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    Authors: Tatjana Traub-Weidinger; Otto Muzik; Lalith Kumar Shiyam Sundar; Susanne Aull-Watschinger; +14 Authors

    The purpose of this study was to establish a non-invasive clinical PET/MR protocol using [18F]-labeled deoxyglucose (FDG) that provides physicians with regional metabolic rate of glucose (MRGlc) values and to clarify the contribution of absolute quantification to clinical management of patients with non-lesional extratemporal lobe epilepsy (ETLE). The study included a group of 15 patients with non-lesional ETLE who underwent a dynamic FDG PET study using a fully-integrated PET/MRI system (Siemens Biograph). FDG tracer uptake images were converted to MRGlc (μmol/100 g/min) maps using an image derived input function that was extracted based on the combined analysis of PET and MRI data. In addition, the same protocol was applied to a group of healthy controls, yielding a normative database. Abnormality maps for ETLE patients were created with respect to the normative database, defining significant hypo- or hyper-metabolic regions that exceeded ±2 SD of normal regional mean MRGlc values. Abnormality maps derived from MRGlc images of ETLE patients contributed to the localization of hypo-metabolic areas against visual readings in 53% and increased the confidence in the original clinical readings in 33% of all cases. Moreover, quantification allowed identification of hyper-metabolic areas that are associated with frequently spiking cortex, rarely acknowledged in clinical readings. Overall, besides providing some confirmatory information to visual readings, quantitative PET imaging demonstrated only a moderate impact on clinical management of patients with complex pathology that leads to epileptic seizures, failing to provide new decisive information that would have changed classification of patients from being rejected to being considered for surgical intervention.

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    Frontiers in Neurology
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      Frontiers in Neurology
      Article . 2020
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    Authors: Tobias Balkenhol; Elisabeth Wallhäusser-Franke; Nicole Rotter; Jérôme J. Servais;

    Objectives: Hearing improves significantly with bimodal provision, i.e., a cochlear implant (CI) at one ear and a hearing aid (HA) at the other, but performance shows a high degree of variability resulting in substantial uncertainty about the performance that can be expected by the individual CI user. The objective of this study was to explore how auditory event-related potentials (AERPs) of bimodal listeners in response to spoken words approximate the electrophysiological response of normal hearing (NH) listeners. Study Design: Explorative prospective analysis during the first 6 months of bimodal listening using a within-subject repeated measures design. Setting: Academic tertiary care center. Participants: Twenty-seven adult participants with bilateral sensorineural hearing loss who received a HiRes 90K CI and continued use of a HA at the non-implanted ear. Age-matched NH listeners served as controls. Intervention: Cochlear implantation. Main Outcome Measures: Obligatory auditory evoked potentials N1 and P2, and the event-related N2 potential in response to monosyllabic words and their reversed sound traces before, as well as 3 and 6 months post-implantation. The task required word/non-word classification. Stimuli were presented within speech-modulated noise. Loudness of word/non-word signals was adjusted individually to achieve the same intelligibility across groups and assessments. Results: Intelligibility improved significantly with bimodal hearing, and the N1–P2 response approximated the morphology seen in NH with enhanced and earlier responses to the words compared to their reversals. For bimodal listeners, a prominent negative deflection was present between 370 and 570 ms post stimulus onset (N2), irrespective of stimulus type. This was absent for NH controls; hence, this response did not approximate the NH response during the study interval. N2 source localization evidenced extended activation of general cognitive areas in frontal and prefrontal brain areas in the CI group. Conclusions: Prolonged and spatially extended processing in bimodal CI users suggests employment of additional auditory–cognitive mechanisms during speech processing. This does not reduce within 6 months of bimodal experience and may be a correlate of the enhanced listening effort described by CI listeners.

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    Frontiers in Neurology
    Article . 2020
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    Article . 2020
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      Frontiers in Neurology
      Article . 2020
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    Authors: Claudia eLainscsek; Claudia eLainscsek; Claudia eLainscsek; Jonathan eWeyhenmeyer; +8 Authors

