Piero Chiacchiaretta

Resting state BOLD functional connectivity at 3T: spin echo versus gradient echo EPI.

Previous evidence showed that, due to refocusing of static dephasing effects around large vessels, spin-echo (SE) BOLD signals offer an increased linearity and promptness with respect to gradient-echo (GE) acquisition, even at low field. These characteristics suggest that, despite the reduced sensitivity, SE fMRI might also provide a potential benefit when investigating spontaneous fluctuations of brain activity. However, there are no reports on the application of spin-echo fMRI for connectivity studies at low field. In this study we compared resting state functional connectivity as measured with GE and SE EPI sequences at 3T. Main results showed that, within subject, the GE sensitivity is overall larger with respect to that of SE, but to a less extent than previously reported for activation studies. Noteworthy, the reduced sensitivity of SE was counterbalanced by a reduced inter-subject variability, resulting in comparable group statistical connectivity maps for the two sequences. Furthermore, the SE method performed better in the ventral portion of the default mode network, a region affected by signal dropout in standard GE acquisition. Future studies should clarify if these features of the SE BOLD signal can be beneficial to distinguish subtle variations of functional connectivity across different populations and/or treatments when vascular confounds or regions affected by signal dropout can be a critical issue.

Sensitivity of BOLD response to increasing visual contrast: spin echo versus gradient echo EPI.

Previous evidence showed that spin-echo (SE) BOLD signals offer an increased linearity and promptness with respect to gradient-echo (GE) acquisition, possibly providing a more accurate estimate of the amplitude of neuronal activity. However there is no evidence that the two sequences differ in representing different activation levels due to changes in stimulus intensity. In this study at 3T we compared GE and SE BOLD responses to visual stimuli at increasing contrast levels (5%, 20%, 60%, and 100%). Both sequences showed a monotonic increase of the BOLD response with stimulus contrast. While the larger sensitivity of GE yielded overall larger signal changes, step-wise increase in activation for GE was significant only when comparing 20% with 5% contrast, whereas for SE a significant increase was observed also when comparing 60% with 20% contrast. Moreover, BOLD responses normalized to the lowest contrast showed that relative increases of SE fMRI signal with increasing stimulus strength are larger with respect to the corresponding values of GE signal. This difference was observed also when excluding voxels attributed to large vessels, suggesting a non negligible role of the extravascular contribution to the modulation of SE fMRI signal with stimulus intensity. These results are shown to be in agreement with theoretical predictions that we derived from a recently proposed model of GE and SE functional signals. The present findings suggest that, despite the limited increase in functional localization accuracy at low field, SE fMRI might offer a potential advantage in distinguishing different levels of stimulus-evoked brain activity.

Functional and neurochemical interactions within the amygdala–medial prefrontal cortex circuit and their relevance to emotional processing

The amygdala–medial prefrontal cortex (mPFC) circuit plays a key role in emotional processing. GABA-ergic inhibition within the mPFC has been suggested to play a role in the shaping of amygdala activity. However, the functional and neurochemical interactions within the amygdala–mPFC circuits and their relevance to emotional processing remain unclear. To investigate this circuit, we obtained resting-state functional magnetic resonance imaging (rs-fMRI) and proton MR spectroscopy in 21 healthy subjects to assess the potential relationship between GABA levels within mPFC and the amygdala–mPFC functional connectivity. Trait anxiety was assessed using the State-Trait Anxiety Inventory (STAI-Y2). Partial correlations were used to measure the relationships among the functional connectivity outcomes, mPFC GABA levels and STAI-Y2 scores. Age, educational level and amount of the gray and white matters within 1H-MRS volume of interest were included as nuisance variables. The rs-fMRI signals of the amygdala and the vmPFC were significantly anti-correlated. This negative functional coupling between the two regions was inversely correlated with the GABA+/tCr level within the mPFC and the STAI-Y2 scores. We suggest a close relationship between mPFC GABA levels and functional interactions within the amygdala–vmPFC circuit, providing new insights in the physiology of emotion.

Temporal summation of the nociceptive withdrawal reflex involves deactivation of posterior cingulate cortex.

Temporal summation of pain sensation is pivotal both in physiological and pathological nociception. In humans, it develops in parallel with temporal summation of the nociceptive withdrawal reflex (NWR) of the lower limb, an objective representation of the temporal processing of nociceptive signals into the spinal cord.

Aortic valve bypass surgery in severe aortic valve stenosis: Insights from cardiac and brain magnetic resonance imaging

Objective To investigate and describe the distribution of aortic and cerebral blood flow (CBF) in patients with severe valvular aortic stenosis (AS) before and after aortic valve bypass (AVB) surgery. Methods We enrolled 10 consecutive patients who underwent AVB surgery for severe AS. Cardiovascular magnetic resonance imaging (CMR) and brain magnetic resonance imaging were performed as baseline before surgery and twice after surgery. Quantitative flow measurements were obtained using 1.5‐T magnetic resonance imaging (MRI) scanner phase‐contrast images of the ascending aorta, descending thoracic aorta (3 cm proximally and distally from the conduit‐to‐aorta anastomosis), and ventricular outflow portion of the conduit. The evaluation of CBF was performed using 3.0‐T MRI scanner arterial spin labeling (ASL) through sequences acquired at the gray matter, dorsal default‐mode network, and sensorimotor levels. Results Conduit flow, expressed as the percentage of total antegrade flow through the conduit, was 63.5 ± 8% and 67.8 ± 7% on early and mid‐term postoperative CMR, respectively (P < .05). Retrograde perfusion from the level of the conduit insertion in the descending thoracic aorta toward the aortic arch accounted for 6.9% of total cardiac output and 11% of total conduit flow. We did not observe any significant reduction in left ventricular stroke volume at postoperative evaluation compared with preoperative evaluation (P = .435). No differences were observed between preoperative and postoperative CBF at the gray matter, dorsal default‐mode network, and sensorimotor levels (P = .394). Conclusions After AVB surgery in patients with severe AS, cardiac output is split between the native left ventricular outflow tract and the apico‐aortic bypass, with two‐thirds of the total antegrade flow passing through the latter and one‐third passing through the former. In our experience, CBF assessment confirms that the flow redistribution does not jeopardize cerebral blood supply.

