The "limbic network," comprising orbitofrontal and anterior temporal cortex, is part of an extended default network: Evidence from multi-echo fMRI.

Resting-state functional magnetic resonance imaging (fMRI) investigations have provided a view of the default network (DN) as composed of a specific set of frontal, parietal, and temporal cortical regions. This spatial topography is typically defined with reference to an influential network parcellation scheme that designated the DN as one of seven large-scale networks (Yeo et al., 2011). However, the precise functional organization of the DN is still under debate, with studies arguing for varying subnetwork configurations and the inclusion of subcortical regions. In this vein, the so-called limbic network-defined as a distinct large-scale network comprising the bilateral temporal poles, ventral anterior temporal lobes, and orbitofrontal cortex-is of particular interest. A large multi-modal and multi-species literature on the anatomical, functional, and cognitive properties of these regions suggests a close relationship to the DN. Notably, these regions have poor signal quality with conventional fMRI acquisition, likely obscuring their network affiliation in most studies. Here, we leverage a multi-echo fMRI dataset with high temporal signal-to-noise and whole-brain coverage, including orbitofrontal and anterior temporal regions, to examine the large-scale network resting-state functional connectivity of these regions and assess their associations with the DN. Consistent with our hypotheses, our results support the inclusion of the majority of the orbitofrontal and anterior temporal cortex as part of the DN and reveal significant heterogeneity in their functional connectivity. We observed that left-lateralized regions within the temporal poles and ventral anterior temporal lobes, as well as medial orbitofrontal regions, exhibited the greatest resting-state functional connectivity with the DN, with heterogeneity across DN subnetworks. Overall, our findings suggest that, rather than being a functionally distinct network, the orbitofrontal and anterior temporal regions comprise part of a larger, extended default network.

The precise functional organization of the default network is still under debate. Limitations in temporal signal-to-noise of functional MRI BOLD signal data may have restricted estimations of the topography of the default network. The "limbic network," defined as a distinct large-scale network comprising bilateral anterior temporal and orbitofrontal cortex, has been affiliated with the default network in nonhuman animal tractography and task-based fMRI studies in humans. We leverage a multi-echo fMRI dataset with high temporal signal-to-noise and whole-brain coverage to examine the large-scale network resting-state functional connectivity of these regions and assess their associations with the default network. Our results support the inclusion of anterior temporal and orbitofrontal cortex as part of the default network. Overall, our findings suggest that, rather than being a functionally distinct limbic network, the anterior temporal and orbitofrontal regions comprise part of an extended default network.

Evaluating the updated LATE-NC staging criteria using data from NACC.

INTRODUCTION: Limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria were updated in 2023. We evaluated this updated staging using National Alzheimer's Coordinating Center data. METHODS: We examined associations of LATE-NC stages with cognition and other neuropathologic changes (NCs), and with cognition while accounting for other NCs, using multilevel regression models. RESULTS: Of 1352 participants, 502 (37%) had LATE-NC (23% stage 1a, 6% stage 1b, 58% stage 2, 13% stage 3). LATE-NC stages were associated with cognition, hippocampal sclerosis of aging (HS-A), Alzheimer's disease NC (ADNC), Lewy bodies (LBs), and hippocampal atrophy. While stage 1b was associated with cognition and HS-A consistent with other stages, it was not associated with ADNC or LBs. All LATE-NC stages remained significantly associated with worse cognition when accounting for other NCs. DISCUSSION: The updated LATE-NC staging criteria capture variations in early TDP-43 pathology spread which are consequential for cognition and associations with other NCs. HIGHLIGHTS: We applied the updated limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria to data from the National Alzheimer's Coordinating Center. LATE-NC stage 1b was identified in 22% of participants with stage 1. In contrast to other LATE-NC stages, stage 1b was not associated with Alzheimer's disease neuropathologic change (ADNC) or Lewy bodies. Stages 1a and 1b were significantly associated with dementia and memory impairment. Stages 1b+ were more strongly tied to dementia than all other neuropathologic changes except high likelihood ADNC.

Diagnosis of Alzheimer's Disease in Clinical Practice: Time to Incorporate Biomarkers?

