A Hypothalamic Mechanism Regulates the Duration of a Migraine Attack: Insights from Microstructural and Temporal Complexity of Cortical Functional Networks Analysis.

The role of the hypothalamus and the limbic system at the onset of a migraine attack has recently received significant interest. We analyzed diffusion tensor imaging (DTI) parameters of the entire hypothalamus and its subregions in 15 patients during a spontaneous migraine attack and in 20 control subjects. We also estimated the non-linear measure resting-state functional MRI BOLD signal's complexity using Higuchi fractal dimension (FD) and correlated DTI/fMRI findings with patients' clinical characteristics. In comparison with healthy controls, patients had significantly altered diffusivity metrics within the hypothalamus, mainly in posterior ROIs, and higher FD values in the salience network (SN). We observed a positive correlation of the hypothalamic axial diffusivity with migraine severity and FD of SN. DTI metrics of bilateral anterior hypothalamus positively correlated with the mean attack duration. Our results show plastic structural changes in the hypothalamus related to the attacks severity and the functional connectivity of the SN involved in the multidimensional neurocognitive processing of pain. Plastic changes to the hypothalamus may play a role in modulating the duration of the attack.

Hypothalamic structural integrity and temporal complexity of cortical information processing at rest in migraine without aura patients between attacks.

The hypothalamus has been attributed an important role during the premonitory phase of a migraine attack. Less is known about the role played by the hypothalamus in the interictal period and its relationship with the putative neurocognitive networks previously identified in the pathophysiology of migraine. Our aim was to test whether the hypothalamic microstructure would be altered during the interictal period and whether this co-existed with aberrant connectivity at cortical level. We collected multimodal MRI data from 20 untreated patients with migraine without aura between attacks (MO) and 20 healthy controls (HC) and studied fractional anisotropy, mean (MD), radial (RD), and axial diffusivity of the hypothalamus ROI as a whole from diffusion tensor imaging (DTI). Moreover, we performed an exploratory analysis of the same DTI metrics separately for the anterior and posterior hypothalamic ROIs bilaterally. From resting-state functional MRI, we estimated the Higuchi's fractal dimension (FD), an index of temporal complexity sensible to describe non-periodic patterns characterizing BOLD signature. Finally, we correlated neuroimaging findings with migraine clinical features. In comparison to HC, MO had significantly higher MD, AD, and RD values within the hypothalamus. These findings were confirmed also in the exploratory analysis on the sub-regions of the hypothalamus bilaterally, with the addition of lower FA values on the posterior ROIs. Patients showed higher FD values within the salience network (SN) and the cerebellum, and lower FD values within the primary visual (PV) network compared to HC. We found a positive correlation between cerebellar and SN FD values and severity of migraine. Our findings of hypothalamic abnormalities between migraine attacks may form part of the neuroanatomical substrate that predisposes the onset of the prodromal phase and, therefore, the initiation of an attack. The peculiar fractal dimensionality we found in PV, SN, and cerebellum may be interpreted as an expression of abnormal efficiency demand of brain networks devoted to the integration of sensory, emotional, and cognitive information related to the severity of migraine.

Neurobiological features and response to eye movement desensitization and reprocessing treatment of posttraumatic stress disorder in patients with breast cancer.

Background: Breast cancer (BC) is one of the most common invasive types of cancer among women, with important consequences on both physical and psychological functioning. Patients with BC have a great risk of developing posttraumatic stress disorder (PTSD), but few studies have evaluated the efficacy of psychological interventions to treat it. Furthermore, no neuroimaging studies have evaluated the neurobiological effects of psychotherapeutic treatment for BC-related PTSD. Objective: The study aimed to evaluate the efficacy of Eye Movement Desensitization and Reprocessing therapy (EMDR) as compared to Treatment as Usual (TAU) in BC patients with PTSD, identifying by electroencephalography (EEG) the neurophysiological changes underlying treatments effect and their correlation with clinical symptoms. Method: Thirty patients with BC and PTSD diagnosis were included, receiving either EMDR (n = 15) or TAU (n = 15). Patients were assessed before and after treatments with clinical questionnaires and EEG. The proportion of patients who no longer meet criteria for PTSD after the intervention and changes in clinical scores, both between and within groups, were evaluated. Two-sample permutation t-tests among EEG channels were performed to investigate differences in power spectral density between groups. Pearson correlation analysis was carried out between power bands and clinical scores. Results: At post-treatment, all patients treated with EMDR no longer met criteria for PTSD, while all patients treated with TAU maintained the diagnosis. A significant decrease in depressive symptoms was found only in the EMDR group, while anxiety remained stable in all patients. EEG results corroborated these findings, showing significant differences in delta and theta bands in left angular and right fusiform gyri only in the EMDR group. Conclusions: It is essential to detect PTSD symptoms in patients with BC, in order to offer proper interventions. The efficacy of EMDR therapy in reducing cancer-related PTSD is supported by both clinical and neurobiological findings.

