Delia Lenzi

Neural Basis of Maternal Communication and Emotional Expression Processing during Infant Preverbal Stage

During the first year of life, exchanges and communication between a mother and her infant are exclusively preverbal and are based on the mothers ability to understand her infants needs and feelings (i.e., empathy) and on imitation of the infants facial expressions; this promotes a social dialog that influences the development of the infant self. Sixteen mothers underwent functional magnetic resonance imaging while observing and imitating faces of their own child and those of someone elses child. We found that the mirror neuron system, the insula and amygdala were more active during emotional expressions, that this circuit is engaged to a greater extent when interacting with ones own child, and that it is correlated with maternal reflective function (a measure of empathy). We also found, by comparing single emotions with each other, that joy expressions evoked a response mainly in right limbic and paralimbic areas; by contrast, ambiguous expressions elicited a response in left high order cognitive and motor areas, which might reflect cognitive effort.

Grey and White Matter Changes at Different Stages of Alzheimer's Disease

This study investigates abnormalities of grey (GM) and white matter (WM) in Alzheimers disease (AD), by modeling the AD pathological process as a continuous course between normal aging and fully developed dementia, with amnesic mild cognitive impairment (aMCI) as an intermediate stage. All subjects (9 AD, 16 aMCI patients, and 13 healthy controls) underwent a full neuropsychological assessment and an MRI examination at 3 Tesla, including a volumetric scan and diffusion tensor (DT)-MRI. The volumes were processed to perform a voxel-based morphometric analysis of GM and WM volume, while DT-MRI data were analyzed using tract based spatial statistics, to estimate changes in fractional anisotropy and mean diffusivity data. GM and WM volume and mean diffusivity and fractional anisotropy were compared across the three groups, and their correlation with cognitive functions was investigated. While AD presented a pattern of widespread GM atrophy, tissue loss was more subtle in patients with aMCI. WM atrophy was mainly located in the temporal lobe, but evidence of WM microscopic damage, assessed by DT-MRI, was also observable in the thalamic radiations and in the corpus callosum. Memory and executive functions correlated with either GM volume or fractional anisotropy in fronto-temporal areas. In conclusion, this study shows a comprehensive assessment of the brain tissue damage across AD evolution, providing insights on different pathophysiological mechanisms (GM atrophy, Wallerian degeneration, and brain disconnection) and their possible association with clinical aspects of cognitive decline.

Effect of corpus callosum damage on ipsilateral motor activation in patients with multiple sclerosis: A functional and anatomical study

Functional MRI (fMRI) studies have shown increased activation of ipsilateral motor areas during hand movement in patients with multiple sclerosis (MS). We hypothesized that these changes could be due to disruption of transcallosal inhibitory pathways. We studied 18 patients with relapsing‐remitting MS. Conventional T1‐ and T2‐weighted images were acquired and lesion load (LL) measured. Diffusion tensor imaging (DTI) was performed to estimate fractional anisotropy (FA) and mean diffusivity (MD) in the body of the corpus callosum (CC). fMRI was obtained during a right‐hand motor task. Patients were studied to evaluate transcallosal inhibition (TCI, latency and duration) and central conduction time (CCT). Eighteen normal subjects were studied with the same techniques. Patients showed increased MD (P < 0.0005) and reduced FA (P < 0.0005) in the body of the CC. Mean latency and duration of TCI were altered in 12 patients and absent in the others. Between‐group analysis showed greater activation in patients in bilateral premotor, primary motor (M1), and middle cingulate cortices and in the ipsilateral supplementary motor area, insula, and thalamus. A multivariate analysis between activation patterns, structural MRI, and neurophysiological findings demonstrated positive correlations between T1‐LL, MD in the body of CC, and activation of the ipsilateral motor cortex (iM1) in patients. Duration of TCI was negatively correlated with activation in the iM1. Our data suggest that functional changes in iM1 in patients with MS during a motor task partially represents a consequence of loss of transcallosal inhibitory fibers. Hum Brain Mapp, 2006.

