Function In Temporal Lobe Epilepsy Research Articles

Olfactory Dysfunction and Limbic Hypoactivation in Temporal Lobe Epilepsy.

The epileptogenic network in temporal lobe epilepsy (TLE) contains structures of the primary and secondary olfactory cortex such as the piriform and entorhinal cortex, the amygdala, and the hippocampus. Olfactory auras and olfactory dysfunction are relevant symptoms of TLE. This study aims to characterize olfactory function in TLE using olfactory testing and olfactory functional magnetic resonance imaging (fMRI). We prospectively enrolled 20 individuals with unilateral TLE (age 45 ± 20 years [mean ± SD], 65% female, 90% right-handed) and 20 healthy individuals (age 33 ± 15 years [mean ± SD], 35% female, 90% right-handed). In the TLE group, the presumed seizure onset zone was left-sided in 75%; in 45% of the individuals with TLE limbic encephalitis was the presumed etiology; and 15% of the individuals with TLE reported olfactory auras. Olfactory function was assessed with a Screening Sniffin' Sticks Test (Burkhart, Wedel, Germany) during a pre-assessment. During a pre-testing, all individuals were asked to rate the intensity, valence, familiarity, and associated memory of five different odors (eugenol, vanillin, phenethyl alcohol, decanoic acid, valeric acid) and a control solution. During the fMRI experiment, all individuals repeatedly smelled eugenol (positively valenced odor), valeric acid (negatively valenced odor), and the control solution and were asked to rate odor intensity on a five-point Likert scale. We acquired functional EPI sequences and structural images (T1, T2, FLAIR). Compared to healthy individuals, individuals with TLE rated the presented odors as more neutral (two-sided Mann-Whitney U tests, FDR-p < 0.05) and less familiar (two-sided Mann-Whitney U tests, FDR-p < 0.05). fMRI data analysis revealed a reduced response contrast in secondary olfactory areas (e.g., hippocampus) connected to the limbic system when comparing eugenol and valeric acid in individuals with TLE when compared with healthy individuals. However, no lateralization effect was obtained when calculating a lateralization index by the number of activated voxels in the olfactory system (two-sided Mann-Whitney U test; U = 176.0; p = 0.525). TLE is characterized by olfactory dysfunction and associated with hypoactivation of secondary olfactory structures connected to the limbic system. These findings contribute to our understanding of the pathophysiology of TLE. This study was preregistered on OSF Registries (www.osf.io).

Abnormalities of regional brain activity and executive function in patients with temporal lobe epilepsy: A cross-sectional and longitudinal resting-state functional MRI study.

We decided to track changes in regional brain activity and executive function in temporal lobe epilepsy (TLE) patients based on cross-sectional and longitudinal designs and sought potential imaging features for follow-up observation. Thirty-two TLE patients and thirty-three healthy controls (HCs) were recruited to detect changes in fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) and to evaluate executive function both at baseline and at two-year (23.3 ± 8.3months) follow-up. Moreover, multivariate pattern analysis (MVPA) was used for follow-up observation. TLE patients displayed lower fALFF values in the right superior frontal gyrus (SFG) and higher ReHo values in the left putamen (PUT) relative to the HCs. Longitudinal analysis revealed that TLE patients at follow-up exhibited higher fALFF values in the left postcentral gyrus (PoCG), higher ReHo values in the left PoCG and the right middle frontal gyrus (MFG), lower ReHo values in the bilateral PUT and the right fusiform gyrus (FFG) compared with these patients at baseline. The executive function was impaired in TLE patients but didn't deteriorate over time. No correlations were discovered between regional brain activity and executive function. The MVPA based on ReHo performed well in differentiating the follow-up group from the baseline group. We revealed the abnormalities in regional brain activity and executive function as well as their longitudinal trends in TLE patients. The ReHo might be a good imaging feature for follow-up observation.

