Sylvain Charron

Motivation and cognitive control in the human prefrontal cortex

The prefrontal cortex (PFC) subserves cognitive control, that is, the ability to select thoughts or actions in relation to internal goals. Little is known, however, about how the PFC combines motivation and the selection processes underlying cognitive control. We used functional magnetic resonance imaging in humans and found that the medial and lateral PFC have a parallel hierarchical organization from posterior to anterior regions for motivating and selecting behaviors, respectively. Moreover, using functional connectivity analyses, we found that functional interactions in this parallel system from medial to lateral PFC regions convey motivational incentives on the basis of rewards/penalties regulating the differential engagement of lateral PFC regions in top-down selection. Our results indicate that motivation is a dissociable function, reveal how the PFC integrates motivation and cognitive control in the service of decision-making, and have major implications for current theories of prefrontal executive function.

Divided Representation of Concurrent Goals in the Human Frontal Lobes

Simultaneously Serving Two Goals What are the neuronal mechanisms underlying dual-task performance? Charron and Koechlin (p. 360) used functional magnetic resonance imaging to study this question under conditions of varying incentive for two tasks. Subjects performed letter-matching tasks either sequentially or concurrently. Reward value for performance of each of the two tasks was manipulated orthogonally. Under conditions of single-task (sequential) performance, they observed bilateral brain activity in the dorsal anterior cingulate and the premotor cortex that correlated with the reward value of the current task. However, under dual-task conditions, activity in these regions on the left corresponded to primary-task reward performance, while on the right, activity corresponded to secondary-task performance. Under dual-task conditions, both reward and stimulus-response representations are thus segregated according to hemisphere. The human brain is limited to accurately negotiate the pursuit of two concurrent goals at the same time. The anterior prefrontal cortex (APC) confers on humans the ability to simultaneously pursue several goals. How does the brain’s motivational system, including the medial frontal cortex (MFC), drive the pursuit of concurrent goals? Using brain imaging, we observed that the left and right MFC, which jointly drive single-task performance according to expected rewards, divide under dual-task conditions: While the left MFC encodes the rewards driving one task, the right MFC concurrently encodes those driving the other task. The same dichotomy was observed in the lateral frontal cortex, whereas the APC combined the rewards driving both tasks. The two frontal lobes thus divide for representing simultaneously two concurrent goals coordinated by the APC. The human frontal function seems limited to driving the pursuit of two concurrent goals simultaneously.

How Sustained Is 24-Hour Diffusion-Weighted Imaging Lesion Reversal? : Serial Magnetic Resonance Imaging in a Patient Cohort Thrombolyzed Within 4.5 Hours of Stroke Onset

Background and Purpose— Here, we assessed how sustained is reversal of the acute diffusion lesion (RAD) observed 24 hours after intravenous thrombolysis, and the relationships between RAD fate and early neurological improvement. Methods— We analyzed 155 consecutive patients thrombolyzed intravenously 152 minutes (median) after stroke onset and who underwent 3 MR sessions: 1 before and 2 after treatment (median times from onset, 25.6 and 54.3 hours, respectively). Using voxel-based analysis of diffusion-weighted imaging (DWI)1, DWI2, and DWI3 lesions on coregistered image data sets, we assessed the outcome of RAD voxels (hyperintense on DWI1 but not on DWI2) as transient or sustained on DWI3, and their relationships with early neurological improvement, defined as &Dgr;National Institutes of Health Stroke Scale ≥8 or National Institutes of Health Stroke Scale ⩽1 at 24 hours. Tmax and apparent diffusion coefficient values were compared between sustained and transient RAD voxels. Results— The median (interquartile range) baseline National Institutes of Health Stroke Scale and DWI1 lesion volume were 11 (7–18) mL and 15.6 (6.0–50.9) mL, respectively. The median (interquartile range) RAD volume on DWI2 was 2.8 (1.1–6.6) mL, of which 70% was sustained on DWI3. Sixteen (10.3%) patients had sustained RAD ≥10 mL. As compared with transient RAD voxels, sustained RAD voxels had nonsignificantly higher baseline apparent diffusion coefficient values (median [interquartile range], 793 [717–887] versus 777 [705–869]×10−6 mm2·s −1, respectively; P=0.08) and significantly better perfusion (Tmax, mean±SD, 6.3±3.2 versus 7.8±4.0 s; P<0.001). At variance with transient RAD, the volume of sustained RAD was associated with early neurological improvement in multivariate analysis (odds ratio, 1.08; 95% confidence interval, [1.01–1.17], per 1-mL increase; P=0.03). Conclusions— After thrombolysis, over two-thirds of the DWI lesion reversal captured on 24-hour follow-up MR is sustained. Sustained DWI lesion reversal volume is a strong imaging correlate of early neurological improvement.

