Gray Matter Abnormalities in Temporal Lobe Epilepsy: Relationships with Resting-State Functional Connectivity and Episodic Memory Performance.

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is necessary to produce reductions in episodic memory recall. The latter, in particular, demonstrates the complex structure/function interactions at work when trying to understand cognition in TLE, suggesting that subtle network effects can emerge bearing specific relationships to hemisphere and the type of pathology

Hippocampal functional connectivity patterns during spatial working memory differ in right versus left temporal lobe epilepsy.

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM task. Results revealed that both TLE groups displayed a negative relation between WM performance and FC between the left hippocampus and ipsilateral parahippocampal gyrus. We also found a positive relationship between performance and FC between the left hippocampus seed and the precuneus, in the right TLE group. Lastly, the left TLE specifically demonstrated a negative relationship between performance and FC between both hippocampi and ipsilateral cerebellar clusters. Our findings indicate that right and left TLE groups may develop different patterns of FC to implement visuospatial WM. Indeed, the present result suggests that FC provides a unique means of identifying abnormalities in brain networks, which cannot be discerned at the level of behavioral output through neuropsychological testing. More broadly, our findings demonstrate that FC methods applied to task-based fMRI provide the opportunity to define specific task-related networks

Extratemporal functional connectivity impairments at rest are related to memory performance in mesial temporal epilepsy.

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of focal epilepsy. At rest, there is evidence that brain abnormalities in MTLE are not limited to the epileptogenic region, but extend throughout the whole brain. It is also well established that MTLE patients suffer from episodic memory deficits. Thus, we investigated the relation between the functional connectivity seen at rest in fMRI and episodic memory impairments in MTLE. We focused on resting state BOLD activity and evaluated whether functional connectivity (FC) differences emerge from MTL seeds in left and right MTLE groups, compared with healthy controls. Results revealed significant FC reductions in both patient groups, localized in angular gyri, thalami, posterior cingulum and medial frontal cortex. We found that the FC between the left non-pathologic MTL and the medial frontal cortex was positively correlated with the delayed recall score of a non-verbal memory test in right MTLE patients, suggesting potential adaptive changes to preserve this memory function. In contrast, we observed a negative correlation between a verbal memory test and the FC between the left pathologic MTL and posterior cingulum in left MTLE patients, suggesting potential functional maladaptative changes in the pathologic hemisphere. Overall, the present study provides some indication that left MTLE may be more impairing than right MTLE patients to normative functional connectivity. Our data also indicates that the pattern of extra-temporal FC may vary as a function of episodic memory material and each hemisphere\u27s capacity for cognitive reorganization

Increased microstructural white matter correlations in left, but not right, temporal lobe epilepsy.

Microstructural white matter tract correlations have been shown to reflect known patterns of phylogenetic development and functional specialization in healthy subjects. The aim of this study was to establish intertract correlations in a group of controls and to examine potential deviations from normality in temporal lobe epilepsy (TLE). We investigated intertract correlations in 28 healthy controls, 21 left TLE (LTLE) and 23 right TLE (RTLE). Nine tracts were investigated, comprising the parahippocampal fasciculi, the uncinate fasciculi, the arcuate fasciculi, the frontoparietal tracts, and the fornix. An abnormal increase in tract correlations was observed in LTLE, while RTLE showed intertract correlations similar to controls. In the control group, tract correlations increased with increasing fractional anisotropy (FA), while in the TLE groups tract correlations increased with decreasing FA. Cluster analyses revealed agglomeration of bilateral pairs of homologous tracts in healthy subjects, with such pairs separated in our LTLE and RTLE groups. Discriminant analyses aimed at distinguishing LTLE from RTLE, revealing that tract correlations produce higher rates of accurate group classification than FA values. Our results confirm and extend previous work by showing that LTLE compared to RTLE patients display not only more extensive losses in microstructural orientation but also more aberrant intertract correlations. Aberrant correlations may be related to pathologic processes (i.e., seizure spread) or to adaptive processes aimed at preserving key cognitive functions. Our data suggest that tract correlations may have predictive value in distinguishing LTLE from RTLE, potentially moving diffusion imaging to a place of greater prominence in clinical practice

Functional connectivity evidence of cortico-cortico inhibition in temporal lobe epilepsy.

