Valeria Blasi

Motor and language DTI Fiber Tracking combined with intraoperative subcortical mapping for surgical removal of gliomas

Preoperative DTI Fiber Tracking (DTI-FT) reconstruction of functional tracts combined with intraoperative subcortical mapping (ISM) is potentially useful to improve surgical procedures in gliomas located in eloquent areas. Aims of the study are: (1) to evaluate the modifications of fiber trajectory induced by the tumor; (2) to validate preoperative DTI-FT results with intraoperative identification of functional subcortical sites through direct subcortical stimulation; (3) to evaluate the impact of preoperative DTI-FT reconstructions in a neuronavigational setup combined with ISM technique on duration and modalities of surgical procedures, and on functional outcome of the patients. Data are available on 64 patients (52 low-grade and 12 high-grade gliomas). DTI-FT was acquired by a 3-T MR scanner with a single-shot EPI sequence (TR/TE 8986/80 ms, b=1000 s/mm) with gradients applied along 32 non-collinear directions. 3D Fast Field Echo (FFE) T1-weighted imaging (TR/TE 8/4 ms) was performed for anatomic guidance. The corticospinal tract (CST), superior longitudinal, inferior fronto-occipital and uncinatus fasciculi were reconstructed. Data were transferred to the neuronavigational system. Functional subcortical sites identified during ISM were correlated with fiber tracts depicted by DTI-FT. In high-grade gliomas, DTI-FT depicted tracts mostly at the tumor periphery; in low-grade gliomas, fibers were frequently located inside the tumor mass. There was a high correlation between DTI-FT and ISM (sensitivity for CST=95%, language tracts=97%). For a proper reconstruction of the tracts, it was necessary to use a low FA threshold of fiber tracking algorithm and to position additional regions of interest (ROIs). The combination of DTI-FT and ISM decreased the duration of surgery, patient fatigue, and intraoperative seizures. Combination of DTI-FT and ISM allows accurate identification of eloquent fiber tracts and enhances surgical performance and safety maintaining a high rate of functional preservation.

Presurgical Functional MR Imaging of Language and Motor Functions: Validation with Intraoperative Electrocortical Mapping

PURPOSEnTo prospectively determine the sensitivity and specificity of functional magnetic resonance (MR) imaging for mapping language and motor functions in patients with a focal mass adjacent to eloquent cortex, by using intraoperative electrocortical mapping (ECM) as the reference standard.nnnMATERIALS AND METHODSnThe ethics committee approved the study, and patients gave written informed consent. Thirty-four consecutive patients (16 women, 18 men; mean age, 43.2 years) were included who met the following three criteria: They had a focal mass in or adjacent to eloquent cortex of the language or motor system, they had the ability to perform the functional MR imaging task, and they had to undergo surgery with intraoperative ECM. Functional MR imaging with verb generation (n = 17) or finger tapping of the contralateral hand (n = 17) was performed at 1.5 T with a block design and an echo-planar gradient-echo T2*-weighted sequence. Cortex essential for language or hand motor functions was mapped with ECM. A site-by-site comparison between functional MR imaging and ECM was performed with the aid of a neuronavigational device. Sensitivity and specificity were calculated according to task performed, histopathologic findings, and tumor grade. Exact 95% confidence intervals were calculated for each sensitivity and specificity value.nnnRESULTSnFor 34 consecutive patients, there were 28 with gliomas, two with metastases, one with meningioma, and three with cavernous angiomas. A total of 251 cortical sites were tested with ECM; overall functional MR imaging sensitivity and specificity were 83% and 82%, respectively. Sensitivity (65%) was lower and specificity (93%) was higher in World Health Organization grade IV gliomas compared with grade II (sensitivity, 93%; specificity, 79%) and III (sensitivity, 93%; specificity, 76%) gliomas. At 3 months after surgery, language proficiency was unchanged in 15 patients; functionality of the contralateral arm was unchanged in 14 patients and improved in one patient.nnnCONCLUSIONnFunctional MR imaging is a sensitive and specific method for mapping language and motor functions.

Effects of aging on mindreading ability through the eyes: An fMRI study

Theory of Mind--ToM, the capacity to understand ones own and other peoples mental states and to refer to them to foresee and explain the behaviour--relies upon a circumscribed neural system: the posterior end of the superior temporal sulcus (pSTS), the adjacent temporo-parietal junction (TPJ), the temporal pole (TP), the medial prefrontal cortex (mPFC) and the adjacent paracingulate cortex. To our knowledge, the neural basis of mentalizing has not yet been studied in a developmental perspective covering old age, so the aim of this work is to compare the neural basis of a specific aspect of ToM, the mindreading ability through the eyes, in healthy young and old subjects. Two groups of healthy adults (young: 25.2 years; old: 65.2 years) were submitted to an fMRI scanning while performing the Reading the Mind in the Eyes test, which requires the attribution of a mental state to the other person focussing only on the eye-gaze. There was no difference in the behavioural performances between young and old and both groups of subjects activated the pSTS and the TP, thus indicating that old people show no impairment of mentalizing circuits. However, a relevant shifting of the neural circuit implied in each group to solve the task emerged. Old subjects showed a more bilateral activation of frontal areas and a stronger involvement of the linguistic components of the mirror neuron system (i.e. area 44), as compared to young. Both young and old participants activated the non-linguistic components of the mirror neuron system, such as area 6. These findings are discussed taking into account the recent literature dealing with cognitive functions during normal aging.

