Timothy M. Ellmore

A Parametric fMRI Study of Overt and Covert Shifts of Visuospatial Attention

It has recently been demonstrated that a cortical network of visuospatial and oculomotor control areas is active for covert shifts of spatial attention (shifts of attention without eye movements) as well as for overt shifts of spatial attention (shifts of attention with saccadic eye movements). Studies examining activity in this visuospatial network during attentional shifts at a single rate have given conflicting reports about how the activity differs for overt and covert shifts. To better understand how the network subserves attentional shifts, we performed a parametric study in which subjects made either overt attentional shifts or covert attentional shifts at three different rates (0.2, 1.0, and 2.0 Hz). At every shift rate, both overt and covert shifts of visuospatial attention induced activations in the precentral sulcus, intraparietal sulcus, and lateral occipital cortex that were of greater amplitude for overt than during covert shifting. As the rate of attentional shifts increased, responses in the visuospatial network increased in both overt and covert conditions but this parametric increase was greater during overt shifts. These results confirm that overt and covert attentional shifts are subserved by the same network of areas. Overt shifts of attention elicit more neural activity than do covert shifts, reflecting additional activity associated with saccade execution. An additional finding concerns the anatomical organization of the visuospatial network. Two distinct activation foci were observed within the precentral sulcus for both overt and covert attentional shifts, corresponding to specific anatomical landmarks. We therefore reappraise the correspondence of these two precentral areas with the frontal eye fields.

H215O PET validation of steady-state arterial spin tagging cerebral blood flow measurements in humans

Steady‐state arterial spin tagging approaches can provide quantitative images of CBF, but have not been validated in humans. The work presented here compared CBF values measured using steady‐state arterial spin tagging with CBF values measured in the same group of human subjects using the H215O IV bolus PET method. Blood flow values determined by H215O PET were corrected for the known effects of incomplete extraction of water across the blood brain barrier. For a cortical strip ROI, blood flow values determined using arterial spin tagging (64 ± 12 cc/100g/min) were not statistically different from corrected blood flow values determined using H215O PET (67 ± 13 cc/100g/min). However, for a central white matter ROI, blood flow values determined using arterial spin tagging were significantly underestimated compared to corrected blood flow values determined using H215O PET. This underestimation could be caused by an underestimation of the arterial transit time for white matter regions. Magn Reson Med 44:450–456, 2000. Published 2000 Wiley‐Liss, Inc.

Intracranial EEG Reveals a Time- and Frequency-Specific Role for the Right Inferior Frontal Gyrus and Primary Motor Cortex in Stopping Initiated Responses

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band (∼16 Hz) for successful versus unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping. In addition, the right IFG response occurred 100–250 ms after the stop signal, a time range consistent with a putative inhibitory control process rather than with stop-signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased GABA inhibition in M1. Together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta frequency band in a right IFG/basal ganglia network, with downstream effects on M1.

Long-lasting cortical plasticity in the object naming system

A single exposure to an object can produce long-lasting behavioral change. Here, using event-related functional magnetic resonance imaging (fMRI), we provide evidence for long-lasting changes in cortical activity associated with perceiving and naming objects. In posterior regions, we observed an immediate (30-second) and long-lasting (3-day) decrease in neural activity after brief (200-ms) exposure to nameable and nonsense objects. In addition, slower-developing decreases in left inferior frontal activity were observed concurrently with increases in left insula activity, only for nameable objects. These time-dependent cortical changes may reflect two distinct learning mechanisms: the formation of sparser, yet more object-form-specific, representations in posterior regions, and experience-induced reorganization of the brain circuitry underlying lexical retrieval in anterior regions.

Variability of the Relationship between Electrophysiology and BOLD-fMRI across Cortical Regions in Humans

The relationship between blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal and the underlying neural electrical activity in humans is a topic of intense interest to systems neuroscience. This relationship has generally been assumed to be invariant regardless of the brain region and the cognitive task being studied. We critically evaluated these assumptions by comparing the BOLD-fMRI response with local field potential (LFP) measurements during visually cued common noun and verb generation in 11 humans in whom 1210 subdural electrodes were implanted. As expected, power in the mid-gamma band (60–120 Hz) correlated positively (r2 = 0.16, p < 10−16) and power in the beta band (13–30 Hz) correlated negatively (r2 = 0.09, p < 10−16) with the BOLD signal change. Beta and mid-gamma band activity independently explain different components of the observed BOLD signal. Importantly, we found that the location (i.e., lobe) of the recording site modulates the relationship between the electrocorticographic (ECoG) signal and the observed fMRI response (p < 10−16, F21,1830 = 52.7), while the type of language task does not. Across all brain regions, ECoG activity in the gamma and beta bands explains 22% of the fMRI response, but if the lobar location is considered, 28% of the variance can be explained. Further evaluation of this relationship at the level of individual gyri provides additional evidence of differences in the BOLD-LFP relationship by cortical locus. This spatial variability in the relationship between the fMRI signal and neural activity carries implications for modeling of the hemodynamic response function, an essential step for interregional fMRI comparisons.

