Quantifying sensory thresholds along the migraine cycle: An exploratory longitudinal study.

BACKGROUND: To date, a number of studies on migraine have cross-sectionally evaluated sensory sensitivity with aversion thresholds/scores along the migraine cycle, reporting a decreased tolerance to sensory stimuli in different sensory modalities. Our hypothesis was that patients with migraine would exhibit heightened sensitivity to sound, light, touch and smell on days where they reported greater headache intensity. METHODS: This is an exploratory, longitudinal study, carried out over the course of 27 days. Aversion thresholds or scores to sound, light, touch and smell were quantified in six patients with migraine (11.33 ± 6.53 headache days/month). RESULTS: Patients reported an increased sensitivity to light (padj = 0.0297), touch (padj = 0.0077), and smell (padj = 0.0201) on days with higher headache intensity. However, a greater sensitivity to sound on days with higher headache intensity was only reported when anxiety levels were high (padj = 1.4e-06). Interestingly, variable levels of tolerance to bothersome light over time can also influence the correlation between light sensitivity and headache intensity (padj = 1.4e-06). CONCLUSIONS: Based on the present findings, future longitudinal studies evaluating sensory threshold changes along the migraine cycle in patients with migraine should account for the increased tolerance to bothersome light over time as well as the effect of anxiety on auditory sensitivity.

Exploring sensory sensitivity, cortical excitability, and habituation in episodic migraine, as a function of age and disease severity, using the pattern-reversal task.

BACKGROUND: Migraine is a cyclic, neurosensory disorder characterized by recurrent headaches and altered sensory processing. The latter is manifested in hypersensitivity to visual stimuli, measured with questionnaires and sensory thresholds, as well as in abnormal cortical excitability and a lack of habituation, assessed with visual evoked potentials elicited by pattern-reversal stimulation. Here, the goal was to determine whether factors such as age and/or disease severity may exert a modulatory influence on sensory sensitivity, cortical excitability, and habituation. METHODS: Two similar experiments were carried out, the first comparing 24 young, episodic migraine patients and 28 healthy age- and gender-matched controls and the second 36 middle-aged, episodic migraine patients and 30 healthy age- and gender-matched controls. A neurologist confirmed the diagnoses. Migraine phases were obtained using eDiaries. Sensory sensitivity was assessed with the Sensory Perception Quotient and group comparisons were carried out. We obtained pattern-reversal visual evoked potentials and calculated the N1-P1 Peak-to-Peak amplitude. Two linear mixed-effects models were fitted to these data. The first model had Block (first block, last block) and Group (patients, controls) as fixed factors, whereas the second model had Trial (all trials) and Group as fixed factors. Participant was included as a random factor in both. N1-P1 first block amplitude was used to assess cortical excitability and habituation was defined as a decrease of N1-P1 amplitude across Blocks/Trials. Both experiments were performed interictally. RESULTS: The final samples consisted of 18 patients with episodic migraine and 27 headache-free controls (first experiment) and 19 patients and 29 controls (second experiment). In both experiments, patients reported increased visual hypersensitivity on the Sensory Perception Quotient as compared to controls. Regarding N1-P1 peak-to-peak data, there was no main effect of Group, indicating no differences in cortical excitability between groups. Finally, significant main effects of both Block and Trial were found indicating habituation in both groups, regardless of age and headache frequency. CONCLUSIONS: The results of this study yielded evidence for significant hypersensitivity in patients but no significant differences in either habituation or cortical excitability, as compared to headache-free controls. Although the alterations in patients may be less pronounced than originally anticipated they demonstrate the need for the definition and standardization of optimal methodological parameters.

Avoidance behaviour modulates but does not condition phonophobia in migraine.

BACKGROUND: Past studies do not account for avoidance behaviour in migraine as a potential confounder of phonophobia. OBJECTIVE: To analyse whether phonophobia is partially driven by avoidance behaviour when using the classic methodology (method of limits). METHODS: This is a case-control study where we tested phonophobia in a cohort of high-frequency/chronic migraine patients (15.5 ± 0.74 headache days/month) and non-headache controls. Auditory stimuli, delivered in both ears, were presented using three different paradigms: the method of limits, the method of constant stimuli, and the adaptive method. Participants were asked to report how bothersome each tone was until a sound aversion threshold was estimated for each method. RESULTS: In this study, we successfully replicate previously reported reduction in sound aversion threshold using three different methods in a group of 35 patients and 25 controls (p < 0.0001). Avoidance behaviour in migraine reduced sound aversion threshold in the method of limits (p = 0.0002) and the adaptive method (p < 0.0001) when compared to the method of constant stimuli. While thresholds in controls remained the same across methods (method of limits, p = 0.9877 and adaptive method, p = 1). CONCLUSION: Avoidance behaviour can exacerbate phonophobia. The current methodology to measure phonophobia needs to be revised.