Antecedentes: El cáncer de mama (CM) es uno de los tipos de cáncer invasivo más comunes entre las mujeres, con importantes consecuencias tanto en el funcionamiento físico como psicológico. Los pacientes con CM tienen un gran riesgo de desarrollar trastorno de estrés postraumático (TEPT), pero solo unos pocos estudios han evaluado la eficacia de las intervenciones psicológicas para tratarlo. Adicionalmente, ningún estudio de neuroimagen ha evaluado los efectos neurobiológicos del tratamiento psicoterapéutico para el TEPT relacionado con CM. Objetivo: el estudio buscó evaluar la eficacia de la terapia de desensibilización y reprocesamiento con movimientos oculares (EMDR) en comparación con el tratamiento habitual (TAU) en pacientes con TEPT en CM, identificando también mediante EEG los cambios neurofisiológicos que subyacen al efecto de los tratamientos y su correlación con los síntomas clínicos. Método: se incluyeron treinta pacientes con diagnóstico de CM y TEPT, recibiendo EMDR (n = 15) o TAU (n = 15). Los pacientes fueron evaluados antes y después de los tratamientos con cuestionarios clínicos y electroencefalografía (EEG). Se evaluó la proporción de pacientes que dejaron de cumplir con los criterios para trastorno de estrés postraumático después de la intervención y los cambios en las puntuaciones clínicas, tanto al interior como entre los grupos. Se realizaron pruebas t de permutación de dos muestras entre canales EEG para investigar las diferencias en la Densidad del Espectro de Potencia entre los grupos. Se realizó un análisis de correlación de Pearson entre bandas de potencia y puntuaciones clínicas. Resultados: En el postratamiento, todos los pacientes tratados con EMDR ya no cumplían con los criterios para TEPT, mientras que todos los pacientes tratados con TAU mantuvieron el diagnóstico. Se encontró una disminución significativa de síntomas depresivos solo en el grupo EMDR, mientras que la ansiedad se mantuvo estable en todos los pacientes. Los resultados del EEG corroboraron estos hallazgos, mostrando diferencias significativas en las bandas delta y theta en los giros angular izquierdo y fusiforme derecho solo en el grupo EMDR. Conclusiones: es esencial detectar los síntomas de TEPT también en pacientes con CM para poder ofrecer intervenciones adecuadas. La eficacia de la terapia EMDR en reducir el trastorno de estrés postraumático relacionado con el cáncer es apoyado tanto por los hallazgos clínicos como neurobiológicos.

fMRI characterisation of widespread brain networks relevant for behavioural variability in fine hand motor control with and without visual feedback.

A bilateral visuo-parietal-motor network is responsible for fine control of hand movements. However, the sub-regions which are devoted to maintenance of contraction stability and how these processes fluctuate with trial-quality of task execution and in the presence/absence of visual feedback remains unclear. We addressed this by integrating behavioural and fMRI measurements during right-hand isometric compression of a compliant rubber bulb, at 10% and 30% of maximum voluntary contraction, both with and without visual feedback of the applied force. We quantified single-trial behavioural performance during 1) the whole task period and 2) stable contraction maintenance, and regressed these metrics against the fMRI data to identify the brain activity most relevant to trial-by-trial fluctuations in performance during specific task phases. fMRI-behaviour correlations in a bilateral network of visual, premotor, primary motor, parietal and inferior frontal cortical regions emerged during performance of the entire feedback task, but only in premotor, parietal cortex and thalamus during the stable contraction period. The trials with the best task performance showed increased bilaterality and amplitude of fMRI responses. With feedback, stronger BOLD-behaviour coupling was found during 10% compared to 30% contractions. Only a small subset of regions in this network were weakly correlated with behaviour without feedback, despite wider network activated during this task than in the presence of feedback. These findings reflect a more focused network strongly coupled to behavioural fluctuations when providing visual feedback, whereas without it the task recruited widespread brain activity almost uncoupled from behavioural performance.

Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks.

Introduction We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway. Methods Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1-400 Hz and 450-750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal. Results Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus. Conclusions This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype.

Multiple frequency functional connectivity in the hand somatosensory network: an EEG study.

