RESUMEN
Researchers who study the human hippocampus are naturally interested in how its subfields function. However, many researchers are precluded from examining subfields because their manual delineation from magnetic resonance imaging (MRI) scans (still the gold standard approach) is time consuming and requires significant expertise. To help ameliorate this issue, we present here two protocols, one for 3T MRI and the other for 7T MRI, that permit automated hippocampus segmentation into six subregions, namely dentate gyrus/cornu ammonis (CA)4, CA2/3, CA1, subiculum, pre/parasubiculum, and uncus along the entire length of the hippocampus. These protocols are particularly notable relative to existing resources in that they were trained and tested using large numbers of healthy young adults (n = 140 at 3T, n = 40 at 7T) whose hippocampi were manually segmented by experts from MRI scans. Using inter-rater reliability analyses, we showed that the quality of automated segmentations produced by these protocols was high and comparable to expert manual segmenters. We provide full open access to the automated protocols, and anticipate they will save hippocampus researchers a significant amount of time. They could also help to catalyze subfield research, which is essential for gaining a full understanding of how the hippocampus functions.
Asunto(s)
Hipocampo , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Hipocampo/diagnóstico por imagen , Masculino , Adulto , Femenino , Adulto Joven , Procesamiento de Imagen Asistido por Computador/métodos , Procesamiento de Imagen Asistido por Computador/normas , Reproducibilidad de los ResultadosRESUMEN
Anti-tumour necrosis factor (TNF) biologicals, Dexamethasone and rIL-7 are of considerable interest in treating COVID-19 patients who are in danger of, or have become, seriously ill. Yet reducing sepsis mortality by lowering circulating levels of TNF lost favour when positive endpoints in earlier simplistic models could not be reproduced in well-conducted human trials. Newer information with anti-TNF biologicals has encouraged reintroducing this concept for treating COVID-19. Viral models have had encouraging outcomes, as have the effects of anti-TNF biologicals on community-acquired COVID-19 during their long-term use to treat chronic inflammatory states. The positive outcome of a large scale trial of dexamethasone, and its higher potency late in the disease, harmonises well with its capacity to enhance levels of IL-7Rα, the receptor for IL-7, a cytokine that enhances lymphocyte development and is increased during the cytokine storm. Lymphoid germinal centres required for antibody-based immunity can be harmed by TNF, and restored by reducing TNF. Thus the IL-7- enhancing activity of dexamethasone may explain its higher potency when lymphocytes are depleted later in the infection, while employing anti-TNF, for several reasons, is much more logical earlier in the infection. This implies dexamethasone could prove to be synergistic with rIL-7, currently being trialed as a COVID-19 therapeutic. The principles behind these COVID-19 therapies are consistent with the observed chronic hypoxia through reduced mitochondrial function, and also the increased severity of this disease in ApoE4-positive individuals. Many of the debilitating persistent aspects of this disease are predictably susceptible to treatment with perispinal etanercept, since they have cerebral origins.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Dexametasona/administración & dosificación , Interleucina-17/administración & dosificación , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , COVID-19/genética , COVID-19/inmunología , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/inmunología , Humanos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Structural integrity of the human hippocampus is widely acknowledged to be necessary for the successful encoding and retrieval of autobiographical memories. However, evidence for an association between hippocampal volume and the ability to recall such memories in healthy individuals is mixed. Here we examined this issue further by combining two approaches. First, we focused on the anatomically distinct subregions of the hippocampus where more nuanced associations may be expressed compared to considering the whole hippocampal volume. A manual segmentation protocol of hippocampal subregions allowed us to separately calculate the volumes of the dentate gyrus/CA4, CA3/2, CA1, subiculum, pre/parasubiculum and uncus. Second, a critical feature of autobiographical memories is that they can span long time periods, and so we sought to consider how memory details persist over time by conducting a longitudinal study whereby participants had to recall the same autobiographical memories on two visits spaced 8 months apart. Overall, we found that there was no difference in the total number of internal (episodic) details produced at Visits 1 and 2. However, further probing of detail subcategories revealed that specifically the amount of subjective thoughts and emotions included during recall had declined significantly by the second visit. We also observed a strong correlation between left pre/parasubiculum volume and the amount of autobiographical memory internal details produced over time. This positive relationship was evident for particular facets of the memories, with remembered events, perceptual observations and thoughts and emotions benefitting from greater volume of the left pre/parasubiculum. These preliminary findings expand upon existing functional neuroimaging evidence by highlighting a potential link between left pre/parasubiculum volume and autobiographical memory. A larger pre/parasubiculum appears not only to protect against memory decay, but may possibly enhance memory persistence, inviting further scrutiny of the role of this brain region in remote autobiographical memory retrieval.
