Bispectral Index Changes Following Boluses of Commonly Used Intravenous Medications During Volatile Anesthesia Identified From Retrospective Data.

BACKGROUND: Although patients are commonly monitored for depth of anesthesia, it is unclear to what extent administration of intravenous anesthetic medications may affect calculated bispectral (BIS) index values under general anesthesia. METHODS: In a retrospective analysis of electronic anesthesia records from an academic medical center, we examined BIS index changes associated with 14 different intravenous medications, as administered in routine practice, during volatile-based anesthesia using a novel screening approach. Discrete-time windows were identified in which only a single drug bolus was administered, and subsequent changes in the BIS index, concentration of volatile anesthetic, and arterial pressure were analyzed. Our primary outcome was change in BIS index, following drug administration. Adjusted 95% confidence intervals were compared to predetermined thresholds for clinical significance. Secondary sensitivity analyses examined the same outcomes, with available data separated according to differences in baseline volatile anesthetic concentrations, doses of the administered medications, and length of time window. RESULTS: The study cohort was comprised of data from 20,170 distinct cases, 54.7% of patients were men, with a median age of 55. In the primary analysis, ketamine at a median dose of 20 mg was associated with a median (confidence limits) increase in BIS index of 3.8 (2.5-5.0). Midazolam (median dose 2 mg) was associated with a median decrease in BIS index of 3.0 (1.5-4.5). Neither of these drug administrations occurred during time periods associated with changes in volatile anesthetic concentration. Analysis for dexmedetomidine was confounded by concomitant decreases in volatile anesthetic concentration. No other medication analyzed, including propofol and common opioids, was associated with a significant change in BIS index. Secondary analyses revealed that similar BIS index changes occurred when midazolam and ketamine were administered at different volatile anesthetic concentrations and different doses, and these changes persisted 11 to 20 minutes postadministration. CONCLUSIONS: Modest, but persistent changes in BIS index occurred following doses of ketamine (increase) and midazolam (decrease) during periods of stable volatile anesthetic administration.

Brain connectivity under light sedation with midazolam and ketamine during task performance and the periodic experience of pain: Examining concordance between different approaches for seed-based connectivity analysis.

This work focused on functional connectivity changes under midazolam and ketamine sedation during performance of a memory task, with the periodic experience of pain. To maximize ability to compare to previous and future work, we performed secondary region of interest (ROI)-to-ROI functional connectivity analyses on these data, using two granularities of scale for ROIs. These findings are compared to the results of a previous seed-to-voxel analysis methodology, employed in the primary analysis. Healthy adult volunteers participated in this randomized crossover 3 T functional MRI study under no drug, followed by subanesthetic doses of midazolam or ketamine achieving minimal sedation. Periodic painful stimulation was delivered while subjects repeatedly performed a memory-encoding task. Atlas-based and network-level ROIs were used from within Conn Toolbox (ver 18). Timing of experimental task events was regressed from the data to assess drug-induced changes in background connectivity, using ROI-to-ROI methodology. Compared to saline, ROI-to-ROI connectivity changes under ketamine did not survive correction for multiple comparisons, thus data presented is from 16 subjects in a paired analysis between saline and midazolam. In both ROI-to-ROI analyses, the predominant direction of change was towards increased connectivity under midazolam, compared to saline. These connectivity increases occurred between functionally-distinct brain areas, with a posterior-predominant spatial distribution that included many long-range connectivity changes. During performance of an experimental task that involved periodic painful stimulation, compared to saline, low-dose midazolam was associated with robust increases in functional connectivity. This finding was concordant across different seed-based analyses for midazolam, but not ketamine. The neuroimaging drug trial from which this data was drawn was pre-registered (NCT-02515890) prior to enrollment of the first subject.

Neutral auditory words immediately followed by painful electric shock may show reduced next-day recollection.