Does Diffusion Lesion Volume Above 70 mL Preclude Favorable Outcome Despite Post-Thrombolysis Recanalization?

Background and Purpose— Whether to withhold recanalization treatment when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is unsettled. Our aim was to assess the impact of recanalization on outcome in patients with baseline DWI lesion ≥70 mL (DWI≥70 mL) treated ⩽4.5 hours from onset. We hypothesized that recanalization is beneficial in a sizeable fraction of these patients and that this is associated with a larger DWI lesion reversal. Methods— We analyzed 267 consecutive patients treated with intravenous recombinant tissue-type plasminogen activator for middle cerebral artery territory stroke in whom an occlusion was present on magnetic resonance angiography and 24-hour recanalization and 90-day clinical outcome could be assessed. After stratification relative to the 70-mL DWI lesion cut point, we calculated the odds ratio for recanalization of the primary arterial occlusive lesion (AOL score ≥2) to predict favorable outcome (modified Rankin scale score ⩽2). DWI lesion reversal was compared between recanalizers with DWI≥70 mL with favorable and unfavorable outcomes. Results— Median (interquartile range) DWI lesion volume was 22 mL (10–60), and median onset time to imaging was 116 minutes (86–151). Twelve (22%) of the 54 patients with DWI≥70 mL experienced favorable outcome, of which 9 had recanalized. In patients with DWI≥70 mL, recanalization was significantly associated with favorable outcome after adjustment for age and National Institutes of Health Stroke Scale (odds ratio =4.72 [1.09–20.32]; P=0.0375). Among recanalizers with DWI≥70 mL, absolute and relative DWI reversal volumes were larger in those with favorable as compared with unfavorable outcome (18.8 mL [12.2–47.6] versus 8.5 mL [4.3–31.1]; P=0.17; and 19.6% [10.9–62.8] versus 8.7% [3.9–16.5], respectively; P=0.049). Conclusions— Patients with DWI lesion volume ≥70 mL can benefit from recanalization after intravenous recombinant tissue-type plasminogen activator. This may partly reflect a larger amount of DWI lesion reversal.

Intermittent theta burst stimulation over left BA10 enhances virtual reality-based prospective memory in healthy aged subjects

Prospective memory (PM) refers to a complex cognitive ability that underpins the delayed execution of previously formulated intentions. PM performance declines early in normal aging and this process is accentuated in Alzheimers disease. The left frontopolar cortex (BA10) has been consistently assigned a major role in PM functioning, but whether it can be noninvasively modulated to enhance PM performance in aged people has not been addressed so far. Here, we investigated the effects of modulating left BA10 by means of theta burst stimulation (TBS), using either excitatory (intermittent TBS), inhibitory (continuous TBS) or control (vertex) TBS in healthy aged subjects. The behavioral effects were assessed using a reliable and ecological virtual reality PM task that included both event- and time-based retrievals. As compared with vertex stimulation, event-based PM performance significantly improved after excitatory stimulation, whereas inhibitory stimulation had no significant effect. Additionally, and across the different types of stimulation, performance for congruent links between the event-based PM cue and the action to be performed was significantly better as compared with incongruent links. In conclusion, intermittent TBS might provide a relevant interventional strategy to counteract the decline of cognitive functions and memory abilities in normal aging.

Comparison between voxel-based and subtraction methods for measuring diffusion-weighted imaging lesion growth after thrombolysis

Background Infarct growth (IG) is used as surrogate end-point in therapeutic trials. For practical reasons, infarct growth is commonly assessed using simple subtraction of acute from follow-up diffusion-weighted imaging (DWI) lesion volumes. However, the volume subtraction method will underestimate true infarct growth in case of diffusion-weighted imaging lesion reversal. Aim To measure the size of the difference between true infarct growth on voxel-based coregistration and infarct growth approximated with simple volume subtraction. Methods We retrospectively analyzed 322 consecutive stroke patients (median (IQR) age: 70 years (57–80), National Institute of Health Stroke Score at admission 14 (8–19)), who underwent a magnetic resonance imaging before (DWI1) and ≈24 h (DWI2) after IV-thrombolysis. IGvoxel-based was defined as the volume of signal changes on DWI2 that did not overlap with that on coregistered DWI1. This was compared with simply subtracting DWI1 from DWI2 lesion volume (IGsubtracted). We also compared these two metrics for the prediction of three-month unfavorable outcome (mRS ≥ 2) using c-statistics of multivariable models, adjusted for age, and National Institute of Health Stroke Score. Results Infarct growth volume metrics were strongly correlated (ρ = 0.94), but IGsubtracted substantially underestimated IGvoxel-based (median (IQR): 9.52 (0.23–38.9) vs. 16.98 (4.4–45.4) mL). Of the 75 patients with shrinking or stable diffusion-weighted imaging lesion using volume subtraction, IGvoxel-based was ≥5 mL in 20 (27% of the subset, 6.2% of the whole population). Moreover, IGvoxel-based better predicted unfavorable outcome than IGsubtracted (c-statistics = 0.86 (95% CI, 0.82–0.90) vs. 0.82 (0.78–0.87), P = 0.003). Conclusion At early post-thrombolysis time points, the simple subtraction of lesion volumes masked substantial diffusion-weighted imaging lesion growth in 6.2% of patients. Although more time-consuming, the voxel-based method may impact results of trials that use infarct growth attenuation as an end-point.