Asunto(s)
Memoria Episódica , Hipocampo/diagnóstico por imagen , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Recuerdo MentalRESUMEN
Retrieval of long-term episodic memories is characterized by synchronized neural activity between hippocampus and ventromedial prefrontal cortex (vmPFC), with additional evidence that vmPFC activity leads that of the hippocampus. It has been proposed that the mental generation of scene imagery is a crucial component of episodic memory processing. If this is the case, then a comparable interaction between the two brain regions should exist during the construction of novel scene imagery. To address this question, we leveraged the high temporal resolution of MEG to investigate the construction of novel mental imagery. We tasked male and female humans with imagining scenes and single isolated objects in response to one-word cues. We performed source-level power, coherence, and causality analyses to characterize the underlying interregional interactions. Both scene and object imagination resulted in theta power changes in the anterior hippocampus. However, higher theta coherence was observed between the hippocampus and vmPFC in the scene compared with the object condition. This interregional theta coherence also predicted whether imagined scenes were subsequently remembered. Dynamic causal modeling of this interaction revealed that vmPFC drove activity in hippocampus during novel scene construction. Additionally, theta power changes in the vmPFC preceded those observed in the hippocampus. These results constitute the first evidence in humans that episodic memory retrieval and scene imagination rely on similar vmPFC-hippocampus neural dynamics. Furthermore, they provide support for theories emphasizing similarities between both cognitive processes and perspectives that propose the vmPFC guides the construction of context-relevant representations in the hippocampus.SIGNIFICANCE STATEMENT Episodic memory retrieval is characterized by a dialog between hippocampus and ventromedial prefrontal cortex (vmPFC). It has been proposed that the mental generation of scene imagery is a crucial component of episodic memory processing. An ensuing prediction would be of a comparable interaction between the two brain regions during the construction of novel scene imagery. Here, we leveraged the high temporal resolution of MEG and combined it with a scene imagination task. We found that a hippocampal-vmPFC dialog existed and that it took the form of vmPFC driving the hippocampus. We conclude that episodic memory and scene imagination share fundamental neural dynamics and the process of constructing vivid, spatially coherent, contextually appropriate scene imagery is strongly modulated by vmPFC.
Asunto(s)
Hipocampo/fisiología , Imaginación/fisiología , Memoria Episódica , Recuerdo Mental/fisiología , Corteza Prefrontal/fisiología , Adulto , Femenino , Humanos , MasculinoRESUMEN
Marked disparities exist across healthy individuals in their ability to imagine scenes, recall autobiographical memories, think about the future and navigate in the world. The importance of the hippocampus in supporting these critical cognitive functions has prompted the question of whether differences in hippocampal grey matter volume could be one source of performance variability. Evidence to date has been somewhat mixed. In this study we sought to mitigate issues that commonly affect these types of studies. Data were collected from a large sample of 217 young, healthy adult participants, including whole brain structural MRI data (0.8â¯mm isotropic voxels) and widely-varying performance on scene imagination, autobiographical memory, future thinking and navigation tasks. We found little evidence that hippocampal grey matter volume was related to task performance in this healthy sample. This was the case using different analysis methods (voxel-based morphometry, partial correlations), when whole brain or hippocampal regions of interest were examined, when comparing different sub-groups (divided by gender, task performance, self-reported ability), and when using latent variables derived from across the cognitive tasks. Hippocampal grey matter volume may not, therefore, significantly influence performance on tasks known to require the hippocampus in healthy people. Perhaps only in extreme situations, as in the case of licensed London taxi drivers, are measurable ability-related hippocampus volume changes consistently exhibited.
