Discordance Between Spatial and Population Correlations From Human Brain Imaging Data
ABSTRACTIt has become increasingly common to probe correlations between human brain imaging measures of receptor/protein binding and function using population‐level brain maps, typically drawn from independent cohorts to estimate correlations across regions. This strategy raises issues of interpretation that we highlight here with both an empirical multimodal brain imaging dataset and simulation studies. Twenty‐four healthy participants completed neuroimaging with both [11C]Cimbi‐36 positron emission tomography and magnetic resonance imaging scans to estimate receptor binding potential (BP) and cerebral blood flow (CBF), respectively, in 18 cortical/subcortical regions. Correlations between BP and CBF were estimated in four ways: (1) Pearson correlation across regions of mean regional BP and CBF from a single or separate cohorts (ρ1.1 and ρ1.2, respectively), to mimic studies using data from independent cohorts; (2) Pearson correlation between BP and CBF across participants in each region (ρ2); or (3) the correlation between BP and CBF across participants across all regions within a single linear mixed effects model (ρ3). We observed a significant positive correlation across regions (ρ^1.1 = 0.672, p = 0.0023; ρ^1.2 = 0.659, p = 0.0030). Region‐specific correlations across participants were substantively lower and not statistically significant (ρ^2: mean = 0.140, range = −0.112–0.336; all p > 0.10), nor when estimated simultaneously within a linear mixed model (ρ^3 = 0.138, p = 0.26). Our simulation study illustrated that regional differences in BP or CBF mean and variance can substantially bias across‐regions correlations and inflate the type‐1 error rate. Our observations allude to ambiguity in the meaning of across‐regions correlations and suggest interpreting them as evidence for a biological relation, which implies a relation across participants, is problematic. Without validated methods that handle confounding and other biases, we urge caution in how future studies interpret across‐regions correlations of population‐level brain maps.
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14
- 10.1176/jnp.17.4.441
- Nov 1, 2005
- The Journal of Neuropsychiatry and Clinical Neurosciences
Blood Flow Imaging of the Brain: 50 Years Experience
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79
- 10.1093/bja/aef155
- Jul 1, 2002
- British Journal of Anaesthesia
In vivo imaging of anaesthetic action in humans: approaches with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)
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116
- 10.1016/j.tips.2010.06.002
- Jul 6, 2010
- Trends in Pharmacological Sciences
Small-animal positron emission tomography as a tool for neuropharmacology
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188
- 10.1176/ajp.156.2.252
- Feb 1, 1999
- American Journal of Psychiatry
This study sought to describe brain regions associated with the personality dimension of introversion/extraversion. Measures of cerebral blood flow (CBF) were obtained from 18 healthy subjects by means of [150]H20 positron emission tomography. Correlations of regional CBF with introversion/extraversion were calculated, and a three-dimensional map of those correlations was generated. Overall, introversion was associated with increased blood flow in the frontal lobes and in the anterior thalamus. Regions in the anterior cingulate gyrus, the temporal lobes, and the posterior thalamus were found to be correlated with extraversion. The findings of the study lend support to the notion that introversion is associated with increased activity in frontal lobe regions. Moreover, the study suggests that individual differences in introversion and extraversion are related to differences in a fronto-striato-thalamic circuit.
- Research Article
101
- 10.1113/jphysiol.2010.192534
- Nov 1, 2010
- The Journal of Physiology
Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity.
- Front Matter
11
- 10.1093/bja/86.5.607
- May 1, 2001
- British Journal of Anaesthesia
Editorial I: Mapping the anatomy of unconsciousness—imaging anaesthetic action in the brain
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259
- 10.1016/j.neuron.2012.09.019
- Nov 1, 2012
- Neuron
High-Resolution fMRI Reveals Laminar Differences in Neurovascular Coupling between Positive and Negative BOLD Responses
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26
- 10.1097/aln.0b013e3182800d58
- Mar 1, 2013
- Anesthesiology
Nitrous oxide, in a concentration of 50% or more, is a known cerebral vasodilator. This study investigated whether a lower dose (30%) of nitrous oxide would also increase cerebral blood flow. In addition, the authors wished to study whether the increase in cerebral blood flow was accompanied by an increase in cerebral metabolism. Multimodal Magnetic Resonance Imaging at 3T was performed, and data were obtained in 17 healthy volunteers during three inhalation conditions: medical air, oxygen-enriched medical air (40% oxygen), and 30% nitrous oxide with oxygen-enriched medical air (40% oxygen). Arterial spin labeling was used to derive the primary tissue specific hemodynamic outcomes: cerebral blood flow, arterial blood volume and arterial transit times. Magnetic Resonance Susceptometry and proton Magnetic Resonance Spectroscopy were used for secondary metabolic outcomes: venous oxygenation, oxygen extraction fraction, cerebral metabolic oxygen rate and prefrontal metabolites. Nitrous oxide in 40% oxygen, but not 40% oxygen alone, significantly increased gray matter cerebral blood flow (22%; P < 0.05) and arterial blood volume (41%; P < 0.05). Venous oxygenation increased in both oxygen and nitrous oxide conditions. Compared with medical air inhalation, nitrous oxide condition caused a significantly larger decrease in oxygen extraction fraction than 40% oxygen alone (mean [SD] 11.3 [5.6]% vs. 8.3 [5.9]% P < 0.05), while global cerebral metabolic rate and prefrontal metabolites remained unchanged. This study demonstrates that 30% nitrous oxide in oxygen-enriched air (40% oxygen) significantly increases cerebral perfusion, and reduces oxygen extraction fraction, reflecting a strong arterial vasodilatory effect without associated increases in metabolism.
