Blood Oxygenation Level-dependent Signal In Regions Research Articles

Evaluation of the effects of DBS in the caudal Zona incerta on brain activity during a working memory task in patients with essential tremor

Essential tremor (ET) is characterized by bilateral upper limb postural and/or kinetic tremor, but also cognitive deficits. Tremor in ET, as well as aspects of cognitive deficits associated with ET, have been suggested to be linked to dysfunction in the cerebello-thalamo-cerebral circuit. In ET patients with disabling and medically intractable motor symptoms, Deep Brain Stimulation (DBS) is effective in reducing tremor. DBS in the caudal Zona incerta (cZi) has been shown to modulate the activity of the sensorimotor cerebello-cerebral circuit during motor tasks. Whether the activity in the cerebello-cerebral circuit is modulated by DBS during tasks involving working memory is unknown. The present study therefore aimed to investigate the possible effects of cZi DBS on working-memory processing in ET patients by means of task-based blood oxygen level-dependent (BOLD) fMRI.Thirteen ET patients completed a working-memory task during DBS OFF and ON conditions. The task involved three conditions: maintenance, manipulation, and control. Behaviorally, there was no significant effect from DBS on accuracy, but a marginally significant Task x DBS interaction was detected for response times (RTs). However, post hoc comparisons for each condition failed to reach statistical significance. FMRI analyses revealed that DBS did not alter BOLD signal in regions of interest (lateral prefrontal cortex, parietal cortex, and the cerebellum), or in a complementary whole-brain analysis.The present study indicates that DBS in the cZi in patients with ET has at most marginal effects on working memory, which is consistent with the results of pre- and post-DBS neuropsychological assessment showing minimal cognitive effects of surgery.

Assessing blood oxygen level-dependent signal variability as a biomarker of brain injury in sport-related concussion.

Mild traumatic brain injury is a complex neurological disorder of significant concern among athletes who play contact sports. Athletes who sustain sport-related concussion typically undergo physical examination and neurocognitive evaluation to determine injury severity and return-to-play status. However, traumatic disruption to neurometabolic processes can occur with minimal detectable anatomic pathology or neurocognitive alteration, increasing the risk that athletes may be cleared for return-to-play during a vulnerable period and receive a repetitive injury. This underscores the need for sensitive functional neuroimaging methods to detect altered cerebral physiology in concussed athletes. The present study compared the efficacy of Immediate Post-concussion Assessment and Cognitive Testing composite scores and whole-brain measures of blood oxygen level-dependent signal variability for classifying concussion status and predicting concussion symptomatology in healthy, concussed and repetitively concussed athletes, assessing blood oxygen level-dependent signal variability as a potential diagnostic tool for characterizing functional alterations to cerebral physiology and assisting in the detection of sport-related concussion. We observed significant differences in regional blood oxygen level-dependent signal variability measures for concussed athletes but did not observe significant differences in Immediate Post-concussion Assessment and Cognitive Testing scores of concussed athletes. We further demonstrate that incorporating measures of functional brain alteration alongside Immediate Post-concussion Assessment and Cognitive Testing scores enhances the sensitivity and specificity of supervised random forest machine learning methods when classifying and predicting concussion status and post-concussion symptoms, suggesting that alterations to cerebrovascular status characterize unique variance that may aid in the detection of sport-related concussion and repetitive mild traumatic brain injury. These results indicate that altered blood oxygen level-dependent variability holds promise as a novel neurobiological marker for detecting alterations in cerebral perfusion and neuronal functioning in sport-related concussion, motivating future research to establish and validate clinical assessment protocols that can incorporate advanced neuroimaging methods to characterize altered cerebral physiology following mild traumatic brain injury.

MP52-11 MICTURITION-ASSOCIATED BRAIN ACTIVITY IN HEALTHY PATIENTS COMPARED TO STROKE SURVIVORS BEFORE AND AFTER TRANSCUTANEOUS SPINAL CORD STIMULATION

