OBJECTIVE:Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7 Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS:We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS:At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50 Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS:EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE:These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

The interthalamic adhesion (IA) connects both thalami. Emerging research suggests it may support thalamo-cortical connectivity and could be involved in neurodevelopmental and neuropsychiatric conditions. However, inconsistent MRI evaluation hinders progress on this subject. We developed SNAP-IA, a standardized anatomical imaging protocol for consistent IA identification and quantification. This work leveraged the expertise from seven research teams (Toulouse, Santiago, Southampton, Lausanne, Tübingen, and Bordeaux). SNAP-IA includes three steps: (1) determination of IA presence/absence on T1-weighted MRI; (2) classification of IA variants (simple, broad, double, bilobar, and filiform); (3) segmentation-based area assessment. It was tested on 500 controls (20–69 yo) and patients (stroke, schizophrenia, bipolar disorder, and ADHD) with 0.6–1 mm isotropic T1-weighted MRI (3T to 9.4T). SNAP-IA application achieved high inter-dataset agreement (mean Dice ≈ 0.92), with an average identification time of 35 s. The IA was absent in 22.8

Memory processing requires coordinated engagement of neuronal populations across brain networks and over time. How such coordination is organized in the human medial temporal lobe (MTL) remains unclear. Here, we show that MTL population activity is dynamically structured by a transient slow-oscillatory architecture that emerges during learning to promote offline consolidation and later recall. Using intracranial recordings that combine single-neuron spiking activity and local field potentials in human participants, we find that mnemonic engagement elicits on-demand slow-oscillatory bursts in the hippocampus. These hippocampal bursts synchronize gamma-band patterns across MTL regions, defining discrete coordination events that pace cross-regional coactivity motifs during learning. These learning-evoked population motifs are selectively reactivated during hippocampal ripples in post-learning rest, and the strength of their reactivation predicts subsequent recall accuracy. Together, these findings identify a multi-scale coordination mechanism that links distributed population activity across learning, consolidation, and recall in humans.

OBJECTIVE:Sleep-predominant network hyperexcitability is increasingly recognized as a potential disease-accelerating comorbidity in Alzheimer's disease (AD). However, its prevalence and risk-factors remain debated, largely due to cohort-specific and methodological differences across studies. In this prospective case-control study, we investigated potential ways of improving detection, from translational approaches focusing on rapid eye movement (REM)-sleep to refined electroencephalogram (EEG) setups and added clinical questionnaires. METHODS:We recruited 30 patients with early-stage AD without a history of epilepsy and 30 age-matched controls. Participants underwent overnight polysomnography with video-EEG. Interictal epileptic discharges (IEDs) were identified through a structured 3-step review by multiple independent experts using recommended criteria. Neuroanatomic patterns and sleep-related abnormalities were investigated as potential risk factors. Clinical symptoms in favor of epileptic seizures were evaluated through a tailored questionnaire at follow-up. RESULTS:IEDs were detected in 3 patients (10%) and 1 control (3.33%), a difference not reaching statistical significance (p = 0.612). Most events occurred during non-REM (NREM) sleep. Eight patients (26.67%) reported symptoms compatible with epileptic seizures-one of whom also presented with IEDs. Patients with IEDs or reported symptoms suggestive of potential seizures exhibited more severe sleep-disordered breathing and reduced precuneus volume compared with those without. INTERPRETATION:Despite efforts to optimize detection accuracy, our findings reveal a lower-than-expected percentage of patients with AD with IEDs, yet support previous findings suggesting that sleep-disordered breathing and specific atrophy patterns could flag at-risk patients, guiding screening in clinical settings. Our findings also favor validation efforts of questionnaires to support the diagnostic process. Finally, we highlight methodological issues in IED detection and call for the re-evaluation and standardization of diagnostic methods and criteria in this population to improve patient care. ANN NEUROL 2026;99:1046-1058.

