood volume is a well-acknowledged fMRI confound. Vascular correction techniques based on cerebrovascular reactivity (CVR) might reduce variance due to baseline cerebral blood volume, however this is predicated on an invariant linear relationship between CVR and BOLD signal magnitude. Cognitive paradigms have relatively low signal, high variance and involve spatially heterogenous cortical regions; it is therefore unclear whether the BOLD response magnitude to complex paradigms can be predicted by CVR. The feasibility of predicting BOLD signal magnitude from CVR was explored in the present work across two experiments using different CVR approaches. The first utilized a large database containing breath-hold BOLD responses and 3 different cognitive tasks. The second experiment, in an independent sample, calculated CVR using the delivery of a fixed concentration of carbon dioxide and a different cognitive task. An atlas-based regression approach was implemented for both experiments to evaluate the shared variance between task-invoked BOLD responses and CVR across the cerebral cortex. Both experiments found significant relationships between CVR and task-based BOLD magnitude, with activation in the right cuneus (R 2 = 0.64) and paracentral gyrus (R 2 = 0.71), and the left pars opercularis (R 2 = 0.67), superior frontal gyrus (R 2 = 0.62) and inferior parietal cortex (R 2 = 0.63) strongly predicted by CVR. The parietal regions bilaterally were highly consistent, with linear regressions significant in these regions for all four tasks. Group analyses showed that CVR correction increased BOLD sensitivity. Overall, this work suggests that BOLD signal response magnitudes to cognitive tasks are predicted by CVR across different regions of the cerebral cortex, providing support for the use of correction based on baseline vascular physiology.

The timing of transcranial magnetic stimulation relative to the phase of prefrontal alpha EEG modulates downstream target engagement

BackgroundThe communication through coherence model posits that brain rhythms are synchronized across different frequency bands and that effective connectivity strength between interacting regions depends on their phase relation. Evidence to support the model comes mostly from electrophysiological recordings in animals while evidence from human data is limited. MethodsHere, an fMRI-EEG-TMS (fET) instrument capable of acquiring simultaneous fMRI and EEG during noninvasive single pulse TMS applied to dorsolateral prefrontal cortex (DLPFC) was used to test whether prefrontal EEG alpha phase moderates TMS-evoked top-down influences on subgenual, rostral and dorsal anterior cingulate cortex (ACC). Six runs (276 total trials) were acquired in each participant. Phase at each TMS pulse was determined post-hoc using single-trial sorting. Results were examined in two independent datasets: healthy volunteers (HV) (n = 11) and patients with major depressive disorder (MDD) (n = 17) collected as part of an ongoing clinical trial. ResultsIn both groups, TMS-evoked functional connectivity between DLPFC and subgenual ACC (sgACC) depended on the EEG alpha phase. TMS-evoked DLPFC to sgACC fMRI-derived effective connectivity (EC) was modulated by EEG alpha phase in healthy volunteers, but not in the MDD patients. Top-down EC was inhibitory for TMS pulses during the upward slope of the alpha wave relative to TMS timed to the downward slope of the alpha wave. Prefrontal EEG alpha phase dependent effects on TMS-evoked fMRI BOLD activation of the rostral anterior cingulate cortex were detected in the MDD patient group, but not in the healthy volunteer group. DiscussionResults demonstrate that TMS-evoked top-down influences vary as a function of the prefrontal alpha rhythm, and suggest potential clinical applications whereby TMS is synchronized to the brain's internal rhythms in order to more efficiently engage deep therapeutic targets.

Impact of Amplitude and Phase of fMRI time series for Functional Connectivity Analysis

PurposeSeveral studies in the field of fMRI have reported the synchrony between the brain regions using instantaneous phase (IP) representation (derived from analytic representation of BOLD time series). We hypothesized that instantaneous amplitude (IA) representation from different brain regions might give additional information to the functional brain networks. To validate this, we explored this representation of resting state BOLD fMRI signal for deriving resting state networks (RSNs) and compared it with the IP representation based RSNs. MethodResting state fMRI data of 100 healthy adults (age=20–35 years, 54 females) from the population of 500 Subjects of HCP dataset were studied. Data was acquired using a 3T scanner in four runs (15-min each) with the phase encoding directions: Left to Right (LR), Right to Left (RL). These four runs were acquired in two sessions, and subjects were asked to keep their eyes open with a fixation on a white cross. The IA and IP representations were derived from a narrow-band filtered BOLD time series using Hilbert transforms and a seed-based approach is used to compute the RSNs in the brain. ResultsThe experimental results demonstrate that within the frequency range 0.01–0.1 Hz, IA representation based RSNs have the highest similarity score between the two sessions for the motor network. Whereas for fronto-parietal network, IP based activation maps have the highest similarity score for all the frequency bands. For higher frequency band (0.198–0.25 Hz) consistency of the obtained RSNs across two sessions reduced for both IA and IP representations. Fusion of IA and IP representations based RSNs in comparison to those of IP based representation, leads to 3–10% improvement in the similarity scores between the default mode network obtained for the two sessions. In addition, the same comparison demonstrates 15–20% improvement for the motor network in the frequency bands: 0.01–0.04 Hz, 0.04–0.07 Hz, slow5 (0.01–0.027 Hz) and slow-4 (0.027–0.073 Hz). It is also observed that the similarity score between two sessions using instantaneous frequency (IF) (derivative of unwrapped IP) representation in exploring functional connectivity (FC) networks is comparable with those obtained using IP representation. ConclusionOur findings suggest that IA-representation based measures can estimate RSNs with the reproducibility between the sessions comparable to that of the IP representation-based methods. This study demonstrates that IA and IP representations contain the complementary information of BOLD signal, and their fusion improves the results of FC.