Asunto(s)
Hipocampo/anatomía & histología , Hipocampo/fisiología , Imaginación/fisiología , Memoria Episódica , Neuroimagen , Navegación Espacial/fisiología , Análisis y Desempeño de Tareas , Pensamiento/fisiología , Adulto , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Individualidad , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
While age-related volumetric changes in human hippocampal subfields have been reported, little is known about patterns of subfield functional connectivity (FC) in the context of healthy ageing. Here we investigated age-related changes in patterns of FC down the anterior-posterior axis of each subfield. Using high resolution structural MRI we delineated the dentate gyrus (DG), CA fields (including separating DG from CA3), the subiculum, pre/parasubiculum, and the uncus in healthy young and older adults. We then used high resolution resting state functional MRI to measure FC in each group and to directly compare them. We first examined the FC of each subfield in its entirety, in terms of FC with other subfields and with neighboring cortical regions, namely, entorhinal, perirhinal, posterior parahippocampal, and retrosplenial cortices. Next, we analyzed subfield to subfield FC within different portions along the hippocampal anterior-posterior axis, and FC of each subfield portion with the neighboring cortical regions of interest. In general, the FC of the older adults was similar to that observed in the younger adults. We found that, as in the young group, the older group displayed intrinsic FC between the subfields that aligned with the tri-synaptic circuit but also extended beyond it, and that FC between the subfields and neighboring cortical areas differed markedly along the anterior-posterior axis of each subfield. We observed only one significant difference between the young and older groups. Compared to the young group, the older participants had significantly reduced FC between the anterior CA1-subiculum transition region and the transentorhinal cortex, two brain regions known to be disproportionately affected during the early stages of age-related tau accumulation. Overall, these results contribute to ongoing efforts to characterize human hippocampal subfield connectivity, with implications for understanding hippocampal function and its modulation in the ageing brain.
Asunto(s)
Envejecimiento/fisiología , Hipocampo/diagnóstico por imagen , Hipocampo/fisiología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Corteza Entorrinal/diagnóstico por imagen , Corteza Entorrinal/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Adulto JovenRESUMEN
It is widely agreed that patients with bilateral hippocampal damage are impaired at binding pairs of words together. Consequently, the verbal paired associates (VPA) task has become emblematic of hippocampal function. This VPA deficit is not well understood and is particularly difficult for hippocampal theories with a visuospatial bias to explain (e.g., cognitive map and scene construction theories). Resolving the tension among hippocampal theories concerning the VPA could be important for leveraging a fuller understanding of hippocampal function. Notably, VPA tasks typically use high imagery concrete words and so conflate imagery and binding. To determine why VPA engages the hippocampus, we devised an fMRI encoding task involving closely matched pairs of scene words, pairs of object words, and pairs of very low imagery abstract words. We found that the anterior hippocampus was engaged during processing of both scene and object word pairs in comparison to abstract word pairs, despite binding occurring in all conditions. This was also the case when just subsequently remembered stimuli were considered. Moreover, for object word pairs, fMRI activity patterns in anterior hippocampus were more similar to those for scene imagery than object imagery. This was especially evident in participants who were high imagery users and not in mid and low imagery users. Overall, our results show that hippocampal engagement during VPA, even when object word pairs are involved, seems to be evoked by scene imagery rather than binding. This may help to resolve the issue that visuospatial hippocampal theories have in accounting for verbal memory.