Focus on how non-cortical regions such as the thalamus contribute to cognitive function has been increasing as it could have profound implications in understanding brain function in both health and disease. Of particular interest is the mediodorsal thalamus (MD) as it has unique connectivity patterns that suggest it can support frontal cortical operations. A subset of MD cells projects diffusely to broad regions of the frontal cortex. These diffusely projecting cells are thought to modulate the way downstream cortical regions respond to signaling from other cortical areas. It is theorized that through this type of modulation the MD supports cognition but there is little empirical evidence in humans for this theory. Damage to the MD will sometimes lead to pronounced impairments in recognition memory, recall memory, and executive function, but these findings are inconsistent. The present study analyzed 22 chronic thalamic stroke patients to relate their MD damage, their cognitive impairment, and network connectivity differences as measured by resting state functional magnetic resonance imaging. While recognition, recall, working memory, language, and executive function were impaired in the thalamic stroke group there was not a detectable link between cognitive impairment and MD damage in particular. Interestingly, the results showed no indication that MD damage disrupts cortico-cortical communication patterns. This result suggests that if the MD plays a prominent role in cortico-cortical modulation it is only during specific tasks or at smaller scales. This study marks a critical first step towards understanding the limitations of MD involvement in modulation of cortico-cortical communication.

We investigated whether the interthalamic adhesion (IA), a midline structure connecting the thalami, is altered in multiple sclerosis (MS) and associated with thalamic damages and cognition. We prospectively included 32 clinically isolated syndrome/early MS, 31 relapsing–remitting MS, 31 primary-progressive MS patients, and 103 matched controls. All underwent anatomical 3 T MRI and completed a comprehensive cognitive battery. IA presence, subtype, and volume were assessed by two blinded readers. Thalamic nuclei and other brain structures were segmented automatically. We compared IA subtypes/volumes across groups, analyzed their predictors, and explored cognitive associations with multivariate regressions. A deep-learning-based IA segmentation tool was also developed and externally validated on 30 new patients. IA prevalence did not differ between MS and controls (81.9

Abstract Objective Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography (SEEG), yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We investigated theta-range EBS (7 Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. Methods We analyzed 1,408 temporal EBS in 25 patients with drug-resistant epilepsy. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and analyzed according to stimulation parameters (frequency, intensity, duration, total charge). Results At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures (e.g., parahippocampal epileptogenic zone: p=0.014). Effects on usual seizure induction were less consistent. Comparisons with 50 Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. No adverse events occured. Significance Theta-range stimulation modulates electrophysiological and clinical responses during SEEG mapping and may provide complementary information to conventional frequencies. These findings support exploring a broader range of stimulation frequencies, rather than relying solely on standard protocols.

Patients with severe anterograde amnesia have been described as "stuck in time"; their mental time travel abilities are altered, and they seem to live in the present. Here, we examine an unusual phenomenon in which severely amnesic patients recurrently report the belief that they have just awakened from an unconscious state. A famous case illustrating this phenomenon was that of Clive Wearing who repeatedly wrote “I am now awake” in his diary. This unique cognitive phenomenon has not been specifically studied until now. We report three new patients who described similar subjective experiences. All three patients suffered from autoimmune encephalitis and showed massive bilateral hippocampal inflammation causing severe anterograde amnesia. We propose to call this phenomenon “Stream of Consciousness Impairment”, a reference to William James’s theory according to which, normally, we experience an uninterrupted flow of consciousness. This condition should be added to the spectrum of neurological symptoms that contribute to the study of memory and consciousness in humans.

BACKGROUND:The interthalamic adhesion (IA) is an anatomical bridge connecting the left and right thalamus. While prior studies have explored its prevalence and function in healthy populations, stroke, hydrocephalus, and schizophrenia, none have examined the IA in the context of Alzheimer's disease (AD). This study aims to analyse the prevalence of the IA in the prodromal to clinical AD continuum and evaluate the association with AD cerebrospinal fluid (CSF) biomarkers and thalamic, hippocampal, and ventricular volumes. METHOD:IA prevalence was assessed in 542 MRIs from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including healthy controls (HC), early mild cognitive impairment (EMCI), late MCI (LMCI), and AD patients. Inter-rater reliability was assessed with Cohen's Kappa, and a chi-squared test (χ2) examined rater differences. Binary and multinomial logistic regressions evaluated the effect of CSF biomarkers, volumes, and clinical data on IA prevalence and type. RESULTS:There were no significant differences in IA prevalence or variants across the four groups. The single IA was the most common type, while bilobar and double variants were less frequent. Post-hoc analysis, however, showed that AD CSF biomarker measures showed positive associations with the broad IA subtype in HC and EMCI. CONCLUSION:The study found no overall differences in IA prevalence or its variants related to prodromal or clinical AD. Still, elevated Aβ42, p-Tau levels, and larger thalamic volume were linked to a higher likelihood of a broad IA. These findings suggest that the IA may be involved in prodromal AD pathophysiological processes.

