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IMPORTANCE: Drug-resistant temporal lobe epilepsy (TLE) has been associated with hippocampal pathology. Most surgical treatment strategies, including resection and responsive neurostimulation (RNS), focus on this disease epicenter; however, imaging alterations distant from the hippocampus, as well as emerging data from responsive neurostimulation trials, suggest conceptualizing TLE as a network disorder. OBJECTIVE: To assess whether brain networks connected to areas of atrophy in the hippocampus align with the topography of distant neuroimaging alterations and RNS response. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case-control study was conducted between July 2009 and June 2022. Data collection for this multicenter, population-based study took place across 4 tertiary referral centers in Montréal, Canada; Querétaro, México; Nanjing, China; and Salt Lake City, Utah. Eligible patients were diagnosed with TLE according to International League Against Epilepsy criteria and received either neuroimaging or neuroimaging and RNS to the hippocampus. Patients with encephalitis, traumatic brain injury, or bilateral TLE were excluded. MAIN OUTCOMES AND MEASURES: Spatial alignment between brain network topographies. RESULTS: Of the 110 eligible patients, 94 individuals diagnosed with TLE were analyzed (51 [54%] female; mean [SD] age, 31.3 [10.9] years). Hippocampal thickness maps in TLE were compared to 120 healthy control individuals (66 [55%] female; mean [SD] age, 29.8 [9.5] years), and areas of atrophy were identified. Using an atlas of normative connectivity (n = 1000), 2 brain networks were identified that were functionally connected to areas of hippocampal atrophy. The first network was defined by positive correlations to temporolimbic, medial prefrontal, and parietal regions, whereas the second network by negative correlations to frontoparietal regions. White matter changes colocalized to the positive network (t93 = –3.82; P = 2.44 × 10−4). In contrast, cortical atrophy localized to the negative network (t93 = 3.54; P = 6.29 × 10−3). In an additional 38 patients (20 [53%] female; mean [SD] age, 35.8 [11.3] years) treated with RNS, connectivity between the stimulation site and atrophied regions within the negative network was associated with seizure reduction (t212 = −2.74; P = .007). CONCLUSIONS AND RELEVANCE: The findings in this study indicate that distributed pathology in TLE may occur in brain networks connected to the hippocampal epicenter. Connectivity to these same networks was associated with improvement following RNS. A network approach to TLE may reveal therapeutic targets outside the traditional target in the hippocampus.

The ILAE Neuroimaging Task Force publishes educational case reports that highlight basic aspects of neuroimaging in epilepsy consistent with the ILAE's educational mission. Subcortical laminar heterotopia, also known as subcortical band heterotopia (SBH) or “double cortex,” is an intriguing and rare congenital malformation of cortical development. SBH lesions are part of a continuum best designated as agyria‐pachygyria‐band‐spectrum. The malformation is associated with epilepsy that is often refractory, as well as variable degrees of developmental delay. Moreover, in an increasing proportion of cases, a distinct molecular‐genetic background can be found. Diagnosing SBH can be a major challenge for many reasons, including more subtle lesions, and “non‐classic” or unusual MRI‐appearances. By presenting an illustrative case, we address the challenges and needs of diagnosing and treating SBH patients in epilepsy, especially the value of high‐resolution imaging and specialized MRI‐protocols.

Cognitive control is required to organize thoughts and actions and is critical for the pursuit of long-term goals. Childhood cognitive control relates to other domains of cognitive functioning and predicts later-life success and well-being. In this study, we used a randomized controlled trial to test whether cognitive control can be improved through a pre-registered 8-week intervention in 235 children aged 6–13 years targeting response inhibition and whether this leads to changes in multiple behavioral and neural outcomes compared to a response speed training. We show long-lasting improvements of closely related measures of cognitive control at the 1-year follow-up; however, training had no impact on any behavioral outcomes (decision-making, academic achievement, mental health, fluid reasoning and creativity) or neural outcomes (task-dependent and intrinsic brain function and gray and white matter structure). Bayesian analyses provide strong evidence of absent training effects. We conclude that targeted training of response inhibition does little to change children’s brains or their behavior.

Autism is a neurodevelopmental condition involving atypical sensory-perceptual functions together with language and socio-cognitive deficits. Previous work has reported subtle alterations in the asymmetry of brain structure and reduced laterality of functional activation in individuals with autism relative to non-autistic individuals (NAI). However, whether functional asymmetries show altered intrinsic systematic organization in autism remains unclear. Here, we examined inter- and intra-hemispheric asymmetry of intrinsic functional gradients capturing connectome organization along three axes, stretching between sensory-default, somatomotor-visual, and default-multiple demand networks, to study system-level hemispheric imbalances in autism. We observed decreased leftward functional asymmetry of language network organization in individuals with autism, relative to NAI. Whereas language network asymmetry varied across age groups in NAI, this was not the case in autism, suggesting atypical functional laterality in autism may result from altered developmental trajectories. Finally, we observed that intra- but not inter-hemispheric features were predictive of the severity of autistic traits. Our findings illustrate how regional and patterned functional lateralization is altered in autism at the system level. Such differences may be rooted in atypical developmental trajectories of functional organization asymmetry in autism.