Neurophysiological correlates of abnormal auditory processing in episodic migraine during the interictal period.

BACKGROUND: The characteristics of the hypersensitivity to auditory stimuli during the interictal period in episodic migraine are discussed. The combined use of event-related potentials, time-frequency power and phase-synchronization can provide relevant information about the time-course of sensory-attentional processing in migraine and its underlying mechanisms. OBJECTIVE: The aim of this nested case-control study was to examine these processes in young, female, episodic migraine patients interictally and compare them to controls using an active auditory oddball task. METHOD: We recorded, using 20 channels, the electrophysiological brain activity of 21 women with episodic migraine without aura and 21 healthy matched controls without family history of migraine, during a novelty oddball paradigm. We collected sociodemographic and clinical data as well as scores related to disability, quality of life, anxiety and depression. We calculated behavioural measures including reaction times, hit rates and false alarms. Spectral power and phase-synchronization of oscillatory activity as well as event-related potentials were obtained for standard stimuli. For target and novel stimuli, event-related potentials were acquired. RESULTS: There were no significant differences at the behavioural level. In migraine patients, we found an increased phase-synchronization at the theta frequency range and a higher N1 response to standard trials. No differences were observed in spectral power. No evidence for a lack of habituation in any of the measures was seen between migraine patients and controls. The Reorienting Negativity was reduced in migraine patients as compared to controls on novel but not on target trials. CONCLUSION: Our findings suggest that migraine patients process stimuli as more salient, seem to allocate more of their attentional resources to their surrounding environment, and have less available resources to reorient attention back to the main task.

Cortical metabolic and structural differences in patients with chronic migraine. An exploratory 18FDG-PET and MRI study.

BACKGROUND: To describe interictal brain structural and metabolic differences between patients with episodic migraine (EM), chronic migraine (CM) and healthy controls (HC). METHODS: This is an exploratory study including right-handed age-matched women with EM, CM and HC. On the same day, a sequential interictal scan was performed with 18FDG-PET and MRI. 3D T1-weighted images were segmented with FreeSurfer, normalized to a reference atlas and the mean values of metabolism, cortical thickness (CTh) and local gyrification index (IGI) were determined. Groups were compared using age-adjusted linear models, corrected for multiple comparisons. 18FDG-PET measurements between groups were also analysed adjusting by patient's age, CTh and lGI. The variables independently associated with diagnosis were obtained using a logistic regression analysis. RESULTS: Fifteen patients (8 EM, 7 CM) and 11 HC were included. Morphometric data showed an increased CTh in 6 frontal areas (L/R-Caudal Middle Frontal, L/R-Rostral Middle Frontal, L-Medial Orbitofrontal and L-Superior Frontal) in CM patients compared to HC without differences for IGI. The structural adjusted analysis in CM showed a statistically significantly hypometabolism in 9 frontal areas (L-Lateral Orbitofrontal, L/R-Medial Orbitofrontal, L-Frontal Superior, R-Frontal pole, R-Parts Triangularis, L/R-Paracentral and R-Precentral) and 7 temporal areas (L/R-Insula, L/R-Inferior temporal, L/R-Temporal pole and R-Banks superior temporal sulcus) compared to HC. EM patients presented intermediate metabolic values ​​between EM and HC (non-significant). CONCLUSIONS: CM patients showed frontotemporal hypometabolism and increased frontal cortical thickness when compared to HC that may explain some cognitive and behavioural pain-processing and sensory integration alterations in CM patients. Combined information from sequential or simultaneous PET and MRI could optimize the study of complex functional neurological disorders such as migraine.

Working memory updating training modulates a cascade of event-related potentials depending on task load.