Enhanced brain motor activity in patients with MS after a single dose of 3,4-diaminopyridine

Background: 3,4-Diaminopyridine (3,4-DAP), a potassium (K+) channel blocker, improves fatigue and motor function in multiple sclerosis (MS). Although it was thought to do so by restoring conduction to demyelinated axons, recent experimental data show that aminopyridines administered at clinical doses potentiate synaptic transmission. Objective: To investigate motor cerebral activity with fMRI and transcranial magnetic stimulation (TMS) after a single oral dose of 3,4-DAP in patients with MS. Methods: Twelve right-handed women (mean ± SD age 40.9 ± 9.3 years) underwent fMRI on two separate occasions (under 3,4-DAP and under placebo) during a simple motor task with the right hand. FMRI data were analyzed with SPM99. After fMRI, patients underwent single-pulse TMS to test motor threshold, amplitude, and latency of motor evoked potentials, central conduction time, and the cortical silent period; paired-pulse TMS to investigate intracortical inhibition (ICI) and intracortical facilitation (ICF); and quantitative electromyography during maximal voluntary contraction. Results: FMRI motor-evoked brain activation was greater under 3,4-DAP than under placebo in the ipsilateral sensorimotor cortex and supplementary motor area (p < 0.05). 3,4-DAP decreased ICI and increased ICF; central motor conduction time and muscular fatigability did not change. Conclusion: 3,4-DAP may modulate brain motor activity in patients with MS, probably by enhancing excitatory synaptic transmission.

Attachment models affect brain responses in areas related to emotions and empathy in nulliparous women

Background: The attachment model, as assessed by means of the Adult Attachment Interview (AAI), is crucial for understanding emotion regulation and feelings of security in human interactions as well as for the construction of the caregiving system. The caregiving system is a set of representations about affiliative behaviors, guided by sensitivity and empathy, and is fully mature in young‐adulthood. Here, we examine how different attachment models influence brain responses in areas related to empathy and emotions in young‐adult subjects with secure and dismissing attachment models. Methods: By means of AAI, we selected 11 nulliparous young‐adult females with a secure model and 12 with a dismissing model. Subjects underwent functional magnetic resonance, whereas imitating or observing and empathizing with infant facial expressions. Subjects were tested for alexithymia and reflective functioning. Results: Dismissing subjects activated motor, mirror, and limbic brain areas to a significantly greater extent, but deactivated the medial orbitofrontal cortex (mOFC) and the perigenual anterior cingulated cortex (pACC). During emotional faces, increased activity in dismissing women was seen in the right temporal pole. Furthermore, greater alexithymia was correlated with greater activity in the entorhinal cortex and greater deactivation in the pACC/mOFC. Conclusions: These findings provide evidence of how the attachment model influences brain responses during a task eliciting attachment. In particular, hyperactivation of limbic and mirror areas may reflect emotional dysregulation of infantile experiences of rejection and lack of protection, whereas increased deactivation of fronto‐medial areas may be the expression of the inhibition of attachment behaviors, which is a typical aspect of dismissing attachment. Hum Brain Mapp, 2013.

Neural basis of attachment-caregiving systems interaction: insights from neuroimaging studies

The attachment and the caregiving system are complementary systems which are active simultaneously in infant and mother interactions. This ensures the infant survival and optimal social, emotional, and cognitive development. In this brief review we first define the characteristics of these two behavioral systems and the theory that links them, according to what Bowlby called the “attachment-caregiving social bond” (Bowlby, 1969). We then follow with those neuroimaging studies that have focused on this particular issue, i.e., those which have studied the activation of the careging system in women (using infant stimuli) and have explored how the individual attachment model (through the Adult Attachment Interview) modulates its activity. Studies report altered activation in limbic and prefrontal areas and in basal ganglia and hypothalamus/pituitary regions. These altered activations are thought to be the neural substrate of the attachment-caregiving systems interaction.

Mothers with depressive symptoms display differential brain activations when empathizing with infant faces

Maternal care during the first year of life provides the foundation for the infants emotional and cognitive development. Depressive symptoms in mothers can undermine their early dyadic interaction, which may lead to various psychopathological disorders with long-term consequences. During this period, the mother-child interaction is exclusively preverbal and is based on the mothers ability to understand her infants needs and feelings (i.e., empathy) and on reciprocal imitation of facial expressions that promote a social dialog that influences the development of the infant self. To study the effects of maternal depressive symptoms on neural circuits underlying these processes, we studied 16 healthy mothers (H) and 14 mothers with depressive symptoms (D), as assessed by the Center for Epidemiologic Studies Depression Scale. Subjects underwent functional magnetic resonance during observation/empathizing (OE) and imitation (IM) of the faces of both their own child and of that of an unknown child aged between 6 and 12 months. During OE, D deactivated the orbital and medial prefrontal cortex to a greater extent (compared with H), thus pointing to an increased internally focused cognitive style during rest. Moreover, D, in respect to H, displayed a greater reactivity of the right amygdala, which may be an expression of emotional dysregulation.

