Shailendra Segobin

Alzheimer’s disease is a neurodegenerative disorder marked by a progressive decline in episodic memory and impaired encoding of new information. While hippocampal atrophy is a hallmark of the disease, several observations suggest that some mechanisms may remain preserved, including familiarity-based recognition. Artistic items, such as music and paintings, are particularly suitable to elicit these spared processes, as they engage reward, emotional, and implicit learning networks that remain intact in this condition. However, the extent to which patients with moderate to severe Alzheimer’s disease can learn new information in these domains remains unclear. Thirty-three patients with Alzheimer’s disease (79.30 ± 5.82 years; mean Mini-Mental State Examination [MMSE] score = 14.76 ± 5.42) and 24 healthy control participants (77.17 ± 4.62 years; mean MMSE score = 28.83 ± 0.92) were included in the protocol. A data-driven stratification based on neuropsychological scores identified two subgroups of patients, classified as moderate and severe cognitive impairments. Participants first completed repeated exposure sessions to unknown musical and pictorial items until they reported a sense of familiarity, assessed by a six-point scale designed for this population. One to two days later, a recognition session during which target items and distractor items were presented was conducted; participants’ performance was also evaluated using the familiarity scale. Structural MRI was acquired to quantify hippocampal atrophy and examine the relationship between grey matter volume and recognition performance. Despite significantly different learning rates across clinical groups (cumulative link mixed model, all pairwise comparisons P < 0.001), 31 patients out of 33 reached the learning criterion for at least one of the two artistic materials. In the recognition session, pairwise comparisons confirmed that all clinical groups significantly discriminated target from distractor items (cumulative link mixed model, all pairwise comparisons P < 0.001), with a gradient of discrimination consistent with disease severity, indicating preserved but modulated familiarity-based recognition. Structural imaging confirmed substantial hippocampal atrophy in both patient subgroups relative to healthy controls (P < 0.001). Multiple regression revealed that higher familiarity scores in recognition session were associated with greater grey matter volume in the right caudate nucleus (cluster-level, PFWE < 0.05). These findings demonstrate that patients with moderate to severe Alzheimer’s disease retain the ability to encode new musical and pictorial information despite pronounced hippocampal atrophy. Familiarity-based mechanisms, supported by subcortical regions, appear to underpin this preserved learning and may offer promising perspectives for care in patients with Alzheimer’s disease.

Severe episodic memory deficits have historically been categorized as diencephalic amnesia, like in Korsakoff’s Syndrome (KS), or as medial temporal lobe (MTL) amnesia, like in Alzheimer’s Disease (AD). However, recent research has highlighted that both MTL and thalamus contribute to episodic memory. We aimed to challenge the traditional distinction by assessing whether subregional volume loss in the MTL and diencephalon reflects the distinct amnesia profiles traditionally associated with KS and AD. This cross-sectional observational study includes 203 subjects, comprising 81 healthy control participants. Of the 122 patients, 42 had amnesia: 18 patients with KS and 24 patients with AD at a dementia stage (dAD); and 80 had mild cognitive disorders: 50 patients with severe alcohol use disorder (AUD) without KS and 30 patients with amnestic mild cognitive impairment (aMCI). High-resolution T1-weighted MRI was used to quantify MTL subregions (anterior/posterior hippocampus, entorhinal cortex, parahippocampal cortex) using the ASHS-T1 pipeline and key diencephalic structures (anterior/mediodorsal thalamic nuclei, mammillothalamic tract) using the HIPS-THOMAS toolbox. Volume loss among patients and regions were compared using a linear mixed model. For each region, correlations between episodic memory and volumes loss were assessed and compared between aMCI/dAD and AUD/KS patients. Results showed no volume difference between patient groups for the anterior and posterior hippocampus and parahippocampal cortex. Entorhinal cortex was more altered in aMCI and dAD than in AUD and KS. KS and AUD patients showed disproportionate structural alterations in thalamic nuclei and mammillothalamic tracts compared with MTL subregions. KS patients showed more severe alterations than all other groups, except for anterior thalamic nuclei for which volume did not differ between KS and dAD. Episodic memory performance of AUD and KS patients correlated with volumes loss in the anterior and mediodorsal thalamic nuclei and mammillothalamic tract, while that of aMCI and dAD patients correlated with volume loss in the anterior hippocampus. Alterations in the MTL and diencephalon are not as clearly dissociated as traditionally proposed in the classification of amnesia. While KS pathology is characterized by more severe diencephalic alterations, only the entorhinal cortex is more damaged in AD than in KS. Neither hippocampal nor anterior thalamic volume loss appears to distinguish between the two types of amnesia, suggesting that structural changes in these two regions jointly participate to the pathophysiology of amnesia whatever the etiology. However, these alterations are not similarly involved in memory deficits, which suggests different architectural and/or functional implications of same-scale volume loss.

