Blood Oxygen Level-dependent Response Research Articles

'I am afraid you will see the stain onmy soul': Direct gaze neural processing inindividuals with PTSD after moral injury recall.

Direct eye contact is essential to understanding others' thoughts and feelings in social interactions. However, those with post-traumatic stress disorder (PTSD) and exposure to moral injury (MI) may exhibit altered theory-of-mind (ToM)/mentalizing processes and experience shame which precludes one's capacity for direct eye contact. We investigated blood oxygenation level-dependent (BOLD) responses associated with direct vs averted gaze using a virtual reality paradigm in individuals with PTSD (n = 28) relative to healthy controls (n = 18) following recall of a MI vs a neutral memory. Associations between BOLD responses and clinical symptomatology were also assessed. After MI recall, individuals with PTSD showed greater activation in the right temporoparietal junction as compared to controls (T = 4.83; pFDR < 0.001; k = 237) during direct gaze. No significant activation occurred during direct gaze after neutral memory recall. Further, a significant positive correlation was found between feelings of distress and right medial superior frontal gyrus activation in individuals with PTSD (T = 5.03; pFDR = 0.049; k = 123). These findings suggest that direct gaze after MI recall prompts compensatory ToM/mentalizing processing. Implications for future interventions aimed at mitigating the effects of PTSD on social functioning are discussed.

Brain activation during fear extinction recall in unmedicated patients with obsessive-compulsive disorder

Specific brain activation patterns during fear conditioning and the recall of previously extinguished fear responses have been associated with obsessive-compulsive disorder (OCD). However, further replication studies are necessary. We measured skin-conductance response and blood oxygenation level-dependent responses in unmedicated adult patients with OCD (n = 27) and healthy participants (n = 22) submitted to a two-day fear-conditioning experiment comprising fear conditioning, extinction (day 1) and extinction recall (day 2). During conditioning, groups differed regarding the skin conductance reactivity to the aversive stimulus (shock) and regarding the activation of the right opercular cortex, insular cortex, putamen, and lingual gyrus in response to conditioned stimuli. During extinction recall, patients with OCD had higher responses to stimuli and smaller differences between responses to conditioned and neutral stimuli. For the entire sample, the higher the response delta between conditioned and neutral stimuli, the greater the dACC activation for the same contrast during early extinction recall. While activation of the dACC predicted the average difference between responses to stimuli for the entire sample, groups did not differ regarding the activation of the dACC during extinction recall. Larger unmedicated samples might be necessary to replicate the previous findings reported in patients with OCD.

Whole-brain, gray, and white matter time-locked functional signal changes with simple tasks and model-free analysis

Recent studies have revealed the production of time-locked blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals throughout the entire brain in response to tasks, challenging the existence of sparse and localized brain functions and highlighting the pervasiveness of potential false negative fMRI findings. "Whole-brain" actually refers to gray matter, the only tissue traditionally studied with fMRI. However, several reports have demonstrated reliable detection of BOLD signals in white matter, which have previously been largely ignored. Using simple tasks and analyses, we demonstrate BOLD signal changes across the whole brain, in both white and gray matters, in similar manner to previous reports of whole brain studies. We investigated whether white matter displays time-locked BOLD signals across multiple structural pathways in response to a stimulus in a similar manner to the cortex. We find that both white and gray matter show time-locked activations across the whole brain, with a majority of both tissue types showing statistically significant signal changes for all task stimuli investigated. We observed a wide range of signal responses to tasks, with different regions showing different BOLD signal changes to the same task. Moreover, we find that each region may display different BOLD responses to different stimuli. Overall, we present compelling evidence that, just like all gray matter, essentially all white matter in the brain shows time-locked BOLD signal changes in response to multiple stimuli, challenging the idea of sparse functional localization and the prevailing wisdom of treating white matter BOLD signals as artifacts to be removed.

Mediating effect of amygdala activity on response to fear vs. happiness in youth with significant levels of irritability and disruptive mood and behavior disorders.

