Browsing by Author "Federico, Paolo"
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- ItemOpen AccessArginine vasopressin and the medial amygdaloid nucleus: a possible role in endogenous antipyresis(1990) Federico, Paolo; Veale, Warren L.
- ItemOpen AccessArtifact reduction in long-term monitoring of cerebral hemodynamics using near-infrared spectroscopy(Society of Photo-optical Instrumentation Engineers, 2015-05-26) Vinette, Sarah; Dunn, Jeff; Slone, Edward; Federico, PaoloNear-infrared spectroscopy (NIRS) is a noninvasive neuroimaging technique used to assess cerebral hemodynamics. Its portability, ease of use, and relatively low operational cost lend itself well to the long-term monitoring of hemodynamic changes, such as those in epilepsy, where events are unpredictable. Long-term monitoring is associated with challenges including alterations in behaviors and motion that can result in artifacts. Five patients with epilepsy were assessed for interictal hemodynamic changes and alterations in behavior or motion. Based on this work, visual inspection was used to identify NIRS artifacts during a period of interest, specifically prior to seizures, in four patients. A motion artifact reduction algorithm (MARA, also known as the spline interpolation method) was tested on these data. Alterations in the NIRS measurements often occurred simultaneously with changes in motion and behavior. Occasionally, sharp shift artifacts were observed in the data. When artifacts appeared as sustained baseline shifts in the data, MARA reduced the standard deviation of the data and the appearance improved. We discussed motion and artifacts as challenges associated with longterm monitoring of cerebral hemodynamics in patients with epilepsy and our group’s approach to circumvent these challenges and improve the quality of the data collected.
- ItemOpen AccessCaffeine Exacerbates Postictal Hypoxia(2019-01-07) Phillips, Thomas James; Teskey, G. Campbell; Mychasiuk, Richelle; Federico, PaoloBackground: Postictal hypoxia (PIH) is a stroke-like event that follows seizures and may be responsible for the postictal state. PIH may also be a contributing factor to the development of seizure-induced brain abnormalities and behavioral dysfunction associated with epilepsy. Caffeine is the world’s most popular drug with ~85% of people in the US consuming it daily. Thus, persons with epilepsy are likely to have caffeine in their system during seizures. This pre-clinical study investigated the acute and chronic effects of caffeine on tissue oxygenation pre- and post-seizure. Methods: We utilized the electrical kindling model in rats. A stimulating/recording electrode was placed into the rat ventral hippocampus (CA3), and an oxygen measuring optrode in dorsal hippocampus (CA1). Rats were administered vehicle (saline) or caffeine (5.0, 10.0, or 15.0 mg/kg) intraperitoneally, 30 minutes prior to an elicited seizure. Hippocampal oxygen levels were continually measured post-injection, and post-seizure, until returning to the normoxic range. Further, rats were administered various agonists and antagonists to determine adenosine receptors role in PIH. Lastly, rats were administered a chronic regime of caffeine to determine the long-term effects of caffeine in relation to PIH. Results: Caffeine at high (15. 0mg/kg) doses, caused a significant drop in pre-seizure hippocampal pO2. Following a seizure, caffeine at 10.0mg/kg and 15.0mg/kg, increased the time below the severe hypoxic threshold (10mmHg). Caffeine’s metabolites, paraxanthine, theobromine, and theophylline also increased the time below the severe hypoxic threshold. Adenosine A1 receptor agonist n6-Cyclopentyladenosine caused a significant drop in pre-seizure mean pO2 and increased the area below severe hypoxic threshold. A2A receptor antagonist SCH-58261 caused a significant drop in pre-seizure mean pO2. The A2B receptor, appeared to have no effect on hippocampal pO2 or PIH. Chronic caffeine consumption resulted in an increase in the area below the severe hypoxic threshold on day 15. Rats became tolerant to the drop-in pre-seizure pO2 via chronic consumption but became sensitized to the postictal severe hypoxia effects. Conclusions: Caffeine exacerbates postictal hypoxia; thus, this research hopes to guide future clinical investigations into the effect of caffeine on postictal blood flow and postictal symptomology in persons with epilepsy.