Biophysical models of human brain represent the latter as a graph of inter-connected neural regions. Building from the model by Naskar et al. (Network Neuroscience, 2021), our motivation was to understand how these brain regions can be connected at neural level to implement some inhibitory control, which calls for inhibitory connectivity rarely considered in such models. In this model, regions are made of inter-connected excitatory and inhibitory pools of neurons, but are long-range connected only via excitatory pools (mutual excitation). We thus extend this model by generalizing connectivity, and we analyse how connectivity affects the behaviour of this model. Focusing on the simplest paradigm made of a Control area and a Target area, we explore four typical kinds of connectivity: mutual excitation, Target inhibition by Control, Control inhibition by Target, and mutual inhibition. For this, we build an analytical sensitivity framework, nesting up sensitivities of isolated pools, of isolated regions, and of the full system. We show that inhibitory control can emerge only in Target inhibition by Control and mutual inhibition connectivities. We next offer an analysis of how the model sensitivities depends on connectivity structure, depending on a parameter controling the strength of the self-inhibition within Target region. Finally, we illustrate the effect of connectivity structure upon control effectivity in response to an external forcing in the Control area. Beyond the case explored here, our methodology to build analytical sensitivities by nesting up levels (pool, region, system) lays the groundwork for expressing nested sensitivities for more complex network configurations, either for this model or any other one.

Distinguishing aetiologies of neurocognitive disorder (NCD) between alcohol-induced pathologies (OH) and Alzheimer’s disease poses a major clinical challenge while dual diagnosis may be common. We aimed to define commonalities and specificities of neurocognitive alterations in OH or Alzheimer's Disease, considering the NCD severity (mild/major). In this retrospective cross-sectional study, we included 203 participants: 50 Mild-NCD-OH patients, 18 Major-NCD-OH patients, 30 Mild-NCD-AD patients, 24 Major-NCD-AD patients, as well as 81 healthy controls. Patients were compared on a neuropsychological and multimodal neuroimaging assessment (grey/white matter density and glucose metabolism). Analyses explored commonalities and specificities of each patient group within each NCD severity. All patient groups had episodic memory impairments, medial temporal lobe damage and hypometabolism in thalami and posteromedial cortex. NCD-AD patients had more severe cognitive deficits than NCD-OH patients, and the reverse pattern was observed for brain damage. NCD-OH patients notably showed more severe thalamic and cingulate alterations. NCD-OH patients also presented cerebellar damage not observed in NCD-AD. Volume deficits in the medial temporal lobe and memory deficits were more severe in Mild-NCD-AD than Mild-NCD-OH, but similar in Major-NCD-AD and Major-NCD-OH. Common alterations are observed in NCD-OH and NCD-AD, mainly within the memory circuit. Only cerebellar damage appears to be specific to NCD-OH. The specificity of NCD-AD deficits relies on their severity since they are also present to a lesser extent in NCD-OH, reinforcing how the neurocognitive phenotypes overlap. These results reaffirm the importance of questioning alcohol consumption in NCD-AD patients and considering an Alzheimer's Disease diagnosis in NCD-OH patients.

Background: Theoretical and empirical contributions have identified insula as key in addiction. However, anatomical modifications of the insula in addictive states, and their variations across substance use disorders (SUDs), remain to be specifically explored. We therefore explored the specificities and commonalities of insula gray matter (GM) alterations in severe alcohol use disorder (sAUD) and severe cocaine use disorder (sCUD). Methods: We explored insula GM volume through a refined parcellation in 12 subregions (six bilateral): anterior inferior cortex (AIC), anterior short gyrus, middle short gyrus, posterior short gyrus, anterior long gyrus (ALG), and posterior long gyrus (PLG). Using a linear mixed model analysis, we explored the insula volume profiles of 50 patients with sAUD, 61 patients with sCUD, and 36 healthy controls (HCs). Results: In both sAUD and sCUD, we showed overall insular lower volume with a right-sided lateralization effect, and a major volume deficit in bilateral ALG. Moreover, differences emerged across groups, with higher left AIC and PLG volume deficits in sCUD compared to sAUD and HC. Conclusions: We offered the first joint exploration of GM insular volumes in two SUD through refined parcellation, thus unveiling the similarities and dissimilarities in volume deficit profiles. Our results bring evidence complementing prior ones suggesting the core role of the right and posterior insula in craving and interoception, two crucial processes in addiction. Left AIC and PLG group differences also show that, while insula is a region of interest in SUD, sCUD and sAUD generate distinct insular profiles, which might parallel clinical differences across SUD.

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.