OBJECTIVE: To investigate the dynamics of communication within the primary somatosensory neuronal network. METHODS: Multichannel EEG responses evoked by median nerve stimulation were recorded from six healthy participants. We investigated the directional connectivity of the evoked responses by assessing the Partial Directed Coherence (PDC) among five neuronal nodes (brainstem, thalamus and three in the primary sensorimotor cortex), which had been identified by using the Functional Source Separation (FSS) algorithm. We analyzed directional connectivity separately in the low (1-200 Hz, LF) and high (450-750 Hz, HF) frequency ranges. RESULTS: LF forward connectivity showed peaks at 16, 20, 30 and 50 ms post-stimulus. An estimate of the strength of connectivity was modulated by feedback involving cortical and subcortical nodes. In HF, forward connectivity showed peaks at 20, 30 and 50 ms, with no apparent feedback-related strength changes. CONCLUSIONS: In this first non-invasive study in humans, we documented directional connectivity across subcortical and cortical somatosensory pathway, discriminating transmission properties within LF and HF ranges. SIGNIFICANCE: The combined use of FSS and PDC in a simple protocol such as median nerve stimulation sheds light on how high and low frequency components of the somatosensory evoked response are functionally interrelated in sustaining somatosensory perception in healthy individuals. Thus, these components may potentially be explored as biomarkers of pathological conditions.

Hand somatosensory subcortical and cortical sources assessed by functional source separation: an EEG study.

We propose a novel electroencephalographic application of a recently developed cerebral source extraction method (Functional Source Separation, FSS), which starts from extracranial signals and adds a functional constraint to the cost function of a basic independent component analysis model without requiring solutions to be independent. Five ad-hoc functional constraints were used to extract the activity reflecting the temporal sequence of sensory information processing along the somatosensory pathway in response to the separate left and right median nerve galvanic stimulation. Constraints required only the maximization of the responsiveness at specific latencies following sensory stimulation, without taking into account that any frequency or spatial information. After source extraction, the reliability of identified FS was assessed based on the position of single dipoles fitted on its retroprojected signals and on a discrepancy measure. The FS positions were consistent with previously reported data (two early subcortical sources localized in the brain stem and thalamus, the three later sources in cortical areas), leaving negligible residual activity at the corresponding latencies. The high-frequency component of the oscillatory activity (HFO) of the extracted component was analyzed. The integrity of the low amplitude HFOs was preserved for each FS. On the basis of our data, we suggest that FSS can be an effective tool to investigate the HFO behavior of the different neuronal pools, recruited at successive times after median nerve galvanic stimulation. As FSs are reconstructed along the entire experimental session, directional and dynamic HFO synchronization phenomena can be studied.

High-gamma band activity of primary hand cortical areas: a sensorimotor feedback efficiency index.

Sensory feedback in motor control is widely recognized to be the key link between the activity of the primary motor cortex to the motor behavior. Through an ad-hoc developed procedure for source extraction (functional source separation), the primary sensory and motor cortex activities (FS(S1) and FS(M1)) were obtained from magnetoencephalographic recordings during a sensorimotor task sequence, and sensorimotor interaction was assessed. Source activity spectral powers were evaluated in the alpha (8-13 Hz), beta (14-32 Hz), gamma1 (33-60 Hz) and gamma2 (61-90 Hz) frequency bands. FS(S1) and FS(M1)had different spectral properties, with FS(S1) prevailing in alpha and FS(M1) in gamma band. Both FS(S1) and FS(M1) were reactive in the different sensorimotor tasks with respect to rest in all frequency bands, except for gamma2. During an isometric contraction, we searched for an index dependent on the performance level and with low variability in the healthy population. We found these properties satisfied within a relationship between FS(S1) and FS(M1) in the gamma2 band. This sensorimotor feedback efficiency index quantitatively estimates the continuous functional balance between primary sensory and motor areas devoted to hand control and seems promising for future developments, as it is easily assessable in patients.

Fetal auditory responses to external sounds and mother's heart beat: detection improved by Independent Component Analysis.

In this paper, we present a magnetoencephalographic study of the fetal auditory response to external stimuli and to the sound of the mother's heartbeat. We describe how an ad hoc functional selection procedure allowed us to isolate the sources in the fetal brain responding to sounds only, after the application to the recorded data of a standard Independent Component Analysis algorithm. In our experiment, acoustic stimuli were delivered to twelve healthy women with uncomplicated pregnancies at a time between 36 and 40 weeks gestational age, with their fetuses in breech presentation. Ultrasound images allowed determination of the region over the women's abdomen nearest to the fetal head, over which both the acoustic stimulator and the MEG sensors were subsequently placed. In 8 out of the 12 cases, our analysis provided consistent evidence of a fetal response both to the mother's heartbeat and to the external auditory stimulation; both were characterized by a clear prominent component at around 200 ms latency, which is widely accepted as the marker of the fetal response to auditory stimuli.