- ItemOpen AccessCellular and Network Substrates of Neuronal Excitability in Relation to Epileptic Seizures(2007-07) Khosravani, Houman; Zamponi, Gerald W.; Federico, PaoloBrain function is, in part, maintained by an appropriate balance between excitatory and inhibitory elements. In relation to excitability, factors such as the complement and distribution of ion channels, properties and composition of synaptic proteins, and dynamics affecting network synchrony all interact to modulate neuronal firing and network activity. In this dissertation, I present a series of three focused studies at the level of ion channels (T-type calcium channels), synaptic transmission (prion protein), and network activity (high frequency oscillations) that affect neuronal excitability. With regards to Cav3.2 T-type voltage-gated calcium channels, I demonstrate that novel missense mutations, as identified in patients with idiopathic generalized epilepsies, can result in alteration of channel biophysical properties. The majority of mutants altered gating properties consistent with greater channel activity. However, most of these biophysical alterations were not large in magnitude suggesting that the role of these channels in relation to other cellular processes may be affected. At the level of synapses, I describe a novel interaction/modulation of NMDA receptor currents by the endogenous prion protein (PrP). Using PrP-null mice, I show that loss of PrP results in enhanced synaptic NMDA currents with greater amplitude and prolonged deactivation kinetics. These changes do not seem to be related to developmental effects and possibly involve an NMDA receptor subunit switch to functional receptors containing NR2D. At the network level, I show that high frequency oscillations in field recordings in vitro and in the EEG from patients with epilepsy are localized to the seizure onset zone and increase over time during the immediate pre-seizure period. This knowledge can be used to better localized seizures for surgical resection, thereby improving seizure control in intractable patients. These three topics and their relevance to hyperexcitable states are discussed in the context of epileptiform seizure activity and neurological disease.
- ItemOpen AccessEstablishing a Framework to Transition High Frequency Oscillations to Routine Clinical Care in Patients with Focal Epilepsy(2016) Spring, Aaron Michael; Federico, Paolo; Agha-Khani, Yahya; Gotman, Jean; Protzner, Andrea B.; Starreveld, Yves Pieter; Teskey, Gordon CampbellHigh frequency oscillations (HFOs), characteristic oscillations observable using electroencephalography (EEG), are a promising and specific marker of the epileptogenic zone (EZ). However, there remain several obstacles to the implementation of HFOs as a prospective tool in the treatment of epilepsy. The identification of HFOs lacks universal standards and demands large time commitments from epileptologists. Therefore, this work involved the implementation and validation of novel frameworks for identifying HFOs, and for evaluating these HFOs as markers of the EZ. An epoched framework was implemented to facilitate the visual identification of HFOs, through which poor reliability was observed between reviewers. Furthermore, it was found that the temporal efficiency of visually evaluating HFOs within the epoched framework marked a substantial improvement over previously reported evaluation times. Using generalizability theory, it was then extended to determine effective methods of achieving highly reliable visual HFO evaluations, which included averaging ratings from at least 12 visual reviewers, or employing a training paradigm to increase the correlation of the ratings across reviewers. A novel surrogate marker (uGIC) of HFO activity was implemented and found to be correlated with HFOs detected algorithmically at low or high thresholds, all of which were found to be markers of the seizure onset zone overall. A retrospective framework was implemented to improve the accuracy of delineating the margins of resection with respect to EEG electrodes. A deformable method of image co-registration and a hybrid method of estimating electrode shift were shown to more effectively compensate for post-surgical shifts in brain anatomy. Resecting the uGIC or detected HFOs were found to have a positive effect on seizure freedom. Notably, the inclusion of lower-threshold oscillations was beneficial in facilitating the visual evaluation of HFOs, and in the identification of the EZ. Together, the findings of the studies undertaken herein provide a comprehensive framework to serve as the basis for transitioning high frequency oscillations to a feasible and meaningful part of the routine pre-surgical work-up in patients with focal epilepsy.