Alcohol use disorder is a chronic disease characterized by an inappropriate pattern of drinking, resulting in negative consequences for the individual's physical, mental and social health. Korsakoff's syndrome is a complication of alcohol use disorder and is characterized by severe memory and executive deficits. The fronto-cerebellar and Papez circuits are structurally affected in patients with alcohol use disorder with and without Korsakoff’s syndrome. The first objective of the present study was to measure the effect of chronic and excessive alcohol consumption on resting-state functional connectivity of these two functional brain networks. The second objective was to identify, for the first time, resting-state functional connectivity abnormalities specific to amnesic patients with Korsakoff’s syndrome. In the present study, a neuropsychological assessment and a resting-state functional magnetic resonance imaging examination were conducted in 31 healthy controls (43.6 ± 6.1 years) and 46 patients (46.6 ± 9.1 years) with alcohol use disorder including 14 patients with Korsakoff’s syndrome (55.5 ± 5.3 years) to examine the effect of chronic and heavy alcohol consumption on functional connectivity of the fronto-cerebellar and the Papez circuits at rest and the specificity of functional connectivity changes in Korsakoff’s syndrome compared to alcohol use disorder without Korsakoff’s syndrome. The resting-state functional connectivity analyses focused on the nodes of the fronto-cerebellar and Papez circuits and combined region of interest and graph theory approaches, and whether these alterations are associated with the neuropsychological profile. In patients pooled together compared to controls, lower global efficiency was observed in the fronto-cerebellar circuit. In addition, certain regions of the fronto-cerebellar and Papez circuits were functionally hyperconnected at rest, which positively correlated with executive functions. Patients with Korsakoff’s syndrome showed lower resting-state functional connectivity, lower local and global efficiency within the Papez circuit compared to those without Korsakoff’s syndrome. Resting-state functional connectivity positively correlated with several cognitive scores in patients with Korsakoff’s syndrome. The fronto-cerebellar and Papez circuits, two normally well-segregated networks, are functionally altered by alcohol use disorder. The Papez circuit attempts to compensate for deficits in the fronto-cerebellar circuit, albeit insufficiently as evidenced by patients’ overall lower cognitive performance. Korsakoff’s syndrome is characterized by altered functional connectivity in the Papez circuit known to be centrally involved in memory.

The experience of an extremely aversive event can produce enduring deleterious behavioral, and neural consequences, among which posttraumatic stress disorder (PTSD) is a representative example. Although adolescence is a period of great exposure to potentially traumatic events, the effects of trauma during adolescence remain understudied in clinical neuroscience. In this exploratory work, we aim to study the whole-cortex functional organization of 14 adolescents with PTSD using a data-driven method tailored to our population of interest. To do so, we built on the network neuroscience framework and specifically on multilayer (multisubject) community analysis to study the functional connectivity of the brain. We show, across different topological scales (the number of communities composing the cortex), a hyper-colocalization between regions belonging to occipital and pericentral regions and hypo-colocalization in middle temporal, posterior–anterior medial, and frontal cortices in the adolescent PTSD group compared to a nontrauma exposed group of adolescents. These preliminary results raise the question of an altered large-scale cortical organization in adolescent PTSD, opening an interesting line of research for future investigations.

Functional neuroimaging has demonstrated the key role played by the insula in severe alcohol use disorder (sAUD), notably through its involvement in craving and body signals processing. However, the anatomical counterpart of these functional modifications in sAUD patients with and without neurological complications remains largely unexplored, especially using state‐of‐the‐art parcellation tools. We thus compared the grey matter volume of insular subregions (form anterior to posterior: anterior inferior cortex, anterior short gyrus, middle short gyrus, posterior short gyrus, anterior long gyrus, posterior long gyrus) in 50 recently detoxified patients with sAUD, 19 patients with Korsakoff's syndrome (KS) and 36 healthy controls (HC). We used a mixed linear model analysis to explore group differences in the six subregions grey matter volume and lateralization differences. Insular macrostructure was globally affected to the same extent in sAUD with and without KS, indicating that these brain abnormalities may be related to alcohol consumption per se, rather than to the presence of alcohol‐related neurological complications. Insular atrophy showed a right‐sided lateralization effect and was especially marked in the posterior insula, a region associated with visceral information processing and the embodiment effect of a substance, from which craving arises. Anatomical damages might thus underlie the previously reported altered insular activations and their behavioural counterparts.

Background: Alzheimer’s disease (AD) and Korsakoff’s syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on global cognitive deficits with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted. Results: For the cingulate gyri, and anterior thalamic nuclei, all patient groups were affected compared to controls but did not differ between each other. Smaller volumes were observed in all patient groups compared to controls in the mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS than AD. MTT volumes were damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD. Conclusions: There are commonalities in the pattern of volume deficits in KS and AD within the Papez circuit with the anterior thalamic nuclei, cingulate cortex and hippocampus (in MAD only) being damaged to the same extent. The specificity of KS relies on the alteration of the MTT and the severity of the MB shrinkage. Further comparative studies including other imaging modalities and a neuropsychological assessment are required.