The brain mechanisms of working memory (WM) training in humans remain unclear. Here we examined how WM updating training modulates a cascade of event-related potentials (ERPs) elicited at different processing stages. We hypothesized that WM updating training results to decreases in the early responses reflecting stimulus selection and response preparation, and increases the late slow responses reflecting maintenance of to-be-remembered materials. Healthy adults were randomized to a WM updating group that trained an adaptive dual n-back task (n = 20), and an active control group that played a computer game (n = 20). Both groups performed three 25-min training sessions per week for five weeks. Pretest-posttest comparisons showed that the training group significantly improved their performance as compared to the active controls, but this was limited to the trained task. In line with our hypothesis, P2-N2-P3 complex showed changes from pre- to posttest. In the training group this was observed as decreased load-effect while in the control group there was an opposite pattern at some latencies. Slow waves elicited during the maintenance were decreased in the easy task and increased in the difficult task. Taken together, our findings suggest that the early and late ERPs are differentially affected by training. When task demands are high, training may lead to an improved ability to actively maintain several stimuli in memory, and when they are low, training results in more efficient processing and automatization.

Unraveling the Role of the Hippocampus in Reversal Learning.

Research in reversal learning has mainly focused on the functional role of dopamine and striatal structures in driving behavior on the basis of classic reinforcement learning mechanisms. However, recent evidence indicates that, beyond classic reinforcement learning adaptations, individuals may also learn the inherent task structure and anticipate the occurrence of reversals. A candidate structure to support such task representation is the hippocampus, which might create a flexible representation of the environment that can be adaptively applied to goal-directed behavior. To investigate the functional role of the hippocampus in the implementation of anticipatory strategies in reversal learning, we first studied, in 20 healthy individuals (11 women), whether the gray matter anatomy and volume of the hippocampus were related to anticipatory strategies in a reversal learning task. Second, we tested 20 refractory temporal lobe epileptic patients (11 women) with unilateral hippocampal sclerosis, who served as a hippocampal lesion model. Our results indicate that healthy participants were able to learn the task structure and use it to guide their behavior and optimize their performance. Participants' ability to adopt anticipatory strategies correlated with the gray matter volume of the hippocampus. In contrast, hippocampal patients were unable to grasp the higher-order structure of the task with the same success than controls. Present results indicate that the hippocampus is necessary to respond in an appropriately flexible manner to high-order environments, and disruptions in this structure can render behavior habitual and inflexible.SIGNIFICANCE STATEMENT Understanding the neural substrates involved in reversal learning has provoked a great deal of interest in the last years. Studies with nonhuman primates have shown that, through repetition, individuals are able to anticipate the occurrence of reversals and, thus, adjust their behavior accordingly. The present investigation is devoted to know the role of the hippocampus in such strategies. Importantly, our findings evidence that the hippocampus is necessary to anticipate the occurrence of reversals, and disruptions in this structure can render behavior habitual and inflexible.

Atypical language organization in temporal lobe epilepsy revealed by a passive semantic paradigm.

BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults and can be successfully cured by surgery. One of the main complications of this surgery however is a decline in language abilities. The magnitude of this decline is related to the degree of language lateralization to the left hemisphere. Most fMRI paradigms used to determine language dominance in epileptic populations have used active language tasks. Sometimes, these paradigms are too complex and may result in patient underperformance. Only a few studies have used purely passive tasks, such as listening to standard speech. METHODS: In the present study we characterized language lateralization in patients with MTLE using a rapid and passive semantic language task. We used functional magnetic resonance imaging (fMRI) to study 23 patients [12 with Left (LMTLE), 11 with Right mesial temporal lobe epilepsy (RMTLE)] and 19 healthy right-handed controls using a 6 minute long semantic task in which subjects passively listened to groups of sentences (SEN) and pseudo sentences (PSEN). A lateralization index (LI) was computed using a priori regions of interest of the temporal lobe. RESULTS: The LI for the significant contrasts produced activations for all participants in both temporal lobes. 81.8% of RMTLE patients and 79% of healthy individuals had a bilateral language representation for this particular task. However, 50% of LMTLE patients presented an atypical right hemispheric dominance in the LI. More importantly, the degree of right lateralization in LMTLE patients was correlated with the age of epilepsy onset. CONCLUSIONS: The simple, rapid, non-collaboration dependent, passive task described in this study, produces a robust activation in the temporal lobe in both patients and controls and is capable of illustrating a pattern of atypical language organization for LMTLE patients. Furthermore, we observed that the atypical right-lateralization patterns in LMTLE patients was associated to earlier age at epilepsy onset. These results are in line with the idea that early onset of epileptic activity is associated to larger neuroplastic changes.