- ItemOpen AccessFrom phantom to patient: implementing simultaneous intracranial EEG and fMRI at 3 tesla(2008) Cunningham, Cameron; Federico, Paolo
- ItemOpen AccessIdentifying the Seizure Onset Zone using Intracranial EEG-fMRI(2018-09-18) Mohammadi, Negar; Federico, Paolo; Agha-Khani, Yahya; Goodyear, Bradley G.; Scantlebury, Morris H.; Sotero Díaz, Roberto C.Simultaneous EEG-fMRI has been an effective technique for identification of the seizure onset zone (SOZ) in patients with refractory epilepsy. Recent studies have shown that using intracranial electrodes (iEEG) combined with fMRI offers unique insight into changes in blood oxygen-level dependent (BOLD) responses associated with interictal epileptiform discharges (IEDs). However, the concordance level between SOZ and IED-related BOLD clusters has not been quantitatively investigated for different brain structures. This thesis aims to identify patient-specific concordance levels between spike-associated BOLD clusters and IED/SOZ originating from temporal and extra-temporal structures. The distances between the BOLD clusters to IED/SOZ locations were measured for 15 patients with focal refractory epilepsy. The results showed that the spike-generating network was better delineated in patients with temporal discharges compared to those with extra-temporal discharges. Also, we observed shorter distances between the BOLD clusters and the SOZ for mesial temporal lobe seizures compared to frontal lobe seizures. Further investigation into the differences between mesial temporal and frontal structures showed that patients with focal impaired awareness seizures had significantly higher concordance for mesial temporal lobe seizures. This key finding suggests that mesial temporal structures limit spike-associated BOLD activation to the SOZ more than the frontal lobe in patients who have spread of ictal activity to subcortical arousal systems. This mechanistic difference was also complemented by our findings pertaining seizure frequency. Specifically, concordance levels in temporal lobe structures were significantly higher for patients with weekly seizures compared to extra-temporal structures. Based on these findings, we suggest that iEEG-fMRI is a useful technique for identifying seizure onset zone for patients with epileptic spikes and seizures originate in the mesial temporal structures. The work presented in this thesis may assist clinicians to better determine the seizure onset zone, guide epilepsy surgery, and improve post-surgical outcomes for epilepsy patients.
- ItemOpen AccessInvestigation of the Pre-ictal State Using Near Infrared Spectroscopy and Functional Magnetic Resonance Imaging(2014-01-29) Vinette, Sarah; Federico, PaoloThe unpredictability of seizures impacts the quality of life of those with epilepsy. Previous studies have reported changes in cerebral hemodynamics prior to the onset of seizures, providing evidence of the existence of a pre-ictal state. In this thesis, near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) techniques were developed to characterize the variation in cerebral hemodynamics prior to seizures, in patients with focal epilepsy. The findings indicate that there are changes in cerebral hemodynamics within both hemispheres minutes prior to seizures. These results provide encouraging evidence that, with further technical improvements in the specificity of these techniques, the identification of such changes could allow sufficient time for measures to be taken to prevent seizure onset, thereby reducing the likelihood of seizures and improving the quality of life of those with epilepsy.