Irritability, characterized by a tendency to exhibit increased anger, is a common clinical problem in youth. Irritability is a significant clinical issue in youth with various psychiatric diagnoses, especially disruptive behavior, and mood disorders (Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct Disorder, and Disruptive Mood Dysregulation Disorder). Although there have been previous studies focusing on functional alteration in the amygdala related to irritability, there is no comprehensive model between emotional, neuronal, and behavioral characteristics. Using an functional magnetic resonance imaging (fMRI) procedure, we investigated the relationships between behavioral irritability, selective impairments in processing facial emotions and the amygdala neural response in youth with increased irritability. Fifty-nine youth with disruptive mood and behavior disorder completed a facial expression processing task with an event-related fMRI paradigm. The severity of irritability was evaluated using the Affective Reactivity Index. In the result of behavioral data, irritability, and reaction time (RT) differences between interpreting negative (fear) and positive (happiness) facial expressions were positively correlated. In the fMRI result, youth showed higher activation in the right cingulate gyrus, bilateral cerebellum, right amygdala, right precuneus, right superior frontal gyrus, right middle occipital gyrus, and middle temporal gyrus, during the happiness condition vs. fear condition. No brain region exhibited greater activation in the fear than in the happiness conditions. In the result of the mediator analysis, increased irritability was associated with a longer RT toward positive vs. negative facial expressions. Irritability was also positively associated with the difference in amygdala blood oxygen level-dependent responses between the two emotional conditions (happiness > fear). This difference in amygdala activity mediated the interaction between irritability and the RT difference between negative and positive facial expressions. We suggest that impairment in the implicit processing of facial emotional expressions with different valences causes distinct patterns of amygdala response, which correlate with the level of irritability. These results broaden our understanding of the biological mechanism of irritability at the neural level and provide information for the future direction of the study.

Effects of NMDA-receptor blockade by ketamine on mentalizing and its neural correlates in humans: a randomized control trial

Schizophrenia is associated with various deficits in social cognition that remain relatively unaltered by antipsychotic treatment. While faulty glutamate signaling has been associated with general cognitive deficits as well as negative symptoms of schizophrenia, no direct link between manipulation of glutamate signaling and deficits in mentalizing has been demonstrated thus far. Here, we experimentally investigated whether ketamine, an uncompetitive N-methyl-D-aspartate receptor antagonist known to induce psychotomimetic effects, influences mentalizing and its neural correlates. In a randomized, placebo-controlled between-subjects experiment, we intravenously administered ketamine or placebo to healthy participants performing a video-based social cognition task during functional magnetic resonance imaging. Psychotomimetic effects of ketamine were assessed using the Positive and Negative Syndrome Scale. Compared to placebo, ketamine led to significantly more psychotic symptoms and reduced mentalizing performance (more “no mentalizing” errors). Ketamine also influenced blood oxygen level dependent (BOLD) response during mentalizing compared to placebo. Specifically, ketamine increased BOLD in right posterior superior temporal sulcus (pSTS) and increased connectivity between pSTS and anterior precuneus. These increases may reflect a dysfunctional shift of attention induced by ketamine that leads to mentalizing deficits. Our findings show that a psychotomimetic dose of ketamine impairs mentalizing and influences its neural correlates, a result compatible with the notion that deficient glutamate signaling may contribute to deficits in mentalizing in schizophrenia. The results also support efforts to seek novel psychopharmacological treatments for psychosis and schizophrenia targeting glutamatergic transmission.

A Different Olfactory Perception in Anosmic Patients: Evidence from Functional MRI

Purpose: Olfactory system is a vital sensory system in mammals, giving them the ability to connect with their environment. Anosmia, or the complete loss of olfaction ability, which could be caused by injuries, is an interesting topic for inspectors with the aim of diagnosing patients. Sniffing test is currently utilized to examine if an individual is suffering from anosmia; however, functional Magnetic Resonance Imaging (fMRI) provides unique information about the structure and function of the different areas of the human brain, and therefore this noninvasive method could be used as a tool to locate the olfactory-related regions of the brain.&#x0D; Materials and Methods: In this study, by recruiting 31 healthy and anosmic individuals, we investigated the neural Blood Oxygenation Level Dependent (BOLD) responses in the olfactory cortices following two odor stimuli, rose and eucalyptus, by using a 3T MR scanner.&#x0D; Results: Comparing the two groups, we observed a network of brain areas being more active in normal individuals when smelling the odors. In addition, a number of brain areas also showed an activation decline during the odor stimuli, which is hypothesized as a resource allocation deactivation.&#x0D; Conclusion: This study illustrated alterations in the brain activity between normal individuals and anosmic patients when smelling odors, and could potentially help for a better anosmia diagnosis in the future.