Anatomic and electro-physiologic connectivity of the language system: A combined DTI-CCEP study

Here we present a novel multimodal analysis of network connectivity in the language system. We assessed connectivity of Brocas area using tractography with diffusion tensor imaging (DTI), and with cortico-cortical evoked potentials (CCEPs) to measure the spread of artificial currents applied directly to human cortex. We found that both the amplitude and latency of CCEP currents significantly correlates (r(2)=0.41, p<10(-16)) with the number of DTI pathways connecting the stimulation and recording loci. This strategy of relating electrical information flow with the neural architecture will likely yield new insights into cognitive processes.

Temporal lobe white matter asymmetry and language laterality in epilepsy patients

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Brocas area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Relationships between essential cortical language sites and subcortical pathways: Clinical article

OBJECT Maps produced using either electrical stimulation or functional imaging have demonstrated a distributed network of cortical regions involved in expressive and receptive language tasks. The pattern of connectivity among components of this network has begun to be explored with diffusion tensor (DT) imaging, but has yet to be completely characterized. In this study the authors used DT imaging-based tractography to examine the interrelationship between cortical areas found to be essential for language by intraoperative electrical stimulation. METHODS The authors localized the arcuate fasciculus (AF), a white matter fiber system connecting frontal and parietotemporal areas in 10 patients, 9 of whom subsequently underwent left hemispheric language mapping. RESULTS The authors found that 81 (79%) of 102 essential language sites (ELSs) were closely related to the AF. Of all ELSs, 59% were located within 7.5 mm of AF fiber pathway terminations, and another 20% contained pathways terminating closer to the AF than would be expected by chance (p < 0.05). Additionally, direct subcortical stimulation of the AF following focal cerebral resections produced transient language deficits. The close spatial relationship found between ELSs and the AF suggests that tractography data alone may be used for localization of ELSs. CONCLUSIONS The deficits evoked by subcortical stimulation validate and demonstrate the utility of this AF localization technique, and provide further evidence that the AF is an important pathway for fluent language. Taken together, these results demonstrate that DT imaging of the AF may be used to predict the location of brain areas that will be eloquent by the standards of stimulation mapping.

Altered nigrostriatal and nigrocortical functional connectivity in rapid eye movement sleep behavior disorder

STUDY OBJECTIVES Rapid eye movement sleep behavior disorder (RBD) is a condition closely associated with Parkinson disease (PD). RBD is a sleep disturbance that frequently manifests early in the development of PD, likely reflecting disruption in normal functioning of anatomical areas affected by neurodegenerative processes. Although specific neuropathological aspects shared by RBD and PD have yet to be fully documented, further characterization is critical to discovering reliable biomarkers that predict PD onset. In the current study, we tested the hypothesis of altered functional connections of the substantia nigra (SN) in patients in whom RBD was diagnosed. DESIGN Between-groups, single time point imaging. SETTING UTHSC-H 3 telsa MRI center. PARTICIPANTS Ten patients with RBD, 11 patients with PD, and 10 age-matched controls. INTERVENTIONS NA. MEASUREMENTS AND RESULTS We measured correlations of SN time series using resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in patients with idiopathic RBD who were at risk for developing PD, patients in whom PD was diagnosed, and age-matched controls. Using voxelwise analysis of variance, different correlations (P < 0.01, whole-brain corrected) between left SN and left putamen were found in patients with RBD compared with controls and patients with PD. SN correlations with right cuneus/precuneus and superior occipital gyrus were significantly different for patients with RBD compared with both controls and patients with PD. CONCLUSIONS The results suggest that altered nigrostriatal and nigrocortical connectivity characterizes rapid eye movement sleep behavior disorder before onset of obvious motor impairment. The functional changes are discussed in the context of degeneration in dopaminergic and cognition-related networks.

Mapping Voxel-Based Statistical Power on Parametric Images

Using a classic technique based on the noncentral F-distribution method for computing statistical power, we developed a general approach to the estimation of voxel-based power in functional brain image data analysis. We applied this method to PET data from a large sample (N = 40) of subjects performing the Wisconsin Card Sorting (WCST) paradigm analyzed with SPM95, produced statistical power maps for a range of samples sizes and smoothing filter widths, and examined the effects of sample size and image smoothing on the expected reliability of activation findings. At an uncorrected alpha of 0.01, a fixed filter size of 10 mm3, and a range of power thresholds, maps revealed that the power to reject the null hypothesis in brain regions implicated in the task at Ns of 5 and 10 may not be sufficient to ensure reliable replication of significant findings and so should be interpreted with caution. At sample sizes approaching 20 subjects, sufficient power was found in the right dorsolateral prefrontal cortex (BA 46/9), right and left inferior parietal lobule (BA 40), and left inferior temporal lobe (BA 37), comprising the cortical network typically observed during the WCST. Filter size needed to maximize power varied widely, but systematically, across the brain, tending to follow known neuroanatomical landmarks. Statistical power considerations in brain imaging studies are critical for controlling the rate of false negatives and assuring reliable detection of cognitive activation. The variation of filter size for maximizing power across the brain suggests that the underlying neuroanatomy of functional units is an important consideration in the a priori selection of filter size.