Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

OBJECTIVE: To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. BACKGROUND: Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. METHODS: In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. RESULTS: The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. CONCLUSION: During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Involvement of the cerebellum in structural connectivity enhancement in episodic migraine.

BACKGROUND: The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. METHODS: To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. RESULTS: We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. CONCLUSIONS: A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.

Insomnia Disorder and Brain's Default-Mode Network.

PURPOSE OF REVIEW: Insomnia disorder (ID) is a prevalent sleep disorder that significantly compromises the physical and mental health of individuals. This article reviews novel approaches in the study of brain networks and impaired function in ID through the application of modern neuroimaging techniques such as functional magnetic resonance imaging (fMRI). RECENT FINDINGS: The default-mode network (DMN) is presumed to be correlated with self-referential information processing, and it appears to be altered or unbalanced in insomnia. A growing body of evidence suggests the lack of deactivation of brain regions comprising the DMN when insomnia patients are at rest. Moreover, core areas of the DMN demonstrate greater activation in insomnia patients when compared to healthy controls in self-referential related tasks. Despite the few studies on the topic, underpinning the correlation between abnormal DMN activity and ID deserves further attention in the future. Implications for therapeutics are briefly outlined.

Three-Dimensional Face Recognition in Mild Cognitive Impairment: A Psychophysical and Structural MR Study.

OBJECTIVES: Mild cognitive impairment (MCI) has been associated with a high risk of conversion to Alzheimer's dementia. In addition to memory complaints, impairments in the visuospatial domain have been reported in this condition. We have previously shown that deficits in perceiving structure-from-motion (SFM) objects are reflected in functional reorganization of brain activity within the visual ventral stream. Here we aimed to identify structural correlates of psychophysical complex face and object recognition performance in amnestic MCI patients (n=30 vs. n=25 controls). This study was, therefore, motivated by evidence from recent studies showing that a combination of visual information across dorsal and ventral visual streams may be needed for the perception of three-dimensional (3D) SFM objects. METHODS: In our experimental paradigm, participants had to discriminate 3D SFM shapes (faces and objects) from 3D SFM meaningless (scrambled) shapes. RESULTS: Morphometric analysis established neuroanatomical evidence for impairment in MCI as demonstrated by smaller hippocampal volumes. We found association between cortical thickness and face recognition performance, comprising the occipital lobe and visual ventral stream fusiform regions (overlapping the known location of face fusiform area) in the right hemisphere, in MCI. CONCLUSIONS: We conclude that impairment of 3D visual integration exists at the MCI stage involving also the visual ventral stream and contributing to face recognition deficits. The specificity of such observed structure-function correlation for faces suggests a special role of this processing pathway in health and disease. (JINS, 2016, 22, 744-754).

Classification of Huntington's disease stage with support vector machines: A study on oculomotor performance.

Alterations in oculomotor performance are among the first observable physical alterations during presymptomatic stages of Huntington's disease (HD). Quantifiable measurements of oculomotor performance have been studied as possible markers of disease status and progression in presymptomatic and early symptomatic stages of HD, on the basis of traditional analysis methods. Whether oculomotor performance can be used to classify individuals according to HD disease stage has yet to be explored via the application of machine-learning methods. In the present study, we report the application of the support vector machine (SVM) algorithm to oculomotor features pooled from a four-task psychophysical experiment. We were able to automatically distinguish control participants from presymptomatic HD (pre-HD) participants with an accuracy of 73.47 %, a sensitivity of 74.31 %, and a specificity of 72.64 %; to distinguish control participants from HD patients with an accuracy of 81.84 %, a sensitivity of 76.19 %, and a specificity of 87.48 %; and to distinguish pre-HD participants from HD patients with an accuracy of 83.54 %, a sensitivity of 92.62 %, and a specificity of 74.45 %. These results demonstrate that the application of supervised classification methods to oculomotor features is a valuable and promising approach to the automatic detection of disease stage in HD.