Microstructural white matter integrity in relation to vascular reactivity in Dutch-type hereditary cerebral amyloid angiopathy

Cerebral Amyloid Angiopathy (CAA) is characterized by cerebrovascular amyloid-β accumulation leading to hallmark cortical MRI markers, such as vascular reactivity, but white matter is also affected. By studying the relationship in different disease stages of Dutch-type CAA (D-CAA), we tested the relation between vascular reactivity and microstructural white matter integrity loss. In a cross-sectional study in D-CAA, 3 T MRI was performed with Blood-Oxygen-Level-Dependent (BOLD) fMRI upon visual activation to assess vascular reactivity and diffusion tensor imaging to assess microstructural white matter integrity through Peak Width of Skeletonized Mean Diffusivity (PSMD). We assessed the relationship between BOLD parameters – amplitude, time-to-peak (TTP), and time-to-baseline (TTB) – and PSMD, with linear and quadratic regression modeling. In total, 25 participants were included (15/10 pre-symptomatic/symptomatic; mean age 36/59 y). A lowered BOLD amplitude (unstandardized β = 0.64, 95%CI [0.10, 1.18], p = 0.02, Adjusted R2 = 0.48), was quadratically associated with increased PSMD levels. A delayed BOLD response, with prolonged TTP (β = 8.34 × 10−6, 95%CI [1.84 × 10−6, 1.48 × 10−5], p = 0.02, Adj. R2 = 0.25) and TTB (β = 6.57 × 10−6, 95%CI [1.92 × 10−6, 1.12 × 10−5], p = 0.008, Adj. R2 = 0.29), was linearly associated with increased PSMD. In D-CAA subjects, predominantly in the symptomatic stage, impaired cerebrovascular reactivity is related to microstructural white matter integrity loss. Future longitudinal studies are needed to investigate whether this relation is causal.

Brain Response to Interferential Current Compared with Alternating Current Stimulation.

Temporal interference (TI) stimulation, which utilizes multiple external electric fields with amplitude modulation for neural modulation, has emerged as a potential noninvasive brain stimulation methodology. However, the clinical application of TI stimulation is inhibited by its uncertain fundamental mechanisms, and research has previously been restricted to numerical simulations and immunohistology without considering the acute in vivo response of the neural circuit. To address the characterization and understanding of the mechanisms underlying the approach, we investigated instantaneous brainwide activation patterns in response to invasive interferential current (IFC) stimulation compared with low-frequency alternative current stimulation (ACS). Results demonstrated that IFC stimulation is capable of inducing regional neural responses and modulating brain networks; however, the activation threshold for significantly recruiting a neural response using IFC was higher (at least twofold) than stimulation via alternating current, and the spatial distribution of the activation signal was restricted. A distinct blood oxygenation level-dependent (BOLD) response pattern was observed, which could be accounted for by the activation of distinct types of cells, such as inhibitory cells, by IFC. These results suggest that IFC stimulation might not be as efficient as conventional brain modulation methods, especially when considering TI stimulation as a potential alternative for stimulating subcortical brain areas. Therefore, we argue that a future transcranial application of TI on human subjects should take these implications into account and consider other stimulation effects using this technique.

Infants' sex affects neural responses to affective touch in early infancy.

Social touch is closely related to the establishment and maintenance of social bonds in humans, and the sensory brain circuit for gentle brushing is already active soon after birth. Brain development is known to be sexually dimorphic, but the potential effect of sex on brain activation to gentle touch remains unknown. Here, we examined brain activation to gentle skin stroking, a tactile stimulation that resembles affective or social touch, in term-born neonates. Eighteen infants aged 11-36 days, recruited from the FinnBrain Birth Cohort Study, were included in the study. During natural sleep, soft brush strokes were applied to the skin of the right leg during functional magnetic resonance imaging (fMRI) at 3cm/s velocity. We examined potential differences in brain activation between males (n=10) and females (n=8) and found that females had larger blood oxygenation level dependent (BOLD) responses (brushing vs. rest) in bilateral orbitofrontal cortex (OFC), right ventral striatum and bilateral inferior striatum, pons, and cerebellum compared to males. Moreover, the psychophysiological interactions (PPI) analysis, setting the left and right OFC as seed regions, revealed significant differences between males and females. Females exhibited stronger PPI connectivity between the left OFC and posterior cingulate or cuneus. Our work suggests that social touch neural responses are different in male and female neonates, which may have major ramifications for later brain, cognitive, and social development. Finally, many of the sexually dimorphic brain responses were subcortical, not captured by surface-based neuroimaging, indicating that fMRI will be a relevant technique for future studies.