In this study, we investigated the effect of experimentally delivered acute pain on memory. Twenty-five participants participated in experimental sessions on consecutive days. The first session involved a categorization task to encourage memory encoding. There were two conditions, presented in randomized order, in which participants listened to a series of words, which were repeated three times. In one condition, one-third of the word items were immediately followed by a painful electrical shock. This word-shock pairing was consistent across repetition and the pain-paired items were presented unpredictably. In the other condition, all word items were not associated with pain. Response times over these repeated presentations were assessed for differences. Explicit memory was tested the following day, employing a Remember-Know assessment of word recognition, with no shocks employed. We found evidence that recollection may be reduced for pain-paired words, as the proportion of correct Remember responses (out of total correct responses) was significantly lower. There were no significant reductions in memory for non-pain items that followed painful stimulation after a period of several seconds. Consistent with the experience of pain consuming working memory resources, we theorize that painful shocks interrupt memory encoding for the immediately preceding experimental items, due to a shift in attention away from the word item.

Anesthesia and the neurobiology of fear and posttraumatic stress disorder.

PURPOSE OF REVIEW: Dysfunction of fear memory systems underlie a cluster of clinically important and highly prevalent psychological morbidities seen in perioperative and critical care patients, most archetypally posttraumatic stress disorder (PTSD). Several sedative-hypnotics and analgesics are known to modulate fear systems, and it is theoretically plausible that clinical decisions of the anesthesiologist could impact psychological outcomes. This review aims to provide a focused synthesis of relevant literature from multiple fields of research. RECENT FINDINGS: There is evidence in some contexts that unconscious fear memory systems are less sensitive to anesthetics than are conscious memory systems. Opiates may suppress the activation of fear systems and have benefit in the prevention of PTSD following trauma. There is inconsistent evidence that the use of propofol and benzodiazepines for sedation following trauma may potentiate the development of PTSD relative to other drugs. The benefits of ketamine seen in the treatment of major depression are not clearly replicated in PTSD-cluster psychopathologies, and its effects on fear processes are complex. SUMMARY: There are multiple theoretical mechanisms by which anesthetic drugs can modulate fear systems and clinically important fear-based psychopathologies. The current state of research provides some evidence to support further hypothesis investigation. However, the absence of effectiveness studies and the inconsistent signals from smaller studies provide insufficient evidence to currently offer firm clinical guidance.

Early immersion in a dedicated one-month Anesthesiology Professional Practice rotation for Post-Graduate Year-1 interns is associated with an increase in scholarly activity during residency.

STUDY OBJECTIVE: Despite the Accreditation Council for Graduate Medical Education scholarly activity requirement, incorporating education on scholarly fundamentals into residency is challenging. We designed and implemented an academic non-clinical rotation for Post Graduate Year-1 (PGY-1) interns and its association with subsequent resident scholarly productivity was determined. We hypothesized that early immersion in such a rotation would be associated with increased scholarly activity during residency. DESIGN: Retrospective educational comparative study, of two cohorts of anesthesiology residents in the graduating classes of 2015-2020. SETTING: Large anesthesiology residency program at a U.S. academic medical center. INTERVENTION: A one-month academic rotation titled Anesthesia Professional Practice for PGY-1 interns has been implemented since 2014. The rotation curriculum broadly covers important topics for scholarly projects and provides introductions to academic faculty and institutional resources. MEASUREMENTS: The scholarly products (abstracts, publications, book chapters, research protocols, and grant applications) were quantified using Scholarly Activity Points, a previously described metric that accounts for significance and the resident's contribution. Total Scholarly Activity Points for each resident and number of publications prior to residency were determined for both cohorts. Segmented regression was employed with Scholarly Activity Points as the outcome; participation in the early immersion rotation and prior publications were used as input variables. MAIN RESULTS: Resident participation in the early immersion rotation was significantly associated with higher Scholarly Activity Points. The confounding variable of pre-residency publication count was not significantly correlated to this increase. CONCLUSIONS: Immersion in a one-month academic program during PGY-1 internship may contribute to increased scholarly productivity during residency.

Opportunities Beyond the Anesthesiology Department: Broader Impact Through Broader Thinking.