Epileptic seizures can initiate a neural circuit and lead to aberrant neural communication with brain areas outside the epileptogenic region. We focus on interictal activity in focal temporal lobe epilepsy and evaluate functional connectivity (FC) differences that emerge as function of bilateral versus strictly unilateral epileptiform activity. We assess the strength of FC at rest between the ictal and non-ictal temporal lobes, in addition to whole brain connectivity with the ictal temporal lobe. Results revealed strong connectivity between the temporal lobes for both patient groups, but this did not vary as a function of unilateral versus bilateral interictal status. Both the left and right unilateral temporal lobe groups showed significant anti-correlated activity in regions outside the epileptogenic temporal lobe, primarily involving the contralateral (non-ictal/non-pathologic) hemisphere, with precuneus involvement prominent. The bilateral groups did not show this contralateral anti-correlated activity. This anti-correlated connectivity may represent a form of protective and adaptive inhibition, helping to constrain epileptiform activity to the pathologic temporal lobe. The absence of this activity in the bilateral groups may be indicative of flawed inhibitory mechanisms, helping to explain their more widespread epileptiform activity. Our data suggest that the location and build up of epilepsy networks in the brain are not truly random, and are not limited to the formation of strictly epileptogenic networks. Functional networks may develop to take advantage of the regulatory function of structures such as the precuneus to instantiate an anti-correlated network, generating protective cortico-cortico inhibition for the purpose of limiting seizure spread or epileptogenesis

Temporal lobe epilepsy and surgery selectively alter the dorsal, not the ventral, default-mode network.

The default-mode network (DMN) is a major resting-state network. It can be divided in two distinct networks: one is composed of dorsal and anterior regions [referred to as the dorsal DMN (dDMN)], while the other involves the more posterior regions [referred to as the ventral DMN (vDMN)]. To date, no studies have investigated the potentially distinct impact of temporal lobe epilepsy (TLE) on these networks. In this context, we explored the effect of TLE and anterior temporal lobectomy (ATL) on the dDMN and vDMN. We utilized two resting-state fMRI sessions from left, right TLE patients (pre-/post-surgery) and normal controls (sessions 1/2). Using independent component analysis, we identified the two networks. We then evaluated for differences in spatial extent for each network between the groups, and across the scanning sessions. The results revealed that, pre-surgery, the dDMN showed larger differences between the three groups than the vDMN, and more particularly between right and left TLE than between the TLE patients and controls. In terms of change post-surgery, in both TLE groups, the dDMN also demonstrated larger changes than the vDMN. For the vDMN, the only changes involved the resected temporal lobe for each ATL group. For the dDMN, the left ATL group showed post-surgical increases in several regions outside the ictal temporal lobe. In contrast, the right ATL group displayed a large reduction in the frontal cortex. The results highlight that the two DMNs are not impacted by TLE and ATL in an equivalent fashion. Importantly, the dDMN was the more affected, with right ATL having a more deleterious effects than left ATL. We are the first to highlight that the dDMN more strongly bears the negative impact of TLE than the vDMN, suggesting there is an interaction between the side of pathology and DM sub-network activity. Our findings have implications for understanding the impact TLE and subsequent ATL on the functions implemented by the distinct DMNs

Emotional/Psychiatric Symptom Change and Amygdala Volume After Anterior Temporal Lobectomy

Introduction Patients who undergo anterior temporal lobectomy (ATL) to treat temporal lobe epilepsy (TLE) often experience worsened or de novo psychiatric symptoms. There is evidence to suggest that the pathophysiology of epilepsy and mood disorders are linked both functionally or structurally in the brain.1,2 While several studies have examined the role that changes in hippocampal volume may play in predicting post-surgical depression, the role of the amygdala in such prediction has been overlooked, despite extensive literature demonstrating its contribution to emotion processing and expression.3,4 The goal of this project was to determine if change in amygdala volume is a predictor of depression and/or anxiety in TLE patients who undergo ATL, with specific attention given to side of surgery. Methods Data was collected from 32 patients who underwent ATLs (19 right, 13 left, matched samples). Pre- and post-surgery Personality Assessment Inventory (PAI) data were collected on 14 ATL patients. The following PAI subscales were utilized in this analysis: Anxiety: PAIANX; Anxiety Related Disorder: PAIARD; Depression: PAIDEP). Volumetric analysis was performed on pre- and post-surgical T1 MRIs using Freesurfer’s longitudinal processing function. Left and right amygdala volumes, change scores, and amygdala asymmetry ratios were calculated taking into account whole brain volume. 55% of the patients were seizurefree after 1 year (RTLE= 8, LTLE= 9); 29% received an Engel Class score of 2 or 3 (RTLE= 7, LTLE= 2