You have accessJournal of UrologyCME1 Apr 2023MP52-11 MICTURITION-ASSOCIATED BRAIN ACTIVITY IN HEALTHY PATIENTS COMPARED TO STROKE SURVIVORS BEFORE AND AFTER TRANSCUTANEOUS SPINAL CORD STIMULATION Sarah Ponce, Veronica Stefania Montero Arcila, Luis Alejandro Morales Ojeda, David Chapman, Rita Jen, Nhi Tuyet Ha, Parag Gad, V. Reggie Edgerton, Evgeniy Kreydin, Kay Jann, and Aidin Abedi Sarah PonceSarah Ponce More articles by this author , Veronica Stefania Montero ArcilaVeronica Stefania Montero Arcila More articles by this author , Luis Alejandro Morales OjedaLuis Alejandro Morales Ojeda More articles by this author , David ChapmanDavid Chapman More articles by this author , Rita JenRita Jen More articles by this author , Nhi Tuyet HaNhi Tuyet Ha More articles by this author , Parag GadParag Gad More articles by this author , V. Reggie EdgertonV. Reggie Edgerton More articles by this author , Evgeniy KreydinEvgeniy Kreydin More articles by this author , Kay JannKay Jann More articles by this author , and Aidin AbediAidin Abedi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003300.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Compared to healthy individuals, stroke survivors with neurogenic lower urinary tract dysfunction (NLUTD) exhibit decreased cortical activity in response to bladder filling and emptying. The use of transcutaneous spinal cord stimulation (TSCS) has been shown to reduce frequency, urgency and incontinence episodes in these individuals. The objective of this study was to determine whether TSCS also leads to normalization of micturition-related brain activity, as compared to healthy controls. METHODS: Twelve stroke patients with post-stroke NLUTD received 12 weeks of TSCS. Each subject also completed simultaneous urodynamics (UDS) and blood-oxygen-level-dependent (BOLD) fMRI before initiation of TSCS and within 72 hours of completing the final TSCS session. Healthy subjects without LUTS completed an identical fMRI-UDS protocol. BOLD signal during the period of maximum urgency (10 seconds preceding a detrusor contraction) was determined using statistical parametric mapping (SPM) and compared between healthy controls and stroke patients before and after TSCS (p<0.01, cluster size ⋝25 voxels). The SPM models were adjusted for age and sex. RESULTS: Compared to healthy controls, stroke survivors prior to TSCS exhibited diminished activation in the right cerebellum, left putamen, right insula, right anterior cingulate gyrus, right precuneus, bilateral medial frontal gyri, and right superior frontal gyrus compared to healthy controls. Following TSCS, there was no significant difference in BOLD signal in these regions between stroke survivors and healthy controls. However, healthy controls continued to exhibit increased activation in the right precentral (motor cortex) and left postcentral (sensory cortex) gyri, left posterior cingulate and left middle temporal gyrus even after TSCS. CONCLUSIONS: Micturition-related brain activity appears to partially revert to the healthy phenotype in stroke survivors following TSCS. Regions, where differences in BOLD signal between healthy controls and stroke subjects diminish following treatment, are known to be involved in LUT control. As expected, the neurosignature of stroke patients did not revert to the healthy phenotype entirely, as indicated by significant remaining differences in BOLD signal in several brain regions following TSCS. Source of Funding: Urology Care Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e706 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sarah Ponce More articles by this author Veronica Stefania Montero Arcila More articles by this author Luis Alejandro Morales Ojeda More articles by this author David Chapman More articles by this author Rita Jen More articles by this author Nhi Tuyet Ha More articles by this author Parag Gad More articles by this author V. Reggie Edgerton More articles by this author Evgeniy Kreydin More articles by this author Kay Jann More articles by this author Aidin Abedi More articles by this author Expand All Advertisement PDF downloadLoading ...