- ItemOpen AccessMethod for Optimizing Quantitative Temporal Lobe Epilepsy MR Imaging(2018-01-17) Basiri, Reza; Lebel, Robert Marc; Federico, Paolo; Agha-Khani, Yahya; Takele Zewdie, Ephrem; Frayne, Richard; Sotero Díaz, Roberto C.Many neurological disorders such as epilepsy rely on MRI for detection of structural abnormalities. However, the current clinical MRI methods are insufficient and insensitive in detection of subtle abnormalities. MRI quantitative T2 mapping is a promising quantitative medical imaging technique as it is highly sensitive to tissue composition. The conventional approach for T2 mapping assumes mono-exponential signal decay; however, this is rarely observed due to transmit field inhomogeneity and miscalibration at high field MRIs. The nonexponentially results in poor fits and a systematic bias in estimated decay rates. A recently proposed fitting method, called stimulated echo correction, uses the same input data but estimates the major confounds associated with mono-exponential fitting. Optimal accuracy and non-optimal precision is achieved in this method. My first aim was to develop a stimulated echo correction based method with fewer parameters and higher precision relative to the original one. The second aim was to implement this new method in order to better identify abnormal brain regions in temporal lobe epilepsy that were poorly visualized on standard images. I hypothesized that my improved stimulated echo correction with fewer parameters would provide more accurate and reliable transverse relaxometry imaging than does conventional or the original stimulated echo correction fitting methods, and would improve our ability to detect subtle irregularities associated with epilepsy. The new method was evaluated with simulated and in-vivo data, in which up to 27% reduction in variance in the new method compared to the original stimulated echo correction was observed. Moreover, the new method had greater reliability in categorizing abnormalities in hippocampal regions when compared with exponential and stimulated echo correction methods. I concluded that the new method is able to reduce the variance in T2 relaxometry from multi-echo spin echo sequences; therefore, this method can potentially help in detection of those lesser obvious hippocampus abnormalities.
- ItemOpen AccessMotor Network Organization in Frontal Lobe Epilepsy(2013-05-31) Woodward, Kristine; Federico, PaoloFrontal lobe epilepsy (FLE) is a seizure disorder that commonly coincides with functional motor deficits. While the source of these deficits is unknown, it is postulated that repeated seizure activity within the frontal lobe might impact the proximate motor network. To examine this hypothesis, motor networks were compared between participants with right FLE, left FLE, and controls using two methods. The first was a task-based fMRI study of brain activation during simple and complex motor tasks, and the second was a resting-state fMRI study of motor network connectivity. Both studies revealed motor network disturbances in participants with FLE, disturbances that were more pronounced in participants with higher seizure burden factors. These results show that motor networks are altered in FLE. In the future, motor fMRI studies may help identify the locations of seizure foci, predict post-surgical motor deficits, and ultimately improve the quality of life of patients with FLE.
- ItemOpen AccessNeurophysiological and diffusion tensor imaging correlates of mild traumatic brain injury in children(2018-07-24) King, Regan; Kirton, Adam; Barlow, Karen; Lebel, Catherine A.; Esser, Michael J.; Federico, PaoloChildren typically recover quickly following a mild traumatic brain injury (mTBI), however up to 15% of children continue to experience symptoms past three months post injury. Currently, underlying mechanisms of persistent post-concussive symptoms (PPCS) in children are unknown. The present thesis uses transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) to characterize the structural and functional characteristics of PPCS in 98 children (aged 8-18) with mTBI, over time. The Post-concussive Symptom Inventory (PCSI) was used to classify post-concussive symptoms in participants as symptomatic or asymptomatic. Twenty-six healthy controls were included for comparison. Neurophysiological data assessing cortical inhibition and facilitation were evaluated alongside symptom status. Associations between symptom status and DTI measures of water diffusion and anisotropy were also assessed in the corticospinal tract (CST), motor fibers of the corpus callosum (CC), and uncinate fasciculus (UF). Differences in neurophysiology were noted between healthy controls and children with mTBI in both inhibitory and excitatory TMS paradigms, further differentiating by symptom status. Differences in inhibitory paradigms were also noted over time. Fractional anisotropy (FA) differed as well in the UF, but not in the CST or CC, of symptomatic children compared to controls. No differences in diffusion metrics were observed over time. In summary, these findings suggest an indirect association of neurophysiology and white matter structure in mTBI recovery. Further exploration of neurophysiological and imaging correlates of PPCS are required to improve recovery and treatment outcomes of mTBI.
