leonides canuet - Academia.edu (original) (raw)

Papers by leonides canuet

Frontiers in Aging Neuroscience, 2022

BackgroundCurrent treatments for Alzheimer’s disease (AD) modulate global neurotransmission but a... more BackgroundCurrent treatments for Alzheimer’s disease (AD) modulate global neurotransmission but are neither specific nor anatomically directed. Tailored stimulation of target nuclei will increase treatment efficacy while reducing side effects. We report the results of the first directional deep brain stimulation (dDBS) surgery and treatment of a patient with AD in an attempt to slow the progression of the disease in a woman with multi-domain, amnestic cognitive status.MethodsWe aimed to assess the safety of dDBS in patients with AD using the fornix as stimulation target (primary objective) and the clinical impact of the stimulation (secondary objective). In a registered clinical trial, a female patient aged 81 years with a 2-year history of cognitive decline and diagnoses of AD underwent a bilateral dDBS surgery targeting the fornix. Stimulation parameters were set between 3.9 and 7.5 mA, 90 μs, 130 Hz for 24 months, controlling stimulation effects by 18F-fluoro-2-deoxy-D-glucose (1...

Frontiers in Neurology, 2022

BackgroundStroke is the second leading cause of death worldwide and it causes important long-term... more BackgroundStroke is the second leading cause of death worldwide and it causes important long-term cognitive and physical deficits that hamper patients' daily activity. Neuropsychological rehabilitation (NR) has increasingly become more important to recover from cognitive disability and to improve the functionality and quality of life of these patients. Since in most stroke cases, restoration of functional connectivity (FC) precedes or accompanies cognitive and behavioral recovery, understanding the electrophysiological signatures underlying stroke recovery mechanisms is a crucial scientific and clinical goal.MethodsFor this purpose, a longitudinal study was carried out with a sample of 10 stroke patients, who underwent two neuropsychological assessments and two resting-state magnetoencephalographic (MEG) recordings, before and after undergoing a NR program. Moreover, to understand the degree of cognitive and neurophysiological impairment after stroke and the mechanisms of recove...

Scientific Reports, 2020

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric disease characterized by ga... more Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric disease characterized by gait disturbance, cognitive deterioration and urinary incontinence associated with excessive accumulation of cerebrospinal fluid (CSF) in the brain ventricles. These symptoms, in particular gait disturbance, can be potentially improved by shunt operation in the early stage of the disease, and the intervention associates with a worse outcome when performed late during the course of the disease. Despite the variable outcome of shunt operation, noninvasive presurgical prediction methods of shunt response have not been established yet. In the present study, we used normalized power variance (NPV), a sensitive measure of the instability of cortical electrical activity, to analyze cortical electrical activity derived from EEG data using exact-low-resolution-electromagnetic-tomography (eLORETA) in 15 shunt responders and 19 non-responders. We found that shunt responders showed significantly highe...

Neuropsychobiology, 2019

Objectives: eLORETA (exact low-resolution brain electromagnetic tomography) is a technique create... more Objectives: eLORETA (exact low-resolution brain electromagnetic tomography) is a technique created by Pascual-Marqui et al. [Int J Psychophysiol. 1994 Oct; 18(1): 49–65] for the 3-dimensional representation of current source density in the brain by electroencephalography (EEG) data. Kurtosis analysis allows for the identification of spiky activity in the brain. In this study, we focused on the evaluation of the reliability of eLORETA kurtosis analysis. For this purpose, the results of eLORETA kurtosis source localization of paroxysmal activity in EEG were compared with those of eLORETA current source density (CSD) analysis of EEG data in 3 epilepsy patients with partial seizures. Methods: EEG was measured using a digital EEG system with 19 channels. We set the bandpass filter at traditional frequency band settings (1–4, 4–8, 8–15, 15–30, and 30–60 Hz) and 5–10 and 20–70 Hz and performed eLORETA kurtosis to compare the source localization of paroxysmal activity with that of visual in...