Classification of Huntington's Disease Stage with Features Derived from Structural and Diffusion-Weighted Imaging.

The purpose of this study was to classify Huntington's disease (HD) stage using support vector machines and measures derived from T1- and diffusion-weighted imaging. The effects of feature selection approach and combination of imaging modalities are assessed. Fourteen premanifest-HD individuals (Pre-HD; on average > 20 years from estimated disease onset), eleven early-manifest HD (Early-HD) patients, and eighteen healthy controls (HC) participated in the study. We compared three feature selection approaches: (i) whole-brain segmented grey matter (GM; voxel-based measure) or fractional anisotropy (FA) values; (ii) GM or FA values from subcortical regions-of-interest (caudate, putamen, pallidum); and (iii) automated selection of GM or FA values with the algorithm Relief-F. We assessed single- and multi-kernel approaches to classify combined GM and FA measures. Significant classifications were achieved between Early-HD and Pre-HD or HC individuals (accuracy: generally, 85% to 95%), and between Pre-HD and controls for the feature FA of the caudate ROI (74% accuracy). The combination of GM and FA measures did not result in higher performances. We demonstrate evidence on the high sensitivity of FA for the classification of the earliest Pre-HD stages, and successful distinction between HD stages.

Cortical responses to Aδ-fiber stimulation: magnetoencephalographic recordings in a subject lacking large myelinated afferents.

Controversy persists over the role of the primary somatosensory cortex (SI) in processing small-fiber peripheral afferent input. We therefore examined subject I.W, who, due to sensory neuronopathy syndrome, has no large-fiber afferents below C3 level. Cortical evoked responses were recorded with a whole-scalp neuromagnetometer to high-intensity electrical stimulation of the distal right radial, median, and tibial nerves and skin over the forearm and mechanical stimulation of (neurologically intact) lip. The responses to electrical stimulation in the Abeta-denervated limbs peaked at 110-140 ms in contralateral SI and at 140-220 ms in contralateral secondary somatosensory cortex (SII), consistent with Adelta-mediated input. I.W. was able to localize pin-prick stimuli with 4 cm accuracy. Responses to laser stimuli on the radial dorsum of the hand peaked in contralateral SII cortex at 215 ms, also compatible with Adelta-mediated input. These results support the role of the SI cortex in processing the sensory discriminative aspects of Adelta-mediated input.

The effect of impulsivity and inhibitory control deficits in the saccadic behavior of premanifest Huntington's disease individuals.

BACKGROUND: This study aims to test response inhibition in premanifest Huntington's disease individuals (Pre-HD), in the context of a saccadic paradigm with working memory demands and fronto-executive load as a way to measure inhibitory control deficits and impulsive behavior in Huntington's disease (HD). METHODS: The oculomotor function of 15 Pre-HD and 22 Control individuals was assessed using an experimental paradigm comprising four horizontal saccadic tasks: prosaccade (PS), antisaccade (AS), 1- or 2-back memory prosaccade (MPS), and 1- or 2-back memory antisaccade (MAS). Success rate, latency, directional and timing errors were calculated for each task. A comprehensive battery of neuropsychological tests was also used to assess the overall cognitive functioning of study participants. Statistical correlations between oculomotor, clinical and cognitive measures were computed for the Pre-HD group. RESULTS: Pre-HD participants showed reduced success rate in the AS task, increased direction errors in the AS and MAS tasks and decreased latency in the MAS task when compared to Controls, despite presenting similar executive and memory scores in the conventional neuropsychological tests applied. Significant associations were identified between specific AS and MAS parameters and disease-related measures, cognitive skills and other oculomotor results of Pre-HD participants. CONCLUSIONS: Our results show that oculomotor performance in premanifest Huntington's disease deteriorates once inhibitory control, working memory and/or fronto-executive load are added to the task. A more automatic pattern of performance, including a faster response time and directionally erroneous eye movements were detected in the oculomotor behavior of the Pre-HD group-these alterations were significantly correlated with disease stage and cognitive status. Our saccadic paradigm was able to capture impulsivity and inhibitory control deficits in a group of Pre-HD individuals on average far from symptom onset, thus holding the potential to identify the earliest disease-related changes.