Hemodynamic timing in resting-state and breathing-task BOLD fMRI

The blood flow response to a vasoactive stimulus demonstrates regional heterogeneity across both the healthy brain and in cerebrovascular pathology. The timing of a regional hemodynamic response is emerging as an important biomarker of cerebrovascular dysfunction, as well as a confound within fMRI analyses. Previous research demonstrated that hemodynamic timing is more robustly characterized when a larger systemic vascular response is evoked by a breathing challenge, compared to when only spontaneous fluctuations in vascular physiology are present (i.e., in resting-state data). However, it is not clear whether hemodynamic delays in these two conditions are physiologically interchangeable, and how methodological signal-to-noise factors may limit their agreement. To address this, we generated whole-brain maps of hemodynamic delays in nine healthy adults. We assessed the agreement of voxel-wise gray matter (GM) hemodynamic delays between two conditions: resting-state and breath-holding. We found that delay values demonstrated poor agreement when considering all GM voxels, but increasingly greater agreement when limiting analyses to voxels showing strong correlation with the GM mean time-series. Voxels showing the strongest agreement with the GM mean time-series were primarily located near large venous vessels, however these voxels explain some, but not all, of the observed agreement in timing. Increasing the degree of spatial smoothing of the fMRI data enhanced the correlation between individual voxel time-series and the GM mean time-series. These results suggest that signal-to-noise factors may be limiting the accuracy of voxel-wise timing estimates and hence their agreement between the two data segments. In conclusion, caution must be taken when using voxel-wise delay estimates from resting-state and breathing-task data interchangeably, and additional work is needed to evaluate their relative sensitivity and specificity to aspects of vascular physiology and pathology.

Conceptual Associations Generate Sensory Predictions.

A crucial ability of the human brain is to learn and exploit probabilistic associations between stimuli to facilitate perception and behavior by predicting future events. Although studies have shown how perceptual relationships are used to predict sensory inputs, relational knowledge is often between concepts rather than percepts (e.g., we learned to associate cats with dogs, rather than specific images of cats and dogs). Here, we asked if and how sensory responses to visual input may be modulated by predictions derived from conceptual associations. To this end we exposed participants of both sexes to arbitrary word-word pairs (e.g., car-dog) repeatedly, creating an expectation of the second word, conditional on the occurrence of the first. In a subsequent session, we exposed participants to novel word-picture pairs, while measuring fMRI BOLD responses. All word-picture pairs were equally likely, but half of the pairs conformed to the previously formed conceptual (word-word) associations, whereas the other half violated this association. Results showed suppressed sensory responses throughout the ventral visual stream, including early visual cortex, to pictures that corresponded to the previously expected words compared with unexpected words. This suggests that the learned conceptual associations were used to generate sensory predictions that modulated processing of the picture stimuli. Moreover, these modulations were tuning specific, selectively suppressing neural populations tuned toward the expected input. Combined, our results suggest that recently acquired conceptual priors are generalized across domains and used by the sensory brain to generate category-specific predictions, facilitating processing of expected visual input.SIGNIFICANCE STATEMENT Perceptual predictions play a crucial role in facilitating perception and the integration of sensory information. However, little is known about whether and how the brain uses more abstract, conceptual priors to form sensory predictions. In our preregistered study, we show that priors derived from recently acquired arbitrary conceptual associations result in category-specific predictions that modulate perceptual processing throughout the ventral visual hierarchy, including early visual cortex. These results suggest that the predictive brain uses prior knowledge across various domains to modulate perception, thereby extending our understanding of the extensive role predictions play in perception.

Functional topography of the neocortex predicts covariation in complex cognitive and basic motor abilities.