Ensuring a productive clinical and research workforce requires bringing together physicians and communities to improve health, by strategic targeting of initiatives with clear and significant public health relevance. Within anesthesiology, the traditional perspective of the field's health impact has focused on providing safe and effective intraoperative care, managing critical illness, and treating acute and chronic pain. However, there are limitations to such a framework for anesthesiology's public health impact, including the transient nature of acute care episodes such as the intraoperative period and critical illness, and a historical focus on analgesia alone-rather than the complex psychosocial milieu-for pain management. Due to the often episodic nature of anesthesiologists' interactions with patients, it remains challenging for anesthesiologists to achieve their full potential for broad impact and leadership within increasingly integrated health systems. To unlock this potential, anesthesiologists should cultivate new clinical, research, and administrative roles within the health system-transcending traditional missions, seeking interdepartmental collaborations, and taking measures to elevate anesthesiologists as dynamic and trusted leaders. This special article examines 3 core themes for how anesthesiologists can enhance their impact within the health care system and pursue new collaborative health missions with nonanesthesiologist clinicians, researchers, and administrative leaders. These themes include (1) reframing of traditional anesthesiologist missions toward a broader health system-wide context; (2) leveraging departmental and institutional support for professional career development; and (3) strategically prioritizing leadership attributes to enhance system-wide anesthesiologist contributions to improving overall patient health.

Midazolam and Ketamine Produce Distinct Neural Changes in Memory, Pain, and Fear Networks during Pain.

BACKGROUND: Despite the well-known clinical effects of midazolam and ketamine, including sedation and memory impairment, the neural mechanisms of these distinct drugs in humans are incompletely understood. The authors hypothesized that both drugs would decrease recollection memory, task-related brain activity, and long-range connectivity between components of the brain systems for memory encoding, pain processing, and fear learning. METHODS: In this randomized within-subject crossover study of 26 healthy adults, the authors used behavioral measures and functional magnetic resonance imaging to study these two anesthetics, at sedative doses, in an experimental memory paradigm using periodic pain. The primary outcome, recollection memory performance, was quantified with d' (a difference of z scores between successful recognition versus false identifications). Secondary outcomes were familiarity memory performance, serial task response times, task-related brain responses, and underlying brain connectivity from 17 preselected anatomical seed regions. All measures were determined under saline and steady-state concentrations of the drugs. RESULTS: Recollection memory was reduced under midazolam (median [95% CI], d' = 0.73 [0.43 to 1.02]) compared with saline (d' = 1.78 [1.61 to 1.96]) and ketamine (d' = 1.55 [1.12 to 1.97]; P < 0.0001). Task-related brain activity was detected under saline in areas involved in memory, pain, and fear, particularly the hippocampus, insula, and amygdala. Compared with saline, midazolam increased functional connectivity to 20 brain areas and decreased to 8, from seed regions in the precuneus, posterior cingulate, and left insula. Compared with saline, ketamine decreased connectivity to 17 brain areas and increased to 2, from 8 seed regions including the hippocampus, parahippocampus, amygdala, and anterior and primary somatosensory cortex. CONCLUSIONS: Painful stimulation during light sedation with midazolam, but not ketamine, can be accompanied by increased coherence in brain connectivity, even though details are less likely to be recollected as explicit memories.

Roadmap for Conducting Neuroscience Research in the COVID-19 Era and Beyond: Recommendations From the SNACC Research Committee.

The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research. At the 2020 Society of Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting, the SNACC Research Committee met virtually to discuss research challenges encountered during the COVID-19 pandemic along with possible strategies for facilitating research activities. These challenges and recommendations are included in this Consensus Statement. The objectives are to: (1) provide an overview of the disruptions and challenges to neuroscience research caused by the COVID-19 pandemic, and; (2) put forth a set of consensus recommendations for strengthening research sustainability during and beyond the current pandemic. Specific recommendations are highlighted for adapting laboratory and human subject study activities to optimize safety. Complementary research activities are also outlined for both laboratory and clinical researchers if specific investigations are impossible because of regulatory or societal changes. The role of virtual platforms is discussed with respect to fostering new collaborations, scheduling research meetings, and holding conferences such that scientific collaboration and exchange of ideas can continue. Our hope is for these recommendations to serve as a valuable resource for investigators in the neurosciences and other research disciplines for current and future research disruptions.

