Ryan C.N. D’Arcy

The application of cognitive event-related brain potentials (ERPs) in language-impaired individuals: review and case studies

There is a substantial body of basic research that has utilized ERPs to investigate the neurological basis of cognition. This research has, in turn, led to the development of practical applications of cognitive ERPs in patient populations. In particular, recent work has focused on the development of ERP-based assessment measures for the neuropsychological assessment of dyslexia and language impairments secondary to stroke. This review describes the innovative assessment methods program (IAMP), an initiative to utilize ERPs for a neuropsychological assessment of patients who cannot be evaluated by traditional methods. The success of this program has demonstrated that ERPs can be used to reliably evaluate an individuals reading and speech comprehension abilities, independent of behavioral and speech production impediments. In contrast to traditional neuropsychological assessment, these ERP methods can discern the cognitive strategies used by an individual to perform a task.

An event-related brain potential study of receptive speech comprehension using a modified Token Test

There is a long and distinguished history of evaluating sensory functions with evoked potentials (EPs). However, the clinical utility of event-related brain potentials (ERPs) in the assessment of cognitive functions remains to be established. We present evidence for the efficacy of ERPs in the assessment of speech comprehension. In this normative study, a version of the Token Test (Boller and Vignolo, 1966, Brain, 89, 815-831: De Renzi and Vignolo, 1962, Brain, 85, 665-678) was modified for computer presentation with simultaneous ERP recordings and then administered to a group of healthy individuals (n = 27). A differential neural response pattern to incorrect and correct test items was obtained for the group and, more importantly, this result was also observed reliably at the individual subject level. This research complements on-going efforts in our laboratory to develop innovative measures for patients that are difficult or impossible to assess due to motoric and/or communicative limitations.

Sensitivity to White Matter fMRI Activation Increases with Field Strength

Functional magnetic resonance imaging (fMRI) activation in white matter is controversial. Given that many of the studies that report fMRI activation in white matter used high field MRI systems, we investigated the field strength dependence of sensitivity to white matter fMRI activation. In addition, we evaluated the temporal signal to noise ratio (tSNR) of the different tissue types as a function of field strength. Data were acquired during a motor task (finger tapping) at 1.5 T and 4 T. Group and individual level activation results were considered in both the sensorimotor cortex and the posterior limb of the internal capsule. We found that sensitivity increases associated with field strength were greater for white matter than gray matter. The analysis of tSNR suggested that white matter might be less susceptible to increases in physiological noise related to increased field strength. We therefore conclude that high field MRI may be particularly advantageous for fMRI studies aimed at investigating activation in both gray and white matter.

White versus gray matter: fMRI hemodynamic responses show similar characteristics, but differ in peak amplitude

BackgroundThere is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation.ResultsExamination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes.ConclusionsOverall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T.

Comparing gray and white matter fMRI activation using asymmetric spin echo spiral

Recent developments have shown that it is possible to detect functional magnetic resonance imaging (fMRI) activation in white matter (WM). Enhanced sensitivity to WM fMRI signals has been associated with the asymmetric spin echo (ASE) spiral sequence. The ASE spiral sequence produces three consecutive images that have equal blood-oxygen level-dependent (BOLD) contrast but increasing T(2) contrast. The current study evaluated whether ASE spiral sensitivity differed between white and gray matter in the corpus callosum, superior parietal lobes, cingulate gyrus, and inferior frontal lobes. Contrast and noise were compared across the three images for each region. Results showed increasing gains in functional contrast in both white and gray matter as a function of T(2) contrast. The third image, with the most T(2) contrast, showed the largest increase in contrast, while changes in noise were maintained. The results suggest that ASE spiral increases fMRI sensitivity globally through the addition of T(2) weighted contrast.

A site directed fMRI approach for evaluating functional status in the anterolateral temporal lobes

Functional magnetic resonance imaging (fMRI) is increasingly being used for neurosurgical planning. One potential application relates to identifying eloquent cortex in regions immediately adjacent to epileptogenic foci in temporal lobe epilepsy (TLE). While medial temporal structures, such as the hippocampus and amygdala, are typically removed during surgery, it is often difficult to determine whether nearby cortical regions in the anterolateral temporal lobe should be spared. An essential first step is to identify a method of activating these regions in healthy individuals. The purpose of this study was to develop a site directed fMRI approach for evaluating functional status in the anterolateral temporal lobes. A picture-word matching task, with object category and level of abstraction factors, was used to characterize temporal lobe activation. Whole brain analysis at the group level confirmed the involvement of the temporal poles as well as adjacent superior, middle and inferior temporal gyri within a larger object recognition network. A region-of-interest analysis on the anterolateral temporal lobe demonstrated that activation varied across conditions and regions for individuals. Importantly, it was possible to detect activation in one or more conditions and/or regions for all individuals--demonstrating that it is possible to evaluate functional status. The findings provide the foundation for a novel fMRI approach in neurosurgical planning for TLE.