Atypical intrinsic neural timescales in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults. Here we profiled local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using resting-state functional magnetic resonance imaging (rs-fMRI), we mapped the whole-brain intrinsic neural timescales (INT), which reflect temporal hierarchies of neural processing. Parallel analysis of structural and diffusion MRI data examined associations with TLE-related structural compromise. Finally, we evaluated the clinical utility of INT. We studied 46 patients with TLE and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region-specific associations to structural alterations and explored the effects of age and epilepsy duration. Supervised machine learning assessed the utility of INT for identifying patients with TLE vs controls and left- vs right-sided seizure onset. Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in the ipsilateral medial and lateral temporal regions, and bilateral sensorimotor cortices as well as thalamus and hippocampus. Findings were similar, albeit with reduced effect sizes, when correcting for structural alterations. INT reductions in TLE increased with advancing disease duration, yet findings differed from the aging effects seen in controls. INT-derived classifiers discriminated patients vs controls (balanced accuracy, 5-fold: 76% ± 2.65%; cross-site, 72%-83%) and lateralized the focus in TLE (balanced accuracy, 5-fold: 96% ± 2.10%; cross-site, 95%-97%), with high accuracy and cross-site generalizability. Findings were consistent across both acquisition sites and robust when controlling for motion and several methodological confounds. Our findings demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which emphasizes promising clinical utility.

Grafted hPSC-derived GABA-ergic interneurons regulate seizures and specific cognitive function in temporal lobe epilepsy

Interneuron loss/dysfunction contributes to spontaneous recurrent seizures (SRS) in chronic temporal lobe epilepsy (TLE), and interneuron grafting into the epileptic hippocampus reduces SRS and improves cognitive function. This study investigated whether graft-derived gamma-aminobutyric acid positive (GABA-ergic) interneurons directly regulate SRS and cognitive function in a rat model of chronic TLE. Human pluripotent stem cell-derived medial ganglionic eminence-like GABA-ergic progenitors, engineered to express hM4D(Gi), a designer receptor exclusively activated by designer drugs (DREADDs) through CRISPR/Cas9 technology, were grafted into hippocampi of chronically epileptic rats to facilitate the subsequent silencing of graft-derived interneurons. Such grafting substantially reduced SRS and improved hippocampus-dependent cognitive function. Remarkably, silencing of graft-derived interneurons with a designer drug increased SRS and induced location memory impairment but did not affect pattern separation function. Deactivation of DREADDs restored both SRS control and object location memory function. Thus, transplanted GABA-ergic interneurons could directly regulate SRS and specific cognitive functions in TLE.

Glymphatic system dysfunction in temporal lobe epilepsy patients with hippocampal sclerosis.

ObjectiveThis study aimed to evaluate glymphatic system function in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS) in comparison to healthy controls, using diffusion tensor imaging (DTI)‐analysis along the perivascular space (ALPS) method. We hypothesized that there is glymphatic system dysfunction in TLE patients with HS.MethodsWe retrospectively enrolled 25 TLE patients with HS and 26 age‐ and sex‐matched healthy controls. All participants underwent DTI with the same 3T magnetic resonance imaging scanner, and the DTI‐ALPS index was calculated. We evaluated the differences in the DTI‐ALPS index between TLE patients with HS and healthy controls. Moreover, we evaluated the correlation between the DTI‐ALPS index and clinical characteristics of epilepsy, including age, age at seizure onset, duration of epilepsy, and number of anti‐seizure medications (ASMs).ResultsThere was a difference in the DTI‐ALPS index between TLE patients with HS and healthy controls. The DTI‐ALPS index in TLE patients with HS was lower than that in healthy controls (1.497 vs. 1.668, P = .015). However, there was no difference in the DTI‐ALPS index between the newly diagnosed TLE patients with HS and the chronic TLE patients with HS. The DTI‐ALPS index was negatively correlated with age (r = −0.420, P = .036). However, the DTI‐ALPS index was not correlated with other clinical characteristics, including age at seizure onset, duration of epilepsy, and number of ASMs.SignificanceOur findings showed that the DTI‐ALPS index was significantly lower in TLE patients with HS than in healthy controls, indicating the presence of glymphatic system dysfunction in TLE patients with HS. Our study also suggests that the DTI‐ALPS method may be useful for evaluating glymphatic system function in epilepsy.