Frontiers in human neuroscience, 2018

Neuropsychobiology, 2017

Healthy aging is associated with impairment in cognitive information processing. Several neuroima... more Healthy aging is associated with impairment in cognitive information processing. Several neuroimaging methods such as functional magnetic resonance imaging, positron emission tomography and near-infrared spectroscopy have been used to explore healthy and pathological aging by relying on hemodynamic or metabolic changes that occur in response to brain activity. Since electroencephalography (EEG) and magnetoencephalography (MEG) are able to measure neural activity directly with a high temporal resolution of milliseconds, these neurophysiological techniques are particularly important to investigate the dynamics of brain activity underlying neurocognitive aging. It is well known that age is a major risk factor for Alzheimer's disease (AD), and that synaptic dysfunction represents an early sign of this disease associated with hallmark neuropathological findings. However, the neurophysiological mechanisms underlying AD are not fully elucidated. This review addresses healthy and pathol...

Cerebellum & ataxias, 2015

Crossed cerebello-cerebral diaschisis (CCCD) conventionally refers to decreased resting cerebral ... more Crossed cerebello-cerebral diaschisis (CCCD) conventionally refers to decreased resting cerebral activity caused by injury to the contralateral cerebellum. We investigated whether functional activation of a contralesional cerebral cortical region controlling a specific task is reduced during task performance in a patient with a unilateral cerebellar lesion. We also examined functional compensation by the corresponding ipsilesional cerebral cortex. It was hypothesized that dysfunction of the primary sensorimotor cortex (SM1) contralateral to the cerebellar lesion would be detected together with a compensatory increase in neural activity of the ipsilesional SM1. To test these possibilities, we conducted non-invasive functional neuroimaging techniques for bilateral SM1 during hand grasping, a task known to activate predominantly the SM1 contralateral to the grasping hand. Activity in SM1 during hand grasping was measured electrophysiologically by magnetoencephalography and hemodynamica...

International Journal of Neurorehabilitation, 2015

measures, including interhemispheric functional connectivity within the motor network [3]. Based ... more measures, including interhemispheric functional connectivity within the motor network [3]. Based on these studies, a successful motor recovery produced by conventional physiotherapy, robot-assisted therapy, or transcranial magnetic stimulation over the motor cortex is likely mediated by cortical network reorganization. These interventions, however, have none or little effects on neurocognitive deficits, which are common manifestations of cortical stroke.

Scientific reports, 2015

Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's ... more Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest p...

Scientific reports, Jan 14, 2015

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, ... more Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, cognitive deterioration and urinary incontinence in elderly individuals. These symptoms can be improved by shunt operation in some but not all patients. Therefore, discovering predictive factors for the surgical outcome is of great clinical importance. We used normalized power variance (NPV) of electroencephalography (EEG) waves, a sensitive measure of the instability of cortical electrical activity, and found significantly higher NPV in beta frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2) in shunt responders compared to non-responders. By utilizing these differences, we were able to correctly identify responders and non-responders to shunt operation with a positive predictive value of 80% and a negative predictive value of 88%. Our findings indicate that NPV can be useful in noninvasively predicting the clinical outcome of shunt operation in patients wit...

Adaptive nonlinear beamformer technique for analyzing magnetoencephalography (MEG) data has been ... more Adaptive nonlinear beamformer technique for analyzing magnetoencephalography (MEG) data has been proved to be powerful tool for both brain research and clinical applications. A general method of analyzing multiple subject data with a formal statistical treatment for the group data has been developed and applied for various types of MEG data. Our latest application of this method was frontal midline theta rhythm (Fmθ), which indicates focused attention and appears widely distributed over medial prefrontal areas in EEG recordings. To localize cortical generators of the magnetic counterpart of Fmθ precisely and identify cortical sources and underlying neural activity associated with mental calculation processing (i.e., arithmetic subtraction), we applied adaptive nonlinear beamformer and permutation analysis on MEG data. As a result, it was indicated that Fmθ is generated in the dorsal anterior cingulate and adjacent medial prefrontal cortex. Gamma event-related synchronization is as an index of activation in right parietal regions subserving mental subtraction associated with basic numerical processing and number-based spatial attention. Gamma desynchronization appeared in the right lateral prefrontal cortex, likely representing a mechanism to interrupt neural activity that can interfere with the ongoing cognitive task. We suggest that the combination of adaptive nonlinear beamformer and permutation analysis on MEG data is quite powerful tool to reveal the oscillatory neuronal dynamics in human brain.

