Limits of 2D-TCA in detecting BOLD responses to epileptic activity

Abstract

Summary Two-dimensional temporal clustering analysis (2D-TCA) is a relatively new functional MRI (fMRI) based technique that breaks blood oxygen level dependent activity into separate components based on timing and has shown potential for localizing epileptic activity independently of electroencephalography (EEG). 2D-TCA has only been applied to detect epileptic activity in a few studies and its limits in detecting activity of various forms (i.e. activation size, amplitude, and frequency) have not been investigated. This study evaluated 2D-TCA’s ability to detect various forms of both simulated epileptic activity and EEG-fMRI activity detected in patients. When applied to simulated data, 2D-TCA consistently detected activity in 6 min runs containing 5 spikes/run, 10 spikes/run, and one 5 s long event with hemodynamic response function amplitudes of at least 1.5%, 1.25%, and 1% above baseline respectively. When applied to patient data, while detection of interictal spikes was inconsistent, 2D-TCA consistently produced results similar to those obtained by EEG-fMRI when at least 2 prolonged interictal events (a few seconds each) occurred during the run. However, even for such cases it was determined that 2D-TCA can only be used to validate localization by other means or to create hypotheses as to where activity may occur, as it also detects changes not caused by epileptic activity.

Resting-state fMRI studies in epilepsy

“…A more recent study suggested that, although simulated data showed a potential advantage of 2D-TCA over EEG-fMRI in detecting activity restricted to deep brain structures, patient data did not show such results [32] . Another concern is that it still lacks specificity for epileptic activity [32] and therefore more studies are warranted.…”

Advantages and disadvantages of a fast fMRI sequence in the context of EEG–fMRI investigation of epilepsy patients: A realistic simulation study

“…The parameters of the simulated time series varied according to the following scenarios, each aiming at testing the impact of one of the postulated signal property: 1) Spiking rates (number of events): time series of 1, 2, or 3 spikes per 2-min background, referred to herein as spr1, spr2, and spr3 respectively, were generated at each level of BOLD signal amplitudes (see 2)). This range of spiking rates is in line with previous studies (LeVan et al, 2010;Khatamian et al, 2011). 2) BOLD signal amplitude: measured in % with respect to the brain global mean signal, and changing between 0.5% and 2%, in steps of 0.5%.…”

Delineating potential epileptogenic areas utilizing resting functional magnetic resonance imaging (fMRI) in epilepsy patients

“…However, the seizure can rarely be localized during an interictal state (Krakow 2008). EEG is overall limited by low spatial resolution and also by the depth of seizure focus (Khatamian 2011, Lopes 2012). …”

“…Using fMRI and EEG, simultaneously, overcomes some of the individual limitations; however, the simultaneous recordings are not sensitive to activity in deep structures and are usually only accurate with patients that experience frequent interictal epileptiform discharges recorded on the scalp (Lopes 2012, Morgan 2004). In addition, this technique is also very cumbersome, time consuming, and expensive to perform and analyze (Khatamian 2011, Morgan 2004). …”

“…In addition, using simulated data Khatamian, et al, (Khatamian 2011), assessed that TCA on fMRI data worked as well as EEG-fMRI results but could only be used to either propose possible locations or validate where activity occurs as determined by other methods. Despite this limited success with TCA, we were motivated by a successful report of our group, generated by a unique patient population.…”