Resting-State Brain Organization Revealed by Functional Covariance Networks

BACKGROUND: Brain network studies using techniques of intrinsic connectivity network based on fMRI time series (TS-ICN) and structural covariance network (SCN) have mapped out functional and structural organization of human brain at respective time scales. However, there lacks a meso-time-scale network to bridge the ICN and SCN and get insights of brain functional organization. METHODOLOGY AND PRINCIPAL FINDINGS: We proposed a functional covariance network (FCN) method by measuring the covariance of amplitude of low-frequency fluctuations (ALFF) in BOLD signals across subjects, and compared the patterns of ALFF-FCNs with the TS-ICNs and SCNs by mapping the brain networks of default network, task-positive network and sensory networks. We demonstrated large overlap among FCNs, ICNs and SCNs and modular nature in FCNs and ICNs by using conjunctional analysis. Most interestingly, FCN analysis showed a network dichotomy consisting of anti-correlated high-level cognitive system and low-level perceptive system, which is a novel finding different from the ICN dichotomy consisting of the default-mode network and the task-positive network. CONCLUSION: The current study proposed an ALFF-FCN approach to measure the interregional correlation of brain activity responding to short periods of state, and revealed novel organization patterns of resting-state brain activity from an intermediate time scale

No effect of 24 h severe energy restriction on appetite regulation and ad libitum energy intake in overweight and obese males

Background/Objectives: Long-term success of weight loss diets might depend on how the appetite regulatory system responds to energy restriction (ER). This study determined the effect of 24 h severe ER on subjective and hormonal appetite regulation, subsequent ad libitum energy intake and metabolism. Subjects/Methods: In randomised order, eight overweight or obese males consumed a 24 h diet containing either 100% (12105 (1174 kJ; energy balance; EB) or 25% (3039 (295) kJ; ER) of estimated daily energy requirements (EER). An individualised standard breakfast containing 25% of EER (3216 (341) kJ) was consumed the following morning and resting energy expenditure, substrate utilisation and plasma concentrations of acylated ghrelin, glucagon-like peptide-1 (GLP-17–36), glucose-dependant insulinotropic peptide (GIP1–42), glucose, insulin and non-esterified fatty acid (NEFA) were determined for 4 h after breakfast. Ad libitum energy intake was assessed in the laboratory on day 2 and via food records on day 3. Subjective appetite was assessed throughout. Results: Energy intake was not different between trials for day 2 (EB: 14946 (1272) kJ; ER: 15251 (2114) kJ; P=0.623), day 3 (EB: 10580 (2457) kJ; 10812 (4357) kJ; P=0.832) or day 2 and 3 combined (P=0.693). Subjective appetite was increased during ER on day 1 (P0.381). Acylated ghrelin, GLP-17–36 and insulin were not different between trials (P>0.104). Post-breakfast area under the curve (AUC) for NEFA (P<0.05) and GIP1–42 (P<0.01) were greater during ER compared with EB. Fat oxidation was greater (P<0.01) and carbohydrate oxidation was lower (P<0.01) during ER, but energy expenditure was not different between trials (P=0.158). Conclusions: These results suggest that 24 h severe ER does not affect appetite regulation or energy intake in the subsequent 48 h. This style of dieting may be conducive to maintenance of a negative EB by limiting compensatory eating behaviour, and therefore may assist with weight loss

Interactive seminars or small group tutorials in preclinical medical education: results of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Learning in small group tutorials is appreciated by students and effective in the acquisition of clinical problem-solving skills but poses financial and resource challenges. Interactive seminars, which accommodate large groups, might be an alternative. This study examines the educational effectiveness of small group tutorials and interactive seminars and students' preferences for and satisfaction with these formats.</p> <p>Methods</p> <p>Students in year three of the Leiden undergraduate medical curriculum, who agreed to participate in a randomized controlled trial (RCT, n = 107), were randomly allocated to small group tutorials (n = 53) or interactive seminars (n = 54). Students who did not agree were free to choose either format (n = 105). Educational effectiveness was measured by comparing the participants' results on the end-of-block test. Data on students' reasons and satisfaction were collected by means of questionnaires. Data was analyzed using student unpaired t test or chi-square test where appropriate.</p> <p>Results</p> <p>There were no significant differences between the two educational formats in students' test grades. Retention of knowledge through active participation was the most frequently cited reason for preferring small group tutorials, while a dislike of compulsory course components was mentioned more frequently by students preferring interactive seminars. Small group tutorials led to greater satisfaction.</p> <p>Conclusions</p> <p>We found that small group tutorials leads to greater satisfaction but not to better learning results. Interactive learning in large groups might be might be an effective alternative to small group tutorials in some cases and be offered as an option.</p