The presence of anhedonia in individuals with subacute and chronic stroke: an exploratory cohort study.

Background: Anhedonia refers to the diminished capacity to experience pleasure. It has been described both as a symptom of depression and an enduring behavioral trait that contributes its development. Specifically, in stroke patients, anhedonia has been closely linked to depression, resulting in reduced sensitivity to everyday pleasures and intrinsic motivation to engage in rehabilitation programs and maintain a healthy active lifestyle. This condition may hinder patients' recovery, diminishing their autonomy, functioning, and quality of life. Objective: We aimed to explore the prevalence and level of anhedonia and those variables that might be associated in patients with both ischemic and hemorrhagic stroke at subacute and chronic phases of the disease. Methods: We conducted an exploratory cohort study with a sample of 125 patients with subacute and chronic stroke presenting upper-limb motor deficits. We measured participants' level of anhedonia with four items from the Beck Depression Inventory-II that describe the symptoms of this condition: loss of pleasure, loss of interest, loss of energy, and loss of interest in sex. We also collected demographic and clinical information and evaluated motor and cognitive functions as well as levels of depression, apathy, and various mood states. The results were compared to a sample of 71 healthy participants of similar age, sex, and level of education. Results: Stroke patients demonstrated a significantly higher prevalence (18.5-19.7%) and level of anhedonia compared to the healthy controls (4.3%), regardless of stroke phase, level of motor impairment, and other clinical variables. Furthermore, post-stroke anhedonia was associated with lower levels of motivation and higher levels of negative mood states such as fatigue and anger in the long term. Importantly, anhedonia level was superior in stroke patients than in healthy controls while controlling for confounding effects of related emotional conditions. Conclusion: This study provides novel evidence on the prevalence, level and factors related to anhedonia post-stroke. We emphasize the importance of assessing and treating anhedonia in this population, as well as conducting large-scale cohort and longitudinal studies to test its influence on long-term functional and emotional recovery.

The influence of temporal unpredictability on the electrophysiological mechanisms of neural entrainment.

Neural entrainment, or the synchronization of endogenous oscillations to exogenous rhythmic events, has been postulated as a powerful mechanism underlying stimulus prediction. Nevertheless, studies that have explored the benefits of neural entrainment on attention, perception, and other cognitive functions have received criticism, which could compromise their theoretical and clinical value. Therefore, the aim of the present study was [1] to confirm the presence of entrainment using a set of pre-established criteria and [2] to establish whether the reported behavioral benefits of entrainment remain when temporal predictability related to target appearance is reduced. To address these points, we adapted a previous neural entrainment paradigm to include: a variable entrainer length and increased target-absent trials, and instructing participants to respond only if they had detected a target, to avoid guessing. Thirty-six right-handed women took part in this study. Our results indicated a significant alignment of neural activity to the external periodicity as well as a persistence of phase alignment beyond the offset of the driving signal. This would appear to indicate that neural entrainment triggers preexisting endogenous oscillations, which cannot simply be explained as a succession of event-related potentials associated with the stimuli, expectation and/or motor response. However, we found no behavioral benefit for targets in-phase with entrainers, which would suggest that the effect of neural entrainment on overt behavior may be more limited than expected. These results help to clarify the mechanistic processes underlying neural entrainment and provide new insights on its applications.

Reward-based decision-making in mesial temporal lobe epilepsy patients with unilateral hippocampal sclerosis pre- and post-surgery.