Functional brain changes in early Parkinson's disease during motor response and motor inhibition

Motor impairment represents the main clinical feature of Parkinsons disease (PD). Cognitive deficits are also frequently observed in patients with PD, with a prominent involvement of executive functions and visuo-spatial abilities. We used event-related functional MRI (fMRI) and a paradigm based on visual attention and motor inhibition (Go/NoGO-task) to investigate brain activations in 13 patients with early PD in comparison with 11 healthy controls. The two groups did not report behavioural differences in task performance. During motor inhibition (NoGO-effect), PD patients compared to controls showed an increased activation in the prefrontal cortex and in the basal ganglia. They also showed a reduced and less coherent hemodynamic response in the occipital cortex. These results indicate that specific cortico-subcortical functional changes, involving not only the fronto-striatal network but also the temporal-occipital cortex, are already present in patients with early PD and no clinical evidence of cognitive impairment. We discuss our findings in terms of compensatory mechanisms (fronto-striatal changes) and preclinical signs of visuo-perceptual deficits and visual hallucinations.

Visual evoked potentials may be recorded simultaneously with fMRI scanning: A validation study

Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data may help to optimize anatomical and temporal resolution in the investigation of cortical function. Successful removal of fMRI scanning artifacts from continuous EEG in simultaneous recordings has been reported. We assessed the feasibility of recording reliable visual evoked potentials (VEPs) during fMRI scanning using available artifact removing procedures. EEG during administration of visual stimuli was recorded using MRI‐compatible 32‐channel equipment in nine normal subjects (mean age, 23.9 ± 2.5 years), with and without fMRI acquisition. fMRI scanning and cardioballistographic artifacts were removed after subtraction of averaged artifact waveforms. Consistency between VEPs waveforms and of P1 and N1 peak latencies and amplitudes in the two conditions was assessed. Good correlation was found between VEP waveforms (Pearsons correlation coefficient: rP between 0.76–0.94 across subjects; P < 0.0001) and between latency or amplitude of P1 and N1 peaks (latencies: r = 0.7, P < 0.035; amplitudes: r > 0.65, P < 0.05; Spearman rank correlation coefficient) in the two recording conditions. No significant differences were found between P1 and N1 parameters in the two conditions (Wilcoxon signed rank test). Consistent VEP waveforms, latencies, and amplitudes with and without fMRI scanning indicate that reliable VEPs may be obtained simultaneously with fMRI recording. This possibility might be helpful by shortening recording times and reducing variability from learning, habituation, and fatigue phenomena from separate recordings for the integration of event‐related EEG and fMRI data. Hum. Brain Mapping 24:291–298, 2005.

Theory of mind in amnestic mild cognitive impairment: an FMRI study.

Theory of Mind (ToM) undergoes changes at the behavioral level in pathological aging (Alzheimers disease (AD)) and at the neural level in physiological aging. The aim was to determine if there are changes in ToM in the behavioral and neural domains in old subjects with high risk of switching from successful to unsuccessful neurocognitive aging. Patients with amnestic mild cognitive impairment (aMCI) syndrome were studied, since aMCI was proposed to fill the gap between normal aging and dementia. Sixteen aMCI patients (mean age 71 years) and fifteen healthy controls (mean age 67 years) with no differences in age or education were subjected to increasingly complex ToM tasks and to fMRI scanning while performing the Reading the Mind in the Eyes test (RME), which attributes mental states by focusing on eye-gaze. aMCI subjects had worse performances in two second order false belief tasks, confirming the decay of ToM on the behavioral level. Despite a minor activation of some components (posterior end of the superior temporal sulcus and temporal pole) of the ToM neural circuit, no significant differences in the behavioral performances to the RME was found in aMCI compared to controls. Probably the preservation of the mirror neuron system (precentral gyrus-BA 6; Broca area - BA 44) and the stronger involvement of frontal areas (middle and medial frontal cortex and anterior cingulate cortex) supplemented the decay of part of the mentalizing neural circuit, preserving task performance.

The shape of motor resonance: Right- or left-handed?

