Marta Maieron

Does Anticipation of Pain Affect Cortical Nociceptive Systems

Anticipation of pain is a complex state that may influence the perception of subsequent noxious stimuli. We used functional magnetic resonance imaging (fMRI) to study changes of activity of cortical nociceptive networks in healthy volunteers while they expected the somatosensory stimulation of one foot, which might be painful (subcutaneous injection of ascorbic acid) or not. Subjects had no previous experience of the noxious stimulus. Mean fMRI signal intensity increased over baseline values during anticipation and during actual stimulation in the putative foot representation area of the contralateral primary somatosensory cortex (SI). Mean fMRI signals decreased during anticipation in other portions of the contralateral and ipsilateral SI, as well as in the anteroventral cingulate cortex. The activity of cortical clusters whose signal time courses showed positive or negative correlations with the individual psychophysical pain intensity curve was also significantly affected during the waiting period. Positively correlated clusters were found in the contralateral SI and bilaterally in the anterior cingulate, anterior insula, and medial prefrontal cortex. Negatively correlated clusters were found in the anteroventral cingulate bilaterally. In all of these areas, changes during anticipation were of the same sign as those observed during pain but less intense (∼30–40% as large as peak changes during actual noxious stimulation). These results provide evidence for top-down mechanisms, triggered by anticipation, modulating cortical systems involved in sensory and affective components of pain even in the absence of actual noxious input and suggest that the activity of cortical nociceptive networks may be directly influenced by cognitive factors.

Functional Responses in the Human Spinal Cord during Willed Motor Actions: Evidence for Side- and Rate-Dependent Activity

Although the spinal cord is the output station of the central motor system, little is known about the relationships between its functional activity and willed movement parameters in humans. We investigated here blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) signal changes in the cervical spinal cord during a simple finger-to-thumb opposition task in 13 right-handed volunteers, using a dedicated array of 16 receive-only surface coils on a 3 Tesla MRI system. In a first experiment, we found significant fMRI signal increases on both sides of the lower cervical spinal cord while subjects performed the motor task at a comfortable pace (∼0.5 Hz) using either hand. Both the spatial extent of movement-related clusters and peak signal increases were significantly higher on the side of the cord ipsilateral to the moving hand than on the contralateral side. Movement-related activity was consistently larger than signal fluctuations during rest. In a second experiment, we recorded spinal cord responses while the same motor sequence was performed using the dominant hand at two different rates (∼0.5 or 1 Hz). The intensity but not the spatial extent of the response was larger during higher rates, and it was higher on the ipsilateral side of the cord. Notwithstanding the limited spatial resolving power of the adopted technique, the present results clearly indicate that the finger movement-related fMRI signals recorded from the spinal cord have a neural origin and that as a result of recent technological advances, fMRI can be used to obtain novel and quantitative physiological information on the activity of spinal circuits.

An ARX model-based approach to trial by trial identification of fMRI-BOLD responses.

Being able to estimate the fMRI-BOLD response following a single task or stimulus is certainly of value, since it allows to characterize its relationship to different aspects either of the stimulus, or of the subjects performance. In order to detect and characterize BOLD responses in single trials, we developed and validated a procedure based on an AutoRegressive model with eXogenous Input (ARX). The use of an individual exogenous input for each voxel makes the modeling sensitive enough to reveal differences across regions, avoiding any a priori assumption about the reference signal. The detection of variability across trials is ensured by a suitable choice, for each voxel, of the order of the moving average, which in our implementation determines the relative delay between the recorded and the reference signal. This is a quality useful in finding different time profiles of activation from high temporal resolution fMRI data. The results obtained from simulated fMRI data resulting from synthetic activations in actual noise indicate that such approach allows to evaluate important features of the response, such as the time to onset, and time to peak. Moreover, the results obtained from real high temporal resolution fMRI data acquired at l.5 T during a motor task are consistent with previous knowledge about the responses of different cortical areas in motor programming and execution. The proposed procedure should also prove useful as a pre-processing step in different approaches to the analysis of fMRI data.

Foreign accent syndrome: a multimodal mapping study.