Association of Video Gaming With Cognitive Performance Among Children

Although most research has linked video gaming to subsequent increases in aggressive behavior in children after accounting for prior aggression, findings have been divided with respect to video gaming's association with cognitive skills. To examine the association between video gaming and cognition in children using data from the Adolescent Brain Cognitive Development (ABCD) study. In this case-control study, cognitive performance and blood oxygen level-dependent (BOLD) signal were compared in video gamers (VGs) and non-video gamers (NVGs) during response inhibition and working memory using task-based functional magnetic resonance imaging (fMRI) in a large data set of 9- and 10-year-old children from the ABCD study, with good control of demographic, behavioral, and psychiatric confounding effects. A sample from the baseline assessment of the ABCD 2.0.1 release in 2019 was largely recruited across 21 sites in the US through public, private, and charter elementary schools using a population neuroscience approach to recruitment, aiming to mirror demographic variation in the US population. Children with valid neuroimaging and behavioral data were included. Some exclusions included common MRI contraindications, history of major neurologic disorders, and history of traumatic brain injury. Participants completed a self-reported screen time survey including an item asking children to report the time specifically spent on video gaming. All fMRI tasks were performed by all participants. Video gaming time, cognitive performance, and BOLD signal assessed with n-back and stop signal tasks on fMRI. Collected data were analyzed between October 2019 and October 2020. A total of 2217 children (mean [SD] age, 9.91 [0.62] years; 1399 [63.1%] female) participated in this study. The final sample used in the stop signal task analyses consisted of 1128 NVGs (0 gaming hours per week) and 679 VGs who played at least 21 hours per week. The final sample used in the n-back analyses consisted of 1278 NVGs who had never played video games (0 hours per week of gaming) and 800 VGs who played at least 21 hours per week. The VGs performed better on both fMRI tasks compared with the NVGs. Nonparametric analyses of fMRI data demonstrated a greater BOLD signal in VGs in the precuneus during inhibitory control. During working memory, a smaller BOLD signal was observed in VGs in parts of the occipital cortex and calcarine sulcus and a larger BOLD signal in the cingulate, middle, and frontal gyri and the precuneus. In this study, compared with NVGs, VGs were found to exhibit better cognitive performance involving response inhibition and working memory as well as altered BOLD signal in key regions of the cortex responsible for visual, attention, and memory processing. The findings are consistent with videogaming improving cognitive abilities that involve response inhibition and working memory and altering their underlying cortical pathways.

Does The Central Nervous System Contribute To Weakness In Those After Anterior Cruciate Ligament Reconstruction?

Anterior cruciate ligament (ACL) injury is common among adolescents and physically active adults. Despite surgical reconstruction and rehabilitation, quadriceps weakness is a persistent hallmark of injury and a challenging clinical limitation during the recovery process. While other clinical populations have identified the central nervous system as a critical determinant for weakness, few studies have explored this relationship in those after ACL injury. PURPOSE: To determine the relationship between brain activity for knee movement and quadriceps weakness in those after ACL reconstruction (ACL-R). METHODS: 22 patients with unilateral ACL-R (8 females; age 22.1 ± 2.6 years; BMI 23.8 ± 3.1; Tegner 8.4 ± 1.0; time from surgery 4.6 ± 2.6 years) participated. Quadriceps weakness was quantified using limb symmetry index (LSI) of peak isokinetic knee extensor torque assessed at 60°/s for each participant. Neural activation patterns were measured using blood-oxygen-level-dependent (BOLD) signals, cluster corrected z-threshold>3.1, p < .05, during repeated cycles of knee flexion/extension in the fMRI scanner. Percent BOLD signal change was calculated for regions selected within the sensorimotor network using the Juelich Histological Atlas. Pearson product-moment correlations were used to determine the relationship between regional BOLD signal and LSI scores. False-discovery rate correction using the Benjamini-Hochberg procedure was applied to adjust for multiple comparisons. RESULTS: Weak adults with ACL-R displayed greater levels of contralateral premotor cortex (r = -.465, p = 0.03), cerebellum (r = -.485, p = 0.02) and lingual gyrus (r = -.519, p = 0.01) activity for knee flexion/extension. CONCLUSIONS: Our data suggest weaker adults with prior ACL-R require greater levels of descending cortical input during a repeated quadriceps contraction compared to those with no persistent strength deficits. Increased neural activity requirements in regions responsible for motor planning and visual-attention may reflect compensatory motor strategies to mitigate losses in function attributable to weakness.

Investigation of Acupuncture-specific BOLD Signal Changes Using Multiband Acquisition and Deconvolution Analysis.