The human mirror neuron system is a fronto-parietal neural pathway which, when activated by action observation, gives rise to an internal simulation of the observed action (motor resonance). Here we demonstrate how handedness shapes the resonant response, by engaging right-handed (RH) and left-handed (LH) subjects in observation and execution of actions preferentially performed by the dominant hand. We hypothesize that since motor resonance reproduces subliminally the specific motor program for the observed action, it should be subject to motor constraints, such as handedness. A conjunction analysis for observed and executed actions revealed that handedness determines a lateralized activation of the areas engaged in motor resonance. Premotor-BA6 and parietal-BA40 are strongly left lateralized in RH subjects observing or moving their right hand, and to a lesser degree their left hand. Extremely LH subjects show a similar pattern of lateralization on the right, while more ambidextrous LH subjects show a more bilateral activation. The activation of a cortical network outside the mirror neuron system is also discussed.

Cerebellar activity switches hemispheres with cerebral recovery in aphasia

The right postero-lateral cerebellum participates with the left frontal lobe in the selection and production of words. Using fMRI, we examined whether cerebellar activity switches hemispheres in parallel with recruitment of putative compensatory right homologous frontal regions in post-stroke aphasia. Re-examining the data of Blasi et al. [Blasi, V., Young, A. C., Tansy, A. P., Petersen, S. E., Snyder, A. Z., & Corbetta, M. (2002). Word retrieval learning modulates right frontal cortex in patients with left frontal damage. Neuron, 36(1), 159-170], we asked: (1) if activity in the right cerebellum was disrupted by a left frontal lesion, (2) if activity switched to the left cerebellum, and (3) if activity in the left cerebellum was modulated by learning, as was right frontal cortex. Fourteen age-matched controls and eight mildly aphasic stroke patients participated. Aphasic participants all had lesions due to unilateral left hemisphere stroke at or near Brocas area. Subjects silently performed a word stem completion task with either novel or repeated items. Activity in right cerebellum of aphasic individuals was minimal and was not modulated by learning, as for controls. However, we observed robust learning-related attenuation of the BOLD signal in the left postero-lateral cerebellum consistent with learning-related effects in right frontal cortex. These findings support the hypothesis that right frontal and left cerebellar circuits are likely to be functionally relevant to recovered/residual verbal function.

Functional magnetic resonance imaging (fMRI) in children sedated with propofol or midazolam.

Magnetic resonance imaging (MRI) requires patient immobility and children generally need to be sedated. The ideal sedative agent for functional MRI (fMRI) should only minimally hamper the neurophysiologic effect of the administered sensorial stimulation. This study compares the effect of propofol and midazolam on the fMRI auditory activation pattern in children. Fourteen children in the 3 to 7 year age group without neurologic or auditory deficits were randomly assigned to receive propofol or midazolam for sedation during auditory fMRI. Two patients in the midazolam group were excluded due to positive baseline MRIs. The children were stimulated using a passive listening task. The fMRI signal was modeled using various functions (hemodynamic response function, temporal derivative, and dispersion derivative) to check for the differing temporal characteristics of the signal between the groups. Patients in the propofol group showed activation only in the primary auditory cortex and exhibited a pattern more similar to that of nonsedated adults. Patients in the midazolam group exhibited a more complex pattern, presenting activation areas other than the primary auditory cortex; a delay in the functional response and higher duration variability were also observed. Our sample sizes are too small to derive a conclusive inference. Our preliminary study encourages the hypothesis that propofol is preferable to midazolam to maintain sedation in 3 to 7-year-old children during auditory fMRI because it facilitates the elicitation of a more focused auditory cortical activation pattern with less temporal and spatial dispersion.

Maturation of preterm newborn brains: a fMRI-DTI study of auditory processing of linguistic stimuli and white matter development.

To evaluate brain development longitudinally in premature infants without abnormalities as compared to healthy full-term newborns, we assessed fMRI brain activity patterns in response to linguistic stimuli and white matter structural development focusing on language-related fibres. A total sample of 29 preterm newborns and 26 at term control newborns underwent both fMRI and DTI. Griffiths test was performed at 6xa0months of corrected age to assess development. Auditory fMRI data were analysed in 17 preterm newborns at three time points [34, 41 and 44xa0weeks of post menstrual age (wPMA)] and in 15 controls, at term. Analysis showed a distinctive pattern of cortical activation in preterm newborns up to 29 wPMA moving from early prevalent left temporal and supramarginal area activation in the preterm period, to a bilateral temporal and frontoopercular activation in the at term equivalent period and to a more fine-grained left pattern of activity at 44 wPMA. At term controls showed instead greater bilateral posterior thalamic activation. The different pattern of brain activity associated to preterm newborns mirrors their white matter maturation delay in peripheral regions of the fibres and thalamo-cortical radiations in subcortical areas of both hemispheres, pointing to different transient thalamo-cortical development due to prematurity. Evidence for functional thalamic activation and more mature subcortical tracts, including thalamic radiations, may represent the substantial gap between preterm and at term infants. The transition between bilateral temporal activations at term age and leftward activations at 44xa0weeks of PMA is correlated to better neuropsychological results in Griffiths test.