Hippocampal dysfunction is associated with early clinical signs of Alzheimer's disease (AD). Due to the limited availability or invasiveness of current biomarkers, the AD diagnosis is usually based on cognitive assessment and structural brain imaging. The recent study by Lalive and colleagues examined the specificity of brain morphometry for the AD diagnosis in a memory clinic cohort with hippocampal-type amnestic syndrome. The results indicate that memory deficits and hippocampal atrophy are similar in AD and non-AD patients, highlighting their low diagnostic specificity. These findings challenge the traditional AD diagnosis and underscore the need for biomarkers to differentiate specific neuropathological entities.

"Mood, psychosis and suicidal behavior in epilepsy".

Epilepsy is a chronic neurological disorder that has complex relations with social, vocational and psychological functioning. Multiple studies showed that frequency of mood disorders in patients with epilepsy is increased and include depression, anxiety and psychosis. We present data from a neurobiological prospective having clinical relevance for epilepsy and comorbidities, including studies in people with late onset epilepsies. Better understanding of neurobiological mechanisms, anatomical, functional, neuroendocrine and molecular basis of psychiatric comorbidities in persons with epilepsy, can advance therapeutic responses. Epilepsy patients have a significantly higher prevalence of depressive symptoms. Many studies showed that depressive symptoms reduce their quality of life. Psychosis in epilepsy is a rare but severe disorder that usually occurs in patients with early onset of seizures, less localised ictal EEG recordings and seizure clustering. Suicide behavior presents an important problem in managing people with epilepsy. Suicidal ideation is not uncommon, and patients also have an increased risk for suicidal attempt or completed suicide. Psychiatric comorbidities present a significant problem and ask for a multidisciplinary approach to optimize treatment of people with epilepsy.

Toddler disorganized attachment in relation to cortical thickness and socioemotional problems in late childhood.

Disorganized attachment is a risk for mental health problems, with increasing work focused on understanding biological mechanisms. Examining late childhood brain morphology may be informative - this stage coincides with the onset of many mental health problems. Past late childhood research reveals promising candidates, including frontal lobe cortical thickness and hippocampal volume. However, work has been limited to Western samples and has not investigated mediation or moderation by brain morphology. Furthermore, past cortical thickness research included only 33 participants. The current study utilized data from 166 children from the GUSTO Asian cohort, who participated in strange situations at 18 months and MRI brain imaging at 10.5 years, with 124 administered the Child Behaviour Checklist at 10.5 years. Results demonstrated disorganization liked to internalizing problems, but no mediation or moderation by brain morphology. The association to internalizing (but not externalizing) problems is discussed with reference to the comparatively higher prevalence of internalizing problems in Singapore.

Resveratrol: A Multifaceted Guardian against Anxiety and Stress Disorders-An Overview of Experimental Evidence.

The medicinal properties of resveratrol have garnered increasing attention from researchers. Extensive data have been accumulated on its use in treating cardiovascular diseases, immune system disorders, cancer, neurological diseases, and behavioral disorders. The protective mechanisms of resveratrol, particularly in anxiety-related stress disorders, have been well documented. However, less attention has been given to the side effects of resveratrol. This review explores not only the mechanisms underlying the anxiolytic effects of resveratrol but also the mechanisms that may lead to increased anxiety following resveratrol treatment. Understanding these mechanisms is crucial for enhancing the efficacy of resveratrol in managing anxiety disorders associated with stress and PTSD.

Long-term outcomes in antibody-negative autoimmune encephalitis: a retrospective study.

