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1.  Enhancement of Functional Connectivity, Working Memory and Inhibitory Control on Multi-modal Brain MR Imaging with Rifaximin in Cirrhosis: Implications for the Gut-Liver-Brain Axis 
Metabolic brain disease  2014;29(4):1017-1025.
Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood.
To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE.
Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks.
Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin.
20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p=0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial.
A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.
PMCID: PMC4155029  PMID: 24590688
2.  Language Lateralization by fMRI and Wada Testing in 229 Epilepsy Patients: Rates and Predictors of Discordance 
Epilepsia  2013;54(2):314-322.
To more definitively characterize Wada/fMRI language dominance discordance rates with the largest sample of epilepsy patients to date, and to examine demographic, clinical, and methodological predictors of discordance.
229 epilepsy patients underwent both a standardized Wada test and a semantic-decision fMRI language protocol in a prospective research study. Language laterality indices were computed for each test using automated and double-blind methods, and Wada/fMRI discordance rates were calculated using objective criteria for discordance. Regression analyses were used to explore a range of variables that might predict discordance, including subject variables, Wada quality indices, and fMRI quality indices.
Key findings
Discordant results were observed in 14% of patients. Discordance was highest among those categorized by either test as having bilateral language. In a multivariate model, the only factor that predicted discordance was the degree of atypical language dominance on fMRI.
FMRI language lateralization is generally concordant with Wada testing. The degree of rightward shift of language dominance on fMRI testing is strongly correlated with Wada/fMRI discordance, suggesting that fMRI may be more sensitive than Wada to right hemisphere language processing, though the clinical significance of this increased sensitivity is unknown. The relative accuracy of fMRI vs. Wada testing for predicting post-surgical language outcome in discordant cases remains a topic for future research.
PMCID: PMC3649863  PMID: 23294162
epilepsy; language lateralization; fMRI; Wada
3.  A Comparison of Two FMRI Methods for Predicting Verbal Memory Decline After Left Temporal Lobectomy: Language Lateralization vs. Hippocampal Activation Asymmetry 
Epilepsia  2009;51(4):618-626.
Language lateralization measured by preoperative fMRI was shown recently to be predictive of verbal memory outcome in patients undergoing left anterior temporal lobe (L-ATL) resection. The aim of this study was to determine whether language lateralization or hippocampal activation asymmetry is a better predictor of memory outcome in this setting.
Thirty L-ATL patients underwent preoperative language fMRI, preoperative hippocampal fMRI using a scene encoding task, and pre- and postoperative neuropsychological testing. A group of 37 right ATL surgery patients who underwent the same testing procedures was included for comparison.
Verbal memory decline occurred in roughly half of the L-ATL patients. Preoperative language lateralization was correlated with postoperative verbal memory change. Hippocampal activation asymmetry was strongly related to side of seizure focus and to Wada memory asymmetry but was unrelated to verbal memory outcome.
Preoperative hippocampal activation asymmetry elicited by a scene encoding task is not predictive of verbal memory outcome. Risk of verbal memory decline is likely to be related to lateralization of material-specific verbal memory networks, which are more closely correlated with language lateralization than with overall asymmetry of episodic memory processes.
PMCID: PMC2945221  PMID: 19817807
temporal lobectomy; fMRI; memory; hippocampus; language dominance
4.  Use of Preoperative Functional MRI to Predict Verbal Memory Decline After Temporal Lobe Epilepsy Surgery 
Epilepsia  2008;49(8):1377-1394.
Verbal memory decline is a frequent complication of left anterior temporal lobectomy (L-ATL). The goal of this study was to determine whether preoperative language mapping using functional magnetic resonance imaging (fMRI) is useful for predicting which patients are likely to experience verbal memory decline after L-ATL.
Sixty L-ATL patients underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language and memory lateralization, and pre- and postoperative neuropsychological testing. Demographic, historical, neuropsychological, and imaging variables were examined for their ability to predict pre- to postoperative memory change.
Verbal memory decline occurred in over 30% of patients. Good preoperative performance, late age at onset of epilepsy, left dominance on fMRI, and left dominance on the Wada test were each predictive of memory decline. Preoperative performance and age at onset together accounted for roughly 50% of the variance in memory outcome (p < .001), and fMRI explained an additional 10% of this variance (p ≤ .003). Neither Wada memory asymmetry nor Wada language asymmetry added additional predictive power beyond these noninvasive measures.