Although higher-order cognitive and lower-order sensorimotor abilities are generally regarded as distinct and studied separately, there is evidence that they not only covary but also that this covariation increases across the lifespan. This pattern has been leveraged in clinical settings where a simple assessment of sensory or motor ability (e.g. hearing, gait speed) can forecast age-related cognitive decline and risk for dementia. However, the brain mechanisms underlying cognitive, sensory, and motor covariation are largely unknown. Here, we examined whether such covariation in midlife reflects variability in common versus distinct neocortical networks using individualized maps of functional topography derived from BOLD fMRI data collected in 769 45-year-old members of a population-representative cohort. Analyses revealed that variability in basic motor but not hearing ability reflected individual differences in the functional topography of neocortical networks typically supporting cognitive ability. These patterns suggest that covariation in motor and cognitive abilities in midlife reflects convergence of function in higher-order neocortical networks and that gait speed may not be simply a measure of physical function but rather an integrative index of nervous system health.

Comparing end-tidal CO2, respiration volume per time (RVT), and average gray matter signal for mapping cerebrovascular reactivity amplitude and delay with breath-hold task BOLD fMRI

Cerebrovascular reactivity (CVR), defined as the cerebral blood flow response to a vasoactive stimulus, is an imaging biomarker with demonstrated utility in a range of diseases and in typical development and aging processes. A robust and widely implemented method to map CVR involves using a breath-hold task during a BOLD fMRI scan. Recording end-tidal CO2 (PETCO2) changes during the breath-hold task is recommended to be used as a reference signal for modeling CVR amplitude in standard units (%BOLD/mmHg) and CVR delay in seconds. However, obtaining reliable PETCO2 recordings requires equipment and task compliance that may not be achievable in all settings. To address this challenge, we investigated two alternative reference signals to map CVR amplitude and delay in a lagged general linear model (lagged-GLM) framework: respiration volume per time (RVT) and average gray matter BOLD response (GM-BOLD). In 8 healthy adults with multiple scan sessions, we compare spatial agreement of CVR maps from RVT and GM-BOLD to those generated with PETCO2. We define a threshold to determine whether a PETCO2 recording has “sufficient” quality for CVR mapping and perform these comparisons in 16 datasets with sufficient PETCO2 and 6 datasets with insufficient PETCO2. When PETCO2 quality is sufficient, both RVT and GM-BOLD produce CVR amplitude maps that are nearly identical to those from PETCO2 (after accounting for differences in scale), with the caveat they are not in standard units to facilitate between-group comparisons. CVR delays are comparable to PETCO2 with an RVT regressor but may be underestimated with the average GM-BOLD regressor. Importantly, when PETCO2 quality is insufficient, RVT and GM-BOLD CVR recover reasonable CVR amplitude and delay maps, provided the participant attempted the breath-hold task. Therefore, our framework offers a solution for achieving high quality CVR maps in both retrospective and prospective studies where sufficient PETCO2 recordings are not available and especially in populations where obtaining reliable measurements is a known challenge (e.g., children). Our results have the potential to improve the accessibility of CVR mapping and to increase the prevalence of this promising metric of vascular health.

BOLD fMRI and DTI fiber tracking for preoperative mapping of eloquent cerebral regions in brain tumor patients: impact on surgical approach and outcome.

Task-based BOLD fMRI and DTI-fiber tracking have become part of the routine presurgical work-up of brain tumor patients in many institutions. However, their potential impact on both surgical treatment and neurologic outcome remains unclear, in despite of the high costs and complex implementation. We retrospectively investigated whether performing fMRI and DTI-ft preoperatively substantially impacted surgical planning and patient outcome in a series of brain tumor patients. We assessed (i) the quality of fMRI and DTI-ft results, by using a scale of 0-2 (0 = failed mapping; 1 = intermediate confidence; 2 = good confidence), (ii) whether functional planning substantially contributed to defining the surgical strategy to be undertaken (i.e., no surgery, biopsy, or resection, with or without ESM), the surgical entry point and extent of resection, and (iii) the incidence of neurological deficits post-operatively. Twenty-seven patients constituted the study population. The mean confidence rating was 1.9/2 for fMRI localization of the eloquent cortex and lateralization of the language function and 1.7/2 for DTI-ft results. Treatment strategy was altered in 33% (9/27) of cases. Surgical entry point was modified in 8% (2/25) of cases. The extent of resection was modified in 40% (10/25). Onepatient (1/25, 4%) developed one new functional deficit post-operatively. Functional MR mapping - which must not be considered an alternative to ESM - has a critical role preoperatively, potentially modifying treatment strategy or increasing the neurosurgeons' confidence in the surgical approach hypothesized based on conventional imaging.

Functional Deficiency of Interneurons and Negative BOLD fMRI Response.