BACKGROUND AND OBJECTIVE: Despite constituting one-third of suspected autoimmune encephalitis (AE) patients, antibody-negative cases without typical AE features are understudied. We aim to characterize the clinical phenotypes and long-term outcomes of "possible only" and "probable" AE cases. METHODS: We conducted a retrospective analysis of adult patients evaluated at Mayo Clinic's Autoimmune Neurology Clinic (01/01/2006-12/31/2020), meeting diagnostic criteria for "possible only" or "probable but antibody-negative" AE, with ≥ 1 year of follow-up. All patients underwent neural antibody testing. RESULTS: Among fifty-one patients, six had a change in diagnosis (non-autoimmune, 2) and were excluded from further analysis. Forty-five patients were analyzed [median age, 61 years (range 20-88); female, 21 (47%); median follow-up, 36 months (range 12-174)]. A nadir modified Rankin Scale (mRS) ≥ 3 was recorded in 41/45 (91%). CSF was inflammatory in 20/44 (45%) and MRI had encephalitic changes in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two patients (4%) had paraneoplastic causation. Relapses (> 3 months from onset) were noted in 14 (31%). Memory dysfunction (69%), attention deficits (38%), and gait instability (29%) were the most frequent at the last follow-up. Most patients (76%) were independent at the last follow-up and only two required an assistive device to ambulate; 11 patients (24%) had poor neurological outcome (mRS ≥ 3). Higher mRS score and gait assistance requirement at 3 months were predictive of poor outcome (P ≤ 0.01). DISCUSSION: Despite significant disability at initial disease stages, most antibody-negative AE patients regain independent functioning. Early functional status and gait assistance requirements may predict long-term prognosis.

The neurobiology and immunology of CASPR2-associated neurological disorders.

CASPR2-associated neurological disorders encompass a wide clinical spectrum broadly divided into overlapping three autoimmune syndromes: CASPR2 limbic encephalitis, Morvan syndrome, and Isaacs syndrome. CASPR2 is a neuronal protein expressed at different sites in the central and peripheral nervous system and has a variety of roles and functions regarding neuronal excitability, synaptic plasticity, and homeostasis of inhibitory networks, most of which are only partially understood. CASPR2 antibodies have various pathogenic effects including internalization of CASPR2, disruption of protein-protein interactions, and, possibly, complement activation. Their pathogenic effect is well demonstrated in the limbic encephalitis phenotype, but the role of pathogenic antibodies in the development of other clinical manifestations is less clear. CASPR2 limbic encephalitis also differ from the other CASPR2-associated disorders in regard to HLA allele and paraneoplastic associations, suggesting it has immunological mechanisms distinct from the other clinical forms. Future studies are needed to better understand how the immunological alterations lead to the different phenotypes associated with CASPR2 antibodies.

Amnestic syndrome in the course of seronegative limbic encephalitis complicated by drug-resistant epilepsy: a case report.

We present the case of a 35-year-old female patient admitted to the hospital with symptoms of rapidly increasing disturbances of consciousness and fever for 48 hours. A lumbar puncture, bacteriological and virological examinations, and initial imaging studies did not show abnormalities. Brain magnetic resonance imaging (MRI), repeated several times, showed hyperintense confluent lesions in both temporal lobes and atrophy of both hippocampi. General examination, cerebrospinal fluid culture, the panel of antineuronal antibodies, and tumor markers remained negative on subsequent repeats. Despite several laboratory and imaging studies, the etiology of the disease could not be established, infections were excluded, and no autoantibodies were found. A diagnosis of probable limbic encephalitis, amnestic syndrome resulting from organic brain damage, and drug-resistant epilepsy was made. The patient, with limbic encephalitis complicated by drug-resistant status epilepticus, was treated with cycles of immunoglobulin and subsequent plasmapheresis. She was then transferred to the Department of Psychiatry for diagnosis and treatment of intermittent psychotic disorders. During hospitalization, the patient was observed to have multiple epileptic seizures with temporal and frontal morphology, amnestic syndrome with confabulations, and periodic psychotic disorders with the occurrence of visual hallucinations. Antiepileptic treatment was escalated by including cenobamate in increasing doses. To control the mental disorders, duloxetine, tiapride, and cognitive function exercises were introduced. There was a slight improvement in memory, a cessation of confabulations, and an emergence of the patient's criticism of the symptoms presented. The psychotic symptoms subsided, and the number of epileptic seizures decreased. The described case portrays a unique co-occurrence of disease symptoms that are difficult to treat. It shows the therapeutic difficulties that can occur in patients with suspected autoimmune encephalitis. Furthermore, it shows the need for multispecialty care of a patient with psychotic symptoms in the course of epilepsy accompanied by amnestic syndrome.