Asunto(s)
Asociación , Hipocampo/fisiología , Reconocimiento Visual de Modelos/fisiología , Lectura , Mapeo Encefálico , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Imaginación , Lingüística , Imagen por Resonancia Magnética , Masculino , Reconocimiento en Psicología , Adulto JovenRESUMEN
The dominant hypothesis of Alzheimer's disease (AD) aetiology, the neuropathological guidelines for diagnosing AD and the majority of high-profile therapeutic efforts, in both research and in clinical practice, have been built around one possible causal factor, amyloid-ß (Aß). However, the causal link between Aß and AD remains unproven. Here, in the context of a detailed assessment of historical and contemporary studies, we raise critical questions regarding the role of Aß in the definition, diagnosis and aetiology of AD. We illustrate that a holistic view of the available data does not support an unequivocal conclusion that Aß has a central or unique role in AD. Instead, the data suggest alternative views of AD aetiology are potentially valid, at this time. We propose that an unbiased way forward for the field, beyond the current Aß-centric approach, without excluding a role for Aß, is required to come to an accurate understanding of AD dementia and, ultimately, an effective treatment.
Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/efectos adversos , Animales , HumanosRESUMEN
The lesion-deficit model dominates neuropsychology. This is unsurprising given powerful demonstrations that focal brain lesions can affect specific aspects of cognition. Nowhere is this more evident than in patients with bilateral hippocampal damage. In the past 60 years, the amnesia and other impairments exhibited by these patients have helped to delineate the functions of the hippocampus and shape the field of memory. We do not question the value of this approach. However, less prominent are the cognitive processes that remain intact following hippocampal lesions. Here, we collate the piecemeal reports of preservation of function following focal bilateral hippocampal damage, highlighting a wealth of information often veiled by the field's focus on deficits. We consider how a systematic understanding of what is preserved as well as what is lost could add an important layer of precision to models of memory and the hippocampus.
Asunto(s)
Amnesia/fisiopatología , Amnesia/psicología , Hipocampo/fisiopatología , HumanosRESUMEN
The basic mechanism of the major neurodegenerative diseases, including neurogenic pain, needs to be agreed upon before rational treatments can be determined, but this knowledge is still in a state of flux. Most have agreed for decades that these disease states, both infectious and non-infectious, share arguments incriminating excitotoxicity induced by excessive extracellular cerebral glutamate. Excess cerebral levels of tumor necrosis factor (TNF) are also documented in the same group of disease states. However, no agreement exists on overarching mechanism for the harmful effects of excess TNF, nor, indeed how extracellular cerebral glutamate reaches toxic levels in these conditions. Here, we link the two, collecting and arguing the evidence that, across the range of neurodegenerative diseases, excessive TNF harms the central nervous system largely through causing extracellular glutamate to accumulate to levels high enough to inhibit synaptic activity or kill neurons and therefore their associated synapses as well. TNF can be predicted from the broader literature to cause this glutamate accumulation not only by increasing glutamate production by enhancing glutaminase, but in addition simultaneously reducing glutamate clearance by inhibiting re-uptake proteins. We also discuss the effects of a TNF receptor biological fusion protein (etanercept) and the indirect anti-TNF agents dithio-thalidomides, nilotinab, and cannabinoids on these neurological conditions. The therapeutic effects of 6-diazo-5-oxo-norleucine, ceptriaxone, and riluzole, agents unrelated to TNF but which either inhibit glutaminase or enhance re-uptake proteins, but do not do both, as would anti-TNF agents, are also discussed in this context. By pointing to excess extracellular glutamate as the target, these arguments greatly strengthen the case, put now for many years, to test appropriately delivered ant-TNF agents to treat neurodegenerative diseases in randomly controlled trials.
Asunto(s)
Corteza Cerebral/metabolismo , Ácido Glutámico/toxicidad , Neuralgia , Enfermedades Neurodegenerativas , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Corteza Cerebral/efectos de los fármacos , Humanos , Neuralgia/inducido químicamente , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/metabolismoRESUMEN
Tumor necrosis factor (TNF) is an ancient and widespread cytokine required in small amounts for much physiological function. Higher concentrations are central to innate immunity, but if unchecked this cytokine orchestrates much chronic and acute disease, both infectious and noninfectious. While being a major proinflammatory cytokine, it also controls homeostasis and plasticity in physiological circumstances. For the last decade or so these principles have been shown to apply to the central nervous system as well as the rest of the body. Nevertheless, whereas this approach has been a major success in treating noncerebral disease, its investigation and potential widespread adoption in chronic neurological conditions has inexplicably stalled since the first open trial almost a decade ago. While neuroscience is closely involved with this approach, clinical neurology appears to be reticent in engaging with what it offers patients. Unfortunately, the basic biology of TNF and its relevance to disease is largely outside the traditions of neurology. The purpose of this review is to facilitate lowering communication barriers between the traditional anatomically based medical specialties through recognition of shared disease mechanisms and thus advance the prospects of a large group of patients with neurodegenerative conditions for whom at present little can be done.