Psychometric and electrodermal activity data from an experimental paradigm of memory encoding with some items periodically followed by painful electric shock.

How pain influences explicit memory is an active area of investigation, and next-day recognition was the primary outcome of this experiment. The data reported here were secondary measures of psychometrics to quantify interindividual variability between subjects and measure electrodermal activity (EDA) changes in response to experimental stimuli. Reliable EDA responses following painful electric shocks were obtained in the Learning portion of the experiment. During next-day testing, however, no reliable EDA responses were elicited, including to previously pain-paired experimental items.

Wellness Principles Correlate With More Favorable Burnout Scores in Junior Anesthesiology Residents.

BACKGROUND: Strategies to prevent or reduce burnout for anesthesiology residents remain relatively unexplored. We aimed to determine if participation in a wellness course would be associated with lower burnout. METHODS: A prospective, case-control survey/questionnaire study was implemented within a single anesthesiology residency in a large academic medical center program. One class participated in an inaugural wellness course (n = 15) promoting particular wellness principles 4 months into their postgraduate year (PGY)-1, while another class with no course participation served as controls (n = 13). Both groups completed the Maslach Burnout Inventory (MBI) 6 months into their PGY-2 year. In addition, a survey measuring their perceived ability to implement wellness principles (regardless of course participation) as well as validated questionnaires measuring stress, depression, and sleep quality were administered. RESULTS: Course participants had a trend toward lower MBI depersonalization scores; however, this was not statistically significant (MBI score 7 versus 12, P = .078, Cohen d 0.71). In a multivariable model, course participation yielded lower exhaustion scores (P = .011) whereas higher stress yielded higher exhaustion scores (P = .013), and higher depression scores yielded higher depersonalization scores (P = .019). A higher perceived ability to implement the wellness principles resulted in significantly better scores in all 3 burnout components (exhaustion P = .049, depersonalization P = .004 achievement P = .001). CONCLUSION: Residents who felt they could implement wellness principles had lower burnout, regardless of course participation. Our brief course exposure had only marginal independent effects, suggesting that more longitudinal and repeated exposures to wellness training are likely required to produce a more effective outcome for mitigating burnout.

Retrospective analysis of cases of intraoperative awareness in a large multi-hospital health system reported in the early postoperative period.

BACKGROUND: Awareness with recall under general anesthesia remains a rare but important issue that warrants further study. METHODS: We present a series of seven cases of awareness that were identified from provider-reported adverse event data from the electronic anesthesia records of 647,000 general anesthetics. RESULTS: The low number of identified cases suggests an under-reporting bias. Themes that emerge from this small series can serve as important reminders to anesthesia providers to ensure delivery of an adequate anesthetic for each patient. Commonalities between a majority of our identified anesthetic awareness cases include: obesity, use of total intravenous anesthesia, use of neuromuscular blockade, and either a lack of processed electroencephalogram (EEG) monitoring or documented high depth of consciousness index values. An interesting phenomenon was observed in one case, where adequately-dosed anesthesia was delivered without technical issue, processed EEG monitoring was employed, and the index value suggested an adequate depth of consciousness throughout the case. CONCLUSIONS: Provider-reported adverse event data in the immediate post-operative period are likely insensitive for detecting cases of intraoperative awareness. Though causation cannot firmly be established from our data, themes identified in this series of cases of awareness with recall under general anesthesia provide important reminders for anesthesia providers to maintain vigilance in monitoring depth and dose of anesthesia, particularly with total intravenous anesthesia.

Memory for non-painful auditory items is influenced by whether they are experienced in a context involving painful electrical stimulation.