Making an Effective Flipped Neuroscience Lab by Approaching Students from Their Emoticons.

During the pandemic, we filmed our neuroscience labs, and now the videos provide a great resource to flip the lab. Our lab, however, covers a wide range of complicated topics, ranging from gross anatomy, immunohistochemistry (IHC) staining, and fluorescence imaging to cockroach microscopic surgery and measuring nerve conduction velocity on worms and human subjects, and it is challenging to get students to finish watching these complicated experiments. The biggest challenge that students face while watching these experiment demonstrations is their own emotions. When we were editing the films of the labs, we did not reduce the complexity, but we explained concepts by using concepts and objects that students are already familiar with so we do not trigger anxiety. To reduce boredom, we employed three major methods: questioning, humor, and increasing the pace. To address potential anxiety or reluctance about the in-person part of the lab, we mention at the beginning of every lab session that making mistakes is completely acceptable and, as they make mistakes, we help them understand what went wrong and how to correct it. We also introduce additional activities in some lab sessions to pique their interest. For instance, we ask students to test the effects of Red Bull on crickets and investigate whether students who play more video games have higher conduction velocities in the median nerve. Thus far, our flipped lab has been quite successful in terms of maintaining video retention rates and in-person attendance rates. A notable example of the effectiveness of improved hands-on skills is the cockroach microscopic surgery. Before implementing the flipped lab, only 10% of students were able to successfully complete the surgery and acquire nerve activity recordings. With the flipped lab, 90% of students were able to obtain a recording independently.

Patterns of Neuropsychiatric Manifestations of Ovarian Teratomas: A Systematic Review of Case Reports.

Ovarian teratomas are germ cell tumors composed of multiple cell types. Ovarian teratomas may express antigens found in the nervous system or neuroendocrine proteins. These neural antigens and neuroendocrine proteins may lead to an autoimmune response with associated encephalitis. There are a growing number of case reports of autoimmune encephalitis in patients with ovarian teratomas. However, the patterns of neuropsychiatric manifestations of ovarian teratomas associated with encephalitis have not been established. The aim of this article is to conduct a systematic review to determine the patterns of neuropsychiatric manifestations of ovarian teratoma-associated encephalitis, focusing on their frequency and clinical course. Thirty-three case reports were collected and analyzed for a systematic review. The studies were full-text, peer-reviewed journal publications from April 2014 to April 2024. Fifty-eight patients were included in our study. The age group of 22-35 years old was the most reported, with 25 (43.1%) patients. The most commonly reported symptoms were memory impairment in 29 (50%) patients, hallucinations in 25 (43.1%) patients, and aggressive behavior in 23 (39.7%) patients. Neuropsychiatric symptoms had a prodromal phase of flu-like symptoms in 31 (53.4%) patients. The neuropsychiatric symptoms preceded the diagnosis of ovarian teratoma in 57 (98.3%) patients. In 53 (91.4%) patients, patients did not respond to psychiatric medications. Autoimmune antibodies to neural antigens were found in 45 (77.6%) patients, with 25 (43.1%) patients having neural tissue present in the teratoma. Treatment of the underlying teratoma and encephalitis led to full recovery in 37 (63.8%) patients. However, long-term outcomes such as relapse and mortality were discussed in only 11 (19.0%) patients. Findings suggest that neuropsychiatric symptoms correlate with teratoma-associated encephalitis and often precede tumor detection. The treatment of the teratoma led to full recovery of the neuropsychiatric manifestations; however, the long-term outcomes of the patients need to be further studied. Future research is needed on the prognosis of patients with neuropsychiatric manifestations of ovarian teratoma.

Neuroimaging insights into poor prognosis paraneoplastic encephalomyelitis: A case report on a challenging diagnosis revealed by MR imaging in a patient with Hodgkin's lymphoma.