- ItemOpen AccessOptical imaging of neuronal activity patterns and seizure propagation in the isolated brain of the guinea pig(1994) Federico, Paolo; MacVicar, Brian A.
- ItemOpen AccessPost-ictal hypoperfusion detected by CT Perfusion(2018-05-07) Li, Emmy; Federico, Paolo; Teskey, Gordon Campbell; Lee, Ting Yim; Menon, Bijoy K.Background: Seizures are often followed by a period of transient neurological dysfunction whereby sensory, cognitive, or motor abilities are impaired. Alterations in cerebral blood flow (CBF) during the postictal period has been proposed as a possible mechanism for this phenomenon. Recent animal studies have shown reduced local CBF at the seizure onset zone (SOZ) lasting up to one hour following seizures (Farrell, et al., 2016). Using arterial spin labeling magnetic resonance imaging (ASL MRI), we have observed postictal hypoperfusion at the SOZ in 75% of patients lasting up to one hour (Gaxiola-Valdez, 2017). The clinical implementation of ASL as a novel tool to identify the SOZ is hampered by the limited availability of MRI on short notice. Computed tomography perfusion (CTP) also measures CBF changes and may circumvent the logistical limitations of MRI. Methods: Fifteen patients with drug resistant focal epilepsy admitted for pre-surgical evaluation were prospectively recruited and underwent CTP scanning within 80 min of a habitual seizure. Patients underwent a second scan in the interictal period after they were seizure-free for at least 24 hours. The acquired scans were visually assessed for perfusion differences and quantitatively assessed to identify areas of significant postictal hypoperfusion. Results: Postictal reductions of >15 CBF units (ml/100g-1/min-1) were seen in 12/15 patients. In 10 of these patients, the location of the hypoperfusion was partially or fully concordant with the presumed SOZ, and all patients localized additional areas of seizure propagation concordant with their electroencephalography (EEG). Conclusions: Postictal hypoperfusion can be measured by CTP. Thus, CTP has the potential to be a cost-effective and readily available tool in localizing the SOZ by measuring postictal CBF changes.
- ItemOpen AccessPostictal behavioural impairments are due to a severe prolonged hypoperfusion/ hypoxia event that is COX-2 dependent(eLife Sciences Publications Ltd, 2016-11-22) Farrell, Jordan; Gaxiola-Valdez, Ismael; Wolff, Marshal; David, Laurence; Dika, Haruna; Geeraert, Bryce; Wang, X Rachel; Singh, Shaily; Spanswick, Simon; Dunn, Jeffrey F.; Antle, Michael; Federico, Paolo; Teskey, G CampbellAbstract Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable.
- ItemOpen AccessReorganization of semantic noun processing in temporal lobe epilepsy(2008) Jensen, Elizabeth Janie; Federico, Paolo
- ItemOpen AccessSafety and feasibility of intracranial eeg in a high-field (3 tesla) environment(2006) Boucousis, Shannon Madeline; Goodyear, Bradley; Federico, Paolo
- ItemRestrictedSimultaneous Intracranial EEG-fMRI for the Study of Epilepsy in Humans at 3.0 T(2015-07-20) Beers, Craig; Federico, PaoloNeuroimaging plays in an important role in the diagnosis and treatment of epilepsy. In this work, a novel multi-modal technique for imaging the hemodynamic correlates of epileptic activity is explored. Simultaneous intracranial electroencephalography functional magnetic resonance imaging (iEEG-fMRI) combines the temporal precision of intracranial EEG with the high spatial resolution of fMRI. Applying this technique in patients with epilepsy, it was found the fMRI signal changes associated with interictal epileptiform discharges (IEDs) are patient-specific rather than consistent across subjects, implying that analyses of iEEG-fMRI data should allow for this variability through flexible analysis methods. In addition, significant fMRI activity was found adjacent to the electrode generating the IEDs in the majority of patients studied. It was determined that a minimum of 30 IEDs are necessary to detect fMRI activity near the active electrode, and the addition of more discharges to the analysis eliminates non-IED related noise providing more precise localization. Lastly, focusing exclusively on patients with mesial temporal lobe IEDs, two distinct patterns of fMRI activity were found: fMRI activity primarily localized to the active mesial temporal lobe, and widespread bilateral fMRI activity throughout the cortex. Notably, the patients with widespread activity were found to have fewer secondarily generalized seizures implying that the widespread fMRI activity may act to inhibit these seizures. In summary, simultaneous iEEG-fMRI is a viable technique for the study of epilepsy and may aid in the localization of the source of seizures and provide new insight into the networks involved in epileptic activity.