3T vs. 7T fMRI: capturing early human memory consolidation after motor task utilizing the observed higher functional specificity of 7T.

Functional magnetic resonance imaging (fMRI) visualizes brain structures at increasingly higher resolution and better signal-to-noise ratio (SNR) as field strength increases. Yet, mapping the blood oxygen level dependent (BOLD) response to distinct neuronal processes continues to be challenging. Here, we investigated the characteristics of 7 T-fMRI compared to 3 T-fMRI in the human brain beyond the effect of increased SNR and verified the benefits of 7 T-fMRI in the detection of tiny, highly specific modulations of functional connectivity in the resting state following a motor task. 18 healthy volunteers underwent two resting state and a stimulus driven measurement using a finger tapping motor task at 3 and 7 T, respectively. The SNR for each field strength was adjusted by targeted voxel size variation to minimize the effect of SNR on the field strength specific outcome. Spatial and temporal characteristics of resting state ICA, network graphs, and motor task related activated areas were compared. Finally, a graph theoretical approach was used to detect resting state modulation subsequent to a simple motor task. Spatial extensions of resting state ICA and motor task related activated areas were consistent between field strengths, but temporal characteristics varied, indicating that 7 T achieved a higher functional specificity of the BOLD response than 3 T-fMRI. Following the motor task, only 7 T-fMRI enabled the detection of highly specific connectivity modulations representing an "offline replay" of previous motor activation. Modulated connections of the motor cortex were directly linked to brain regions associated with memory consolidation. These findings reveal how memory processing is initiated even after simple motor tasks, and that it begins earlier than previously shown. Thus, the superior capability of 7 T-fMRI to detect subtle functional dynamics promises to improve diagnostics and therapeutic assessment of neurological diseases.

Neural correlates of context-dependent extinction recall in social anxiety disorder: relevance of intrusions in response to aversive social experiences.

There are phenomenological similarities between social anxiety disorder (SAD) and posttraumatic stress disorder, such as a provoking aversive event, posttraumatic stress symptoms (e.g. intrusions) in response to these events and deficient (context-dependent) fear conditioning processes. This study investigated the neural correlates of context-dependent extinction recall and fear renewal in SAD, specifically in patients with intrusions in response to an etiologically relevant aversive social event. During functional magnetic resonance imaging a two-day context-dependent fear conditioning paradigm was conducted in 54 patients with SAD and 54 healthy controls (HC). This included fear acquisition (context A) and extinction learning (context B) on one day, and extinction recall (context B) as well as fear renewal (contexts C and A) one day later. The main outcome measures were blood oxygen level-dependent responses in regions of interest and skin conductance responses. Patients with SAD showed reduced differential conditioned amygdala activation during extinction recall in the safe extinction context and during fear renewal in the acquisition context compared to HC. Patients with clinically relevant intrusions moreover exhibited hypoactivation of the ventromedial prefrontal cortex (vmPFC) during extinction learning, extinction recall, and fear renewal in a novel context, while amygdala activation more strongly decreased during extinction learning and increased during fear renewal in the acquisition context compared with patients without intrusions. Our study provides first evidence that intrusions in SAD are associated with similar deficits in context-dependent regulation of conditioned fear via the vmPFC as previously demonstrated in posttraumatic stress disorder.