Asunto(s)
Encéfalo/fisiopatología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/fisiopatología , Neurología/tendencias , Factor de Necrosis Tumoral alfa/fisiología , Factor de Necrosis Tumoral alfa/uso terapéutico , Animales , Humanos , Plasticidad NeuronalRESUMEN
Most people will experience or witness a traumatic event. A common occurrence after trauma is the experience of involuntary emotional memories of the traumatic event, herewith "flashbacks". Some individuals, however, report no flashbacks. Prospective work investigating psychological factors associated with an absence of flashbacks is lacking. We performed an individual participant data meta-analysis on 16 experiments (n = 458) using the trauma film paradigm to investigate the association of emotional response to traumatic film footage and commonly collected baseline characteristics (trait anxiety, current depression, trauma history) with an absence of analogue flashbacks. An absence of analogue flashbacks was associated with low emotional response to the traumatic film footage and, to a lesser extent, low trait anxiety and low current depression levels. Trauma history and recognition memory for the film were not significantly associated with an absence of analogue flashbacks. Understanding why some individuals report an absence of flashbacks may aid preventative treatments against flashback development.
Asunto(s)
Emociones , Recuerdo Mental , Heridas y Lesiones/psicología , Adulto , Ansiedad/psicología , Depresión/psicología , Femenino , Humanos , Masculino , Estimulación Luminosa , Reconocimiento en Psicología , Adulto JovenRESUMEN
The depth, pattern, timing and duration of unconsciousness, including sleep, vary greatly in inflammatory disease, and are regarded as reliable indicators of disease severity. Similarly, these indicators are applicable to the encephalopathies of sepsis, malaria, and trypanosomiasis, and to viral diseases such as influenza and AIDS. They are also applicable to sterile neuroinflammatory states, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke and type-2 diabetes, as well as in iatrogenic brain states following brain irradiation and chemotherapy. Here we make the case that the cycles of unconsciousness that constitute normal sleep, as well as its aberrations, which range from sickness behavior through daytime sleepiness to the coma of inflammatory disease states, have common origins that involve increased inflammatory cytokines and consequent insulin resistance and loss of appetite due to reduction in orexigenic activity. Orexin reduction has broad implications, which are as yet little appreciated in the chronic inflammatory conditions listed, whether they be infectious or sterile in origin. Not only is reduction in orexin levels characterized by loss of appetite, it is associated with inappropriate and excessive sleep and, when dramatic and chronic, leads to coma. Moreover, such reduction is associated with impaired cognition and a reduction in motor control. We propose that advanced understanding and appreciation of the importance of orexin as a key regulator of pathways involved in the maintenance of normal appetite, sleep patterns, cognition, and motor control may afford novel treatment opportunities.
Asunto(s)
Encefalopatías/complicaciones , Inflamación/etiología , Insulina/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuropéptidos/metabolismo , Trastornos del Sueño-Vigilia/etiología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Humanos , OrexinasRESUMEN
We focus on emerging roles for microglia in synaptic plasticity, cognition and disease. We outline evidence that ramified microglia, traditionally thought to be functionally "resting" (i.e. quiescent) in the normal brain, in fact are highly dynamic and plastic. Ramified microglia continually and rapidly extend processes, contact synapses in an activity and experience dependent manner, and play a functionally dynamic role in synaptic plasticity, possibly through release of cytokines and growth factors. Ramified microglial also contribute to structural plasticity through the elimination of synapses via phagocytic mechanisms, which is necessary for normal cognition. Microglia have numerous mechanisms to monitor neuronal activity and numerous mechanisms also exist to prevent them transitioning to an activated state, which involves retraction of their surveying processes. Based on the evidence, we suggest that maintaining the ramified state of microglia is essential for normal synaptic and structural plasticity that supports cognition. Further, we propose that change of their ramified morphology and function, as occurs in inflammation associated with numerous neurological disorders such as Alzheimer's and Parkinson's disease, disrupts their intricate and essential synaptic functions. In turn altered microglia function could cause synaptic dysfunction and excess synapse loss early in disease, initiating a range of pathologies that follow. We conclude that the future of learning and memory research depends on an understanding of the role of non-neuronal cells and that this should include using sophisticated molecular, cellular, physiological and behavioural approaches combined with imaging to causally link the role of microglia to brain function and disease including Alzheimer's and Parkinson's disease and other neuropsychiatric disorders.