The functional deficiency of the inhibitory system typically appears during development and can progress to psychiatric disorders or epilepsy, depending on its severity, in later years. It is known that interneurons, the major source of GABAergic inhibition in the cerebral cortex, can make direct connections with arterioles and participate in the regulation of vasomotion. The goal of this study was to mimic the functional deficiency of interneurons through the use of localized microinjections of the GABA antagonist, picrotoxin, in such a concentration that it did not elicit epileptiform neuronal activity. First, we recorded the dynamics of resting-state neuronal activity in response to picrotoxin injections in the somatosensory cortex of an awake rabbit; second, we assessed the altered neuronal and hemodynamic responses to whisker stimulation using BOLD fMRI and electrophysiology recordings; third, we evaluated brain tissue oxygen levels before and after picrotoxin injection. Our results showed that neuronal activity typically increased after picrotoxin administration, the BOLD responses to stimulation became negative, and the oxygen response was nearly abolished. Vasoconstriction during the resting baseline was not observed. These results indicate that picrotoxin provoked imbalanced hemodynamics either due to increased neuronal activity, decreased vascular response, or a combination of both.

Widespread fMRI BOLD Signal Overactivations during Cognitive Control in Older Adults Are Not Matched by Corresponding Increases in fPET Glucose Metabolism.

A common observation in fMRI studies using the BOLD signal is that older adults, compared with young adults, show overactivations, particularly during less demanding tasks. The neuronal underpinnings of such overactivations are not known, but a dominant view is that they are compensatory in nature and involve recruitment of additional neural resources. We scanned 23 young (20-37 years) and 34 older (65-86 years) healthy human adults of both sexes with hybrid positron emission tomography/MRI. The radioligand [18F]fluoro-deoxyglucose was used to assess dynamic changes in glucose metabolism as a marker of task-dependent synaptic activity, along with simultaneous fMRI BOLD imaging. Participants performed two verbal working memory (WM) tasks: one involving maintenance (easy) and one requiring manipulation (difficult) of information in WM. Converging activations to the WM tasks versus rest were observed for both imaging modalities and age groups in attentional, control, and sensorimotor networks. Upregulation of activity to WM-demand, comparing the more difficult to the easier task, also converged between both modalities and age groups. For regions in which older adults showed task-dependent BOLD overactivations compared with the young adults, no corresponding increases in glucose metabolism were found. To conclude, findings from the current study show that task-induced changes in the BOLD signal and synaptic activity as measured by glucose metabolism generally converge, but overactivations observed with fMRI in older adults are not coupled with increased synaptic activity, which suggests that these overactivations are not neuronal in origin.SIGNIFICANCE STATEMENT Findings of increased fMRI activations in older compared with younger adults have been suggested to reflect increased use of neuronal resources to cope with reduced brain function. The physiological underpinnings of such compensatory processes are poorly understood, however, and rest on the assumption that vascular signals accurately reflect neuronal activity. Comparing fMRI and simultaneously acquired functional positron emission tomography as an alternative index of synaptic activity, we show that age-related overactivations do not appear to be neuronal in origin. This result is important because mechanisms underlying compensatory processes in aging are potential targets for interventions aiming to prevent age-related cognitive decline.

Potential sensitive period effects of maltreatment on amygdala, hippocampal and cortical response to threat.

Childhood maltreatment is a leading risk factor for psychopathology, though it is unclear why some develop risk averse disorders, such as anxiety and depression, and others risk-taking disorders including substance abuse. A critical question is whether the consequences of maltreatment depend on the number of different types of maltreatment experienced at any time during childhood or whether there are sensitive periods when exposure to particular types of maltreatment at specific ages exert maximal effects. Retrospective information on severity of exposure to ten types of maltreatment during each year of childhood was collected using the Maltreatment and Abuse Chronology of Exposure scale. Artificial Intelligence predictive analytics were used to delineate the most important type/time risk factors. BOLD activation fMRI response to threatening versus neutral facial images was assessed in key components of the threat detection system (i.e., amygdala, hippocampus, anterior cingulate, inferior frontal gyrus and ventromedial and dorsomedial prefrontal cortices) in 202 healthy, unmedicated, participants (84 M/118 F, 23.2 ± 1.7 years old). Emotional maltreatment during teenage years was associated with hyperactive response to threat whereas early childhood exposure, primarily to witnessing violence and peer physical bullying, was associated with an opposite pattern of greater activation to neutral than fearful faces in all regions. These findings strongly suggest that corticolimbic regions have two different sensitive period windows of enhanced plasticity when maltreatment can exert opposite effects on function. Maltreatment needs to be viewed from a developmental perspective in order to fully comprehend its enduring neurobiological and clinical consequences.