Reappraisal-related downregulation of amygdala BOLD activation occurs only during the late trial window

During cognitive reappraisal, an individual reinterprets the meaning of an emotional stimulus to regulate the intensity of their emotional response. Prefrontal cortex activity has been found to support reappraisal and is putatively thought to downregulate the amygdala response to these stimuli. The timing of these regulation-related responses during the course of a trial, however, remains poorly understood. In the current fMRI study, participants were instructed to view or reappraise negative images and then rate how negative they felt following each image. The hemodynamic response function was estimated in 11 regions of interest for the entire time course of the trial including image viewing and rating. Notably, within the amygdala there was no evidence of downregulation in the early (picture viewing) window of the trial, only in the late (rating) window, which also correlated with a behavioral measure of reappraisal success. With respect to the prefrontal regions, some (e.g., inferior frontal gyrus) showed reappraisal-related activation in the early window, whereas others (e.g., middle frontal gyrus) showed increased activation primarily in the late window. These results highlight the temporal dynamics of different brain regions during emotion regulation and suggest that the amygdala response to negative images need not be immediately dampened to achieve successful cognitive reappraisal.

Improved Activation and Hemodynamic Response Function of Olfactory fMRI Using Simultaneous Multislice with Reduced TR Acquisition

Objectives. The respiration could decrease the time synchronization between odor stimulation and data acquisition, consequently deteriorating the functional activation and hemodynamic response function (HRF) in olfactory functional magnetic resonance imaging (fMRI) with a conventional repetition time (TR). In this study, we aimed to investigate whether simultaneous multislice (SMS) technology with reduced TR could improve the blood oxygen level-dependent (BOLD) activation and optimize HRF modeling in olfactory fMRI. Methods. Sixteen young healthy subjects with normal olfaction underwent olfactory fMRI on a 3T MRI scanner using a 64 channel head coil. FMRI data were acquired using SMS acceleration at three different TRs: 3000 ms, 1000 ms, and 500 ms. Both metrics of BOLD activation (activated voxels, mean, and maximum t -scores) and the HRF modeling (response height and time to peak) were calculated in the bilateral amygdalae, hippocampi, and insulae. Results. The 500 ms and 1000 ms TRs both significantly improved the number of activated voxels, mean, and maximum t -score in the amygdalae and insulae, compared with a 3000 ms TR (all P < 0.05 ). But the increase of these metrics in the hippocampi did not reach a statistical significance (all P > 0.05 ). No significant difference in any BOLD activation metrics between TR 500 ms and 1000 ms was observed in all regions of interest (ROIs) (all P > 0.05 ). The HRF curves showed that higher response height and shorter time to peak in all ROIs were obtained at 500 ms and 1000 ms TRs compared to 3000 ms TR. TR 500 ms had a more significant effect on response height than TR 1000 ms in the amygdalae ( P = 0.017 ), and there was no significant difference in time to peak between TR 500 ms and 1000 ms in all ROIs (all P > 0.05 ). Conclusions. The fast image acquisition technique of SMS with reduced TR could significantly improve the functional activation and HRF curve in olfactory fMRI.

Assessment of fNIRS Signal Processing Pipelines: Towards Clinical Applications

Functional Near-Infrared Spectroscopy (fNIRS) captures activations and inhibitions of cortical areas and implements a viable approach to neuromonitoring in clinical research. Compared to more advanced methods, continuous wave fNIRS (CW-fNIRS) is currently used in clinics for its simplicity in mapping the whole sub-cranial cortex. Conversely, it often lacks hardware reduction of confounding factors, stressing the importance of a correct signal processing. The proposed pipeline includes movement artifact reduction (MAR), bandpass filtering (BPF), and principal component analysis (PCA). Eight MAR algorithms were compared among 23 young adult volunteers under motor-grasping task. Single-subject examples are shown followed by the percentage in energy reduction (ERD%) statistics by single steps and cumulative values. The block average of the hemodynamic response function was compared with generalized linear model fitting. Maps of significant activation/inhibition were illustrated. The mean ERD% of pre-processed signals concerning the initial raw signal energy reached 4%. A tested multichannel MAR variant showed overcorrection on 4-fold more expansive windows. All of the MAR algorithms found similar activations in the contralateral motor area. In conclusion, single channel MAR algorithms are suggested followed by BPF and PCA. The importance of whole cortex mapping for fNIRS integration in clinical applications was also confirmed by our results.