Comparison of Visual and Auditory Modalities for Upper-Alpha EEG-Neurofeedback.

Electroencephalography (EEG) neurofeedback (NF) training has been shown to produce long-lasting effects on the improvement of cognitive function as well as the normalization of aberrant brain activity in disease. However, the impact of the sensory modality used as the NF reinforcement signal on training effectiveness has not been systematically investigated. In this work, an EEG-based NF-training system was developed targeting the individual upper-alpha (UA) band and using either a visual or an auditory reinforcement signal, so as to compare the effects of the two sensory modalities. Sixteen healthy volunteers were randomly assigned to the Visual or Auditory group, where a radius-varying sphere or a volume-varying sound, respectively, reflected the relative amplitude of UA measured at EEG electrode Cz. Each participant underwent a total of four NF sessions, of approximately 40 min each, on consecutive days. Both groups showed significant increases in UA at Cz within sessions, and also across sessions. Effects subsequent to NF training were also found beyond the target frequency UA and scalp location Cz, namely in the lower-alpha and theta bands and in posterior brain regions, respectively. Only small differences were found on the EEG between the Visual and Auditory groups, suggesting that auditory reinforcement signals may be as effective as the more commonly used visual signals. The use of auditory NF may potentiate training protocols conducted under mobile conditions, which are now possible due to the increasing availability of wireless EEG systems.

Association between Adipokines and Biomarkers of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Adipose tissue dysfunction has been implicated in the pathophysiology of Alzheimer's disease. However, the involvement of adipokines, particularly adiponectin, remains unclear. OBJECTIVE: To compare serum and cerebrospinal fluid (CSF) levels of adiponectin, leptin and leptin-to-adiponectin ratio in patients within the spectrum of Alzheimer's disease and evaluate their relationship with classical biomarkers and their value as markers of progression. METHODS: Amnestic mild cognitive impairment (MCI, n = 71) and Alzheimer's dementia (AD, n = 53) subjects were consecutively recruited for serum and CSF adiponectin and leptin determination using an analytically validated commercial enzyme-linked immunosorbent assay (ELISA). Correlations were explored using adjusted Spearman's correlation coefficients. A logistic regression model and ROC analysis were performed to evaluate the staging predictive value of adipokines. RESULTS: Serum adiponectin was 33% higher in AD when compared to MCI patients. Adiponectin CSF levels, similar in both groups, were positively correlated with Aß42 and cognitive function, though only in women. The area under the ROC curve was 0.673 (95% CI:0.57-0.78) for serum adiponectin as predictor of dementia stage and the cut-off 10.85µg/ml maximized the sum of specificity (87%) and sensitivity (44%). CONCLUSION: Although longitudinal studies are required, we hypothesize that higher serum adiponectin in AD patients constitutes a strategy to compensate possible central signaling defects. In addition, adiponectin might be specifically assigned to neuroprotective functions in women and eventually involved in the female-biased incidence of Alzheimer's disease.

Actor's and observer's primary motor cortices stabilize similarly after seen or heard motor actions.