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by g... more Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by gait disturbance, cognitive impairment and urinary incontinence that affect elderly individuals. These symptoms can potentially be reversed by cerebrospinal fluid (CSF) drainage or shunt operation. Prior to shunt operation, drainage of a small amount of CSF or "CSF tapping" is usually performed to ascertain the effect of the operation. Unfortunately, conventional neuroimaging methods such as single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), as well as electroencephalogram (EEG) power analysis seem to have failed to detect the effect of CSF tapping on brain function. In this work, we propose the use of Neuronal Activity Topography (NAT) analysis, which calculates normalized power variance (NPV) of EEG waves, to detect cortical functional changes induced by CSF tapping in iNPH. Based on clinical improvement by CSF tapping and shunt operation, we classified 24 iNPH patients into responders (N = 11) and nonresponders (N = 13), and performed both EEG power analysis and NAT analysis. We also assessed correlations between changes in NPV and changes in functional scores on gait and cognition scales before and after CSF tapping. NAT analysis showed that after CSF tapping there was a significant decrease in alpha NPV at the medial frontal cortex (FC) (Fz) in responders, while nonresponders exhibited an increase in alpha NPV at the right dorsolateral prefrontal cortex (DLPFC) (F8). Furthermore, we found correlations between cortical functional changes and clinical symptoms. In particular, delta and alpha NPV changes in the left-dorsal FC (F3) correlated with changes in gait status, while alpha and beta NPV changes in the right anterior prefrontal cortex (PFC) (Fp2) and left DLPFC (F7) as well as alpha NPV changes in the medial FC (Fz) correlated with changes in gait velocity. In addition, alpha NPV changes in the right DLPFC (F8) correlated with changes in WMS-R Mental Control scores in iNPH patients. An additional analysis combining the changes in values of alpha NPV over the left-dorsal FC (Δalpha-F3-NPV) and the medial FC (Δalpha-Fz-NPV) induced by CSF tapping (cut-off value of Δalpha-F3-NPV + Δalpha-Fz-NPV = 0), could correctly identified "shunt responders" and "shunt nonresponders" with a positive predictive value of 100% (10/10) and a negative predictive value of 66% (2/3). In contrast, EEG power spectral analysis showed no function related changes in cortical activity at the frontal cortex before and after CSF tapping. These results indicate that the clinical changes in gait and response suppression induced by CSF tapping in iNPH patients manifest as NPV changes, particularly in the alpha band, rather than as EEG power changes. Our findings suggest that NAT analysis can detect CSF tapping-induced functional changes in cortical activity, in a way that no other neuroimaging methods have been able to do so far, and can predict clinical response to shunt operation in patients with iNPH.

PLoS ONE, 2011

Background: It is unclear whether, like in schizophrenia, psychosis-related disruption in connect... more Background: It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits. Methodology/Principal Findings: Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinicallymatched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called ''lagged phase synchronization'' was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Broca's area correlating with auditory hallucination scores. Conclusions/Significance: In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity.