PurposeWe investigated the temporal dynamics of blood oxygen level-dependent (BOLD) signal responses during various stimuli, including real acupuncture, sham acupuncture, and palm scrubbing. For this purpose, deconvolution analysis was used to perform measurements using multi-band (MB) echo-planar imaging (EPI), which can improve time resolution, and to analyze brain responses without an expected reference function.MethodsWe devided 26 healthy right-handed adults into a group of 13 who received real acupuncture stimulation with manual manipulation and the other group of 13 who received sham acupuncture and palm scrubbing tactical stimulations. Data analysis was performed with a combination of analysis packages.ResultsWe found stimulus-specific impulse responses of the BOLD signal in various brain regions. During real acupuncture, activated areas were observed in the secondary somatosensory cortex (SII) and insula during stimulation and in the anterior cingulate cortex (ACC), supplementary motor area (SMA), and thalamus after the stimulation. During sham acupuncture, activated areas were observed in the SII, insula, and thalamus during simulation. During the scrubbing condition, activated areas were observed in the contralateral primary somatosensory cortex (SI), SII, insula, and thalamus during stimulation. In particular, during the real acupuncture condition, significantly delayed and long-sustained increased signals were observed in several brain regions, in contrast to the signals induced with sham acupuncture and palm scrubbing.CoclusionWe speculated that the delayed and long-sustained signal increases were caused by peripheral nociceptors, flare responses, and time-consuming processing in the central nervous system. We used deconvolution analysis with MB EPI and tent functions to identify the delayed increase in the BOLD signal in the area related to pain perception specifically observed in real acupuncture stimulation. We propose that the specific BOLD signal change observed in this study will lead to the elucidation of the mechanism underlying the therapeutic effect of acupuncture stimulation.

A randomized, placebo-controlled, phase 1 study to evaluate the effects of TAK-063 on ketamine-induced changes in fMRI BOLD signal in healthy subjects

RationalePhosphodiesterase 10A inhibitor TAK-063 has shown effects that suggest efficacy in schizophrenia treatment.ObjectiveThis randomized, double-blind, placebo-controlled, incomplete-crossover study investigated effects of single oral administration of TAK-063 on ketamine-induced changes in blood oxygen level-dependent (BOLD) signal in healthy males.MethodsHealthy men aged 18 to 45 years with normal magnetic resonance imaging (MRI) scans and electroencephalogram measurements at screening were eligible. Each subject was randomized to one of nine treatment schedules: all subjects received placebo and two of three doses of TAK-063 followed by ketamine. The primary endpoint was ketamine-induced brain activity in select regions of the brain during resting state. Secondary endpoints included pharmacokinetic parameters of TAK-063, proportion of subjects with treatment-emergent adverse events (AEs), and percentage of subjects meeting criteria for abnormal safety laboratory tests and vital sign measurements.ResultsThe study comprised 27 subjects. Prior to ketamine infusion, TAK-063 exerted region-specific effects on resting state functional MRI (fMRI) BOLD signal. After ketamine administration, TAK-063 reduced the Cohen’s effect size for resting-state fMRI BOLD signal in key brain regions examined, and exerted similar effects on BOLD signal during the working memory task across all doses. TAK-063 was safe and well tolerated.ConclusionsOur results are consistent with non-clinical studies of ketamine and TAK-063 and clinical studies of ketamine and risperidone. It is unknown whether these data are predictive of potential antipsychotic efficacy, and further analyses are required.

Convergence of BOLD and ERP measures of neural reactivity to emotional faces in children and adolescents with and without anxiety disorders

The neural bases of emotion are commonly measured using blood-oxygen-level-dependent (BOLD) signal and the late positive potential (LPP) event-related potential (ERP) component, but rarely together in the same individuals. Despite evidence of developmental changes in processing socio-emotional signals (e.g., faces) as reflected by both BOLD and LPP indices of brain maturation, the literature on the correspondence between these measures is limited to healthy adults, leaving questions regarding such correspondence across development and in clinical populations unaddressed. We examined the relationship between BOLD and LPP during an emotional face processing task in a large sample of youth (N = 70; age 7–19 years) with and without anxiety disorders, and tested whether BOLD signal in regions corresponding to LPP may account for age-related decreases in LPP. Greater activation in bilateral inferior frontal gyrus (IFG)/orbitofrontal gyrus (OFG), left supplementary motor area, right superior parietal lobule, and bilateral amygdala correlated with enhanced LPP to emotional faces in both anxious and healthy youth. Older youth exhibited reduced activation in bilateral IFG/OFG and bilateral amygdala, as well as reduced LPP. Decreased right IFG/OFG activation mediated the association between age and LPP. These findings support correspondence between these measures and need for multi-method approaches and indicate that age-related decreases in LPP may be driven, in part, by decreased IFG/OFG activation.

Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men.

Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.

Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex

The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.

Regional brain signal variability: a novel indicator of pain sensitivity and coping.