The ILAE Neuroimaging Task Force aims to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Previous quantitative MRI studies have established important imaging markers of epilepsy‐related pathology, including features sensitive to hippocampal cell loss and reactive astrogliosis. Here, we review the case of a female with pediatric drug‐resistant epilepsy. Throughout her course of treatment, she had seven MRI investigations at several centers; the first three did not follow optimized epilepsy imaging protocols whereas the remaining four adhered to HARNESS‐MRI protocols (harmonized neuroimaging of epilepsy structural sequences). Visual inspection of a set of HARNESS‐MR images revealed conspicuous left hippocampal hyperintensity which may have been initially overlooked on non‐optimized MR images. Quantitative analysis of these multimodal imaging data along hippocampal subfields provided clear evidence of hippocampal sclerosis, with increased atrophy, increased mean diffusivity, increased T2‐FLAIR signal, and lower qT1 values observed in the anterior portions of the left, compared to the right hippocampus. The patient underwent a left anterior temporal lobectomy with amygdalohippocampectomy at age 16 years. Histopathology of the resected specimen also confirmed hippocampal sclerosis with widespread gliosis and focal neuronal loss in the hippocampal subfields overlapping with regions of multimodal quantitative alterations. The patient remains seizure‐free one year after surgery. Collectively, this case highlights the need for optimized data acquisition protocols early in the treatment of epilepsy and supports quantitative analysis of MRI contrasts to enhance personalized diagnosis and prognosis of drug‐resistant patients with epilepsy.

The default mode network (DMN) is a set of widely distributed brain regions in the parietal, temporal and frontal cortex. These regions often show reductions in activity during attention-demanding tasks but increase their activity across multiple forms of complex cognition, many of which are linked to memory or abstract thought. Within the cortex, the DMN has been shown to be located in regions furthest away from those contributing to sensory and motor systems. Here, we consider how our knowledge of the topographic characteristics of the DMN can be leveraged to better understand how this network contributes to cognition and behaviour.

Autism symptomology has a profound impact on cognitive and affective functioning, yet we know relatively little about how it shapes patterns of ongoing thought. In an exploratory study in a large population of neurotypical individuals, we used experience sampling to characterise the relationship between ongoing cognition and self-reported autistic traits. We found that with increasing autistic symptom score, cognition was characterised by thinking more in words than images. Analysis of structural neuroimaging data found that autistic traits linked to social interaction were associated with greater cortical thickness in a region of lingual gyrus (LG) within the occipital cortex. Analysis of resting state functional neuroimaging data found autistic traits were associated with stronger connectivity between the LG and a region of motor cortex. Importantly, the strength of connectivity between the LG and motor cortex moderated the link between autistic symptoms and thinking in words: individuals showing higher connectivity showed a stronger association between autistic traits and thinking in words. Together we provide behavioural and neural evidence linking autistic traits to the tendency to think in words which may be rooted in underlying cortical organisation. These observations lay the groundwork for research into the form and content of self-generated thoughts in individuals with the established diagnosis of autism.

AbstractRapid advances in neuroimaging and network science have produced powerful tools and measures to appreciate human brain organization at multiple spatial and temporal scales. It is now possible to obtain increasingly meaningful representations of whole-brain structural and functional brain networks and to formally assess macroscale principles of network topology. In addition to its utility in characterizing healthy brain organization, individual variability, and life span-related changes, there is high promise of network neuroscience for the conceptualization and, ultimately, management of brain disorders. In the current review, we argue for a science of the human brain that, while strongly embracing macroscale connectomics, also recommends awareness of brain properties derived from meso- and microscale resolutions. Such features include MRI markers of tissue microstructure, local functional properties, as well as information from nonimaging domains, including cellular, genetic, or chemical data. Integrating these measures with connectome models promises to better define the individual elements that constitute large-scale networks, and clarify the notion of connection strength among them. By enriching the description of large-scale networks, this approach may improve our understanding of fundamental principles of healthy brain organization. Notably, it may also better define the substrate of prevalent brain disorders, including stroke, autism, as well as drug-resistant epilepsies that are each characterized by intriguing interactions between local anomalies and network-level perturbations.