Asymmetric Weighting to Optimize Regional Sensitivity in Combined fMRI-MEG Maps.

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are neuroimaging techniques that measure inherently different physiological processes, resulting in complementary estimates of brain activity in different regions. Combining the maps generated by each technique could thus provide a richer understanding of brain activation. However, present approaches to integration rely on a priori assumptions, such as expected patterns of brain activation in a task, or use fMRI to bias localization of MEG sources, diminishing fMRI-invisible sources. We aimed to optimize sensitivity to neural activity by developing a novel method of integrating data from the two imaging techniques. We present a data-driven method of integration that weights fMRI and MEG imaging data by estimates of data quality for each technique and region. This method was applied to a verbal object recognition task. As predicted, the two imaging techniques demonstrated sensitivity to activation in different regions. Activity was seen using fMRI, but not MEG, throughout the medial temporal lobes. Conversely, activation was seen using MEG, but not fMRI, in more lateral and anterior temporal lobe regions. Both imaging techniques were sensitive to activation in the inferior frontal gyrus. Importantly, integration maps retained activation from individual activation maps, and showed an increase in the extent of activation, owing to greater sensitivity of the integration map than either fMRI or MEG alone.

Tracking cognitive changes in new‐onset epilepsy: Functional imaging challenges

Functional imaging has potential for tracking changes in cognition during the onset and evolution of epilepsy. Although the concept of imaging such changes over time is an exciting new direction, feasibility remains an open question. The current article outlines a case example in which functional magnetic resonance imaging (fMRI) and event‐related potentials (ERPs) were used to monitor memory changes before and after selective temporal lobe resection. From this example, three key methodologic challenges for new‐onset epilepsy are identified and discussed. The first challenge relates to the interpretation of results in regions near epileptogenic tissue. We argue that this is best addressed by collecting information from multiple modalities to test for convergent evidence. The second challenge relates to optimizing the methods for sensitivity to detecting changes. In this case, enhanced imaging methods and a region‐of‐interest approach provide necessary focus. The third and final challenge relates to the practical difficulties of conducting research in new‐onset epilepsy cases. We suggest that greater integration of imaging research within the clinical setting is needed.

Multimodal characterization of the semantic N400 response within a rapid evaluation brain vital sign framework

BackgroundFor nearly four decades, the N400 has been an important brainwave marker of semantic processing. It can be recorded non-invasively from the scalp using electrical and/or magnetic sensors, but largely within the restricted domain of research laboratories specialized to run specific N400 experiments. However, there is increasing evidence of significant clinical utility for the N400 in neurological evaluation, particularly at the individual level. To enable clinical applications, we recently reported a rapid evaluation framework known as “brain vital signs” that successfully incorporated the N400 response as one of the core components for cognitive function evaluation. The current study characterized the rapidly evoked N400 response to demonstrate that it shares consistent features with traditional N400 responses acquired in research laboratory settings—thereby enabling its translation into brain vital signs applications.MethodsData were collected from 17 healthy individuals using magnetoencephalography (MEG) and electroencephalography (EEG), with analysis of sensor-level effects as well as evaluation of brain sources. Individual-level N400 responses were classified using machine learning to determine the percentage of participants in whom the response was successfully detected.ResultsThe N400 response was observed in both M/EEG modalities showing significant differences to incongruent versus congruent condition in the expected time range (p < 0.05). Also as expected, N400-related brain activity was observed in the temporal and inferior frontal cortical regions, with typical left-hemispheric asymmetry. Classification robustly confirmed the N400 effect at the individual level with high accuracy (89%), sensitivity (0.88) and specificity (0.90).ConclusionThe brain vital sign N400 characteristics were highly consistent with features of the previously reported N400 responses acquired using traditional laboratory-based experiments. These results provide important evidence supporting clinical translation of the rapidly acquired N400 response as a potential tool for assessments of higher cognitive functions.