Variability in blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals reflects the moment-by-moment fluctuations in resting-state fMRI (rs-fMRI) activity within specific areas of the brain. Regional BOLD signal variability was recently proposed to serve an important functional role in the efficacy of neural systems because of its relationship to behavioural performance in aging and cognition studies. We previously showed that individuals who better cope with pain have greater fluctuations in interregional functional connectivity, but it is not known whether regional brain signal variability is a mechanism underlying pain coping. We tested the hypothesis that individual pain sensitivity and coping is reflected by regional fMRI BOLD signal variability within dynamic pain connectome-brain systems implicated in the pain experience. We acquired resting-state fMRI and assessed pain threshold, suprathreshold temporal summation of pain, and the impact of pain on cognition in 80 healthy right-handed individuals. We found that regional BOLD signal variability: (1) inversely correlated with an individual's temporal summation of pain within the ascending nociceptive pathway (primary and secondary somatosensory cortex), default mode network, and salience network; (2) was correlated with an individual's ability to cope with pain during a cognitive interference task within the periaqueductal gray, a key opiate-rich brainstem structure for descending pain modulation; and (3) provided information not captured from interregional functional connectivity. Therefore, regional BOLD variability represents a pain metric with potential implications for prediction of chronic pain resilience vs vulnerability.

Correlation between baseline blood pressure and the brainstem FMRI response to isometric forearm contraction in human volunteers: a pilot study.

It has been shown previously that changes in brainstem neural activity correlate with changes in both mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) during static handgrip (SHG). However, the relationship between baseline MAP and brainstem neural activity is unclear. We investigated changes in blood oxygen level-dependent (BOLD) signal induced by SHG in 12 young adults using BOLD functional magnetic resonance imaging (FMRI). An estimation of the blood pressure response to SHG was obtained in seven subjects during a session outside the MRI scanner and was used to model the blood pressure response to SHG inside the scanner. SHG at 40% of maximum grip increased MAP (mean ± s.d.) at the end of the 180-s squeeze from 85 ± 6 mm Hg to 108 ± 15 mm Hg, P = 0.0001. The brainstem BOLD signal change associated with SHG was localised to the ventrolateral medulla. This regional BOLD signal change negatively correlated with baseline MAP, r = -0.61, P = 0.01. This relationship between baseline MAP and brainstem FMRI responses to forearm contraction is suggestive of a possible role for brainstem activity in the control of MAP and may provide mechanistic insights into neurogenic hypertension.

Neuroimaging of executive function in survivors of pediatric brain tumors and healthy controls.

Research on the long-term sequelae of treatment for pediatric brain tumors has identified significant neurocognitive deficits experienced by many survivors. Despite indications of deficits based on cognitive assessment, the identification of specific neurobiological mechanisms of these deficits using neuroimaging techniques has yet to be considered. This study used norm-referenced standardized assessment and functional MRI (fMRI) to examine attention and executive functioning deficits of survivors of pediatric brain tumors, as compared with healthy children. Survivors of pediatric brain tumors performed more poorly than healthy children on measures of overall cognitive ability, attention, and executive function during testing, as well as on a working memory task during fMRI. Survivors showed lower blood-oxygen level dependent (BOLD) signal in bilateral frontal regions associated with sustained attention (BA6/8) and greater BOLD signal in left cingulate regions associated with complex problem-solving and performance monitoring (BA32) during working memory task completion. Both group and brain activation accounted for significant variance in neurocognitive functioning. Survivors of pediatric brain tumor and healthy children differed in brain activation during completion of a working memory task, and brain activation was associated with deficits noted in testing. These findings may improve understanding of mechanisms of cognitive deficits and avenues for intervention for children with brain tumors.

Functional MRI of facial emotion processing in left temporal lobe epilepsy

Temporal lobe epilepsy (TLE) may negatively affect the ability to recognize emotions. This study aimed to determine the cortical correlates of facial emotion processing (happy, sad, fearful, and neutral) in patients with well-characterized left TLE (LTLE) and to examine the effect of seizure control on emotion processing. We enrolled 34 consecutive patients with LTLE and 30 matched healthy control (HC) subjects. Participants underwent functional MRI (fMRI) with an event-related facial emotion recognition task. The seizures of seventeen patients were controlled (no seizure in at least 3months; LTLE−sz), and 17 continued to experience frequent seizures (LTLE+sz). Mood was assessed with the Beck Depression Inventory (BDI) and the Profile of Mood States (POMS). There were no differences in demographic characteristics and measures of mood between HC subjects and patients with LTLE. In patients with LTLE, fMRI showed decreased blood oxygenation level dependent (BOLD) signal in the hippocampus/parahippocampus and cerebellum in processing of happy faces and increased BOLD signal in occipital regions in response to fearful faces. Comparison of groups with LTLE+sz and LTLE−sz showed worse BDI and POMS scores in LTLE+sz (all p<0.05) except for POMS tension/anxiety (p=0.067). Functional MRI revealed increased BOLD signal in patients with LTLE+sz in the left precuneus and left parahippocampus for “fearful” faces and in the left periarcheocortex for “neutral” faces. There was a correlation between the fMRI and Total Mood Disturbance in the left precuneus in LTLE−sz (p=0.019) and in LTLE+sz (p=0.018). Overall, LTLE appears to have a relatively minor effect on the cortical underpinnings of facial emotion processing, while the effect of seizure state (controlled vs. not controlled) is more pronounced, indicating a significant relationship between seizure control and emotion processing.