    Time series analysis with delay differential equations (DDEs) reveals nonlinear properties of the underlying dynamical system and can serve as a non-linear time-domain classification tool. Here global DDE models were used to analyze short segments of simulated time series from a known dynamical system, the Rössler system, in high noise regimes. In a companion paper, we apply the DDE model developed here to classify short segments of encephalographic (EEG) data recorded from patients with Parkinson's disease and healthy subjects. Nine simulated subjects in each of two distinct classes were generated by varying the bifurcation parameter b and keeping the other two parameters (a and c) of the Rössler system fixed. All choices of b were in the chaotic parameter range. We diluted the simulated data using white noise ranging from 10dB to -30dB signal-to-noise ratios (SNR). Structure selection was supervised by selecting the number of terms, delays, and order of nonlinearity of the model DDE model that best linearly separated the two classes of data. The distances d from the linear dividing hyperplane was then used to assess the classification performance by computing the area A' under the ROC curve. The selected model was tested on untrained data using repeated random sub-sampling validation. DDEs were able to accurately distinguish the two dynamical conditions, and moreover, to quantify the changes in the dynamics. There was a significant correlation between the dynamical bifurcation parameter b of the simulated data and the classification parameter d from our analysis. This correlation still held for new simulated subjects with new dynamical parameters selected from each of the two dynamical regimes. Furthermore, the correlation was robust to added noise, being significant even when the noise was greater than the signal. We conclude that DDE models may be used as a generalizable and reliable classification tool for even small segments of noisy data.

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    Frontiers in Neurology
    Article . 2013
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      Article . 2013
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    Authors: Claudio eLiguori; Mariangela ePierantozzi; Enrica eOlivola; Nicola B Mercuri; +1 Authors
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    Frontiers in Neurology
    Article . 2015
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      Article . 2015
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    Authors: PEYMAN eADJAMIAN;

    In recent years there has been a significant increase in the use of electroencephalography (EEG) and magnetoencephalography (MEG) to investigate changes in oscillatory brain activity associated with tinnitus with many conflicting results. Current view of the underlying mechanism of tinnitus is that it results from changes in brain activity in various structures of the brain as a consequence of sensory deprivation. This in turn gives rise to increased spontaneous activity and/or synchrony in the auditory centres but also involves modulation from non-auditory processes from structures of the limbic and paralimbic system. Some of the neural changes associated with tinnitus may be assessed non-invasively in humans with MEG and EEG (M/EEG) in ways which are superior to animal studies and other non-invasive imaging techniques. However, both MEG and EEG have their limitations and research results can be misinterpreted in the absence of sufficient understanding of these limitations. In this article, I intend to provide a brief review of these techniques, describe what the recorded signals reflect in terms of the underlying neural activity, and their strengths and limitations. I also discuss some pertinent methodological issues involved in tinnitus related studies and concludes with suggestions to minimise possible discrepancies between results. The overall message is that while MEG and EEG are extremely useful techniques, the interpretation of results from tinnitus studies requires much caution given the individual variability in oscillatory activity and the limits of these techniques.

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    Article . 2014
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    Frontiers in Neurology
    Article . 2014
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    Authors: Garofalo, S. (Sara); Justicia, A. (Azucena); Arrondo, G. (Gonzalo); Ermakova, A.O. (Anna O.); +6 Authors

    Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (n = 12), or without (n = 17), a history of psychotic symptoms, along with a sample of healthy controls (n = 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (p < 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiological mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.

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    Apollo
    Article . 2017
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    Frontiers in Neurology
    Article . 2017 . Peer-reviewed
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    Apollo
    Article . 2017
    License: CC BY
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      Apollo
      Article . 2017
      License: CC BY
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      Frontiers in Neurology
      Article . 2017 . Peer-reviewed
      Data sources: Frontiers
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      Apollo
      Article . 2017
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    Authors: Mortaheb, Sepehr; Filippini, Maria Maddalena; Kaux, Jean-François; Annen, Jitka; +5 Authors

    Background and Objectives: Persistent post-concussive symptoms (PCS) consist of neurologic and psychological complaints persisting after a mild traumatic brain injury (mTBI). It affects up to 50% of mTBI patients, may cause long-term disability, and reduce patients' quality of life. The aim of this review was to examine the possible use of different neuroimaging modalities in PCS. Methods: Articles from Pubmed database were screened to extract studies that investigated the relationship between any neuroimaging features and symptoms of PCS. Descriptive statistics were applied to report the results. Results: A total of 80 out of 939 papers were included in the final review. Ten examined conventional MRI (30% positive finding), 24 examined diffusion weighted imaging (54.17% positive finding), 23 examined functional MRI (82.61% positive finding), nine examined electro(magneto)encephalography (77.78% positive finding), and 14 examined other techniques (71% positive finding). Conclusion: MRI was the most widely used technique, while functional techniques seem to be the most sensitive tools to evaluate PCS. The common functional patterns associated with symptoms of PCS were a decreased anti-correlation between the default mode network and the task positive network and reduced brain activity in specific areas (most often in the prefrontal cortex). Significance: Our findings highlight the importance to use functional approaches which demonstrated a functional alteration in brain connectivity and activity in most studies assessing PCS.