Effects of ulotaront on brain circuits of reward, working memory, and emotion processing in healthy volunteers with high or low schizotypy

Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptor agonist without antagonist activity at dopamine D2 or the serotonin 5-HT2A receptors, has demonstrated efficacy in the treatment of schizophrenia. Here we report the phase 1 translational studies that profiled the effect of ulotaront on brain responses to reward, working memory, and resting state connectivity (RSC) in individuals with low or high schizotypy (LS or HS). Participants were randomized to placebo (n = 32), ulotaront (50 mg; n = 30), or the D2 receptor antagonist amisulpride (400 mg; n = 34) 2 h prior to functional magnetic resonance imaging (fMRI) of blood oxygen level-dependent (BOLD) responses to task performance. Ulotaront increased subjective drowsiness, but reaction times were impaired by less than 10% and did not correlate with BOLD responses. In the Monetary Incentive Delay task (reward processing), ulotaront significantly modulated striatal responses to incentive cues, induced medial orbitofrontal responses, and prevented insula activation seen in HS subjects. In the N-Back working memory task, ulotaront modulated BOLD signals in brain regions associated with cognitive impairment in schizophrenia. Ulotaront did not show antidepressant-like biases in an emotion processing task. HS had significantly reduced connectivity in default, salience, and executive networks compared to LS participants and both drugs reduced this difference. Although performance impairment may have weakened or contributed to the fMRI findings, the profile of ulotaront on BOLD activations elicited by reward, memory, and resting state is compatible with an indirect modulation of dopaminergic function as indicated by preclinical studies. This phase 1 study supported the subsequent clinical proof of concept trial in people with schizophrenia.Clinical trial registration: Registry# and URL: ClinicalTrials.gov NCT01972711, https://clinicaltrials.gov/ct2/show/NCT01972711

Dorsal striatal response to taste is modified by obesity and insulin resistance.

In preclinical models, insulin resistance in the dorsal striatum (DS) contributes to overeating. Although human studies support the concept of central insulin resistance, they have not investigated its effect on consummatory reward-induced brain activity. Taste-induced activation was assessed in the caudate and putamen of the DS with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Three phenotypically distinct groups were studied: metabolically healthy lean, metabolically healthy obesity, and metabolically unhealthy obesity (MUO; presumed to have central insulin resistance). Participants with MUO also completed a weight loss intervention followed by a second functional magnetic resonance imaging session. The three groups were significantly different at baseline consistent with the design. The metabolically healthy lean group had a primarily positive BOLD response, the MUO group had a primarily negative BOLD response, and the metabolically healthy obesity group had a response in between the two other groups. Food craving was predicted by taste-induced activation. After weight loss in the MUO group, taste-induced activation increased in the DS. These data support the hypothesis that insulin resistance and obesity contribute to aberrant responses to taste in the DS, which is only partially attenuated by weight loss. Aberrant responses to food exposure may be a barrier to weight loss.

FMRI with whole-brain coverage, 75-ms temporal resolution and high SNR by combining HiHi reshuffling and multiband imaging

Increasing the temporal resolution of the blood‑oxygen level-dependent (BOLD) response is usually accompanied by a decrease in repetition time and therefore also a reduction of the magnetic resonance (MR) signal due to incomplete T1 relaxation and thus a loss of signal-to-noise ratio (SNR). A previous data reordering method can achieve higher temporal sampling rate without the loss of SNR but at the cost of increased scan time. In this proof-of-principle work, we show that combining HiHi reshuffling with multiband acceleration allows us to measure the in vivo BOLD response with a 75-ms sampling rate that is decoupled from the acquisition repetition time (here 1.5 s and hence higher SNR) while covering the entire forebrain with 60 2-mm slices in a ~ 35-min scan. We provide single-voxel time-courses of the BOLD responses in the primary visual and primary motor cortices in three fMRI experiments on a 7 T scanner - 1 male (scanned twice on different days for test-retest reproducibility) and 1 female participant.

Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia.

To examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular pain. Twelve subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: (1) chronic ocular pain; (2) presence of ocular pain over 1 week recall; and (3) presence of photophobia. All individuals underwent an ocular surface examination to capture tear parameters before and 4-6 weeks after BoNT-A injections. Using an event-related fMRI design, subjects were presented with light stimuli during two fMRI scans, once before and 4-6 weeks after BoNT-A injection. Light evoked unpleasantness ratings were reported by subjects after each scan. Whole brain blood oxygen level dependent (BOLD) responses to light stimuli were analyzed. At baseline, all subjects reported unpleasantness with light stimulation (average: 70.8 ± 32.0). Four to six weeks after BoNT-A injection, unpleasantness scores decreased (48.1 ± 33.6), but the change was not significant. On an individual level, 50% of subjects had decreased unpleasantness ratings in response to light stimulation compared to baseline ("responders," n = 6), while 50% had equivalent (n = 3) or increased (n = 3) unpleasantness ("non-responders"). At baseline, several differences were noted between responders and non-responders; responders had higher baseline unpleasantness ratings to light, higher symptoms of depression, and more frequent use of antidepressants and anxiolytics, compared to non-responders. Group analysis at baseline displayed light-evoked BOLD responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, midcingulate cortex (MCC), bilateral frontal pole, bilateral cerebellar hemispheric lobule VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, S2 cortices, cerebellar hemispheric lobule VI, cerebellar crus I, and left cerebellar crus II. BoNT-A responders displayed activation of the spinal trigeminal nucleus at baseline where non-responders did not. BoNT-A injections modulate light-evoked activation of pain-related brain systems and photophobia symptoms in some individuals with chronic ocular pain. These effects are associated with decreased activation in areas responsible for processing the sensory-discriminative, affective, dimensions, and motor responses to pain.