Association of abstinence-induced alterations in working memory function and COMT genotype in smokers

The common methionine (met) for valine (val) at codon 158 (val(158)met) polymorphism in the catechol-O-methyltransferase (COMT) gene has been associated with nicotine dependence, alterations in executive cognitive function, and abstinence-induced working memory deficits in smokers. We sought to replicate the association of the COMT val allele with abstinence-induced alterations in working memory-related activity in task-positive (executive control) and task-negative (default mode network) regions. Forty smokers (20 val/val and 20 met/met) performed an N-back task while undergoing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) on two separate occasions: following 72h of confirmed abstinence and during smoking as usual. An independent sample of 48 smokers who completed the identical N-back task during fMRI in smoking vs. abstinence for another study was used as a validation sample. Contrary to expectations, genotype by session interactions on BOLD signal in executive control regions (dorsolateral prefrontal cortex and dorsal cingulate/medial prefrontal cortex) revealed significant abstinence-induced reductions in the met/met group, but not the val/val group. Results also revealed that val/val smokers may exhibit less suppression of activation in task-negative regions such as the posterior cingulate cortex during abstinence (vs. smoking). These patterns were confirmed in the validation sample and in the whole-brain analysis, though the regions differed from the a priori regions of interest (ROIs) (e.g., precuneus, insula). The COMT val(158)met polymorphism was associated with abstinence-related working memory deficits in two independent samples of smokers. However, inconsistencies compared to prior findings and across methods (ROI vs. whole-brain analysis) highlight the challenges inherent in reproducing results of imaging genetic studies in addiction.

Direct Evidence for Attention-Dependent Influences of the Frontal Eye-Fields on Feature-Responsive Visual Cortex

Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for “spatial” attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level–dependent (BOLD) signals in visual areas processing “target feature” but not in “distracter feature”–processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial “feature”-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.

Childhood maltreatment and response to novel face stimuli presented during functional magnetic resonance imaging in adults

Facial cues contain important information for guiding social interactions, but not all humans are equally expert at face processing. A number of factors, both genetic and environmental, contribute to differences in face-processing ability. For example, both heritable individual differences in temperament and exposure to childhood maltreatment are associated with alterations in face processing ability and social function. Understanding the neural correlates of alterations in face-processing ability can provide insights into how genetic and environmental risk factors impair social functioning. We examined the association between childhood maltreatment and blood-oxygenation-level-dependent (BOLD) signal as measured in functional magnetic resonance imaging (fMRI) in a group of young adults with an inhibited temperament. We hypothesized that childhood maltreatment exposure would correlate positively with BOLD signal in regions subserving face processing and novelty detection during viewing of novel compared to familiar faces. Functional magnetic resonance imaging (fMRI) degree of exposure to childhood maltreatment was positively correlated with BOLD signal in the bilateral fusiform gyri and the left hippocampus. These fMRI findings suggest that young adults with an inhibited temperament and a history of maltreatment may be particularly vulnerable to neural alterations. These differences could be related to a heightened sensitivity to potential threat—for example, from new people–and may contribute to both the altered social functioning and increased incidence of anxiety disorders in these individuals.