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    Authors: Laura Mirandola; Laura Mirandola; Daniela Ballotta; Francesca Talami; +8 Authors

    Objective: To evaluate local and distant blood oxygen level dependent (BOLD) signal changes related to interictal epileptiform discharges (IED) in drug-resistant temporal lobe epilepsy (TLE).Methods: Thirty-three TLE patients undergoing EEG–functional Magnetic Resonance Imaging (fMRI) as part of the presurgical workup were consecutively enrolled. First, a single-subject spike-related analysis was performed: (a) to verify the BOLD concordance with the presumed Epileptogenic Zone (EZ); and (b) to investigate the Intrinsic Connectivity Networks (ICN) involvement. Then, a group analysis was performed to search for common BOLD changes in TLE.Results: Interictal epileptiform discharges were recorded in 25 patients and in 19 (58%), a BOLD response was obtained at the single-subject level. In 42% of the cases, BOLD changes were observed in the temporal lobe, although only one patient had a pure concordant finding, with a single fMRI cluster overlapping (and limited to) the EZ identified by anatomo-electro-clinical correlations. In the remaining 58% of the cases, BOLD responses were localized outside the temporal lobe and the presumed EZ. In every patient, with a spike-related fMRI map, at least one ICN appeared to be involved. Four main ICNs were preferentially involved, namely, motor, visual, auditory/motor speech, and the default mode network. At the single-subject level, EEG–fMRI proved to have high specificity (above 65%) in detecting engagement of an ICN and the corresponding ictal/postictal symptom, and good positive predictive value (above 67%) in all networks except the visual one. Finally, in the group analysis of BOLD changes related to IED revealed common activations at the right precentral gyrus, supplementary motor area, and middle cingulate gyrus.Significance: Interictal temporal spikes affect several distant extra-temporal areas, and specifically the motor/premotor cortex. EEG–fMRI in patients with TLE eligible for surgery is recommended not for strictly localizing purposes rather it might be useful to investigate ICNs alterations at the single-subject level.

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    DOAJ
    Article . 2021
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    Frontiers in Neurology
    Article . 2021
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      Frontiers in Neurology
      Article . 2021
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    Authors: Nazanin eBaradaran; Sun Nee eTan; Aiping eLiu; Ahmad eAshoori; +6 Authors

    Objective: 1) To determine the brain connectivity pattern associated with clinical rigidity scores in Parkinson's disease (PD) and 2) to determine the relation between clinically-assessed rigidity and quantitative metrics of motor performance.Background: Rigidity, the resistance to passive movement, is exacerbated in PD by asking the subject to move the contralateral limb, implying that rigidity involves a distributed brain network. Rigidity mainly affects subjects when they attempt to move; yet the relation between clinical rigidity scores and quantitative aspects of motor performance are unknown.Methods: Ten clinically diagnosed PD patients (off medication) and ten controls were recruited to perform an fMRI squeeze-bulb tracking task that included both visually guided and internally guided features. The direct functional connectivity between anatomically defined regions of interest was assessed with Dynamic Bayesian Networks (DBNs). Tracking performance was assessed by fitting Linear Dynamical System (LDS) models to the motor performance, and was compared to the clinical rigidity scores. A cross-validated Least Absolute Shrinkage and Selection Operator (LASSO) regression method was used to determine the brain connectivity network that best predicted clinical rigidity scores.Results: The damping ratio of the LDS models significantly correlated with clinical rigidity scores (p < 10-4). An fMRI connectivity network in subcortical and primary and premotor cortical regions accurately predicted clinical rigidity scores (p < 10-5). Conclusions: A widely distributed cortical/subcortical network is associated with rigidity observed in PD patients, which reinforces the importance of altered functional connectivity in the pathophysiology of PD. PD subjects with higher rigidity scores tend to have less overshoot in their tracking performance, and damping ratio may represent a robust, quantitative marker of the motoric effects of increasing rigidity.