Pramipexole Enhances Reward Learning by Preserving Value Estimates

BackgroundDopamine D2-like agonists show promise as treatments for depression. They are thought to act by enhancing reward learning; however, the mechanisms by which they achieve this are not clear. Reinforcement learning accounts describe 3 distinct candidate mechanisms: increased reward sensitivity, increased inverse decision–temperature, and decreased value decay. As these mechanisms produce equivalent effects on behavior, arbitrating between them requires measurement of how expectations and prediction errors are altered. We characterized the effects of 2 weeks of the D2-like agonist pramipexole on reward learning and used functional magnetic resonance imaging measures of expectation and prediction error to assess which of these 3 mechanistic processes were responsible for the behavioral effects. MethodsForty healthy volunteers (50% female) were randomized to 2 weeks of pramipexole (titrated to 1 mg/day) or placebo in a double-blind, between-subject design. Participants completed a probabilistic instrumental learning task before and after the pharmacological intervention, with functional magnetic resonance imaging data collected at the second visit. Asymptotic choice accuracy and a reinforcement learning model were used to assess reward learning. ResultsPramipexole increased choice accuracy in the reward condition with no effect on losses. Participants who received pramipexole had increased blood oxygen level–dependent response in the orbital frontal cortex during the expectation of win trials but decreased blood oxygen level–dependent response to reward prediction errors in the ventromedial prefrontal cortex. This pattern of results indicates that pramipexole enhances choice accuracy by reducing the decay of estimated values during reward learning. ConclusionsThe D2-like receptor agonist pramipexole enhances reward learning by preserving learned values. This is a plausible mechanism for pramipexole’s antidepressant effect.

P.097 Effect of stimulation site on brain network activity and phonemic verbal fluency: an fMRI study.

Background: In Parkinson’s disease, deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) produces comparable motor benefits. Although both increases the risk of cognition and verbal fluency (VF) decline, the risk is greater following STN-DBS. The consequences of stimulating these different sites on brain network activity is unknown. We use functional magnetic resonance imaging (fMRI) during in vivo stimulation to investigate differences between STN-DBS and GPi-DBS and correlate with change in VF. Methods: Left-sided, stimulation-cycling block-design fMRI was acquired at 3-Tesla in 51 STN-DBS and 15 GPi-DBS following routine clinical programming. Blood oxygen level-dependent (BOLD) response to stimulation was compared between groups. Phonemic VF was assessed pre- and postoperatively. Results: Voxel-wise t-test between STN-DBS and GPi-DBS BOLD response maps revealed areas of significant difference (p&lt;0.001) in the left frontal operculum and the left caudate head. Stimulation BOLD response appears to show slight inverse correlation with postoperative VF decline. The trend is reversed at the left frontal operculum in STN-DBS compared to GPi-DBS. Conclusions: Decline in VF in PD-DBS seems associated with the stimulation BOLD response at the left frontal operculum and the left caudate head. The effect differs depending on stimulation site, suggesting differing effects on brain network activity.

Decontextualized fear memories? Stronger conditioned fear responses during extinction learning and extinction recall in a safe context predict the development of long-term analog intrusions.