Sulcus-Based MR Analysis of Focal Cortical Dysplasia Located in the Central Region

Objective Focal cortical dysplasias (FCDs) are mainly located in the frontal region, with a particular tropism for the central sulcus. Up to 30% of lesions are undetected (magnetic resonance [MR]-negative FCD patients) or belatedly diagnosed by visual analysis of MR images. We propose an automated sulcus-based method to analyze abnormal sulcal patterns associated with central FCD, taking into account the normal interindividual sulcal variability. Methods We retrospectively studied 29 right-handed patients with FCD in the central region (including 12 MR negative histologically-confirmed cases) and 29 right-handed controls. The analysis of sulcal abnormalities from T1-weighted MR imaging (MRI) was performed using a graph-based representation of the cortical folds and an automated sulci recognition system, providing a new quantitative criterion to describe sulcal patterns, termed sulcus energy. Results Group analysis showed that the central sulcus in the hemisphere ipsilateral to the FCD exhibited an abnormal sulcal pattern compared with controls (p = 0.032). FCDs were associated with abnormal patterns of the central sulci compared with controls (p = 0.006), a result that remained significant when MR-negative and MR-positive patients were considered separately, while the effects of sex, age and MR-field were not significant. At the individual level, sulcus energy alone failed to detect the FCD lesion. We found, however, a significant association between maximum z-scores and the site of FCD (p = 0.0046) which remained significant in MR-negative (p = 0.024) but not in MR-positive patients (p = 0.058). The maximum z-score pointed to an FCD sulcus in four MR-negative and five MR-positive patients. Conclusions We identified abnormal sulcal patterns in patients with FCD of the central region compared with healthy controls. The abnormal sulcal patterns ipsilateral to the FCD and the link between sulcus energy and the FCD location strengthen the interest of sulcal abnormalities in FCD patients.

ASPECTS (Alberta Stroke Program Early CT Score) Assessment of the Perfusion–Diffusion Mismatch

Background and Purpose— Rapid and reliable assessment of the perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch is required to promote its wider application in both acute stroke clinical routine and trials. We tested whether an evaluation based on the Alberta Stroke Program Early CT Score (ASPECTS) reliably identifies the PWI/DWI mismatch. Methods— A total of 232 consecutive patients with acute middle cerebral artery stroke who underwent pretreatment magnetic resonance imaging (PWI and DWI) were retrospectively evaluated. PWI-ASPECTS and DWI-ASPECTS were determined blind from manually segmented PWI and DWI volumes. Mismatch-ASPECTS was defined as the difference between PWI-ASPECTS and DWI-ASPECTS (a high score indicates a large mismatch). We determined the mismatch-ASPECTS cutoff that best identified the volumetric mismatch, defined as VolumeTmax>6s/VolumeDWI≥1.8, a volume difference≥15 mL, and a VolumeDWI<70 mL. Results— Inter-reader agreement was almost perfect for PWI-ASPECTS (&kgr;=0.95 [95% confidence interval, 0.90–1]), and DWI-ASPECTS (&kgr;=0.96 [95% confidence interval, 0.91–1]). There were strong negative correlations between volumetric and ASPECTS-based assessments of DWI lesions (&rgr;=−0.84, P<0.01) and PWI lesions (&rgr;=-0.90, P<0.01). Receiver operating characteristic curve analysis showed that a mismatch-ASPECTS ≥2 best identified a volumetric mismatch, with a sensitivity of 0.93 (95% confidence interval, 0.89–0.98) and a specificity of 0.82 (95% confidence interval, 0.74–0.89). Conclusions— The mismatch-ASPECTS method can detect a true mismatch in patients with acute middle cerebral artery stroke. It could be used for rapid screening of patients with eligible mismatch, in centers not equipped with ultrafast postprocessing software.