Paraneoplastic encephalomyelitis (PEM) is a rare complication associated with malignancies, often presenting before the cancer diagnosis. A 42-year-old male with a history of chronic smoking presented with acute urinary retention and neurological deficits, all evolving in a febrile context with general deterioration. Laboratory tests were conducted, followed by a cerebral MRI which revealed multiple T2 and FLAIR hyperintense lesions in the periventricular and periaqueductal regions, medial temporal lobes, and bilateral postero-medial thalamus. Enhanced CT scans of the chest and abdomen identified multiple cervical, axillary, and inguinal lymphadenopathies. Subsequently, an ultrasound-guided biopsy of a cervical node was performed. His condition deteriorated rapidly, requiring intubation and sedation. A subsequent MRI revealed worsening cerebral and spinal cord lesions with new contrast enhancement in the brainstem. The differential diagnosis included toxic/metabolic and paraneoplastic causes. Biopsy results confirmed Hodgkin's lymphoma, leading to a diagnosis of progressive paraneoplastic encephalomyelitis (PEM). Despite adequate treatment, the patient's condition worsened, leading to death from pneumonitis and metabolic complications. This case underscores the importance of considering PEM in patients with neurological deficits and malignancy, with MRI playing a crucial role in diagnosis. Early detection and treatment are essential to improving outcomes.

Case report: Bridging limbic network epilepsy with psychiatric, memory, and sleep comorbidities: case illustrations of reversible psychosis symptoms during continuous, high-frequency ANT-DBS.

The network nature of focal epilepsy is exemplified by mesial temporal lobe epilepsy (mTLE), characterized by focal seizures originating from the mesial temporal neocortex, amygdala, and hippocampus. The mTLE network hypothesis is evident in seizure semiology and interictal comorbidities, both reflecting limbic network dysfunction. The network generating seizures also supports essential physiological functions, including memory, emotion, mood, and sleep. Pathology in the mTLE network often manifests as interictal behavioral disturbances and seizures. The limbic circuit is a vital network, and here we review one of the most common focal epilepsies and its comorbidities. We describe two people with drug resistant mTLE implanted with an investigational device enabling continuous hippocampal local field potential sensing and anterior nucleus of thalamus deep brain stimulation (ANT-DBS) who experienced reversible psychosis during continuous high-frequency stimulation. The mechanism(s) of psychosis remain poorly understood and here we speculate that the anti-epileptic effect of high frequency ANT-DBS may provide insights into the physiology of primary disorders associated with psychosis.

Proteomic evidence of depression-associated astrocytic dysfunction in the human male olfactory bulb.

The olfactory bulb (OB), a major structure of the limbic system, has been understudied in human investigations of psychopathologies such as depression. To explore more directly the molecular features of the OB in depression, a global comparative proteome analysis was carried out with human post-mortem OB samples from 11 males having suffered from depression and 12 healthy controls. We identified 188 differentially abundant proteins (with adjusted p < 0.05) between depressed cases and controls. Gene ontology and gene enrichment analyses suggested that these proteins are involved in biological processes including the complement and coagulation cascades. Cell type enrichment analysis displayed a significant reduction in several canonical astrocytic proteins in OBs from depressed patients. Furthermore, using RNA-fluorescence in-situ hybridization, we observed a decrease in the percentage of ALDH1L1+ cells expressing canonical astrocytic markers including ALDOC, NFIA, GJA1 (connexin 43) and SLC1A3 (EAAT1). These results are consistent with previous reports of downregulated astrocytic marker expression in other brain regions in depressed patients. We also conducted a comparative phosphoproteomic analysis of OB samples and found a dysregulation of proteins involved in neuronal and astrocytic functions. To determine whether OB astrocytic abnormalities is specific to humans, we also performed proteomics on the OB of socially defeated male mice, a commonly used model of depression. Cell-type specific analysis revealed that in socially defeated animals, the most striking OB protein alterations were associated with oligodendrocyte-lineage cells rather than with astrocytes, highlighting an important species difference. Overall, this study further highlights cerebral astrocytic abnormalities as a consistent feature of depression in humans.

Correlation between semiautomated magnetic resonance imaging volumetry of the cingulate gyrus and interictal epileptiform discharge lateralization in dogs with idiopathic epilepsy.