Difficulties in the context-dependent modulation of conditioned fear are known for posttraumatic stress disorder and may explain the occurrence of intrusive memories in safe contexts. The current study therefore investigated if reduced context-dependent modulation of conditioned fear and its underlying neural circuitry constitute risk factors for the development of analog intrusions in response to an experimental trauma. Eighty-five healthy women participated in the trauma film paradigm to investigate the development of analog intrusions as well as explicit memory for an experimental trauma after one week and three months, respectively. Before, participants underwent a context-dependent fear conditioning paradigm during functional magnetic resonance imaging with fear acquisition in context A and extinction training in context B on a first day, as well as extinction recall in context B and fear renewal in a novel context C one day later. Skin conductance responses (SCRs) and blood oxygen level dependent responses were main outcome measures. In addition to stronger fear acquisition in context A, stronger conditioned fear responses in the safe context B, as indicated by stronger conditioned SCRs or stronger activation of fear expressing regions during extinction learning and recall, predicted the development of long-term analog intrusions. Stronger fear responses in safe and danger contexts were risk factors for the development of long-term analog intrusions and point to decontextualized fear memories and difficulties in the context-dependent modulation of conditioned fear. Altered fear conditioning processes and reduced storage of contextual information may cause the occurrence of fear independent of context.

Relation of BOLD response to food-specific and generic motor response inhibition tasks to body fat gain in adults with overweight and obesity

BackgroundLow inhibitory control has been theorized to contribute to the development and maintenance of obesity. Knowledge on the neurobiological indicators of inhibitory control deficits predicting future weight gain is limited. The current study examined if individual differences in blood-oxygenation-level-dependent (BOLD) activity associated with food-specific and general motor response inhibition predict future body fat change in adults with overweight or obesity. MethodsBOLD activity and behavioral responses of adults with overweight or obesity (N = 160) were recorded while performing a food-specific stop signal task (n = 92) or a generic stop signal task (n = 68). Percent body fat was measured at baseline, posttest, 3-month, and 6-month follow-up. ResultsElevated BOLD activity in somatosensory (postcentral gyrus), and attention (precuneus) regions during successful inhibition in the food-specific stop signal task and elevated BOLD activity in a motor region (anterior cerebellar lobe) in the generic stop signal task predicted greater body fat gain over 6-month follow-up. Elevated BOLD activity in inhibitory control regions (inferior-, middle-, superior frontal gyri) and error monitoring regions (anterior cingulate cortex, insula) during erroneous responses in the generic stop signal task predicted body fat loss. ConclusionsResults suggest that improving motor response inhibition and error monitoring may facilitate weight loss in adults with overweight and obesity.

Optimizing cognitive neuroscience experiments for separating event- related fMRI BOLD responses in non-randomized alternating designs.

Functional magnetic resonance imaging (fMRI) has revolutionized human brain research. But there exists a fundamental mismatch between the rapid time course of neural events and the sluggish nature of the fMRI blood oxygen level-dependent (BOLD) signal, which presents special challenges for cognitive neuroscience research. This limitation in the temporal resolution of fMRI puts constraints on the information about brain function that can be obtained with fMRI and also presents methodological challenges. Most notably, when using fMRI to measure neural events occurring closely in time, the BOLD signals may temporally overlap one another. This overlap problem may be exacerbated in complex experimental paradigms (stimuli and tasks) that are designed to manipulate and isolate specific cognitive-neural processes involved in perception, cognition, and action. Optimization strategies to deconvolve overlapping BOLD signals have proven effective in providing separate estimates of BOLD signals from temporally overlapping brain activity, but there remains reduced efficacy of such approaches in many cases. For example, when stimulus events necessarily follow a non-random order, like in trial-by-trial cued attention or working memory paradigms. Our goal is to provide guidance to improve the efficiency with which the underlying responses evoked by one event type can be detected, estimated, and distinguished from other events in designs common in cognitive neuroscience research. We pursue this goal using simulations that model the nonlinear and transient properties of fMRI signals, and which use more realistic models of noise. Our simulations manipulated: (i) Inter-Stimulus-Interval (ISI), (ii) proportion of so-called null events, and (iii) nonlinearities in the BOLD signal due to both cognitive and design parameters. We offer a theoretical framework along with a python toolbox called deconvolve to provide guidance on the optimal design parameters that will be of particular utility when using non-random, alternating event sequences in experimental designs. In addition, though, we also highlight the challenges and limitations in simultaneously optimizing both detection and estimation efficiency of BOLD signals in these common, but complex, cognitive neuroscience designs.