In this study, we sought to examine the effect of experimentally induced somatic pain on memory. Subjects heard a series of words and made categorization decisions in two different conditions. One condition included painful shocks administered just after presentation of some of the words; the other condition involved no shocks. For the condition that included painful stimulations, every other word was followed by a shock, and subjects were informed to expect this pattern. Word lists were repeated three times within each condition in randomized order, with different category judgments but consistent pain-word pairings. After a brief delay, recognition memory was assessed. Non-pain words from the pain condition were less strongly encoded than non-pain words from the completely pain-free condition. Recognition of pain-paired words was not significantly different than either subgroup of non-pain words. An important accompanying finding is that response times to repeated experimental items were slower for non-pain words from the pain condition, compared to non-pain words from the completely pain-free condition. This demonstrates that the effect of pain on memory may generalize to non-pain items experienced in the same experimental context.

The triple variable index combines information generated over time from common monitoring variables to identify patients expressing distinct patterns of intraoperative physiology.

BACKGROUND: Mean arterial pressure (MAP), bispectral index (BIS), and minimum alveolar concentration (MAC) represent valuable, yet dynamic intraoperative monitoring variables. They provide information related to poor outcomes when considered together, however their collective behavior across time has not been characterized. METHODS: We have developed the Triple Variable Index (TVI), a composite variable representing the sum of z-scores from MAP, BIS, and MAC values that occur together during surgery. We generated a TVI expression profile, defined as the sequential TVI values expressed across time, for each surgery where concurrent MAP, BIS, and MAC monitoring occurred in an adult patient (≥18 years) at the University of Pittsburgh Medical Center between January and July 2014 (n = 5296). Patterns of TVI expression were identified using k-means clustering and compared across numerous patient, procedure, and outcome characteristics. TVI and the triple low state were compared as prediction models for 30-day postoperative mortality. RESULTS: The median frequency MAP, BIS, and MAC were recorded was one measurement every 3, 5, and 5 min. Three expression patterns were identified: elevated, mixed, and depressed. The elevated pattern displayed the highest average MAP, BIS, and MAC values (86.5 mmHg, 45.3, and 0.98, respectively), while the depressed pattern displayed the lowest values (76.6 mmHg, 38.0, 0.66). Patterns (elevated, mixed, depressed) were distinct across the following characteristics: average patient age (52, 53, 54 years), American Society of Anesthesiologists Physical Status 4 (6.7, 16.1, 27.3%) and 5 (0.1, 0.6, 1.6%) categories, cardiac (2.2, 6.5, 16.1%) and emergent (5.8, 10.5, 12.8%) surgery, cardiopulmonary bypass use (0.3, 2.6, 9.8%), intraoperative medication administration including etomidate (3.0, 7.3, 12.6%), hydromorphone (47.6, 26.3, 25.2%), ketamine (11.2, 4.6, 3.0%), dexmedetomidine (18.4, 16.6, 13.6%), phenylephrine (74.0, 74.8, 83.0), epinephrine (2.0, 6.0, 18.0%), norepinephrine (2.4, 7.5, 21.2%), vasopressin (3.4, 7.6, 21.0%), succinylcholine (74.0, 69.0, 61.9%), intraoperative hypotension (28.8, 33.0, 52.3%) and the triple low state (9.4, 30.3, 80.0%) exposure, and 30-day postoperative mortality (0.8, 2.7, 5.6%). TVI was a better predictor of patients that died or survived in the 30 days following surgery compared to cumulative triple low state exposure (AUC 0.68 versus 0.62, p < 0.05). CONCLUSIONS: Surgeries that share similar patterns of TVI expression display distinct patient, procedure, and outcome characteristics.

Financial Incentive, in Place of Nonclinical Time, Increases Faculty Involvement and Improves Resident Didactic Evaluation Scores in an Anesthesiology Residency Training Program.