BACKGROUND: Brain imaging suggests the involvement of the limbic system, particularly the cingulate gyrus (GC), in dogs with idiopathic epilepsy (IE). HYPOTHESIS: A correlation exists between the side of interictal epileptiform discharges (IEDs) and the volume of the ipsilateral GC (GCe) in dogs with IE. ANIMALS: Dogs admitted to the neurological consultation (32 with epileptic seizures and 13 control) were included. METHODS: This retrospective, blinded study followed the International Veterinary Epilepsy Task Force recommendations for diagnosing IE at the Tier III confidence level. The IE group included 18 and 14 dogs with IEDs in the left and right hemispheres, respectively (median age: 36 months, median weight: 19.5 kg), whereas the control group included 13 dogs (median age: 32 months, median weight: 20 kg). Whole-brain and GC-volumetric assessments were performed by a semiautomated method. RESULTS: In the control group, the volume of the GC was: left, from 743.63 to 1001.61 mm3, right, from 789.35 to 1015.86 mm3. In the study group, the volume of the GC was: left, from 720.88 to 1054.9 mm3 and right, from 566.29 to 987.77 mm3. In dogs with IE, GCe volume was significantly lower than the mean volume of the GC in the control group relative to total intracranial volume (TIV; P = .00044). CONCLUSIONS AND CLINICAL IMPORTANCE: Alterations in the volume of the GC provide insights into structural changes during IE. The use of semiautomatic volumetry provides an advantage by reducing the potential for human error.

Pain in Parkinson's disease: a neuroanatomy-based approach.

Parkinson's disease is a progressive neurodegenerative disorder characterized by the deposition of misfolded alpha-synuclein in different regions of the central and peripheral nervous system. Motor impairment represents the signature clinical expression of Parkinson's disease. Nevertheless, non-motor symptoms are invariably present at different stages of the disease and constitute an important therapeutic challenge with a high impact for the patients' quality of life. Among non-motor symptoms, pain is frequently experienced by patients, being present in a range of 24-85% of Parkinson's disease population. Moreover, in more than 5% of patients, pain represents the first clinical manifestation, preceding by decades the exordium of motor symptoms. Pain implies a complex biopsychosocial experience with a downstream complex anatomical network involved in pain perception, modulation, and processing. Interestingly, all the anatomical areas involved in pain network can be affected by a-synuclein pathology, suggesting that pathophysiology of pain in Parkinson's disease encompasses a 'pain spectrum', involving different anatomical and neurochemical substrates. Here the various anatomical sites recruited in pain perception, modulation and processing are discussed, highlighting the consequences of their possible degeneration in course of Parkinson's disease. Starting from peripheral small fibres neuropathy and pathological alterations at the level of the posterior laminae of the spinal cord, we then describe the multifaceted role of noradrenaline and dopamine loss in driving dysregulated pain perception. Finally, we focus on the possible role of the intertwined circuits between amygdala, nucleus accumbens and habenula in determining the psycho-emotional, autonomic and cognitive experience of pain in Parkinson's disease. This narrative review provides the first anatomically driven comprehension of pain in Parkinson's disease, aiming at fostering new insights for personalized clinical diagnosis and therapeutic interventions.

Anti-AMPA receptor encephalitis with myasthenia gravis: A sinister combination associated with a high risk for underlying malignancy.

A rare subtype of autoimmune encephalitis consists of antibodies targetting the alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptor in the central nervous system. We describe the clinical presentation and autoimmune profile of the first case of alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis with concurrent anti-acetylcholine receptor antibodies in Pakistan. The patient was a 58-year-old male who presented with the characteristic symptoms of limbic encephalitis with memory loss, irritability, agitation, and confusion. Antibodies against the alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptor were detected in both serum and cerebrospinal fluid by indirect immunofluorescence. Computerised tomography of the chest showed an anterior mediastinal mass. The patient was treated with high dose Methylprednisolone and five sessions of plasma exchange. There was a short period of improvement; however, the patient now continues to exhibit irritability, aphasia, confusion, and memory loss. Video-assisted thoracoscopic surgery for mediastinal mass resection and histological testing was planned, however after review by the interventional radiologist the associated risks were deemed too high to proceed with the procedure and biopsy was not done.

How fiber bundle alterations differ in presumed LATE and amnestic Alzheimer's disease.