The impact of processing speed on cognition in temporal lobe epilepsy

PurposeTo characterize the impact of slowed processing speed on the efficiency of broader cognitive function in temporal lobe epilepsy (TLE). MethodsParticipants included 100 patients with TLE and 89 healthy controls (mean ages 36.8 and 33.6, respectively) administered a neuropsychological battery consisting of 15 cognitive metrics. Confirmatory factor analysis using structural equation modeling (SEM) latent variable modeling demonstrated a cognitive structure representing the domains of verbal intelligence, immediate memory, delayed memory, executive function, working memory, and processing speed. Furthermore, the latent variable measurement model determined the direct and indirect relationships of verbal intelligence and processing speed with immediate memory, delayed memory, executive function, and working memory. ResultsFollowing SEM of hypothesized structural models, the results demonstrated that, among controls, intelligence had a direct and unmediated (by processing speed) relationship with all identified cognitive domains. In contrast, among participants with TLE, processing speed mediated the relationship between verbal intelligence and performance across all cognitive domains. ConclusionSlowing of cognitive/psychomotor processing speed appears to play a critical mediating role in the broader cognitive status of participants with TLE and may serve as a target through which to attempt to exert a broad positive impact on neuropsychological status.

Evaluation of Hippocampal Function in Temporal Lobe Epilepsy: Spatial Bayesian Variable Selection and Grouping the Regression Coefficient in Multilevel Functional Magnetic Resonance Imaging Data Analysis.

Background: A pre-surgical evaluation of cognitive functions in patients with mesial temporal lobe epilepsy (mTLE) is critical. The limitations of the usual brain analysis model were resolved by the spatial Bayesian variable selection (SBVS) method. An Ising and Dirichlet Process (Ising-DP) model considers SBVS and the grouping of a large number of voxels. The present study aimed to identify brain areas involved in episodic memory in patients with right mTLE and controls via the Ising-DP model. The model was extended to include between-subject factors (BSFs), and the results were compared with other classical methods.Methods: The present cross-sectional study was conducted on 15 patients with right mTLE and 20 controls in Tehran, Iran, in 2018. During functional magnetic resonance imaging, the subjects were tested with the face-encoding memory task, followed by a recognition memory test. The participants demographic factors such as age, sex, marital status, area of residence, and years of schooling were considered to comprise BSFs. The independent t test, the chi-square test, and the correlation test were conducted using the SPSS software (version 20.0). The image processing was carried out using SPM (version 12.0) and MATLAB (version R2014a).Results: The Ising-DP model appropriately (R2=0.642) detected activated hippocampal areas. The model adjusted for BSFs indicated a better fit by the significant effect of age (P((γ]>0.91), sex (P[γ]>0.87), and years of schooling (P[γ]>0.89). The heat maps exhibited decreased activation in the right hippocampal region in the patients compared with the controls (P<0.0001). Right hippocampal activity had a significant positive correlation with the recognition memory test in the mTLE group (r=0.665) and the control group (r=0.593)Conclusion: The Ising-DP model was sufficiently sensitive to detect activated areas in our patients with right mTLE during the face-encoding memory task. Since the model adjusted for BSFs improved sensitivity, we recommend the use of more detailed BSFs such as seizure history in future research.

Alterations Functional Connectivity in Temporal Lobe Epilepsy and Their Relationships With Cognitive Function: A Longitudinal Resting-State fMRI Study.

Background: Cognitive impairments in temporal lobe epilepsy (TLE) patients has been described as a chronically progressive feature of the disease. However, how severe recurrent seizures modify neuronal circuits in the human brain and subsequently degrade cognitive function, remains largely unknown. Here, we aimed to investigate longitudinal alterations by functional magnetic resonance imaging (fMRI) in TLE patients and to assess how those alterations are related to cognitive function performance.Methods: Sixteen TLE patients and 20 normal controls (NCs) were recruited for a study to observe longitudinal alterations in resting-state functional connectivity (FC) and to estimate alertness, orientation, and executive function both at baseline and at a follow-up time ~3 years later.Results: TLE patients, compared with NCs, showed impaired executive function, intrinsic alertness, and phasic alertness and exhibited lengthened reaction time (RT) in the spatial cue and center cue conditions at baseline. The orienting function of TLE patients was declined at follow-up compared to the baseline. Cross-sectional analysis demonstrated that TLE patients displayed significantly greater positive correlation than NCs between the right dorsolateral prefrontal cortex (DLPFC) and the right inferior parietal lobule (IPL) and right superior frontal gyrus (SFG). Furthermore, among TLE patients, the longitudinal study revealed a decrease in correlation between the right DLPFC and the right SFG compared to the baseline. In addition, there was a significant negative correlation between the longitudinal change in FC and the change in orienting function in TLE subjects.Conclusions: Abnormal connectivity between the DLPFC and the SFG suggests the potential of longitudinal resting-state fMRI to delineate regions relevant to cognitive dysfunction for disease progression.