Effective Connectivity during an Avoidance-Based Pavlovian-to-Instrumental Transfer Task

Pavlovian-to-instrumental transfer (PIT) refers to a phenomenon whereby a classically conditioned stimulus (CS) impacts the motivational salience of instrumental behavior. We examined behavioral response patterns and functional magnetic resonance imaging (fMRI) based effective connectivity during an avoidance-based PIT task. Eleven participants (8 females; Mage = 28.2, SD = 2.8, range = 25–32 years) completed the task. Effective connectivity between a priori brain regions engaged during the task was determined using hemodynamic response function group iterative multiple model estimation (HRF-GIMME). Participants exhibited behavior that was suggestive of specific PIT, a CS previously associated with a reinforcing outcome increased instrumental responding directed at the same outcome. We did not find evidence for general PIT; a CS did not significantly increase instrumental responding towards a different but related outcome. Using HRF-GIMME, we recovered effective connectivity maps among corticostriatal circuits engaged during the task. Group-level paths revealed directional effects from left putamen to right insula and from right putamen to right cingulate. Importantly, a direct effect of specific PIT stimuli on blood–oxygen-level-dependent (BOLD) activity in the left putamen was found. Results provide initial evidence of effective connectivity in key brain regions in an avoidance-based PIT task network. This study adds to the literature studying PIT effects in humans and employing GIMME models to understand how psychological phenomena are supported in the brain.

Longitudinal Resting-State fMRI Study: A Seed-Based Connectivity Analysis in Patients with Ischemic Stroke and Intracerebral Hemorrhage

The primary aim of the research was to compare the impact of post-ischemic and hemorrhagic stroke on brain connectivity and recovery using resting-state functional magnetic resonance imaging (rsfMRI). We serially imaged 20 stroke patients, ten with ischemic (IS) and 10 with intracerebral hemorrhage (ICH), at 1, 3, and 12 months after ictus. Data from ten healthy volunteers were obtained from a publically available imaging dataset. All functional and structural images underwent standard processing for brain extraction, realignment, serial registration, unwrapping, and de-noising using SPM12. A seed-based group analysis using CONN software was used to evaluate the Default Mode (DMN) and the Sensorimotor Network (SMN) connections by applying bivariate correlation and hemodynamic response function (hrf) weighting. In comparison to healthy controls (HC), both IS and ICH exhibited disrupted interactions (decreased connectivity) between these two networks at 1M. Interactions then increased by 12M in each group. Temporally, each group exhibited a minimal increase in connectivity at 3M as compared to 12M. Overall, the ICH patients exhibited a greater magnitude of connectivity disruption compared to IS patients, despite a significant intra-subject reduction in hematoma volume. We did not observe any significant correlation between change in connectivity and recovery as measured on the National Institute Stroke Scale (NIHSS) at any time point. These finding demonstrate that largest changes in functional connectivity occur earlier (3M) rather than later (12M) and show subtle differences between IS and ICH during recovery and should be explored further in larger samples.

Effective Connectivity During an Avoidance-Based Pavlovian-to-Instrumental Transfer Task