BACKGROUND: Correct functioning of the reward processing system is critical for optimizing decision-making as well as preventing the development of addictions and/or neuropsychiatric symptoms such as depression, apathy, and anhedonia. Consequently, patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis (mTLE-UHS) represent an excellent opportunity to study the brain networks involved in this system. OBJECTIVE: The aim of the current study was to evaluate decision-making and the electrophysiological correlates of feedback processing in a sample of mTLE-UHS patients, compared to healthy controls. In addition, we assessed the impact of mesial temporal lobe surgical resection on these processes, as well as general, neuropsychological functioning. METHOD: 17 mTLE-UHS patients and 17 matched healthy controls completed: [1] a computerized version of the Game of Dice Task, [2] a Standard Iowa Gambling Task, and [3] a modified ERP version of a probabilistic gambling task coupled with multichannel electroencephalography. Neuropsychological scores were also obtained both pre- and post-surgery. RESULTS: Behavioral analyses showed a pattern of increased risk for the mTLE-UHS group in decision-making under ambiguity compared to the control group. A decrease in the amplitude of the Feedback Related Negativity (FRN), a weaker effect of valence on delta power, and a general reduction of delta and theta power in the mTLE-UHS group, as compared to the control group, were also found. The beta-gamma activity associated with the delivery of positive reward was similar in both groups. Behavioral performance and electrophysiological measures did not worsen post-surgery. CONCLUSIONS: Patients with mTLE-UHS showed impairments in decision-making under ambiguity, particularly when they had to make decisions based on the outcomes of their choices, but not in decision-making under risk. No group differences were observed in decision-making when feedbacks were random. These results might be explained by the abnormal feedback processing seen in the EEG activity of patients with mTLE-UHS, and by concomitant impairments in working memory, and memory. These impairments may be linked to the disruption of mesial temporal lobe networks. Finally, feedback processing and decision-making under ambiguity were already affected in mTLE-UHS patients pre-surgery and did not show evidence of clear worsening post-surgery.

Neural signatures for active maintenance and interference during working memory updating.

Although working memory (WM) is amongst the most studied neurocognitive functions, temporal patterns of its component processes are not fully understood. We examined the neural underpinnings of active maintenance and interference management in the n-back task by manipulating load (1-back vs 3-back) and including so-called lure stimuli. ERPs of 27 young adults revealed that the 1-back condition enabling active maintenance showed a positive slow wave (PSW) prior to the next stimulus (-600-0 ms) and augmented P2 (190-290 ms) and P3b (330-430 ms) responses after the stimulus appeared, albeit the latter effects were driven by the initial PSW. Moreover, PSW amplitude correlated negatively with reaction time in the 1-back condition. Responses to lures showed interference, accompanied with different ERP effects for the two load levels. Our results support the view that PSW reflects efficient WM maintenance and suggest two distinct neuronal correlates for interference in WM.

Auditory Target and Novelty Processing in Patients with Unilateral Hippocampal Sclerosis: A Current-Source Density Study.

The capacity to respond to novel events is crucial for adapting to the constantly changing environment. Here, we recorded 29-channel Event Related Brain Potentials (ERPs) during an active auditory novelty oddball paradigm and used for the first time Current Source Density-transformed Event Related Brain Potentials and associated time-frequency spectra to study target and novelty processing in a group of epileptic patients with unilateral damage of the hippocampus (N = 18) and in healthy matched control participants (N = 18). Importantly, we used Voxel-Based Morphometry to ensure that our group of patients had a focal unilateral damage restricted to the hippocampus and especially its medial part. We found a clear deficit for target processing at the behavioral level. In addition, compared to controls, our group of patients presented (i) a reduction of theta event-related synchronization (ERS) for targets and (ii) a reduction and delayed P3a source accompanied by reduced theta and low-beta ERS and alpha event-related synchronization (ERD) for novel stimuli. These results suggest that the integrity of the hippocampus might be crucial for the functioning of the complex cortico-subcortical network involved in the detection of novel and target stimuli.

Neurophysiological correlates of cognitive flexibility and feedback processing in violent juvenile offenders.

The persistence of aggressive criminal behavior is recurrently observed in offenders despite being previously advised on the negative consequences of their actions. One possible explanation for the continuation of aggressive behaviors could be that they are the consequence of either possible deficits in cognitive flexibility (set-shifting) or in altered feedback processing. Event-related brain potentials (ERPs) were used to investigate both processes in non-psychopathic violent juvenile offenders. A modified version of the Wisconsin Card Sorting Test (WCST) was used to disentangle the ERP components associated with cognitive set-switching processes (P3) from feedback processing (Frontal-Related Negativity, FRN; P3). The results showed a reduction in the amplitude of the P3 component for the presentation of switch informative signals, related to set-switching processes, in the offender group. Interestingly, a larger amplitude of the P3 related to feedback processing as well as the FRN was observed in this population, probably indicating increased reliance on external feedback processing. At the behavioral level, the offender group presented a larger amount of issues with failures in implementing the new sorting rule. This behavioral pattern could be related to deficits in the ability to switch to another behavior and an altered pattern in processing the feedback information related to the precision of their performance. These observations highlight the possible role of cognitive set-switching and reward sensibility in the maintenance of harmful behaviors in juvenile offenders.