Transcranial direct current stimulation over the primary motor cortex during fMRI

Measurements of motor evoked potentials (MEPs) have shown that anodal and cathodal transcranial direct current stimulations (tDCS) have facilitatory or inhibitory effects on corticospinal excitability in the stimulated area of the primary motor cortex (M1). Here, we investigated the online effects of short periods of anodal and cathodal tDCS on human brain activity of healthy subjects and associated hemodynamics by concurrent blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T. Using a block design, 20s periods of tDCS at 1mA intensity over the left M1 altered with 20s periods without tDCS. In different fMRI runs, the effect of anodal or cathodal tDCS was assessed at rest or during finger tapping. A control experiment was also performed, in which the electrodes were placed over the left and right occipito-temporo-parietal junction. Neither anodal nor cathodal tDCS over the M1 for 20s stimulation duration induced a detectable BOLD signal change. However, in comparison to a voluntary finger tapping task without stimulation, anodal tDCS during finger tapping resulted in a decrease in the BOLD response in the supplementary motor area (SMA). Cathodal stimulation did not result in significant change in BOLD response in the SMA, however, a tendency toward decreased activity could be seen. In the control experiment neither cathodal nor anodal stimulation resulted in a significant change of BOLD signal during finger tapping in any brain area including SMA, PM, and M1. These findings demonstrate that the well-known polarity-dependent shifts in corticospinal excitability that have previously been demonstrated using measurements of MEPs after M1 stimulation are not paralleled by analogous changes in regional BOLD signal. This difference implies that the BOLD signal and measurements of MEPs probe diverse physiological mechanisms. The MEP amplitude reflects changes in transsynaptic excitability of large pyramidal neurons while the BOLD signal is a measure of net synaptic activity of all cortical neurons.

The role of the GABAergic and dopaminergic systems in the brain response to an intragastric load of alcohol in conscious rats

The brain's response to ethanol intake has been extensively investigated using electrophysiological recordings, brain lesion techniques, and c-Fos immunoreactivity. However, few studies have investigated this phenomenon using functional magnetic resonance imaging (fMRI). In the present study, we used fMRI to investigate the blood oxygenation level-dependent (BOLD) signal response to an intragastric (IG) load of ethanol in conscious, ethanol-naive rats. An intragastrically infused 10% ethanol solution induced a significant decrease in the intensity of the BOLD signal in several regions of the brain, including the bilateral amygdala (AMG), nucleus accumbens (NAc), hippocampus, ventral pallidum, insular cortex, and cingulate cortex, and an increase in the BOLD signal in the ventral tegmental area (VTA) and hypothalamic regions. Treatment with bicuculline, which is an antagonist of the gamma-aminobutyric acid A (GABAA) receptor, increased the BOLD signal intensity in the regions that had shown decreases in the BOLD signal after the IG infusion of 10% ethanol solution, but it did not affect the BOLD signal increase in the hypothalamus. Treatment with SCH39166, which is an antagonist of D1-like receptors, eliminated the increase in the BOLD signal intensity in the hypothalamic areas but did not affect the BOLD signal decrease following the 10% ethanol infusion. These results indicate that an IG load of ethanol caused both a GABAA receptor–mediated BOLD decrease in the limbic system and the cortex and a D1-like receptor-mediated BOLD increase in the hypothalamic regions in ethanol-naive rats.

Early Suppressive Mechanisms and the Negative Blood Oxygenation Level-Dependent Response in Human Visual Cortex

Functional magnetic resonance imaging (fMRI) studies of early sensory cortex often measure stimulus-driven increases in the blood oxygenation level-dependent (BOLD) signal. However, these positive responses are frequently accompanied by reductions in the BOLD signal in adjacent regions of cortex. Although this negative BOLD response (NBR) is thought to result from neuronal suppression, the precise relationship between local activity, suppression, and perception remains unknown. By measuring BOLD signals in human primary visual cortex while varying the baseline contrast levels in the region affected by the NBR, we tested three physiologically plausible computational models of neuronal modulation that could explain this phenomenon: a subtractive model, a response gain model, and a contrast gain model. We also measured the ability of isoluminant contrast to generate an NBR. We show that the NBR can be modeled as a pathway-specific contrast gain modulation that is strongest outside the fovea. We found a similar spatial bias in a psychophysical study using identical stimuli, although these data indicated a response gain rather than a contrast gain mechanism. We reconcile these findings by proposing (1) that the NBR is associated with a long-range suppressive mechanism that hyperpolarizes a subset of magnocellularly driven neurons at the input to V1, (2) that this suppression is broadly tuned to match the spatial features of the mask region, and (3) that increasing the baseline contrast in the suppressed region drives all neurons in the input layer, reducing the relative contribution of the suppressing subpopulation in the fMRI signal.