LncRNA ILF3-AS1 mediated the occurrence of epilepsy through suppressing hippocampal miR-212 expression.

Increased expression of some matrix metalloproteinases (MMPs) is closely associated with epilepsy. However, factors that promote their expression have not been clarified. Long noncoding RNAs (lncRNAs) play crucial roles in the development of human diseases, including various cancers, but its potential function in temporal lobe epilepsy (TLE) has remained unexplored. In this study, we showed that hippocampal and serum ILF3-AS1 levels are higher in TLE patients than in matched controls. Interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced ILF3-AS1 expression in astrocytes, while ectopic expression of ILF3-AS1 enhanced IL-6 and TNF-α expression. Ectopic ILF3-AS1 in astrocytes also increased expression of MMP2, MMP3, MMP9 and MMP14, but suppressed expression of miR-212. Consistent with that finding, miR-212 levels were lower in the hippocampus and serum of TLE patients than their controls. This suggests that ILF3-AS1 promotes expression of inflammatory cytokines and MMPs by targeting miR-212 and that ILF3-AS1 plays a crucial role in the development of TLE.

Altered upright face recognition and presence of face inversion effect in temporal lobe epilepsy: An event-related potential study.

Facial recognition can be assessed by examining an event-related potential component, namely the N170. The amplitude of the N170 is larger in response to inverted faces than to upright faces. To examine facial processing in patients with temporal lobe epilepsy (TLE), we investigated the amplitude of the N170, the face inversion effect, and the association between social functioning and face-specific configuration processing. Sixteen patients with TLE and 17 normal controls (NC) participated in this study. Event-related potentials in response to upright or inverted neutral faces and bicycles were recorded. Social functioning was assessed by the socioeconomic status of the participants using the 5-point Hollingshead-Redlich Scale. Compared with NC, patients with TLE had decreased N170 amplitudes. The inversion effect was observed for face stimuli in both groups; however, no inversion effect was observed for bicycle stimuli. Additionally, in TLE patients, but not in NC, socioeconomic status was significantly correlated with the N170 amplitudes in response to upright faces. In a social context, upright faces are processed as a whole. This process is impaired in TLE. Conversely, inverted faces are processed analytically. This function is normal in TLE. Abnormal face-specific configuration processing may contribute to lower social functioning in TLE.

Altered Frontal Lobe Network Function in Temporal Lobe Epilepsy Revealed by Graph Theory Analysis (P1.279)

Altered Frontal Lobe Network Function in Temporal Lobe Epilepsy Revealed by Graph Theory Analysis (P1.279)

Depressive Symptoms Contribute to Executive Deficits in Temporal Lobe Epilepsy.

This study examined the contribution of depression to reduced executive functioning in temporal lobe epilepsy (TLE) using three groups: TLE only (TLE; N=29), TLE+depression (TLE+DEP) (N=22), and nonneurologic participants with depression (DEP; N=31). Participants completed the Delis-Kaplan Executive Function System. Individuals with TLE performed worse than the DEP group on many tests of executive functions. Among the TLE participants, those with depression demonstrated poorer executive functioning. These findings support the notion that depression may further contribute to executive difficulties in individuals with TLE. Depression treatment in this population could lead to improvements in cognition.

Cerebral Hemispheric Lateralization Associated with Hippocampal Sclerosis May Affect Interictal Cardiovascular Autonomic Functions in Temporal Lobe Epilepsy.

It is well established that the temporal lobe epilepsy (TLE) is linked to the autonomic nervous system dysfunctions. Seizures alter the function of different systems such as the respiratory, cardiovascular, gastrointestinal, and urogenital systems. The aim of this work was to evaluate the possible factors which may be involved in interictal cardiovascular autonomic function in temporal lobe epilepsy with complex partial seizures, and with particular attention to hippocampal sclerosis. The study was conducted in 30 patients with intractable temporal lobe epilepsy (19 with left hippocampal sclerosis, 11 with right hippocampal sclerosis). All subjects underwent four tests of cardiac autonomic function: heart rate changes in response to deep breathing, heart rate, and blood pressure variations throughout resting activity and during hand grip, mental stress, and orthostatic tests. Our results show that the right cerebral hemisphere predominantly modulates sympathetic activity, while the left cerebral hemisphere mainly modulates parasympathetic activity, which mediated tachycardia and excessive bradycardia counterregulation, both of which might be involved as a mechanism of sudden unexpected death in epilepsy patients (SUDEP).

