Deep-brain stimulation of the human nucleus accumbens-medial septum enhances memory formation.

Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson's disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study.

Background and objectives: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson's disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity. Methods: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS. Discussion: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.

Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome.

BACKGROUND: Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, in vivo detailed evaluation of hippocampal changes in PCS patients, validated on post-mortem samples of COVID-19 patients at the acute phase, would shed light into the relationship between COVID-19 and cognition. METHODS: Hippocampal subfields volume, microstructure, and perfusion were evaluated in 84 PCS patients and compared to 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) and neurofilament light chain (NfL) were evaluated. Besides, biomarker immunodetection in seven hippocampal necropsies of patients at the acute phase were contrasted against eight controls. FINDINGS: In vivo analyses revealed that hippocampal grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, and functional connectivity changes in PCS patients. Hippocampal structural and functional alterations were related to cognitive dysfunction, particularly attention and memory. GFAP, MOG, CCL11 and NfL biomarkers revealed alterations in PCS, and showed associations with hippocampal volume changes, in selective hippocampal subfields. Moreover, post mortem histology showed the presence of increased GFAP and CCL11 and reduced MOG concentrations in the hippocampus in post-mortem samples at the acute phase. INTERPRETATION: The current results evidenced that PCS patients with cognitive sequalae present brain alterations related to cognitive dysfunction, accompanied by a cascade of pathological alterations in blood biomarkers, indicating axonal damage, astrocyte alterations, neuronal injury, and myelin changes that are already present from the acute phase. FUNDING: Nominative Grant FIBHCSC 2020 COVID-19. Department of Health, Community of Madrid. Instituto de Salud Carlos III through the project INT20/00079, co-funded by European Regional Development Fund "A way to make Europe" (JAMG). Instituto de Salud Carlos III (ISCIII) through Sara Borrell postdoctoral fellowship Grant No. CD22/00043) and co-funded by the European Union (MDC). Instituto de Salud Carlos III through a predoctoral contract (FI20/000145) (co-funded by European Regional Development Fund "A way to make Europe") (MVS). Fundación para el Conocimiento Madri+d through the project G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).

A new set of estimated cardiorespiratory fitness equations are associated with cognitive performance in older adults.

This study aimed to develop new equations to estimate cardiorespiratory fitness specifically for older adults and, secondly, to analyze the associations of cardiorespiratory fitness, both objectively measured and estimated using new equations, with cognitive performance. Ninety-two older adults (41 females, 65-75 years) from baseline data of a randomized controlled trial were analyzed ("ClinicalTrials.gov" Identifier: NCT03923712). Participants completed 4 measurement sessions including (i) physiological and health indicators in a laboratory setting, (ii) field-based fitness tests, (iii) sociodemographic and physical activity questionnaires, and (iv) a battery of neuropsychological tests to evaluate cognitive performance. The main findings were as follows: (i) a set of new equations with good predictive value for estimated cardiorespiratory fitness were developed (74-87%), using different scenarios of complexity and/or equipment requirements, and (ii) higher estimated cardiorespiratory fitness, even using its simplest equation (eCRF = - 1261.99 + 1.97 × 6 min walking test (m) + 1.12 × bioimpedance basal metabolic rate (kcal/day) + 5.25 × basal heart rate (bpm)), was associated with better cognitive performance evaluated by several neuropsychological tests (i.e., language, cognitive flexibility, fluency, attention, and working memory), similar to using objectively measured cardiorespiratory fitness. In summary, a new set of estimated cardiorespiratory fitness equations have been developed with predictive values ranging from 74 to 87% that could be used based on necessity, availability of equipment, resources, or measurement context. Moreover, similar to objectively measured cardiorespiratory fitness, this measure of estimated cardiorespiratory fitness was positively associated with performance on language, fluency, cognitive flexibility, attention, and working memory, independently of sex, age, and education level.

Neuropsychological and Neuropsychiatric Features of Chronic Migraine Patients during the Interictal Phase.

This study aimed to examine the presence of neuropsychological deficits and their relationships with clinical, pharmacological, and neuropsychiatric characteristics in chronic migraine (CM) patients assessed during a headache-free period. We enrolled 39 CM patients (mean age: 45.4 years; male/female ratio: 3/36) and 20 age-, sex-, and education-matched healthy controls (HCs, mean age: 45.5 years; male/female ratio: 2/18) in a case-control study. All CM patients underwent a full and extensive clinical, neuropsychiatric, and neuropsychological evaluation to evaluate cognitive domains, including sustained attention (SA), information processing speed (IPS), visuospatial episodic memory, working memory (WM), and verbal fluency (VF), as well as depressive and anxiety symptoms. CM patients exhibited higher scores than HCs for all clinical and neuropsychiatric measures, but no differences were found in personality characteristics. Although more than half of the CM patients (54%) showed mild-to-severe neuropsychological impairment (NI), with the most frequent impairments occurring in short- and long-term verbal episodic memory and inhibitory control (in approximately 90% of these patients), almost half of the patients (46%) showed no NI. Moreover, the severity of NI was positively associated with the number of pharmacological treatments received. Remarkably, disease-related symptom severity and headache-related disability explained global neuropsychological performance in CM patients. The presence of cognitive and neuropsychiatric dysfunction during the interictal phase occurred in more than half of CM patients, increasing migraine-related disability and possibly exerting a negative impact on health-related quality of life and treatment adherence.

A Causal Analysis of the Effect of Age and Sex Differences on Brain Atrophy in the Elderly Brain.