BACKGROUND: Providing clinical faculty to lead high-quality resident didactic sessions remains a challenge for academic departments that host graduate medical education training programs. In an effort to both reduce costs and to continue to recruit faculty to give lectures, our department began to incentivize clinicians with a $500 stipend in place of a nonclinical day to present didactics. Our hypothesis is that with financial incentive, more attendings would present didactics and the quality would improve. METHODS: Residents routinely evaluate all didactic sessions using a Likert scale of 1 to 5. Residents also answer yes or no to indicate whether the presenter should return. We compared academic year (AY) 2016, in which faculty were incentivized with nonclinical time, with AY 2017 and AY 2018, in which incentive came in the form of a $500 stipend. For each, the mean Likert score and percentage of positive responses for lecturer returning were calculated. A 1-way ANOVA and post hoc t tests were performed to determine significant changes. RESULTS: Comparing AY 2016 (before the incentive switch) with AY 2017 and AY 2018, there was more faculty involvement in resident didactic after implementing the financial incentive. The quality of lectures also improved after the incentive switch, according to resident evaluations. There were higher overall Likert scores in AY 2018 and a higher percentage of positive responses to the question of whether presenters should return in AY 2017 and AY 2018, compared with AY 2016. CONCLUSIONS: After implementation of a financial incentive in place of nonclinical time, more faculty became involved in lectures and overall lecture quality improved as measured by resident evaluations.

Cortical Networks Involved in Memory for Temporal Order.

We examined the neurobiological basis of temporal resetting, an aspect of temporal order memory, using a version of the delayed-match-to-multiple-sample task. While in an fMRI scanner, participants evaluated whether an item was novel or whether it had appeared before or after a reset event that signified the start of a new block of trials. Participants responded "old" to items that were repeated within the current block and "new" to both novel items and items that had last appeared before the reset event (pseudonew items). Medial-temporal, prefrontal, and occipital regions responded to absolute novelty of the stimulus-they differentiated between novel items and previously seen items, but not between old and pseudonew items. Activation for pseudonew items in the frontopolar and parietal regions, in contrast, was intermediate between old and new items. The posterior cingulate cortex extending to precuneus was the only region that showed complete temporal resetting, and its activation reflected whether an item was new or old according to the task instructions regardless of its familiarity. There was also a significant Condition (old/pseudonew) × Familiarity (second/third presentations) interaction effect on behavioral and neural measures. For pseudonew items, greater familiarity decreased response accuracy, increased RTs, increased ACC activation, and increased functional connectivity between ACC and the left frontal pole. The reverse was observed for old items. On the basis of these results, we propose a theoretical framework in which temporal resetting relies on an episodic retrieval network that is modulated by cognitive control and conflict resolution.

Human Posterior Insula Functional Connectivity Differs Between Electrical Pain and the Resting State.

The objective in this study was to directly compare MRI-based functional connectivity between conditions of rest and painful electrical nerve stimulation for key regions involved in pain processing: the anterior and posterior insula and the anterior cingulate cortex. Electric nerve stimulation, rated 7/10 for pain, was delivered to the right index finger of 14 healthy pain-free adult volunteers in four 30-sec blocks and continuously for 2 min. Functional connectivity maps obtained at rest and during both pain tasks were compared using seed time courses from the left anterior and posterior insula and anterior cingulate. Significant Pain versus Rest connectivity differences were consistently shown for the posterior insula, notably to the posterior cingulate and precuneus, while minimal and inconsistent differences were observed for the anterior insula and anterior cingulate. This study reinforces the known differences that can occur with changes in seed region selection in functional connectivity analysis. It also presents preliminary evidence that functional connectivity for the left posterior insula can potentially differentiate the presence of acute right-sided electrical pain from the nonpainful resting state.

Optimizing and Interpreting Insular Functional Connectivity Maps Obtained During Acute Experimental Pain: The Effects of Global Signal and Task Paradigm Regression.

The insula is uniquely located between the temporal and parietal cortices, making it anatomically well-positioned to act as an integrating center between the sensory and affective domains for the processing of painful stimulation. This can be studied through resting-state functional connectivity (fcMRI) imaging; however, the lack of a clear methodology for the analysis of fcMRI complicates the interpretation of these data during acute pain. Detected connectivity changes may reflect actual alterations in low-frequency synchronous neuronal activity related to pain, may be due to changes in global cerebral blood flow or the superimposed task-induced neuronal activity. The primary goal of this study was to investigate the effects of global signal regression (GSR) and task paradigm regression (TPR) on the changes in functional connectivity of the left (contralateral) insula in healthy subjects at rest and during acute painful electric nerve stimulation of the right hand. The use of GSR reduced the size and statistical significance of connectivity clusters and created negative correlation coefficients for some connectivity clusters. TPR with cyclic stimulation gave task versus rest connectivity differences similar to those with a constant task, suggesting that analysis which includes TPR is more accurately reflective of low-frequency neuronal activity. Both GSR and TPR have been inconsistently applied to fcMRI analysis. Based on these results, investigators need to consider the impact GSR and TPR have on connectivity during task performance when attempting to synthesize the literature.