Correlations between Limbic White Matter and Cognitive Function in Temporal-Lobe Epilepsy, Preliminary Findings.

The limbic system is presumed to have a central role in cognitive performance, in particular memory. The purpose of this study was to investigate the relationship between limbic white matter microstructure and neuropsychological function in temporal-lobe epilepsy (TLE) patients using diffusion tensor imaging (DTI). Twenty-one adult TLE patients, including 7 non-lesional (nlTLE) and 14 with unilateral mesial temporal sclerosis (uTLE), were studied with both DTI and hippocampal T2 relaxometry. Correlations were performed between fractional anisotropy (FA) of the bilateral fornix and cingulum, hippocampal T2, neuropsychological tests. Positive correlations were observed in the whole group for the left fornix and processing speed index. In contrast, memory tests did not show significant correlations with DTI findings. Subgroup analysis demonstrated an association between the left fornix and processing speed in nlTLE but not uTLE. No correlations were observed between hippocampal T2 and test scores in either the TLE group as a whole or after subgroup analysis. Our findings suggest that integrity of the left fornix specifically is an important anatomical correlate of cognitive function in TLE patients, in particular patients with nlTLE.

Elemental spatial and temporal association formation in left temporal lobe epilepsy.

The mesial temporal lobe (MTL) is typically understood as a memory structure in clinical settings, with the sine qua non of MTL damage in epilepsy being memory impairment. Recent models, however, understand memory as one of a number of higher cognitive functions that recruit the MTL through their reliance on more fundamental processes, such as “self-projection” or “association formation”. We examined how damage to the left MTL influences these fundamental processes through the encoding of elemental spatial and temporal associations. We used a novel fMRI task to image the encoding of simple visual stimuli, either rich or impoverished, in spatial or spatial plus temporal information. Participants included 14 typical adults (36.4 years, sd. 10.5 years) and 14 patients with left mesial temporal lobe damage as evidenced by a clinical diagnosis of left temporal lobe epilepsy (TLE) and left MTL impairment on imaging (34.3 years, sd. 6.6 years). In-scanner behavioral performance was equivalent across groups. In the typical group whole-brain analysis revealed highly significant bilateral parahippocampal activation (right > left) during spatial associative processing and left hippocampal/parahippocampal deactivation in joint spatial-temporal associative processing. In the left TLE group identical analyses indicated patients used MTL structures contralateral to the seizure focus differently and relied on extra-MTL regions to a greater extent. These results are consistent with the notion that epileptogenic MTL damage is followed by reorganization of networks underlying elemental associative processes. In addition, they provide further evidence that task-related fMRI deactivation can meaningfully index brain function. The implications of these findings for clinical and cognitive neuropsychological models of MTL function in TLE are discussed.

S12-2. Possible application of mismatch negativity in patients with epilepsy in a clinical research

It is well known that the mismatch negativity (MMN) has multiple generators: one in the temporal lobe and another in the frontal lobe. To investigate the effect of an epileptic focus on MMN, we compared the MMN of patients with temporal lobe epilepsy (TLE) with various seizure frequencies with the MMN of healthy controls. The MMN was consistently altered in TLE with the use of multiple types of stimuli. The MMN was enhanced at fronto-central sites and reduced at mastoid sites. TLE patients with lower seizure frequencies showed larger MMN amplitudes for deviant responses to phonetic stimulation at Fz. Taken together, our findings show that epileptic foci in the temporal lobe affect frontal and temporal function differently. The diminished MMN at mastoid sites may reflect dysfunction of the temporal lobe in TLE. In contrast, the enhanced MMN at fronto-central sites may reflect an increase in hyperexcitability or hypersynchronous activity. The results are consistent with previous reports of changes in frontal lobe function in TLE. In addition, we present a case of longitudinal changes of the MMN in TLE.