INTRODUCTION: Typical Alzheimer's disease (AD) and limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but are associated with distinct proteinopathies. METHODS: We investigated white matter (WM) fiber bundle alterations, using fixel-based analysis, a state-of-the-art diffusion magnetic resonance imaging model, in early AD, presumed LATE, and controls. We also investigated regional cortical atrophy. RESULTS: Both amnestic AD and presumed LATE patients exhibited WM alterations in tracts of the temporal and limbic lobes and in callosal fibers connecting superior frontal gyri. In addition, presumed LATE patients showed alterations in callosal fibers connecting the middle frontal gyri and in the cerebello-thalamo-cortical tract. Cortical thickness was reduced in regions connected by the most altered tracts. DISCUSSION: These findings, the first to describe WM fiber bundle alterations in presumed LATE, are consistent with results on cortical atrophy and with the staging system of tau or TDP-43 accumulation. HIGHLIGHTS: Fixel-based analysis revealed white matter (WM) fiber bundle alterations in presumed limbic-predominant age-related TAR DNA-binding protein 43 encephalopathy (LATE) patients identified by isolated episodic/limbic amnesia, the absence of positive Alzheimer's disease (AD) biomarkers, and no other neurological diagnosis after 2 years of follow-up. Presumed LATE and amnestic AD shared similar patterns of WM alterations in fiber bundles of the limbic and temporal lobes, in congruence with their similar limbic cognitive phenotype. Presumed LATE differed from AD by the alteration of the callosal fibers connecting the middle frontal gyri and of the cerebello-thalamo-cortical tract. WM fiber bundle alterations were consistent with results on regional cortical atrophy. The different anatomical patterns of WM degeneration could provide information on the propagation pathways of distinct proteinopathies.

The Association between Individual Food Groups, Limbic System White Matter Tracts, and Episodic Memory: Initial Data from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) Study.

(1) Background: Many studies link food intake with clinical cognitive outcomes, but evidence for brain biomarkers, such as memory-related limbic white matter (WM) tracts, is limited. We examined the association between food groups, limbic WM tracts integrity, and memory performance in community-dwelling individuals. (2) Methods: We included 117 non-demented individuals (ALBION study). Verbal and visual episodic memory tests were administered, and a composite z-score was calculated. Diffusion tensor imaging tractography was applied for limbic WM tracts (fornix-FX, cingulum bundle-CB, uncinate fasciculus-UF, hippocampal perforant pathway zone-hPPZ). Food intake was evaluated through four 24-h recalls. We applied linear regression models adjusted for demographics and energy intake. (3) Results: We found significant associations between (a) higher low-to-moderate alcohol intake and higher FX fractional anisotropy (FA), (b) higher full-fat dairy intake and lower hPPZ FA, and (c) higher red meat and cold cuts intake and lower hPPZ FA. None of the food groups was associated with memory performance. (4) Conclusions: Despite non-significant associations between food groups and memory, possibly due to participants' cognitive profile and/or compensatory mechanisms, the study documented a possible beneficial role of low-to-moderate alcohol and a harmful role of full-fat dairy and red meat and cold cuts on limbic WM tracts.

Six types of loves differentially recruit reward and social cognition brain areas.

Feelings of love are among the most significant human phenomena. Love informs the formation and maintenance of pair bonds, parent-offspring attachments, and influences relationships with others and even nature. However, little is known about the neural mechanisms of love beyond romantic and maternal types. Here, we characterize the brain areas involved in love for six different objects: romantic partner, one's children, friends, strangers, pets, and nature. We used functional magnetic resonance imaging (fMRI) to measure brain activity, while we induced feelings of love using short stories. Our results show that neural activity during a feeling of love depends on its object. Interpersonal love recruited social cognition brain areas in the temporoparietal junction and midline structures significantly more than love for pets or nature. In pet owners, love for pets activated these same regions significantly more than in participants without pets. Love in closer affiliative bonds was associated with significantly stronger and more widespread activation in the brain's reward system than love for strangers, pets, or nature. We suggest that the experience of love is shaped by both biological and cultural factors, originating from fundamental neurobiological mechanisms of attachment.