Pain does not follow the boxcar model: temporal dynamics of the BOLD fMRI signal during constant current painful electric nerve stimulation.

UNLABELLED: The temporal dynamics of the blood oxygen level-dependent (BOLD) signal, especially for painful stimulations, is not completely understood. In this study, the BOLD signal response to a long painful electrical stimulation (a continuous painful stimulation of 2 minutes) is directly compared to that of a short painful stimulation (four 30-second periods of painful stimulation interleaved with 30-second rest) in an effort to further probe the relationship between the temporal dynamics of the BOLD signal during constant-intensity pain stimulation. Time course analysis showed that both stimulation protocols produced 3 similarly timed peaks in both data sets, suggesting an early and delayed BOLD response to painful stimulation initiation, and a response related to stimulus termination. Despite the continuous stimulation, the BOLD signal returned to baseline in the 2-minute task. Even with this signal discrepancy, however, the activation maps of the 2 pain tasks differed only slightly, suggesting that the bulk of the activation is determined by the sharp rise in BOLD signal with stimulus onset. These findings imply that the BOLD signal response time course is not directly reflective of pain perception. PERSPECTIVE: This article demonstrates that the BOLD signal for a painful stimulation contains multiple peaks and does not maintain the constant level during stimulation that is assumed in typical analysis. Although these dynamics should be accounted for in future studies because of their ability to confound results, their presence did not significantly alter the overall group maps.

Comparison between end-tidal CO2 and respiration volume per time for detecting BOLD signal fluctuations during paced hyperventilation.

Respiratory motion and capnometry monitoring were performed during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) of the brain while a series of paced hyperventilation tasks were performed that caused significant hypocapnia. Respiration volume per time (RVT) and end-tidal carbon dioxide (ETCO(2)) were determined and compared for their ability to explain BOLD contrast changes in the data. A 35% decrease in ETCO(2) was observed along with corresponding changes in RVT. A best-fit ETCO(2) response function, with an average initial peak delay time of 12 s, was empirically determined. ETCO(2) data convolved with this response function was more strongly and prevalently correlated to BOLD signal changes than RVT data convolved with the corresponding respiration response function. The results suggest that ETCO(2) better models BOLD signal fluctuations in fMRI experiments with significant transient hypocapnia. This is due to hysteresis in the ETCO(2) response when moving from hypocapnia to normocapnia, compared to moving from normocapnia to hypocapnia.

The impact of physiologic noise correction applied to functional MRI of pain at 1.5 and 3.0 T.

This study quantified the impact of the well-known physiologic noise correction algorithm RETROICOR applied to a pain functional magnetic resonance imaging (FMRI) experiment at two field strengths: 1.5 and 3.0 T. In the 1.5-T acquisition, there was an 8.2% decrease in time course variance (σ) and a 227% improvement in average model fit (increase in mean R(2)(a)). In the 3.0-T acquisition, significantly greater improvements were seen: a 10.4% decrease in σ and a 240% increase in mean R(2)(a). End-tidal carbon dioxide data were also collected during scanning and used to account for low-frequency changes in cerebral blood flow; however, the impact of this correction was trivial compared to applying RETROICOR. Comparison between two implementations of RETROICOR demonstrated that oversampled physiologic data can be applied by either downsampling or modification of the timing in the RETROICOR algorithm, with equivalent results. Furthermore, there was no significant effect from manually aligning the physiologic data with corresponding image slices from an interleaved acquisition, indicating that RETROICOR accounts for timing differences between physiologic changes and MR signal changes. These findings suggest that RETROICOR correction, as it is commonly implemented, should be included as part of the data analysis for pain FMRI studies performed at 1.5 and 3.0 T.