To detect automatically focal cortical dysplasia (FCD) type II in patients with extratemporal epilepsy initially diagnosed as MRI-negative on routine inspection of 1.5 and 3.0T scans.

Evidence for disease progression in the mesiotemporal lobe is mainly derived from global volumetry of the hippocampus. In this study, we tracked progressive structural changes in the hippocampus, amygdala, and entorhinal cortex in drug-resistant temporal lobe epilepsy at a subregional level. Furthermore, we evaluated the relation between disease progression and surgical outcome.

Diffusion tensor imaging (DTI) tractography has shown tract-specific pathology in temporal lobe epilepsy (TLE). This technique normally yields a single value per diffusion parameter per tract, potentially reducing the sensitivity for the detection of focal changes. Our goal was to spatially characterize diffusion abnormalities of fasciculi carrying temporal lobe connections.

Although experimental work has provided evidence that the thalamus is a crucial relay structure in temporal lobe epilepsy (TLE), the relation of the thalamus to neocortical pathology remains unclear. To assess thalamocortical network pathology in TLE, we mapped pointwise patterns of thalamic atrophy and statistically related them to neocortical thinning.

Nearly one-third of patients with focal epilepsy experience disabling seizures that are refractory to pharmacotherapy. Drug-resistant focal epilepsy is, however, potentially curable by surgery. Although lesions associated with the epileptic focus can often be accurately detected by MRI, in many patients conventional imaging based on visual evaluation is unable to pinpoint the surgical target. Patients with so-called cryptogenic epilepsy represent one of the greatest clinical challenges in many tertiary epilepsy centers. In recent years, it has become increasingly clear that epilepsies that are considered cryptogenic are not necessarily nonlesional, the primary histopathological substrate being subtle cortical dysplasia. This Review considers the application of new advances in brain imaging, such as MRI morphometry, computational modeling and diffusion tensor imaging. By revealing dysplastic lesions that previously eluded visual assessments, quantitative structural MRI methods such as these have clearly demonstrated an increased diagnostic yield of epileptic lesions, and have provided successful surgical options to an increasing number of patients with 'cryptogenic' epilepsy.

To assess the reproducibility of neocortical atrophy and its clinical significance across the spectrum of temporal lobe epilepsy (TLE), in particular with respect to postsurgical outcome.

Schizophrenia is widely recognized as a neurodevelopmental disorder. Abnormal cortical development in otherwise typically developing children and adolescents may be revealed using polygenic risk scores for schizophrenia (PRS-SCZ).

Objectives/AimsCognitive impairment is a common comorbidity of epilepsy, and can be more burdensome than seizures themselves. Temporal and frontal lobe epilepsy (TLE, FLE) are accompanied by multi-domain cognitive impairment. While the underlying neural substrates have been extensively investigated in TLE, functional imaging studies in FLE are scarce. Here, we aimed to: (i) investigate systems-level neural processes accounting for cognitive dysfunction in FLE; (ii) directly compare FLE and TLE patients, establishing commonalities and differences; and (iii) decode the potential influence of clinical characteristics on cognitive network architecture.MethodsWe capitalized on a large, single-centre sample of 172 adult participants (56 with FLE, 64 with TLE, 52 with controls) who were investigated via: (i) an extensive neuropsychological test battery that included attention, psychomotor speed, language, working memory, executive function, and episodic memory tests; and (ii) four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in age of epilepsy onset, disease duration, and antiseizure medication load. We mapped task-related brain activation and deactivation using a novel multiscale approach, and tracked reorganization in FLE and TLE. We complemented voxel-based maps with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional networks, and (ii) the principal functional connectivity gradient, that encodes a continuous transition from lower-level (sensory) to higher-order (transmodal) brain areas.ResultsWe find that cognitive impairment in FLE is accompanied by broadly reduced activation across frontoparietal attentional and executive networks, and reduced default-mode network deactivation, indicating large-scale disorganization of task-related recruitment, particularly during working memory. Patterns of dysfunction in FLE and TLE are broadly similar, but some traits are syndrome-specific: impaired task-related deactivation of the default-mode network is more prominent in FLE, while impaired recruitment of posterior language areas is more marked in TLE. More severe epilepsy, as tracked by age at onset, epilepsy duration, seizure frequency, time since last seizure, and propensity for focal-to-bilateral tonic-clonic seizures, relates to more marked cognitive network disorganization both in FLE and TLE.ConclusionsOur study elucidates neural processes underlying cognitive impairment in the most common focal epilepsies, identifies frontoparietal executive alterations as a shared biological signature, irrespective of seizure focus localization, and shows that temporal lobe language alterations are TLE-specific. The highlighted systems-level behaviour may be amenable to future remediation strategies, including neurostimulation.