We quantified rhythmic brain activity, recorded with whole-scalp magnetoencephalography (MEG), of 13 healthy subjects who were performing, seeing, or hearing the tapping of a drum membrane with the right index finger. In the actor's primary motor (M1) cortex, the level of the approximately 20-Hz brain rhythms started to decrease, as a sign of M1 activation, approximately 2 s before the action and then increased, with a clear rebound approximately 0.6 s after the tapping, as a sign of M1 stabilization. A very similar time course occurred in the M1 cortex of the observer: the activation, although less vigorous than in the actor, started approximately 0.8 s before the action and was followed by a rebound. When the subject just heard the tapping sound, no preaction activation was visible, but a rebound followed the sound. The approximately 10-Hz somatosensory rhythm, which also started to decrease before own and viewed actions, returned to the baseline level approximately 0.6 s later after own actions than observed actions. This delay likely reflects proprioceptive input to the cortex, available only during own actions, and therefore could be related to the brain signature of the sense of agency. The strikingly similar motor cortex reactivity during the first and third person actions expands previous data on brain mechanisms of intersubjective understanding. Besides motor cortex activation before own and observed (predicted) actions, the M1 cortex of both the viewer and the listener stabilized in a very similar manner after brisk motor actions.

Evidence of vibrotactile input to human auditory cortex.

Low frequency vibrations can be detected by both tactile and auditory systems. The aim of the present study is to find out, by means of whole-scalp magnetoencephalography (MEG), whether vibrotactile stimulation alone would activate human auditory cortical areas. We recorded MEG signals from eleven normal-hearing adults to 200-Hz vibrations (on average 19.5 dB above the individual tactile detection threshold), delivered to right-hand fingertips. All subjects reported a perception of a sound when they touched the vibrating tube, and they reported to perceive nothing when not touching the tube. The vibrotactile stimuli elicited clear and reproducible vibrotactile evoked fields (VTEFs) in ten subjects, whereas no MEG responses were observed when the tube was not touched. First responses to the vibrotactile stimuli, peaking around 60 ms, originated in the primary somatosensory cortex in all subjects. They were followed by activations in the auditory cortices, either bilaterally (N = 5) or unilaterally (N = 5), and by activations in the secondary somatosensory (SII) cortex, either contralaterally (N = 3) or ipsilaterally (N = 4). Both the SII and auditory activations consisted of transient responses at 100-200 ms. Additional auditory sustained activation was identified in nine subjects, either bilaterally (N = 2) or ipsilaterally (N = 7), at 200-700 ms. Our results suggest convergence of vibrotactile input to the auditory cortex in normal-hearing adults, in agreement with results previously obtained in a congenitally deaf adult.

Touch activates human auditory cortex.

Vibrotactile stimuli can facilitate hearing, both in hearing-impaired and in normally hearing people. Accordingly, the sounds of hands exploring a surface contribute to the explorer's haptic percepts. As a possible brain basis of such phenomena, functional brain imaging has identified activations specific to audiotactile interaction in secondary somatosensory cortex, auditory belt area, and posterior parietal cortex, depending on the quality and relative salience of the stimuli. We studied 13 subjects with non-invasive functional magnetic resonance imaging (fMRI) to search for auditory brain areas that would be activated by touch. Vibration bursts of 200 Hz were delivered to the subjects' fingers and palm and tactile pressure pulses to their fingertips. Noise bursts served to identify auditory cortex. Vibrotactile-auditory co-activation, addressed with minimal smoothing to obtain a conservative estimate, was found in an 85-mm3 region in the posterior auditory belt area. This co-activation could be related to facilitated hearing at the behavioral level, reflecting the analysis of sound-like temporal patterns in vibration. However, even tactile pulses (without any vibration) activated parts of the posterior auditory belt area, which therefore might subserve processing of audiotactile events that arise during dynamic contact between hands and environment.

Hands help hearing: facilitatory audiotactile interaction at low sound-intensity levels.

Auditory and vibrotactile stimuli share similar temporal patterns. A psychophysical experiment was performed to test whether this similarity would lead into an intermodal bias in perception of sound intensity. Nine normal-hearing subjects performed a loudness-matching task of faint tones, adjusting the probe tone to sound equally loud as a reference tone. The task was performed both when the subjects were touching and when they were not touching a tube that vibrated simultaneously with the probe tone. The subjects chose on average 12% lower intensities (p < 0.01) for the probe tone when they touched the tube, suggesting facilitatory interaction between auditory and tactile senses in normal-hearing subjects.