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    DOAJ
    Article . 2013
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    Frontiers in Neurology
    Article . 2013
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      Article . 2013
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      Frontiers in Neurology
      Article . 2013
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    Authors: Martina Minnerop; Martina Minnerop; Carla Gliem; Cornelia Kornblum; +1 Authors

    Neuroimaging in myotonic dystrophies provided a major contribution to the insight into brain involvement which is highly prevalent in these multisystemic disorders. Particular in Myotonic Dystrophy Type 1, conventional MRI first revealed hyperintense white matter lesions, predominantly localized in the anterior temporal lobe. Brain atrophy and ventricle enlargement were additional early findings already described almost 30 years ago. Since then, more advanced and sophisticated imaging methods have been applied in Myotonic Dystrophy Types 1 and 2. Involvement of actually normal appearing white matter and widespread cortical affection in PET studies were key results toward the recognition of diffuse and not only focally localized brain pathology in vivo. Later, structural abnormalities of both, gray and white matter, have been found in both forms of the disorder, albeit more prominent in myotonic dystrophy type 1. In Type 1, a consistent widespread cortical and subcortical involvement of gray and white matter affecting all lobes, brainstem and cerebellum was observed. Spectroscopy studies gave additional evidence of neuronal and glial damage in both types. Central questions regarding the origin and spatiotemporal evolution of the CNS involvement and its relevance for clinical symptoms had already been raised 30 years ago, however are still not answered. Results of correlation analyses between neuroimaging and clinical parameters are diverse and with few exceptions not well reproducible across studies. It may be related to the fact that most of the reported studies included only small numbers of subjects, sometimes even not separating Myotonic Dystrophy Type 1 from Type 2. But this heterogeneity may also support the current point of view that the clinical impairments are not simply linked to specific and regionally circumscribed structural or functional brain alterations. It seems more convincing that disturbed networks build the functional and structural substrate of clinical symptoms in these disorders as it is proposed in other neuropsychiatric diseases. Consecutively, structural and functional network analyses may provide additional information regarding the link between brain pathology and clinical symptoms. Up to now, only cross-sectional neuroimaging studies have been published. To analyze the temporal evolution of brain affection, longitudinal studies are urgently needed, and systematic natural history data would be useful to identify potential biomarkers for therapeutic studies.

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    Article . 2018
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    Frontiers in Neurology
    Article . 2018
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      Article . 2018
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      Frontiers in Neurology
      Article . 2018
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    Authors: Tatjana Traub-Weidinger; Otto Muzik; Lalith Kumar Shiyam Sundar; Susanne Aull-Watschinger; +14 Authors

    The purpose of this study was to establish a non-invasive clinical PET/MR protocol using [18F]-labeled deoxyglucose (FDG) that provides physicians with regional metabolic rate of glucose (MRGlc) values and to clarify the contribution of absolute quantification to clinical management of patients with non-lesional extratemporal lobe epilepsy (ETLE). The study included a group of 15 patients with non-lesional ETLE who underwent a dynamic FDG PET study using a fully-integrated PET/MRI system (Siemens Biograph). FDG tracer uptake images were converted to MRGlc (μmol/100 g/min) maps using an image derived input function that was extracted based on the combined analysis of PET and MRI data. In addition, the same protocol was applied to a group of healthy controls, yielding a normative database. Abnormality maps for ETLE patients were created with respect to the normative database, defining significant hypo- or hyper-metabolic regions that exceeded ±2 SD of normal regional mean MRGlc values. Abnormality maps derived from MRGlc images of ETLE patients contributed to the localization of hypo-metabolic areas against visual readings in 53% and increased the confidence in the original clinical readings in 33% of all cases. Moreover, quantification allowed identification of hyper-metabolic areas that are associated with frequently spiking cortex, rarely acknowledged in clinical readings. Overall, besides providing some confirmatory information to visual readings, quantitative PET imaging demonstrated only a moderate impact on clinical management of patients with complex pathology that leads to epileptic seizures, failing to provide new decisive information that would have changed classification of patients from being rejected to being considered for surgical intervention.

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    Article . 2020
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    Frontiers in Neurology
    Article . 2020
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      Article . 2020
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    Authors: Tobias Balkenhol; Elisabeth Wallhäusser-Franke; Nicole Rotter; Jérôme J. Servais;

    Objectives: Hearing improves significantly with bimodal provision, i.e., a cochlear implant (CI) at one ear and a hearing aid (HA) at the other, but performance shows a high degree of variability resulting in substantial uncertainty about the performance that can be expected by the individual CI user. The objective of this study was to explore how auditory event-related potentials (AERPs) of bimodal listeners in response to spoken words approximate the electrophysiological response of normal hearing (NH) listeners. Study Design: Explorative prospective analysis during the first 6 months of bimodal listening using a within-subject repeated measures design. Setting: Academic tertiary care center. Participants: Twenty-seven adult participants with bilateral sensorineural hearing loss who received a HiRes 90K CI and continued use of a HA at the non-implanted ear. Age-matched NH listeners served as controls. Intervention: Cochlear implantation. Main Outcome Measures: Obligatory auditory evoked potentials N1 and P2, and the event-related N2 potential in response to monosyllabic words and their reversed sound traces before, as well as 3 and 6 months post-implantation. The task required word/non-word classification. Stimuli were presented within speech-modulated noise. Loudness of word/non-word signals was adjusted individually to achieve the same intelligibility across groups and assessments. Results: Intelligibility improved significantly with bimodal hearing, and the N1–P2 response approximated the morphology seen in NH with enhanced and earlier responses to the words compared to their reversals. For bimodal listeners, a prominent negative deflection was present between 370 and 570 ms post stimulus onset (N2), irrespective of stimulus type. This was absent for NH controls; hence, this response did not approximate the NH response during the study interval. N2 source localization evidenced extended activation of general cognitive areas in frontal and prefrontal brain areas in the CI group. Conclusions: Prolonged and spatially extended processing in bimodal CI users suggests employment of additional auditory–cognitive mechanisms during speech processing. This does not reduce within 6 months of bimodal experience and may be a correlate of the enhanced listening effort described by CI listeners.