Cerebellar volume is linked to cognitive function in temporal lobe epilepsy: A quantitative MRI study

IntroductionChronic intractable temporal lobe epilepsy (TLE) is associated with certain comorbidities including cognitive impairment. A less common condition among patients with TLE is intermittent explosive disorder (IED), a specific form of aggressive behavior that has been linked to low intelligence and structural pathology in the amygdala. We aimed to identify other neuroanatomical substrates of both cognitive dysfunction and IED in patients with TLE, with special focus on the cerebellum, a brain region known to participate in functional networks involved in neuropsychological and affective processes. MethodsMagnetic resonance imaging-based volumetric data from 60 patients with temporal lobe epilepsy (36 with and 24 without IED) were evaluated. Cerebellar, hippocampal, and total brain volumes were processed separately. In a total of 50 patients, the relationship between volumetric measurements and clinical and neuropsychological data (full-scale, verbal, and performance intelligence quotients) was analyzed. ResultsIntermittent explosive disorder in patients with TLE was not significantly linked to any of the regional volumes analyzed. However, cognitive performance showed a significant association both with total brain volume and cerebellar volume measurements, whereby the left cerebellar volume showed the strongest association. A deviation from normal cerebellar volumes was related to lower intelligence. Of note, left cerebellar volume was influenced by age and duration of epilepsy. Hippocampal volumes had a minor influence on cognitive parameters. ConclusionOur findings suggest that cerebellar volume is not linked to IED in patients with TLE but is significantly associated with cognitive dysfunction. Our findings support recent hypotheses proposing that the cerebellum has a relevant functional topography.

Fine structure of hippocampal mossy fiber synapses following rapid high‐pressure freezing

Synapses of hippocampal neurons play important roles in learning and memory processes and are involved in aberrant hippocampal function in temporal lobe epilepsy. Major neuronal types in the hippocampus as well as their input and output synapses are well known, but it has remained an open question to what extent conventional electron microscopy (EM) has provided us with the real appearance of synaptic fine structure under in vivo conditions. There is reason to assume that conventional aldehyde fixation and dehydration lead to protein denaturation and tissue shrinkage, likely associated with the occurrence of artifacts. However, realistic fine-structural data of synapses are required for our understanding of the transmission process and for its simulation. Here, we used high-pressure freezing and cryosubstitution of hippocampal tissue that was not subjected to aldehyde fixation and dehydration in ethanol to monitor the fine structure of an identified synapse in the hippocampal CA3 region, that is, the synapse between granule cell axons, the mossy fibers, and the proximal dendrites of CA3 pyramidal neurons. Our results showed that high-pressure freezing nicely preserved ultrastructural detail of this particular synapse and allowed us to study rapid structural changes associated with synaptic plasticity.

Role of Functional MRI in Presurgical Evaluation of Memory Function in Temporal Lobe Epilepsy

Many diagnostic tools have been employed to predict the likelihood of a postoperative memory decline after a standard temporal lobectomy, including the intracarotid amobarbital testing (IAT) or Wada, regarded as the gold standard test for over the past half a century. Functional MRI (fMRI) is also a promising tool in that regard. Its routine use to predict the postoperative memory decline has been limited because of the varied study paradigms, discrepancies in analysis, and interpretation of the results. Based on the existing literatures, fMRI cannot replace IAT for the routine presurgical evaluation of the patients with temporal lobe epilepsy (TLE) yet. Large multicentre studies with a panel of memory test are required to determine the full potential of fMRI and use it reliably to replace IAT in the routine clinical practice. In this paper, we review various aspects of memory fMRI, including the experimental designs, data analysis, and findings.

Implementing a Brief Exam to Identify Frontotemporal disease-associated Deficits in ALS Patients

Flaherty-Craig completed her doctorate in clinical neuropsychology with thesis research focused on executive functioning in temporal lobe epilepsy at the Union Institute and University in 1998. After her clinical fellowship in Neurorehabilitation at the Penn State University Hospital Rehabilitation Center as a post doctorate, she joined the faculty of Neurology in 2003, where she continues to pursue a multifaceted across-the-lifespan research program including pediatric oncology, developmental disorders and frontotemporal disease (FTD). Her dementia studies have resulted in the development of a published brief exam (2006) for detection of the FTD prodrome. A refinement of this approach, published in 2009, allowed for the identification of the three subtypes of the FTD prodrome upon completion of a 20 min brief exam. This exam is now being applied to a multi-center study involving 14 ALS Multidisciplinary Clinics across the United States. Recently published (2011) validation studies have related the FTD cognitive prodrome to difficulties with both verbal and nonverbal problem solving, accompanied by loss of insight. It is expected that this work will lead to the development of innovative remediation approaches to compensate for deterioration in judgment capacities in a broad spectrum of conditions that affect the frontal lobe, from developmental disorders to emerging FTD. Areas of impact are expected to include treatment compliance, safety and quality of life with respect to both the affected individual and caregivers.