Konstantinos Polyzoidis

Investigating the Role of Alpha and Beta Rhythms in Functional Motor Networks

It is recognized that lower electroencephalography (EEG) frequencies correspond to distributed brain activity over larger spatial regions than higher frequencies and are associated with coordination. In motor processes it has been suggested that this is not always the case. Our objective was to explore this contradiction. In our study, seven healthy subjects performed four motor tasks (execution and imagery of right hand and foot) under EEG recording. Two cortical source models were defined, model «A» with 16 regions of interest (ROIs) and model «B» with 20 ROIs over the sensorimotor cortex. Functional connectivity was calculated by Directed Transfer Function for alpha and beta rhythm networks. Four graph properties were calculated for each network: characteristic path length (CPL), clustering coefficient (CC), density (D) and small-world-ness (SW). Different network modules and in-degrees of nodes were also calculated and depicted in connectivity maps. Analysis of variance was used to determine statistical significance of observed differences in the network properties between tasks, between rhythms and between ROI models. Consistently on both models, CPL and CC were lower and D was higher in beta rhythm networks. No statistically significant difference was observed for SW between rhythms or for any property between tasks on any model. Comparing the models we observed lower CPL for both rhythms, lower CC in alpha and higher CC in beta when the number of ROIs increased. Also, denser networks with higher SW were correlated with higher number of ROIs. We propose a non-exclusive model where alpha rhythm uses greater wiring costs to engage in local information progression while beta rhythm coordinates the neurophysiological processes in sensorimotor tasks.

A Systematic Review of Investigations into Functional Brain Connectivity Following Spinal Cord Injury

Background: Complete or incomplete spinal cord injury (SCI) results in varying degree of motor, sensory and autonomic impairment. Long-lasting, often irreversible disability results from disconnection of efferent and afferent pathways. How does this disconnection affect brain function is not so clear. Changes in brain organization and structure have been associated with SCI and have been extensively studied and reviewed. Yet, our knowledge regarding brain connectivity changes following SCI is overall lacking. Methods: In this study we conduct a systematic review of articles regarding investigations of functional brain networks following SCI, searching on PubMed, Scopus and ScienceDirect according to PRISMA-P 2015 statement standards. Results: Changes in brain connectivity have been shown even during the early stages of the chronic condition and correlate with the degree of neurological impairment. Connectivity changes appear as dynamic post-injury procedures. Sensorimotor networks of patients and healthy individuals share similar patterns but new functional interactions have been identified as unique to SCI networks. Conclusions: Large-scale, multi-modal, longitudinal studies on SCI patients are needed to understand how brain network reorganization is established and progresses through the course of the condition. The expected insight holds clinical relevance in preventing maladaptive plasticity after SCI through individualized neurorehabilitation, as well as the design of connectivity-based brain-computer interfaces and assistive technologies for SCI patients.

Functional Brain Connectivity during Multiple Motor Imagery Tasks in Spinal Cord Injury

Reciprocal communication of the central and peripheral nervous systems is compromised during spinal cord injury due to neurotrauma of ascending and descending pathways. Changes in brain organization after spinal cord injury have been associated with differences in prognosis. Changes in functional connectivity may also serve as injury biomarkers. Most studies on functional connectivity have focused on chronic complete injury or resting-state condition. In our study, ten right-handed patients with incomplete spinal cord injury and ten age- and gender-matched healthy controls performed multiple visual motor imagery tasks of upper extremities and walking under high-resolution electroencephalography recording. Directed transfer function was used to study connectivity at the cortical source space between sensorimotor nodes. Chronic disruption of reciprocal communication in incomplete injury could result in permanent significant decrease of connectivity in a subset of the sensorimotor network, regardless of positive or negative neurological outcome. Cingulate motor areas consistently contributed the larger outflow (right) and received the higher inflow (left) among all nodes, across all motor imagery categories, in both groups. Injured subjects had higher outflow from left cingulate than healthy subjects and higher inflow in right cingulate than healthy subjects. Alpha networks were less dense, showing less integration and more segregation than beta networks. Spinal cord injury patients showed signs of increased local processing as adaptive mechanism. This trial is registered with NCT02443558.

Molecular Abnormalities in Gliomas

Gliomas constitute the most common type of primary brain tumour. They are derived from glial cells of astrocytic, oligodendroglial and ependymal origin. According to histologic type, the most frequently reported neoplasms are the astrocytic tumours, which account for approximately 40% of the cases reported. Oligodendrogliomas and ependymomas are less common tumours accounting for 3.2% and 3–9% of all primary central nervous system (CNS) neoplasms, respectively.