OBJECTIVE:The pre-surgical evaluation of epilepsy relies on the electrophysiological recordings of spontaneous seizures. During this period drug dose decreases increase the likelihood of seizures transitioning the brain from a low to high seizure likelihood state, so-called pro-ictal state. This study aimed to identify the dynamic brain changes characteristic of this transition from 386 ten-minute segments of intracranial EEG recordings of 29 patients with drug-refractory temporal lobe epilepsy. METHODS:We studied brain dynamics through mean phase locking value and relative power in gamma band, and autocorrelation function width. We further explored interactions with pro-ictal factors, such as rate of interictal spikes and high frequency oscillations, circadian and multi-day cycles, and clinical outcomes. RESULTS:We observed significant increases in gamma power in the epileptogenic zone, and critical slowing in both the epileptogenic zone and presumably healthy cortex. These changes were linked with increases in spike and high frequency oscillations rate. CONCLUSIONS:Brain dynamics changed on the slow time scale - from the beginning to the end of the multi-day interval - but did not change in the short-term during the pre-ictal interval, thus could reflect pro-ictal changes. SIGNIFICANCE:We highlight gamma power and critical slowing indices as markers of pro-ictal brain states, as well as their potential to track the seizure-related brain mechanisms during the presurgical evaluation of epilepsy patients.

Both thalami can be connected by the Interthalamic Adhesion (IA), a white matter tract that crosses the 3rd ventricle. Its presence varies among individuals and remains poorly understood. This study examines the IA's prevalence, anatomical variations, genetic determinants, and cognitive associations. Data from 591 healthy subjects (25-35 years) from the Human Connectome Project were analyzed, and grouped into monozygotic (MZ) or dizygotic (DZ) twins, non-twin siblings, and unrelated individuals. MRI was used to characterize the IA, while neuropsychological assessments and Freesurfer parcellations were used to assess cognition and anatomical differences between subjects with or without an IA. The IA was absent in 12.7% of subjects, more commonly in males (20.0%) than females (6.3%). No significant differences in age, education, or cognition were found between individuals with or without an IA. IA absence was associated with increased cerebrospinal fluid volumes, enlarged third ventricles, and thinning in several cortical areas. Genetic analysis on the IA presence or absence revealed a heritability estimate of 34% with a higher concordance among MZ twins (96%) than in other groups. The remaining 4% discrepancy was observed in male pairs only. This study underscores the genetic basis of IA, highlighting sexual dimorphism and neuroanatomical differences associated with its absence, despite unaffected cognition in healthy individuals.

The thalamus, traditionally viewed as a sensory relay station, is now recognized for its critical role in higher-order cognitive functions, including memory. While most research has focused on its distinct nuclei, the thalamus also contains crucial white matter tracts, such as the mammillothalamic tract (MTT), part of the Papez circuit. Despite its established role in memory, the MTT remains underappreciated in studies on the cognitive role of the thalamus, increasing the risk of misattributing memory functions to nearby thalamic nuclei. This study investigates the memory impact of thalamic strokes by considering disruption to the MTT. We examined 40 patients with chronic ischemic thalamic lesions and 45 healthy controls using neuropsychological assessments, focusing on the Free and Cued Selective Reminding Test (FCSRT) and high-resolution structural neuroimaging. Advanced imaging techniques, such as symptom mapping and disconnectome analyses, were employed to analyze the relationships between lesion sites, tract disconnections, and cognitive outcomes. Additionally, the expression of calbindin-rich matrix cells and parvalbumin-rich core cells was examined to assess how the connectivity property of thalamic cells, and its disruption, can relate to cognitive deficits following a thalamic stroke. Patients with left-sided thalamic lesions, especially those involving the MTT, showed significant memory impairments. Symptom mapping identified a specific cluster of lesioned voxels in the left anterior-lateral thalamus, including the MTT, as being strongly associated with poorer memory performance. Disconnectome analysis confirmed that verbal memory deficits were associated with disruption of the MTT. Furthermore, a striking overlap was observed between the critical regions linked to memory deficits and calbindin-rich thalamic areas. However, this calbindin-rich region was also disrupted in patients without memory impairment, revealing that MTT disruption, and not lesions to this region, induced memory deficits in these patients. The identified FCSRT deficit cluster overlapped with brain regions consistently linked to memory processes following fMRI meta-analytic mapping of memory-related keywords. These findings challenge the traditional focus on thalamic nuclei and connector hubs, indicating a need to reappraise the importance of the MTT in memory impairment after a thalamic stroke. This study advocates for a shift in thalamic research, emphasizing the need to investigate tract-specific contributions and disruptions of the MTT but also of other tracts such as the interthalamic adhesion or amygdalofugal pathway, rather than holding only to a "nuclei-centric" view of the thalamus.