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15
- 10.1002/jmri.25022
- Aug 6, 2015
- Journal of magnetic resonance imaging : JMRI
How far is arterial spin labeling MRI from a clinical reality? Insights from arterial spin labeling comparative studies in Alzheimer's disease and other neurological disorders.
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- 10.1176/ajp.155.8.1125
- Aug 1, 1998
- American Journal of Psychiatry
Brain Imaging in Clinical Psychiatry
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137
- 10.1152/ajplegacy.1974.227.6.1444
- Dec 1, 1974
- American Journal of Physiology-Legacy Content
Cerebral energy metabolism, pH, and blood flow during seizures in the cat
- Research Article
- 10.1161/str.49.suppl_1.wp169
- Jan 22, 2018
- Stroke
Introduction: Adverse changes in blood pressure (BP) over the life course can lead to adverse cerebrovascular outcomes, including reduced blood flow. In this life-course, longitudinal, population-based study, we investigated the link between midlife to late life changes in BP and cerebral blood flow (CBF) in old age. Methods: From the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study (2002-2011), 2491 individuals (mean age (SD): midlife 49.7 (6.1) and late-life 79.8 (4.7) years old) were included. BP was measured at three different time points: 1 in mid-life, and 2 in late-life measured 5 years apart (mean follow-up time 30.1 years). With linear mixed models, annual changes in BP were estimated for each participant (mmHg/year). Participants were categorized in tertiles of changes in systolic, pulse pressure and diastolic BP. Total CBF was measured in the last late-life visit with the Phase-Contrast MRI and standardized for brain parenchymal volume (mL/min/100mL). Results: Overall, each mmHg/year increase in systolic BP was associated with 3.2 mL/min/100 mL (95% CI: 0.7-5.7)) higher CBF. Mean (SE) CBF in low, middle and high tertiles of change in systolic BP were 56.0 (0.4), 56.6 (0.4) and 57.5 (0.4) mL/min/100mL respectively (P for trend: 0.01). A similar increase in total CBF was observed for an increase in pulse pressure: each mmHg/year increase in pulse pressure was associated with 6.3 mL/min/100mL (95% CI: 3.8-8.7) higher total CBF. In contrast, an increase in diastolic BP was linked with lower CBF: each mmHg/year increase in diastolic BP was associated with 6.3 mL/min/100mL (95% CI: 3.3-9.4) lower CBF. Mean (SE) CBF in low, middle and high tertiles of changes in diastolic BP were 57.3 (0.4), 57.3 (0.4) and 55.5 (0.4) mL/min/100mL respectively (P for trend: <0.001). All these associations were independent of sociodemographic and cardiovascular factors and antihypertensive medications. Conclusion: In an over 30 years of midlife to late-life follow up, we observed that individuals with increasing systolic BP and pulse pressure have higher CBF in old age. Conversely, increase in diastolic BP is associated with lower CBF. The mechanisms behind the link between long-term BP alterations and CBF need to be elucidated.
- Research Article
175
- 10.1152/ajplegacy.1973.224.1.122
- Jan 1, 1973
- American Journal of Physiology-Legacy Content
Brain blood flow in the conscious and anesthetized rat.
- Research Article
5
- 10.1002/mrm.25073
- Dec 24, 2013
- Magnetic Resonance in Medicine
We recently presented a method for the quantitative measurement of the arterial input function which allows for determination of absolute cerebral blood flow (CBF) values without adjustable parameters. The aim of the present work is to estimate absolute CBF values by using this new technique and to compare it with the gold standard for cerebral perfusion, H(2)(15)O positron emission tomography. Pigs (13) were comparatively investigated by each method performing multiple measurement runs. The reproducibility of both methods was assessed by a voxel-wise correlation of repeated measurements. An intersubject evaluation was performed on median whole-brain CBF estimates. The mean CBF (MRI) was 20±4mL/100g/min for gray matter, the mean CBF (positron emission tomography) was 24±6mL/100g/min for gray and white matter. The reproducibility for MRI correlated with r = 0.85 and P<0.0001, for positron emission tomography with r = 0.76 and P<0.0001. The correlation for the median whole-brain CBF in MRI and positron emission tomography was r = 0.60 and P = 0.04. The proposed method allows for determination of quantitative CBF without normalization factors. The relatively low estimates of absolute CBF most likely results from the higher age of the pigs as compared to other studies. The intermediate correlation between both methods is caused by physiological intraindividual fluctuations of the CBF and by a limited reproducibility of both methods.
- Research Article
129
- 10.1176/jnp.2006.18.3.318
- Jul 1, 2006
- The Journal of Neuropsychiatry and Clinical Neurosciences
In this study, the authors systematically reviewed structural and functional neuroimaging studies of cannabis use. Structural abnormalities generally have not been identified with chronic use. Regular users demonstrate reciprocal changes in brain activity globally and in cerebellar and frontal regions. Abstinence results in decreases, and administration results in increases correlating with subjective intoxication. Chronic use and cannabis administration result in attenuated brain activity in task-activated regions or activation of compensatory regions. Findings correlate partially with neuropsychological data, but generalization is limited by the lack of use of diagnostic criteria, appropriately paired neuropsychological testing or means to better quantify cannabis use and abstinence.
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