PLoS ONE, 2012

Background: The apolipoprotein E epsilon 4 (APOE-4) is associated with a genetic vulnerability to... more Background: The apolipoprotein E epsilon 4 (APOE-4) is associated with a genetic vulnerability to Alzheimer's disease (AD) and with AD-related abnormalities in cortical rhythms. However, it is unclear whether APOE-4 is linked to a specific pattern of intrinsic functional disintegration of the brain after the development of the disease or during its different stages. This study aimed at identifying spatial patterns and effects of APOE genotype on resting-state oscillations and functional connectivity in patients with AD, using a physiological connectivity index called ''lagged phase synchronization''. Methodology/Principal Findings: Resting EEG was recorded during awake, eyes-closed state in 125 patients with AD and 60 elderly controls. Source current density and functional connectivity were determined using eLORETA. Patients with AD exhibited reduced parieto-occipital alpha oscillations compared with controls, and those carrying the APOE-4 allele had reduced alpha activity in the left inferior parietal and temporo-occipital cortex relative to noncarriers. There was a decreased alpha2 connectivity pattern in AD, involving the left temporal and bilateral parietal cortex. Several brain regions exhibited increased lagged phase synchronization in low frequencies, specifically in the theta band, across and within hemispheres, where temporal lobe connections were particularly compromised. Areas with abnormal theta connectivity correlated with cognitive scores. In patients with early AD, we found an APOE-4-related decrease in interhemispheric alpha connectivity in frontal and parieto-temporal regions. Conclusions/Significance: In addition to regional cortical dysfunction, as indicated by abnormal alpha oscillations, there are patterns of functional network disruption affecting theta and alpha bands in AD that associate with the level of cognitive disturbance or with the APOE genotype. These functional patterns of nonlinear connectivity may potentially represent neurophysiological or phenotypic markers of AD, and aid in early detection of the disorder.

Schizophrenia Research, 2009

Psychophysiology, 2010

Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is the most common psychophysiolog... more Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is the most common psychophysiological index of sensorimotor gating. Several studies have investigated the relationship of PPI of ASR to schizotypy in Caucasians. However, little has been reported on this relationship in Asians. We investigated a possible relationship between PPI of ASR and schizotypy in 79 healthy Japanese subjects. Schizotypy was assessed by the Schizotypal personality Questionnaire (SPQ). PPI was evaluated at signal-to-noise ratios (SnRs: difference between background noise intensity and prepulse intensity) of 112, 116, and 120 dB. The total SPQ score, cognitive/perceptual score, and interpersonal score correlated negatively with PPI at SnR of 116 and 120 dB. We conclude that PPI is associated with the trait of schizotypy in healthy Asian subjects.

Journal of Neuropsychiatry, 2011

International Congress Series, 2007

Although delusions are quite common symptoms among psychiatric patients, few neuroimaging studies... more Although delusions are quite common symptoms among psychiatric patients, few neuroimaging studies have explored the neural correlates of delusions. In this study we used magnetoencephalography (MEG) to directly image brain activity associated with delusions in acute psychosis of epilepsy patients. Two female patients aged 65 and 68 years with temporal lobe epilepsy were studied. We obtained topographic images of the excess kurtosis (g2), the statistical index of spiky activities, from unaveraged MEG measurements using an analysis called "synthetic aperture magnetometry" (SAM). In both patients, the excess kurtosis (g2) images showed spiky activity over the right inferior parietal cortex during the delusional state. A second MEG measurement after delusions were resolved with antipsychotic medication showed no excess kurtosis image in the right parietal cortex. Our results indicate association of the right inferior parietal region with the experience of delusions in these patients. We suggest that MEG with SAM analysis is useful in the identification of abnormal activity in acute psychotic disorders.

Evidence-Based Mental Health, 1999

In patients with major depression, is slow, repetitive transcranial magnetic stimulation (rTMS) e... more In patients with major depression, is slow, repetitive transcranial magnetic stimulation (rTMS) effective for relieving depressive symptoms? Design 2 week randomised, double blind, placebo controlled trial. Setting {Psychiatric department of a general hospital}* in Israel. Patients 70 patients (mean age 59 y, 76% women) who had major depression according to the DSM-IV; were right handed; had normal neurological and general physical examination results; did not have a history of major brain trauma, seizure disorder, or substance abuse; and were not medication resistant. Follow up was 96%.