Asunto(s)
Aprendizaje/fisiología , Microglía/fisiología , Enfermedades Neurodegenerativas/fisiopatología , Plasticidad Neuronal , Animales , Encéfalo/fisiología , Humanos , Memoria/fisiología , Ratones , RatasRESUMEN
When a memory is forgotten, is it lost forever? Our study shows that selective attention can restore forgotten items to visual short-term memory (VSTM). In our two experiments, all stimuli presented in a memory array were designed to be equally task relevant during encoding. During the retention interval, however, participants were sometimes given a cue predicting which of the memory items would be probed at the end of the delay. This shift in task relevance improved recall for that item. We found that this type of cuing improved recall for items that otherwise would have been irretrievable, providing critical evidence that attention can restore forgotten information to VSTM. Psychophysical modeling of memory performance has confirmed that restoration of information in VSTM increases the probability that the cued item is available for recall but does not improve the representational quality of the memory. We further suggest that attention can restore discrete items to VSTM.
Asunto(s)
Atención/fisiología , Señales (Psicología) , Memoria a Corto Plazo/fisiología , Adulto , Humanos , Recuerdo Mental , Adulto JovenRESUMEN
Involuntary autobiographical memories (IAMs) are typically discussed in the context of negative memories such as trauma 'flashbacks'. However, IAMs occur frequently in everyday life and are predominantly positive. In spite of this, surprisingly little is known about how such positive IAMs arise. The trauma film paradigm is often used to generate negative IAMs. Recently an equivalent positive film was developed inducing positive IAMs (Davies, Malik, Pictet, Blackwell, & Holmes, 2012). The current study is the first to investigate which variables (emotional reaction to the film; recognition memory of the film; participant characteristics) would best predict the frequency of positive IAMs. Higher levels of positive mood change to the film were significantly associated with the number of positive IAMs recorded in the subsequent week. Results demonstrate the importance of positive emotional reaction at the time of an event for subsequent positive IAMs.
Asunto(s)
Emociones/fisiología , Imaginación/fisiología , Memoria Episódica , Memoria/fisiología , Adolescente , Adulto , Señales (Psicología) , Femenino , Humanos , Masculino , Reconocimiento en Psicología/fisiología , Adulto JovenRESUMEN
Over a decade's experience of post-stroke rehabilitation by administering the specific anti-TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral levels of TNF. We propose that this TNF persistence, and cerebral disease chronicity, largely arises from a positive autocrine feedback loop of this cytokine, allowing the persistence of microglial activation caused by the excess TNF that these cells produce. It appears that many of these observations have never been exploited to construct a broad understanding and treatment of certain chronic, yet reversible, neurological illnesses. We propose that this treatment allows these chronically activated microglia to revert to their normal quiescent state, rather than simply neutralizing the direct harmful effects of this cytokine after its release from microglia. Logically, this also applies to the chronic cerebral aspects of various other neurological conditions characterized by activated microglia. These include long COVID, Lyme disease, post-stroke syndromes, traumatic brain injury, chronic traumatic encephalopathy, post-chemotherapy, post-irradiation cerebral dysfunction, cerebral palsy, fetal alcohol syndrome, hepatic encephalopathy, the antinociceptive state of morphine tolerance, and neurogenic pain. In addition, certain psychiatric states, in isolation or as sequelae of infectious diseases such as Lyme disease and long COVID, are candidates for being understood through this approach and treated accordingly. Perispinal etanercept provides the prospect of being able to treat various chronic central nervous system illnesses, whether they are of infectious or non-infectious origin, through reversing excess TNF generation by microglia.