Preoperative fMRI is useful for identifying patients at high risk for verbal memory decline prior to L-ATL surgery. Lateralization of language is correlated with lateralization of verbal memory, whereas Wada memory testing is either insufficiently reliable or insufficiently material-specific to accurately localize verbal memory processes.
PMCID: PMC2943848  PMID: 18435753
fMRI; memory; temporal lobectomy; language dominance; Wada test
5.  Concussion Symptom Inventory: An Empirically Derived Scale for Monitoring Resolution of Symptoms Following Sport-Related Concussion 
Self-report post-concussion symptom scales have been a key method for monitoring recovery from sport-related concussion, to assist in medical management, and return-to-play decision-making. To date, however, item selection and scaling metrics for these instruments have been based solely upon clinical judgment, and no one scale has been identified as the “gold standard”. We analyzed a large set of data from existing scales obtained from three separate case–control studies in order to derive a sensitive and efficient scale for this application by eliminating items that were found to be insensitive to concussion. Baseline data from symptom checklists including a total of 27 symptom variables were collected from a total of 16,350 high school and college athletes. Follow-up data were obtained from 641 athletes who subsequently incurred a concussion. Symptom checklists were administered at baseline (preseason), immediately post-concussion, post-game, and at 1, 3, and 5 days post-injury. Effect-size analyses resulted in the retention of only 12 of the 27 variables. Receiver-operating characteristic analyses were used to confirm that the reduction in items did not reduce sensitivity or specificity. The newly derived Concussion Symptom Inventory is presented and recommended as a research and clinical tool for monitoring recovery from sport-related concussion.
PMCID: PMC2800775  PMID: 19549721
Brain injury; Post-concussion; Scale
6.  FMRI and Wada Studies in Patients with Interhemispheric Dissociation of Language Functions 
Epilepsy & behavior : E&B  2008;13(2):350-356.
Rare patients with chronic epilepsy show interhemispheric dissociation of language functions on intracarotid amobarbital (Wada) testing. We encountered four patients with interhemispheric dissociation in 490 consecutive Wada language tests. In all cases, performance on overt speech production tasks was supported by the hemisphere contralateral to the seizure focus, while performance on comprehension tasks was served by the hemisphere with the seizure focus. These data suggest that speech production capacity is more likely to shift hemispheres than is language comprehension. Wada and fMRI language lateralization scores were discordant in three of the four patients. However, the two methods aligned more closely when Wada measures loading on comprehension were used for calculating lateralization scores. Thus, interhemispheric dissociation of language functions could explain some cases of discordance on Wada/fMRI language comparisons, particularly when the fMRI measure used is not sensitive to speech production processes.
PMCID: PMC2593837  PMID: 18504162
language dissociation; language mapping; fMRI; Wada test; intracarotid amobarbital test; epilepsy; interhemispheric dissociation; discordance
7.  A Comparison of Five FMRI Protocols for Mapping Speech Comprehension Systems 
Epilepsia  2008;49(12):1980-1997.
Many fMRI protocols for localizing speech comprehension have been described, but there has been little quantitative comparison of these methods. We compared five such protocols in terms of areas activated, extent of activation, and lateralization.
FMRI BOLD signals were measured in 26 healthy adults during passive listening and active tasks using words and tones. Contrasts were designed to identify speech perception and semantic processing systems. Activation extent and lateralization were quantified by counting activated voxels in each hemisphere for each participant.
Passive listening to words produced bilateral superior temporal activation. After controlling for pre-linguistic auditory processing, only a small area in the left superior temporal sulcus responded selectively to speech. Active tasks engaged an extensive, bilateral attention and executive processing network. Optimal results (consistent activation and strongly lateralized pattern) were obtained by contrasting an active semantic decision task with a tone decision task. There was striking similarity between the network of brain regions activated by the semantic task and the network of brain regions that showed task-induced deactivation, suggesting that semantic processing occurs during the resting state.
FMRI protocols for mapping speech comprehension systems differ dramatically in pattern, extent, and lateralization of activation. Brain regions involved in semantic processing were identified only when an active, non-linguistic task was used as a baseline, supporting the notion that semantic processing occurs whenever attentional resources are not controlled. Identification of these lexical-semantic regions is particularly important for predicting language outcome in patients undergoing temporal lobe surgery.
PMCID: PMC2645716  PMID: 18513352
language; fMRI; speech; comprehension; semantics; temporal lobe

Results 1-7 (7)