Commercial BCI Control and Functional Brain Networks in Spinal Cord Injury: A Proof-of-Concept

Spinal Cord Injury (SCI), along with disability, results in changes of brain organization and structure. While sensorimotor networks of patients and healthy individuals share similar patterns, unique functional interactions have been identified in SCI networks. Brain-Computer Interfaces (BCIs) have emerged as a promising technology for movement restoration and rehabilitation of SCI patients. We describe an experimental methodology to combine high-resolution electroencephalography (EEG) for investigation of functional connectivity following SCI and non-invasive BCI control of robotic arms. Two BCI-naïve female subjects, a SCI patient and a healthy control subject participated in the proof-of-concept implementation. They were instructed to perform motor imagery (MI) while watching multiple movements of either arms or legs during walking, while under 128-channel EEG recording. They were, subsequently, asked to control two robotic arms (Mercury v2.0) using a commercial class EEG-BCI. They both achieved comparable performance levels of robotic control, 52.5% for the SCI patient and 56.9% for the healthy control. We performed a feasibility analysis of functional networks on the EEG-BCI recordings. Visual MI allows training on multiple imagined movements and shows promise in investigating differences in functional cortical networks associated with different motor tasks. This approach could allow the implementation of functional network-based BCIs in the future for complex movement control.

Positron emission tomography imaging in gliomas

Glioma, the most frequent primary brain tumor in adults, is a highly infiltrative tumor exhibiting resistance to most treatments and associated with short survival of patients. Positron emission tomography (PET) imaging using various tracers takes advantage of the increased metabolic rate of neoplastic cells, in order to detect tumors and validate the treatment response. The most frequently used PET tracer, the (18)F-fluorodeoxyglucose (FDG), is useful during the initial and follow-up assessment of patients with gliomas because it can assist in the selection of the initial biopsy site and to assess early response to a given therapeutic intervention. Furthermore, when there is tumor re-growth after an initial remission, FDG-PET can differentiate between true tumor recurrence versus necrosis from radiation therapy. Newly developed PET tracers may exhibit better sensitivity than FDG to diagnose primary brain tumors, but may occasionally produce false positive results in various conditions. In any event, PET is a useful tool in patients with central nervous system cancer during both initial assessment and follow-up.

Abstract 791: Low DARPP32 and related profiles in glioblastomas

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC DARPP32 (PPP1R1B, an inhibitor of protein phosphatase-1) plays a central role in dopamine signalling in the brain and has been associated with a number of diverse conditions, ranging from nicotine dependence to cancer drug resistance, while its overexpression has been reported as pro-oncogenic in various epithelial cancers. Since data on this molecule in astrocytic carcinogenesis are missing, this study focused on DARPP32 expression and related profiles in astrocytic gliomas. In a panel of 157 routinely diagnosed astrocytic glioma tissues we assessed (i) relative expression of DARPP32 along with 21 additional transcript targets from key regulators in signalling pathways commonly disturbed in glioblastomas (GBM), (ii) genomic status of selected genes and (iii) activation status of the Akt and Stat pathways. Normal brain tissues expressed DARPP32 at considerable levels. In comparison, the expression of this molecule was strongly decreased (low = decrease of >1 order of magnitude) according to histological grade, more frequently in grade IV (GBM, 89/116 [77%]) than in grade III (11/22 [50%]) and grade II (4/19 [21%]) tumors (p<0.0001). Low DARPP32 was associated with EGFR gene amplification (p=0.0006) and mRNA/protein overexpression; high pro-angiogenic VEGF isoform (p=0.0002) and hTERT expression (p=0.0008); low SRC/STAT expression (STAT3, 5A and 5B ps<0.0001) but common Stat3 (p=0.0003) and Akt/PKB phosphorylation (p=0.0036). Two specific Akt deactivating phosphatases, PHLPP2 and PHLPP1 were also identified to be downregulated/absent in GBM (63% and 23%, respectively), in line with their proposed tumor suppressor role. Strikingly, low expression of these two genes almost coincided with low DARPP32, with strongly decreased DARPP32/PHLPP2 and DARPP32/PHLPP2/PHLPP1 in 54% and 17.2% of GBMs, respectively. In 66 out of the 116 GBM patients with known follow-up, this latter profile was associated with a slightly better survival (log rank, p=0.0496); all corresponding tumors had activated Akt-Thr308 but lacked EGFR/EGFRvIII, MET, SRC, STATs, TERT (12/12), and VEGF isoform (8/12) overexpression, and 12q gene amplification (10/12). In conclusion, DARPP32 expression is strongly decreased in high grade astrocytic tumors where, in contrast to what has been described for common epithelial cancers, low DARPP32 seems to be related to pro-oncogenic and adverse prognostic parameters. This study also demonstrates that, except for PTEN, additional phosphatases regulating Akt signalling are commonly missing in GBM, mostly in parallel with low DARPP32. Further dissecting the molecular environment accompanying the decreased expression of these genes seems important for understanding the behaviour of this highly heterogeneous group of tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 791.