Asunto(s)
Enfermedades del Sistema Nervioso , Factor de Necrosis Tumoral alfa , Humanos , Enfermedad Crónica , Citocinas , Etanercept/farmacología , Etanercept/uso terapéutico , Microglía , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/fisiología , Retroalimentación FisiológicaRESUMEN
We share data from N = 217 healthy adults (mean age 29 years, range 20-41; 109 females, 108 males) who underwent extensive cognitive assessment and neuroimaging to examine the neural basis of individual differences, with a particular focus on a brain structure called the hippocampus. Cognitive data were collected using a wide array of questionnaires, naturalistic tests that examined imagination, autobiographical memory recall and spatial navigation, traditional laboratory-based tests such as recalling word pairs, and comprehensive characterisation of the strategies used to perform the cognitive tests. 3 Tesla MRI data were also acquired and include multi-parameter mapping to examine tissue microstructure, diffusion-weighted MRI, T2-weighted high-resolution partial volume structural MRI scans (with the masks of hippocampal subfields manually segmented from these scans), whole brain resting state functional MRI scans and partial volume high resolution resting state functional MRI scans. This rich dataset will be of value to cognitive and clinical neuroscientists researching individual differences, real-world cognition, brain-behaviour associations, hippocampal subfields and more. All data are freely available on Dryad.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Imagen por Resonancia Magnética , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Cognición , Hipocampo/diagnóstico por imagen , NeuroimagenRESUMEN
People vary substantially in their capacity to recall past experiences, known as autobiographical memories. Here we investigated whether the volumes of specific hippocampal subfields were associated with autobiographical memory retrieval ability. We manually segmented the full length of the two hippocampi in 201 healthy young adults into DG/CA4, CA2/3, CA1, subiculum, pre/parasubiculum and uncus, in the largest such manually segmented subfield sample yet reported. Across the group we found no evidence for an association between any subfield volume and autobiographical memory recall ability. However, when participants were assigned to lower and higher performing groups based on their memory recall scores, we found that bilateral CA2/3 volume was significantly and positively associated with autobiographical memory recall performance specifically in the lower performing group. We further observed that this effect was attributable to posterior CA2/3. By contrast, semantic details from autobiographical memories, and performance on a range of laboratory-based memory tests, did not correlate with CA2/3 volume. Overall, our findings highlight that posterior CA2/3 may be particularly pertinent for autobiographical memory recall. They also reveal that there may not be direct one-to-one mapping of posterior CA2/3 volume with autobiographical memory ability, with size mattering perhaps only in those with poorer memory recall.
Asunto(s)
Memoria Episódica , Adulto Joven , Humanos , Región CA3 Hipocampal , Hipocampo , Recuerdo Mental , Trastornos de la Memoria , Imagen por Resonancia MagnéticaRESUMEN
Conduction velocity is the speed at which electrical signals travel along axons and is a crucial determinant of neural communication. Inferences about conduction velocity can now be made in vivo in humans using a measure called the magnetic resonance (MR) g-ratio. This is the ratio of the inner axon diameter relative to that of the axon plus the myelin sheath that encases it. Here, in the first application to cognition, we found that variations in MR g-ratio, and by inference conduction velocity, of the parahippocampal cingulum bundle were associated with autobiographical memory recall ability in 217 healthy adults. This tract connects the hippocampus with a range of other brain areas. We further observed that the association seemed to be with inner axon diameter rather than myelin content. The extent to which neurites were coherently organised within the parahippocampal cingulum bundle was also linked with autobiographical memory recall ability. Moreover, these findings were specific to autobiographical memory recall and were not apparent for laboratory-based memory tests. Our results offer a new perspective on individual differences in autobiographical memory recall ability, highlighting the possible influence of specific white matter microstructure features on conduction velocity when recalling detailed memories of real-life past experiences.