Identification of Reliable Sulcal Patterns of the Human Rolandic Region

A major feature of the human cortex is its huge morphological variability. Although a comprehensive literature about the sulco-gyral pattern of the central region is available from post-mortem data, a reliable and reproducible characterization from in vivo data is still lacking. The aim of this study is to test the reliability of morphological criteria of the central region sulci used in post-mortem data, when applied to in vivo magnetic resonance imaging (MRI) data. Thirty right-handed healthy individuals were included in the study. Automated segmentation and three dimensional (3D) surface-based rendering were obtained from clinical 3D T1-weighted MRI. Two senior radiologists labeled the three sulci composing the central region (precentral [PreCS], central [CS] and postcentral [PostCS]) and analyzed their morphological variations using 47 standard criteria derived from Ono’s atlas based on post-mortem data. For each criterion, inter-rater concordance and comparison with the occurrence frequency provided in Ono’s atlas were estimated. Overall, the sulcal pattern criteria derived from MRI data were highly reproducible between the raters with a high mean inter-rater concordance in the three sulci (CS: κ = 0.92 in left hemisphere/κ = 0.91 in right hemisphere; PreCS: κ = 0.91/κ = 0.93; PostCS: κ = 0.84/0.79). Only a very limited number of sulcal criteria significantly differed between the in vivo and the post-mortem data (CS: 2 criteria in the left hemisphere/3 criteria in the right hemisphere; PreCS: 3 in the left and right hemispheres; PostCS: 3 in the left hemisphere and 5 in the right hemisphere). Our study provides a comprehensive description of qualitative sulcal patterns in the central region from in vivo clinical MRI with high agreement with previous post-mortem data. Such identification of reliable sulcal patterns of the central region visible with standard clinical MRI data paves the way for the detection of subtle variations of the central sulcation associated with variations of normal or pathological functioning.

Do Fluid-Attenuated Inversion Recovery Vascular Hyperintensities Represent Good Collaterals before Reperfusion Therapy?

The authors evaluated 244 consecutive patients eligible for reperfusion therapy with MCA stroke and pretreatment MR imaging with both FLAIR and PWI. The FLAIR vascular hyperintensity score was based on ASPECTS, ranging from 0 (no FLAIR vascular hyperintensity) to 7 (FLAIR vascular hyperintensities abutting all ASPECTS cortical areas). The hypoperfusion intensity ratio was defined as the ratio of the time-to-maximum >10-second over time-to-maximum >6-second lesion volumes. The FLAIR vascular hyperintensities were more extensive in patients with good collaterals than those with poor collaterals. The FLAIR vascular hyperintensity score was independently associated with good collaterals. They conclude that the ASPECTS assessment of FLAIR vascular hyperintensities could be used to rapidly identify patients more likely to benefit from reperfusion therapy. BACKGROUND AND PURPOSE: In acute ischemic stroke, whether FLAIR vascular hyperintensities represent good or poor collaterals remains controversial. We hypothesized that extensive FLAIR vascular hyperintensities correspond to good collaterals, as indirectly assessed by the hypoperfusion intensity ratio. MATERIALS AND METHODS: We included 244 consecutive patients eligible for reperfusion therapy with MCA stroke and pretreatment MR imaging with both FLAIR and PWI. The FLAIR vascular hyperintensity score was based on ASPECTS, ranging from 0 (no FLAIR vascular hyperintensity) to 7 (FLAIR vascular hyperintensities abutting all ASPECTS cortical areas). The hypoperfusion intensity ratio was defined as the ratio of the time-to-maximum >10-second over time-to-maximum >6-second lesion volumes. The median hypoperfusion intensity ratio was used to dichotomize good (low hypoperfusion intensity ratio) versus poor (high hypoperfusion intensity ratio) collaterals. We then studied the association between FLAIR vascular hyperintensity extent and hypoperfusion intensity ratio. RESULTS: Hypoperfusion was present in all patients, with a median hypoperfusion intensity ratio of 0.35 (interquartile range, 0.19–0.48). The median FLAIR vascular hyperintensity score was 4 (interquartile range, 3–5). The FLAIR vascular hyperintensities were more extensive in patients with good collaterals (hypoperfusion intensity ratio ≤0.35) than with poor collaterals (hypoperfusion intensity ratio >0.35; P for Trend = .016). The FLAIR vascular hyperintensity score was independently associated with good collaterals (P for Trend = .002). CONCLUSIONS: In patients eligible for reperfusion therapy, FLAIR vascular hyperintensity extent was associated with good collaterals, as assessed by the pretreatment hypoperfusion intensity ratio. The ASPECTS assessment of FLAIR vascular hyperintensities could be used to rapidly identify patients more likely to benefit from reperfusion therapy.