Impaired cortical deactivation during hand movement in the relapsing phase of multiple sclerosis: a cross-sectional and longitudinal fMRI study:

Background: Little is known about the cortical activation changes during clinical relapses in multiple sclerosis (MS). Objective: To assess cross-sectional and longitudinal differences in functional magnetic resonance imaging (fMRI) cortical patterns between the relapsing and stable phases of MS. Methods: We studied 32 patients with relapsing–remitting MS with mild disability: 19 within 48 h of symptom onset of a new relapse (G1) and 13 in the stable phase, relapse-free for at least 6 months (G2). All patients underwent fMRI twice, upon entry (time 1) and 30–50 days later (time 2), during right-hand movement. Results: No between-group differences were observed in age, disability or T2 lesion load. Between-group analysis showed a significant difference in the ipsilateral precentral gyrus (IPG) activation at time 1. Activity differences in the IPG expressed reduced deactivation in G1 compared with G2. Longitudinal changes in brain activity in the IPG were significantly greater in G1 than G2. G1 patients with a slow clinical recovery (n = 8) showed different activity at baseline and greater activity changes over time in the IPG than patients with a fast recovery (n = 11). Conclusion: This study shows that the relapsing phase is associated with reduced brain deactivation in the IPG, which is more marked in patients with a slow clinical recovery. Increased cortical excitability associated with inflammation may determine functional modifications within the ipsilateral motor area.

Evidence of Impaired Brain Activity Balance after Passive Sensorimotor Stimulation in Multiple Sclerosis

Objectives Examination of sensorimotor activation alone in multiple sclerosis (MS) patients may not yield a comprehensive view of cerebral response to task stimulation. Additional information may be obtained by examining the negative BOLD response (deactivation). Aim of this work was to characterize activation and deactivation patterns during passive hand movements in MS patients. Methods 13 relapsing remitting-MS patients (RRMS), 18 secondary progressive-MS patients (SPMS) and 15 healthy controls (HC) underwent an fMRI study during passive right-hand movements. Activation and deactivation contrasts in the three groups were entered into ANOVA, age and gender corrected. Post-hoc analysis was performed with one-sample and two-sample t-tests. For each patient we obtained lesion volume (LV) from both T1- and T2-weighted images. Results Activations showed a progressive extension to the ipsilateral brain hemisphere according to the group and the clinical form (HC<RRMS<SPMS). Significant deactivation of the ipsilateral cortical sensorimotor areas was reduced in both patient groups with respect to HC. Deactivation of posterior cortical areas belonging to the default mode network (DMN), was increased in RRMS, but not in SPMS, with respect to HC. The amount of activation in the contralateral sensorimotor cortex was significantly correlated with that of deactivation in the DMN in HC and RRMS, but not in SPMS. Both increased activation and decreased deactivation patterns correlated with LV. Conclusion In RRMS patients, increased cortical activation was associated with increased deactivation of the posterior cortex suggesting a greater resting-state activity in the DMN, probably aimed at facilitating sensorimotor circuit engagement during task performance. In SPMS the coupling between increased sensorimotor activation/increased DMN deactivation was not observed suggesting disorganization between anticorrelated functional networks as a consequence of a higher level of disconnection.

Anatomical Functional Changes in a Patient Presenting a Complex Malformation of Cortical Development

The authors describe a case of right fronto-parietal micropoligyria associated with small schizencephaly clefts and the presence of a frontal open-lip schizencephaly with corpus callosum agenesis. A functional magnetic resonance imaging (fMRI) study was performed to evaluate the possible reorganization of cortical functions in a patient presenting a complex malformation pattern and to investigate which cortical areas were activated during left finger movements. An fMRI study was performed during the execution of a repetitive index finger-to-thumb opposition movement with the right hand and the left hand in 2 separate sessions. Movement of the right hand induced a normal motor activation pattern involving the contralateral left sensory-motor cortex. Movement of the left hand produced significant activation of brain cortex. This fMRI study highlights the compensatory role of the ipsilateral cortical pathways in hand movements in the case of a complex brain malformation that involves the main motor activation areas.