- ItemOpen AccessA Study on Cross-Frequency Coupling Effects on Intra-cranial EEG (iEEG) Data of Epileptic Patients(2020-12) Bazhan, Yanina; Braverman, Elena; Vasudevan, Kris; Zinchenko, Yuriy; Federico, PaoloHuman epilepsy is ascribed to neuronal disorder of the brain. Neuronal activity of drug-resistant epileptic patients awaiting resection surgeries is routinely studied using intracranial electroencephalogram (iEEG) recording techniques. Analysis methods applied to the measured iEEG data seek answers to the neuronal behaviour at different stages or ictal periods of a seizure. Cross-frequency coupling (CFC) that influences the phase and amplitude of the frequencies of neuronal signals is a basic brain activity striking a relationship between normal and disorder conditions. Shedding light on the CFC in measured iEEG data of epilepsy patients in vivo is important to understanding of and mediation to seizures. In this thesis, we examine a few CFC metrics, such as the generalized linear model (GLM), the modulation index (MI) and the phase-locking value (PLV). We compute the numerical values for these metrics to establish cross-frequency coupling “within” signals and also “between” brain regions of four different iEEG datasets of epileptic patients. Finally, we draw some preliminary conclusions on the results and suggest future directions.
- ItemOpen AccessTesting ASPECTS Reliability Using Color Coded Algorithm Enhanced Gray- White Matter Non Contrast CT(2018-07-09) Hafeez, Moiz; Menon, Bijoy K.; Qiu, Wu; Federico, Paolo; Demchuk, Andrew M.; Krupinski, Elizabeth A.; Sajobi, Tolulope T.The Alberta Stroke Program Early CT Score (ASPECTS) is widely used to assess and diagnose Acute Ischemic Stroke Patients (AIS). Inter-rater reliability for ASPECTS however, is very poor even amongst physicians with extensive expertise. Much of this limitation has to do with the lack of agreement amongst physicians in identifying Early Ischemic Changes (EIC) on Non- Contrast Computed Tomography (NCCT) scans. This lack of agreement is due to the extremely subtle findings that the human eye is exposed to on gray scale NCCT scans during the acute period of ischemia. We therefore sought to use post processing algorithms to develop Color- Coded Algorithm Enhanced Gray- White Matter (AEGWM) NCCT scans. Increased differentiation between Gray- White matter on AEGWM NCCT scans was developed to act as a powerful imaging tool allowing for better delineation of EIC for AIS patients. In this thesis I investigated the utility of AEGWM NCCT scans for the purposes of detecting EIC in AIS patients. Overall, we found that AEGWM scans performed better as opposed to gray scale NCCT scans when using DWI as ground truth. In addition, inter rater agreement increased consistently across raters of all levels of expertise while using AEGWM scans. Although with some limitations, the use of AEGWM scans may be a promising research direction to pursue for future work.
- ItemOpen AccessThe pre-ictal state in focal epilepsy(2011) Slone, Edward; Federico, Paolo; Dunn, Jeffrey F.