Orientation in time is a central aspect of human cognition. Because orientation in time is intimately related to autobiographical episodic memory, most amnesic patients suffer from temporal disorientation. Patients with severe anterograde amnesia have been described as "stuck in time"; their mental time travel abilities are altered, and they seem to live in the present. Here, we look at the very special situation of complete temporal disorientation, to the point where the patient seems to have no sense of the passage of time. A famous case illustrating this phenomenon was that of Clive Wearing who repeatedly wrote “I am now awake” in his diary, showing his recurrent belief that he had just awakened from an unconscious state. This unique cognitive phenomenon has not been specifically studied. We report cases involving three patients who described similar experiences. All three patients suffer from autoimmune encephalitis and show massive bilateral hippocampal inflammation causing severe anterograde amnesia. We propose to call this phenomenon “Stream of Consciousness Impairment”, a reference to William James’s theory according to which, normally, there is an uninterrupted flow of consciousness. This condition could be added to the spectrum of neurological disorders that contribute to the study of consciousness in humans.

Background Thalamic strokes produce neurological, cognitive, and behavioral symptoms depending on the thalamic nuclei involved. While traditionally associated with severe cognitive deficits, recent studies suggest more modest impairments. This study aims to identify the factors that influence the severity of cognitive impairment following thalamic stroke. Methods We recruited 40 patients (mean age 51.1) with chronic isolated thalamic stroke and 45 healthy subjects (mean age 48.5) who underwent neuroimaging and neuropsychological assessment. Cluster and principal component analyses were used to discriminate patients from healthy subjects based on cognitive tasks. Disconnectome maps and cortical thickness were analyzed to understand the distant impact of thalamic strokes. Results Two cognitive profiles emerged from the cluster analysis. Cluster 1 included mostly healthy subjects ( n = 43) and patients with no or minor deficits ( n = 20). Cluster 2 included patients ( n = 19) and two healthy subjects with severe deficits in verbal memory, executive functions, and attention. Cluster 1 encompassed all patients with right thalamic stroke, while Cluster 2 included all patients with bilateral stroke or mammillothalamic tract interruption. Patients with left-sided stroke were equally divided between clusters. Significant differences between clusters included age, education, interthalamic adhesion disruption, lesion volume, and location. Patients with left-sided stroke in Cluster 2 had more lateral thalamic lesions and greater disruption of the anterior thalamic projection. Conclusions Contrary to common expectations, our findings suggest that many patients with thalamic stroke have relatively good cognitive outcomes. In contrast, we identified the factors behind poor outcomes that will help clinicians.

The thalamus has a key role in mediating cortical-subcortical interactions but is often neglected in neuroimaging studies, which mostly focus on changes in cortical structure and activity. One of the main reasons for the thalamus being overlooked is that the delineation of individual thalamic nuclei via neuroimaging remains controversial. Indeed, neuroimaging atlases vary substantially regarding which thalamic nuclei are included and how their delineations were established. Here, we review current and emerging methods for thalamic nuclei segmentation in neuroimaging data and consider the limitations of existing techniques in terms of their research and clinical applicability. We address these challenges by proposing a roadmap to improve thalamic nuclei segmentation in human neuroimaging and, in turn, harmonize research approaches and advance clinical applications. We believe that a collective effort is required to achieve this. We hope that this will ultimately lead to the thalamic nuclei being regarded as key brain regions in their own right and not (as often currently assumed) as simply a gateway between cortical and subcortical regions.