O042. Phase-dependent defective functional activity of the default mode network and facilitated temporal processing of nociceptive stimuli in cluster headache

Background In cluster headache (CH) during the active period we described a facilitated temporal summation (TS) of nociceptive signals at spinal level linked to a defective suprapinal control of pain and followed by a normalization of the values during the remission period [1]. TS of sensory neuronal responses to nociceptive stimuli is a form of central plasticity that shifts the sensory information from tactile to nociceptive before transmitting the nociceptive information to brain areas mediating pain sensation. This feature of the sensory system results pivotal in physiological nociception, for discrimination between innocuous and potentially dangerous stimulation, as well as in pathological nociception, for induction and maintenance of the central sensitization, subsequently resulting in pain chronification [2]. In this study we sought to determine which brain sites are involved in the modulation of temporal processing of pain sensation in CH subjects during both the active and remission period. We utilized functional magnetic resonance imaging (fMRI) to compare the Blood Oxygenation Level Dependent (BOLD) signal changes related to the temporal summation threshold (TST) of the nociceptive withdrawal reflex (NWR). We used the single NWR response as control stimulus.

Reduced Dynamic Coupling Between Spontaneous BOLD-CBF Fluctuations in Older Adults: A Dual-Echo pCASL Study

Measurement of the dynamic coupling between spontaneous Blood Oxygenation Level Dependent (BOLD) and cerebral blood flow (CBF) fluctuations has been recently proposed as a method to probe resting-state brain physiology. Here we investigated how the dynamic BOLD-CBF coupling during resting-state is affected by aging. Fifteen young subjects and 17 healthy elderlies were studied using a dual-echo pCASL sequence. We found that the dynamic BOLD-CBF coupling was markedly reduced in elderlies, in particular in the left supramarginal gyrus, an area known to be involved in verbal working memory and episodic memory. Moreover, correcting for temporal shift between BOLD and CBF timecourses resulted in an increased correlation of the two signals for both groups, but with a larger increase for elderlies. However, even after temporal shift correction, a significantly decreased correlation was still observed for elderlies in the left supramarginal gyrus, indicating that the age-related dynamic BOLD-CBF uncoupling in this region is more pronounced and can be only partially explained with a simple time-shift between the two signals. Interestingly, these results were observed in a group of elderlies with normal cognitive functions, suggesting that the study of dynamic BOLD-CBF coupling during resting-state is a promising technique, potentially able to provide early biomarkers of functional changes in the aging brain.

ASL 3.0 T Perfusion Studies

Perfusion refers to the delivery of oxygen, glucose and other nutrients to tissues by means of blood flow and its disruption is commonly reported in different pathologies. In particular, changes in brain perfusion is found in most brain diseases, ranging from stroke to neurodegenerative and neoplastic disorders. In this chapter the basic physics and physiological principles of Arterial Spin Labeling (ASL) brain perfusion measurement are discussed, together with research and clinical applications of this promising noninvasive technique.

3.0 T Diffusion Studies

Diffusion refers to the random translational motion of molecules, also called Brownian motion, resulting from the thermal energy carried by these molecules. In the human body, we mostly consider diffusion of water molecules. In this chapter, the basic principles that render the MRI signal sensitive to diffusion are discussed together with applications in clinical and research studies.

Effect of Continuous Touch on Brain Functional Connectivity Is Modified by the Operator’s Tactile Attention

Touch has been always regarded as a powerful communication channel playing a key role in governing our emotional wellbeing and possibly perception of self. Several studies demonstrated that the stimulation of C-tactile afferent fibers, essential neuroanatomical elements of affective touch, activates specific brain areas and the activation pattern is influenced by subject’s attention. However, no research has investigated how the cognitive status of who is administering the touch produces changes in brain functional connectivity of touched subjects. In this functional magnetic resonance imaging (fMRI) study, we investigated brain connectivity while subjects were receiving a static touch by an operator engaged in either a tactile attention or auditory attention task. This randomized-controlled single-blinded study enrolled 40 healthy right-handed adults and randomly assigned to either the operator tactile attention (OTA) or the operator auditory attention (OAA) group. During the five fMRI resting-state runs, the touch was delivered while the operator focused his attention either: (i) on the tactile perception from his hands (OTA group); or (ii) on a repeated auditory stimulus (OAA group). Functional connectivity analysis revealed that prolonged sustained static touch applied by an operator engaged with focused tactile attention produced a significant increase of anticorrelation between posterior cingulate cortex (PCC-seed) and right insula (INS) as well as right inferior-frontal gyrus but these functional connectivity changes are markedly different only after 15 min of touching across the OTA and OAA conditions. Interestingly, data also showed anticorrelation between PCC and left INS with a distinct pattern over time. Indeed, the PCC-left INS anticorrelation is showed to start and end earlier compared to that of PCC-right INS. Taken together, the results of this study showed that if a particular cognitive status of the operator is sustained over time, it is able to elicit significant effects on the subjects’ functional connectivity patterns involving cortical areas processing the interoceptive and attentional value of touch.