The present study explored the functional neuroanatomy of Foreign Accent Syndrome (FAS) in an Italian native speaker who developed an altered speech rhythm and melody following a circumscribed tumour to the left precentral gyrus. Structural, functional, fibre tracking and intraoperative findings were combined. No signs of dysarthria, apraxia of speech, or aphasia nor other cognitive deficits were detected, except for the fact that the patient was perceived as a non-native speaker. The patient fMRI maps were compared with a control group of 12 healthy controls. During counting, sentences and pseudoword pronunciation the patient showed an additional increased sparse activation in areas around the pre/postcentral gyrus corresponding to those involved in phonation (i.e., larynx motor area). The intraoperative cortical stimulation mapping evidenced a mouth motor representation close to the tumour, a motor type of speech arrest site just below it, and anteriorly a proper speech arrest site. Our results are discussed within the current neurolinguistic models of speech production, and emphasize the importance of the primary motor cortex. We argue that this FAS case should be thought of as a disorder of the feedforward control commands, in particular of the articulator velocity and position maps which are hypothesized to lie along the caudoventral portion of the precentral gyrus.

Modulation of hand motor-related area during motor imagery and motor execution before and after middle 2/5 of the MS6 line scalp acupuncture stimulation: An fMRI study.

Scalp acupuncture (SA) combines the concept of cerebral cortex organization with the principles of acupuncture. The SA stimulates sections of the cerebral cortex. We studied the functional modulation of the left hand sensorimotor area induced by SA in order to investigate the specificity of the SA-related functional effects of the middle 2/5 of the MS6 line of the left side, which corresponds to the upper limb motor segment of the primary motor area. To this purpose, we compared the pre- and post-SA functional activation patterns during an implicit motor imagery task (handedness decision in which participants simulated rotational hand movements) and an explicit manual motor execution task. Feet and mouth movements, and the fMRI changes in their respective representations were used as control conditions. Only SA on the hand area of the left side (as compared to the mouth and the foot representations which were used as control conditions) exerted a release effect on the right hand area. In addition, an increased activation of the superior parietal lobe was seen, which is involved in movement control and planning. Taken together, these preliminary findings may shed light on the SA effects and confirm a prolonged effect of SA even after cessation of needling stimulation.

A multimodal mapping study of conduction aphasia with impaired repetition and spared reading aloud

The present study explores the functional neuroanatomy of the phonological production system in an Italian aphasic patient (SP) who developed conduction aphasia of the reproduction type following brain surgery. SP presented with two peculiar features: (1) his lesion was localized in the superior temporal gyrus, just posterior to the primary auditory cortex and anterior/inferior to and neighboring the Sylvian parietal temporal (Spt) area, and (2) he presented with severely impaired repetition and spelling from dictation of words and pseudowords but spared reading-aloud of words and pseudowords. Structural, functional, fiber tracking and intraoperative findings were combined to analyze SPs pattern of performance within a widely used sensorimotor control scheme of speech production. We found a dissociation between an interrupted sector of the arcuate fasciculus terminating in STG, known to be involved in phonological processing, and a part of the arcuate fasciculus terminating in MTG, which is held to be involved in lexical-semantic processing. We argue that this phonological deficit should be interpreted as a disorder of the feedback system, in particular of the auditory and somatosensory target maps, which are assumed to be located along the Spt area. In patient SP, the spared part of the left arcuate fasciculus originating in MTG may support an unimpaired reading performance, while the damaged part of the left arcuate fasciculus originating in STG may be responsible for his impaired repetition and spelling from dictation.

The role of perfusion and diffusion MRI in the assessment of patients affected by probable idiopathic normal pressure hydrocephalus. A cohort-prospective preliminary study

BackgroundInvasive tests measuring resistance to cerebral spinal fluid (CSF) outflow and the effect of temporary drainage of CSF are used to select candidates affected by idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. Neither test, however, completely excludes patients from treatment. Perfusion and diffusion magnetic resonance imaging (MRI) are non-invasive techniques that might be of value in selecting patients for surgical treatment and understanding brain changes in iNPH patients. The aim of this study was to understand the role of perfusion and diffusion MRI in selecting candidates for shunt surgery and to investigate the relationship between cerebral perfusion and possible microstructural changes in brain tissue before and after invasive tests, and after ventricular-peritoneal (VP) shunt implantation, to better clarify pathophysiological mechanisms underlying iNPH.MethodsTwenty-three consecutive patients with probable iNPH were included in this study. Patients underwent a clinical and neuroradiological evaluation before and after invasive tests, and after surgery. Only patients who showed a positive result in at least one of the invasive tests were submitted for VP shunt implantation. Perfusion and diffusion magnetic resonance imaging (MRI) was performed before and after invasive tests and after shunt surgery.ResultsThirteen patients underwent surgery and all showed clinical improvement after VP shunt implantation and a significant increase in perfusion in both periventricular white matter (PVWM) and basal ganglia (BG) regions. The 10 patients that did not have surgery showed after invasive tests, a significant reduction in perfusion in both PVWM and BG regions. Comparing the changes in perfusion with those of diffusion in positive patients we found a significant positive correlation in BG and a significant inverse correlation in PVWM area.ConclusionsPerfusion MRI is a non-invasive technique that could be useful together with invasive tests in selecting patients for surgical treatment. Furthermore, the relationship between perfusion and diffusion data could better clarify pathophysiological mechanisms underlying iNPH. In PVWM area we suggest that interstitial edema could reduce microvascular blood flow and interfere with the blood supply to these regions. In BG regions we suggest that a chronic hypoxic insult caused by blood hypo-perfusion produces a chronic cytotoxic edema. Both in PVWM and in BG regions, pathophysiological mechanisms could be modified after VP-shunt implantation.