Pavlovian-to-instrumental transfer (PIT) refers to a phenomenon whereby a classically conditioned stimulus (CS) impacts the motivational salience of instrumental behavior. We examined behavioral response patterns and functional magnetic resonance imaging (fMRI) based effective connectivity during an avoidance-based PIT task. Eleven participants (8 females; Mage = 28.2, SD = 2.8, range = 25-32 years) completed the task. Effective connectivity between a priori brain regions engaged during the task was determined using hemodynamic response function group iterative multiple model estimation (HRF-GIMME). Behaviorally, participants exhibited specific PIT, a CS previously associated with a reinforcing outcome increased instrumental responding directed at the same outcome. We did not find evidence for general PIT; a CS did not significantly increase instrumental responding towards a different but related outcome. Using HRF-GIMME, we recovered effective connectivity maps among corticostriatal circuits engaged during the task. Group-level paths revealed directional effects from left putamen to right insula and from right putamen to right cingulate. Importantly, a direct effect of specific PIT stimuli on blood-oxygen-level-dependent (BOLD) activity in the left putamen was found. Results provide initial evidence of effective connectivity in key brain regions in an avoidance-based PIT task network. This study adds to the literature studying PIT effects in humans and employing GIMME models to understand how psychological phenomena are supported in the brain.

The Temporal Dedifferentiation of Global Brain Signal Fluctuations During Human Brain Aging

The variation of brain organization as healthy aging has been discussed widely using resting-state functional magnetic resonance imaging. Previous conclusions may be misinterpreted without considering the effects of global signal (GS) on local activities and the variation of GS as age is still unknown. To fill this gap, we systematically examined the correlation between GS fluctuations and age. Correlations were evaluated between age and parameters of GS fluctuations including power at each frequency point, spectral centroids, and trends of power spectra. Data with hemodynamic response function (HRF) de-convolution and head motion parameter were further analyzed to test whether the age effect of GS fluctuations has neural origins. GS fluctuations varied as age in three ways. First, general GS power reductions were found in both time and frequency dimensions. Second, the GS power at lower frequencies transferring to higher frequencies was observed. Third, more evenly distributed power across frequencies was showed in aging brain. These trends were partly impacted by HRF de-convolution, but not by head motion. These results suggest that GS fluctuations are weaker and more evenly distributed across frequencies in elderly brain. It may indicate the temporal dedifferentiation hypothesis of brain aging from the global signal level.

Not All Lesioned Tissue Is Equal: Identifying Pericavitational Areas in Chronic Stroke With Tissue Integrity Gradation via T2w T1w Ratio

Stroke-related tissue damage within lesioned brain areas is topologically non-uniform and has underlying tissue composition changes that may have important implications for rehabilitation. However, we know of no uniformly accepted, objective non-invasive methodology to identify pericavitational areas within the chronic stroke lesion. To fill this gap, we propose a novel magnetic resonance imaging (MRI) methodology to objectively quantify the lesion core and surrounding pericavitational perimeter, which we call tissue integrity gradation via T2w T1w ratio (TIGR). TIGR uses standard T1-weighted (T1w) and T2-weighted (T2w) anatomical images routinely collected in the clinical setting. TIGR maps are analyzed with relation to subject-specific gray matter and cerebrospinal fluid thresholds and binned to create a false colormap of tissue damage within the stroke lesion, and these are further categorized into low-, medium-, and high-damage areas. We validate TIGR by showing that the cerebral blood flow within the lesion reduces with greater tissue damage (p = 0.005). We further show that a significant task activity can be detected in pericavitational areas and that medium-damage areas contain a significantly lower magnitude of hemodynamic response function than the adjacent damaged areas (p &lt; 0.0001). We also demonstrate the feasibility of using TIGR maps to extract multivariate brain–behavior relationships (p &lt; 0.05) and show general agreement in location compared to binary lesion, T1w-only, and T2w-only maps but that the extent of brain behavior maps may depend on signal sensitivity as denoted by the sparseness coefficient (p &lt; 0.0001). Finally, we show the feasibility of quantifying TIGR in early and late subacute stroke phases, where higher-damage areas were smaller in size (p = 0.002) and that lesioned voxels transition from lower to higher damage with increasing time post-stroke (p = 0.004). We conclude that TIGR is able to (1) identify tissue damage gradient within the stroke lesion across different post-stroke timepoints and (2) more objectively delineate lesion core from pericavitational areas wherein such areas demonstrate reasonable and expected physiological and functional impairments. Importantly, because T1w and T2w scans are routinely collected in the clinic, TIGR maps can be readily incorporated in clinical settings without additional imaging costs or patient burden to facilitate decision processes related to rehabilitation planning.