Preserved Error-Monitoring in Borderline Personality Disorder Patients with and without Non-Suicidal Self-Injury Behaviors.

BACKGROUND: The presence of non-suicidal self-injury acts in Borderline Personality Disorder (BPD) is very prevalent. These behaviors are a public health concern and have become a poorly understood phenomenon in the community. It has been proposed that the commission of non-suicidal self-injury might be related to a failure in the brain network regulating executive functions. Previous studies have shown that BPD patients present an impairment in their capacity to monitor actions and conflicts associated with the performance of certain actions, which suppose an important aspect of cognitive control. METHOD: We used Event Related Potentials to examine the behavioral and electrophysiological indexes associated with the error monitoring in two BPD outpatients groups (17 patients each) differentiated according to the presence or absence of non-suicidal self-injury behaviors. We also examined 17 age- and intelligence- matched healthy control participants. RESULTS: The three groups did not show significant differences in event-related potentials associated with errors (Error-Related Negativity and Pe) nor in theta power increase following errors. CONCLUSIONS: This is the first study investigating the behavioral and electrophysiological error monitoring indexes in BPD patients characterized by their history of non-suicidal self-injury behaviors. Our results show that error monitoring is preserved in BPD patients and suggest that non-suicidal self-injury acts are not related to a dysfunction in the cognitive control mechanisms.

Neurophysiological correlates of error monitoring and inhibitory processing in juvenile violent offenders.

Performance monitoring is crucial for well-adapted behavior. Offenders typically have a pervasive repetition of harmful-impulsive behaviors, despite an awareness of the negative consequences of their actions. However, the link between performance monitoring and aggressive behavior in juvenile offenders has not been closely investigated. Event-related brain potentials (ERPs) were used to investigate performance monitoring in juvenile non-psychopathic violent offenders compared with a well-matched control group. Two ERP components associated with error monitoring, error-related negativity (ERN) and error-positivity (Pe), and two components related to inhibitory processing, the stop-N2 and stop-P3 components, were evaluated using a combined flanker-stop-signal task. The results showed that the amplitudes of the ERN, the stop-N2, the stop-P3, and the standard P3 components were clearly reduced in the offenders group. Remarkably, no differences were observed for the Pe. At the behavioral level, slower stop-signal reaction times were identified for offenders, which indicated diminished inhibitory processing. The present results suggest that the monitoring of one's own behavior is affected in juvenile violent offenders. Specifically, we determined that different aspects of executive function were affected in the studied offenders, including error processing (reduced ERN) and response inhibition (reduced N2 and P3). However, error awareness and compensatory post-error adjustment processes (error correction) were unaffected. The current pattern of results highlights the role of performance monitoring in the acquisition and maintenance of externalizing harmful behavior that is frequently observed in juvenile offenders.

Hippocampus-dependent strengthening of targeted memories via reactivation during sleep in humans.

Recent accumulating evidence in animals and humans has shown that memory strengthening occurs, at least partially, during sleep and relies on the covert reactivation of individual memory episodes. However, it remains to be determined whether the hippocampus critically promotes memory consolidation via the reactivation of individual memories during sleep. To investigate the hippocampal-dependent nature of this phenomenon in humans, we selected two groups of chronic temporal lobe epileptic (TLE) patients with selective unilateral (TLE+UHS) or bilateral (TLE+BHS) hippocampal sclerosis and a group of matched healthy controls, and we requested them to learn the association of sounds cueing the appearance of words. On the basis of other similar behavioral paradigms in healthy populations, sounds that cued only half of the learned memories were presented again during the slow-wave sleep stage (SWS) at night, thus promoting memory reactivation of a select set of encoded episodes. A memory test administered on the subsequent day showed that the strengthening of reactivated memories was observed only in the control subjects and TLE+UHS patients. Importantly, the amount of memory strengthening was predicted by the volume of spared hippocampus. Thus, the greater the structural integrity of the hippocampus, the higher the degree of memory benefit driven by memory reactivation. Finally, sleep-specific neurophysiological responses, such as spindles and slow waves, differed between the sample groups, and the spindle density during SWS predicted the degree of memory benefit observed on day 2. Taken together, these findings demonstrate that the hippocampus plays a crucial role in the consolidation of memories via covert reactivation during sleep.