Improving the reliability of single-subject fMRI by weighting intra-run variability

At present, functional magnetic resonance imaging (fMRI) is one of the most useful methods of studying cognitive processes in the human brain in vivo, both for basic science and clinical goals. Although neuroscience studies often rely on group analysis, clinical applications must investigate single subjects (patients) only. Particularly for the latter, issues regarding the reliability of fMRI readings remain to be resolved. To determine the ability of intra-run variability (IRV) weighting to consistently detect active voxels, we first acquired fMRI data from a sample of healthy subjects, each of whom performed 4 runs (4 blocks each) of self-paced finger-tapping. Each subjects data was analyzed using single-run general linear model (GLM), and each block was then analyzed separately to calculate the IRV weighting. Results show that integrating IRV information into standard single-subject GLM activation maps significantly improved the reliability (p=0.007) of the single-subject fMRI data. This suggests that taking IRV into account can help identify the most constant and relevant neuronal activity at the single-subject level.

Involuntary switching into the native language induced by electrocortical stimulation of the superior temporal gyrus: A multimodal mapping study

We describe involuntary language switching from L2 to L1 evoked by electro-stimulation in the superior temporal gyrus in a 30-year-old right-handed Serbian (L1) speaker who was also a late Italian learner (L2). The patient underwent awake brain surgery. Stimulation of other portions of the exposed cortex did not cause language switching as did not stimulation of the left inferior frontal gyrus, where we evoked a speech arrest. Stimulation effects on language switching were selective, namely, interfered with counting behaviour but not with object naming. The coordinates of the positive site were combined with functional and fibre tracking (DTI) data. Results showed that the language switching site belonged to a significant fMRI cluster in the left superior temporal gyrus/supramarginal gyrus found activated for both L1 and L2, and for both the patient and controls, and did not overlap with the inferior fronto-occipital fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the superior longitudinal fasciculus (SLF). This area, also known as Stp, has a role in phonological processing. Language switching phenomenon we observed can be partly explained by transient dysfunction of the feed-forward control mechanism hypothesized by the DIVA (Directions Into Velocities of Articulators) model (Golfinopoulos, E., Tourville, J. A., & Guenther, F. H. (2010). The integration of large-scale neural network modeling and functional brain imaging in speech motor control.

Attempts at memory control induce dysfunctional brain activation profiles in Generalized Anxiety Disorder: An exploratory fMRI study

Suppression of aversive memories through memory control has historically been proposed as a central psychological defense mechanism. Inability to suppress memories is considered a central psychological trait in several psychiatric disorders, including Generalized Anxiety Disorder (GAD). Yet, few studies have attempted the focused identification of dysfunctional brain activation profiles when patients with Generalized Anxiety Disorders attempt memory control. Using a well-characterized behavioral paradigm we studied brain activation profiles in a group of adult GAD patients and well-matched healthy controls (HC). Participants learned word-association pairs before imaging. During fMRI when presented with one word of the pair, they were instructed to either suppress memory of, or retrieve the paired word. Subsequent behavioral testing indicated both GAD and HC were able to engage in the task, but attempts at memory control (suppression or retrieval) during fMRI revealed vastly different activation profiles. GAD were characterized by substantive hypo-activation signatures during both types of memory control, with effects particularly strong during suppression in brain regions including the dorsal anterior cingulate and the ventral prefrontal cortex. Attempts at memory control in GAD fail to engage brain regions to the same extent HC, providing a putative neuronal signature for a well-established psychological characteristic of the illness.