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    Frontiers in Neurology
    Article . 2020
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    Article . 2020
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      Frontiers in Neurology
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    Authors: Claudia eLainscsek; Claudia eLainscsek; Claudia eLainscsek; Jonathan eWeyhenmeyer; +8 Authors

    Time series analysis with delay differential equations (DDEs) reveals nonlinear properties of the underlying dynamical system and can serve as a non-linear time-domain classification tool. Here global DDE models were used to analyze short segments of simulated time series from a known dynamical system, the Rössler system, in high noise regimes. In a companion paper, we apply the DDE model developed here to classify short segments of encephalographic (EEG) data recorded from patients with Parkinson's disease and healthy subjects. Nine simulated subjects in each of two distinct classes were generated by varying the bifurcation parameter b and keeping the other two parameters (a and c) of the Rössler system fixed. All choices of b were in the chaotic parameter range. We diluted the simulated data using white noise ranging from 10dB to -30dB signal-to-noise ratios (SNR). Structure selection was supervised by selecting the number of terms, delays, and order of nonlinearity of the model DDE model that best linearly separated the two classes of data. The distances d from the linear dividing hyperplane was then used to assess the classification performance by computing the area A' under the ROC curve. The selected model was tested on untrained data using repeated random sub-sampling validation. DDEs were able to accurately distinguish the two dynamical conditions, and moreover, to quantify the changes in the dynamics. There was a significant correlation between the dynamical bifurcation parameter b of the simulated data and the classification parameter d from our analysis. This correlation still held for new simulated subjects with new dynamical parameters selected from each of the two dynamical regimes. Furthermore, the correlation was robust to added noise, being significant even when the noise was greater than the signal. We conclude that DDE models may be used as a generalizable and reliable classification tool for even small segments of noisy data.

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    Frontiers in Neurology
    Article . 2013
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    Authors: Claudio eLiguori; Mariangela ePierantozzi; Enrica eOlivola; Nicola B Mercuri; +1 Authors
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    Article . 2015
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    Authors: PEYMAN eADJAMIAN;

    In recent years there has been a significant increase in the use of electroencephalography (EEG) and magnetoencephalography (MEG) to investigate changes in oscillatory brain activity associated with tinnitus with many conflicting results. Current view of the underlying mechanism of tinnitus is that it results from changes in brain activity in various structures of the brain as a consequence of sensory deprivation. This in turn gives rise to increased spontaneous activity and/or synchrony in the auditory centres but also involves modulation from non-auditory processes from structures of the limbic and paralimbic system. Some of the neural changes associated with tinnitus may be assessed non-invasively in humans with MEG and EEG (M/EEG) in ways which are superior to animal studies and other non-invasive imaging techniques. However, both MEG and EEG have their limitations and research results can be misinterpreted in the absence of sufficient understanding of these limitations. In this article, I intend to provide a brief review of these techniques, describe what the recorded signals reflect in terms of the underlying neural activity, and their strengths and limitations. I also discuss some pertinent methodological issues involved in tinnitus related studies and concludes with suggestions to minimise possible discrepancies between results. The overall message is that while MEG and EEG are extremely useful techniques, the interpretation of results from tinnitus studies requires much caution given the individual variability in oscillatory activity and the limits of these techniques.

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    Authors: Garofalo, S. (Sara); Justicia, A. (Azucena); Arrondo, G. (Gonzalo); Ermakova, A.O. (Anna O.); +6 Authors

    Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (n = 12), or without (n = 17), a history of psychotic symptoms, along with a sample of healthy controls (n = 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (p < 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiological mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.

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    Apollo
    Article . 2017
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    Frontiers in Neurology
    Article . 2017 . Peer-reviewed
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