The interthalamic adhesion (IA) is a structure that connects the median borders of both thalami. Its anatomical variants and functions remain poorly studied. The main objective of this study was to explore the role of the IA on cognition. 42 healthy subjects and 40 patients with chronic isolated thalamic strokes underwent a neuroimaging and a neuropsychological assessment. The presence, absence, or lesion of the IA and its anatomical variants were evaluated. 76

The precise and fleeting moment of rich recollection triggered by an environmental cue is difficult to reproduce in the lab. However, epilepsy patients can experience sudden reminiscences after intracranial electrical brain stimulation (EBS). In these cases, the transient brain state related to the activation of the engram and its conscious perception can be recorded using intracerebral EEG (iEEG).We collected various EBS-induced reminiscences for iEEG analysis, classifying them as follows: no or weak details (familiarity); moderate details and context (semantic and personal semantic memories); high details and context (episodic). Nine brain areas were selected within the temporal lobes (including the hippocampus and temporal neocortex, ipsi- and contralateral) and the insula, defining a network (each area as a node). Functional connectivity was measured by estimating pair-wise non-linear correlations between signals recorded from these brain regions during different memory events.Seventeen reminiscences in six patients (2 episodic, 10 personal semantic, 2 semantic memories, 5 familiar objects, 1 déjà-rêvé) were compared to 18 control experiential phenomena (unrelated to reminiscence), 18 negative EBS (which failed to elicit memories or other phenomena) in the same locations, and pre-EBS baseline activity.The global functional connectivity in the network was higher following EBS-induced reminiscences than during baseline activity, control phenomena, or negative EBS. The degree of connectivity increased with the complexity of memories; it was higher for detailed and contextualized memories like episodic memories. More significant links compared to baseline (edges with higher non-linear correlation relative to baseline) were observed for episodic memories than for less contextualized memories. These increases in connectivity occurred in all frequency bands, except the delta band.Our results support understanding declarative memory retrieval as having a multiplexed organization. They also show that richer memories activated by intracranial EBS are related to more complex connectivity patterns across medial and neocortical temporal lobe structures.

The hippocampus is generally considered to have relatively late involvement in recognition memory, its main electrophysiological signature being between 400 and 800 ms after stimulus onset. However, most electrophysiological studies have analyzed the hippocampus as a single responsive area, selecting only a single-site signal exhibiting the strongest effect in terms of amplitude. These classical approaches may not capture all the dynamics of this structure, hindering the contribution of other hippocampal sources that are not located in the vicinity of the selected site. We combined intracerebral electroencephalogram recordings from epileptic patients with independent component analysis during a recognition memory task involving the recognition of old and new images. We identified two sources with different responses emerging from the hippocampus: a fast one (maximal amplitude at ∼250 ms) that could not be directly identified from raw recordings and a latter one, peaking at ∼400 ms. The former component presented different amplitudes between old and new items in 6 out of 10 patients. The latter component had different delays for each condition, with a faster activation (∼290 ms after stimulus onset) for recognized items. We hypothesize that both sources represent two steps of hippocampal recognition memory, the faster reflecting the input from other structures and the latter the hippocampal internal processing. Recognized images evoking early activations would facilitate neural computation in the hippocampus, accelerating memory retrieval of complementary information. Overall, our results suggest that the hippocampal activity is composed of several sources with an early activation related to recognition memory.

Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation. HIPS was incorporated into THalamus Optimized Multi-Atlas Segmentation (THOMAS) pipeline, a method developed and optimized for WMn MRI. HIPS-THOMAS was compared to a convolutional neural network (CNN)-based segmentation method and THOMAS modified for the use of T1w images (T1w-THOMAS). The robustness and accuracy of the three methods were tested across different image contrasts (MPRAGE, SPGR, and MP2RAGE), scanner manufacturers (PHILIPS, GE, and Siemens), and field strengths (3 T and 7 T). HIPS-transformed images improved intra-thalamic contrast and thalamic boundaries, and HIPS-THOMAS yielded significantly higher mean Dice coefficients and reduced volume errors compared to both the CNN method and T1w-THOMAS. Finally, all three methods were compared using the frequently travelling human phantom MRI dataset for inter- and intra-scanner variability, with HIPS displaying the least inter-scanner variability and performing comparably with T1w-THOMAS for intra-scanner variability. In conclusion, our findings highlight the efficacy and robustness of HIPS in enhancing thalamic nuclei segmentation from standard T1w MRI.