We studied how brain volume loss in old age is affected by age, the APOE gene, sex, and the level of education completed. The quantitative characterization of brain volume loss at an old age relative to a young age requires-at least in principle-two MRI scans, one performed at a young age and one at an old age. There is, however, a way to address this problem when having only one MRI scan obtained at an old age. We computed the total brain losses of elderly subjects as a ratio between the estimated brain volume and the estimated total intracranial volume. Magnetic resonance imaging (MRI) scans of 890 healthy subjects aged 70 to 85 years were assessed. A causal analysis of factors affecting brain atrophy was performed using probabilistic Bayesian modelling and the mathematics of causal inference. We found that both age and sex were causally related to brain atrophy, with women reaching an elderly age with a 1% larger brain volume relative to their intracranial volume than men. How the brain ages and the rationale for sex differences in brain volume losses during the adult lifespan are questions that need to be addressed with causal inference and empirical data. The graphical causal modelling presented here can be instrumental in understanding a puzzling scientific area of study-the biological aging of the brain.

Prediction of Chronological Age in Healthy Elderly Subjects with Machine Learning from MRI Brain Segmentation and Cortical Parcellation.

Normal aging is associated with changes in volumetric indices of brain atrophy. A quantitative understanding of age-related brain changes can shed light on successful aging. To investigate the effect of age on global and regional brain volumes and cortical thickness, 3514 magnetic resonance imaging scans were analyzed using automated brain segmentation and parcellation methods in elderly healthy individuals (69-88 years of age). The machine learning algorithm extreme gradient boosting (XGBoost) achieved a mean absolute error of 2 years in predicting the age of new subjects. Feature importance analysis showed that the brain-to-intracranial-volume ratio is the most important feature in predicting age, followed by the hippocampi volumes. The cortical thickness in temporal and parietal lobes showed a superior predictive value than frontal and occipital lobes. Insights from this approach that integrate model prediction and interpretation may help to shorten the current explanatory gap between chronological age and biological brain age.

Neuropsychiatric Symptoms in Clinically Defined Parkinson's Disease: An Updated Review of Literature.

Background: Neuropsychiatric symptoms (NPS) are a common and potentially serious manifestation of Parkinson's disease (PD) but are frequently overlooked in favor of a focus on motor symptomatology. Here, we conducted a literature review of the prevalence and type of NPS experienced by PD patients with a clinically defined course of their illness. Methods: We identified reports of NPS in patients with PD and mean disease duration over 3 years. Three databases-PubMed, Scopus, and Dialnet-were searched for relevant literature published between 2010 and 2020. Predefined exclusion criteria were applied prior to a descriptive analysis of the literature base. Results: In all, 87 unique reports were identified and 30 met inclusion and exclusion criteria. These included 7142 patients with PD (male: 67.3%; mean age: 66.2 years; mean disease duration: 6.7 years). The most frequent NPS were mood disorders (apathy, depression, and anxiety), psychosis, and impulse control disorders (ICD). Treatment with dopamine agonists was identified as an important risk factor for ICD. Co-occurrence of NPS and cognitive dysfunction was also evidenced in a number of studies. Patients with more significant cognitive deficits and higher levels of NPS appeared to be of older age with a longer disease duration and to have more severe motor symptoms. Conclusions: NPS, most commonly mood disorders (apathy, depression, and anxiety), psychosis, and ICDs are frequent manifestations of PD. The results of this review reflect the need to develop unified validated assessment protocols for NPS in PD, as well as to improve their management in clinical practice.

Subthalamic Beta Activity in Parkinson's Disease May Be Linked to Dorsal Striatum Gray Matter Volume and Prefrontal Cortical Thickness: A Pilot Study.

Background: Excessive oscillations at beta frequencies (13-35 Hz) in the subthalamic nucleus (STN) represent a pathophysiological hallmark of Parkinson's disease (PD), which correlates well with parkinsonian symptoms and is reduced in response to standard disease treatments. However, the association of disease-specific regional gray matter (GM) atrophy or cortical thickness (CT) with the presence of STN beta oscillatory activity has been poorly investigated but is of relevance given the potential of these variables for extracting information about PD pathophysiology. This exploratory study investigated the involvement of regional GM volume and CT in the basal ganglia-cortical network and its potential association with the presence of STN beta oscillatory activity in PD. Methods: We acquired preoperative GM densities on T1-weighted magnetic resonance imaging scans and we carried out regional estimation of GM volume and CT. LFP activities from the STN were recorded post-operatively in 7 cognitively preserved PD patients off dopaminergic medication undergoing deep-brain stimulation surgery. Oscillatory beta power was determined by power spectral density of 4-min resting state STN LFP activity. Spearman partial correlations and regression analysis were used to screen the presence of STN beta power for their relationship with GM volume and CT measurements. Results: After controlling for the effects of age, educational level, and disease duration, and after correcting for multiple testing, enhanced STN beta power showed significant and negative correlations between, first, volume of the right putamen and left caudate nucleus, and second, smaller CT in frontal regions involving the left rostral middle frontal gyrus (MFG) and left medial orbitofrontal gyrus. A lower volume in the right putamen and a lower CT in the left MFG demonstrated the strongest associations with increased STN beta power. Conclusions: These tentative results seem to suggest that STN LFP beta frequencies may be mainly linked to different but ongoing parallel neurodegenerative processes, on the one hand, to GM volume reduction in dorsal striatum, and on the other hand, to CT reduction of prefrontal-"associative" regions. These findings could further delineate the brain structural interactions underpinning the exaggerated STN beta activity commonly observed in PD patients.

Intra- and interhemispheric symmetry of subcortical brain structures: a volumetric analysis in the aging human brain.

Here, we address the hemispheric interdependency of subcortical structures in the aging human brain. In particular, we investigated whether subcortical volume variations can be explained by the adjacency of structures in the same hemisphere or are due to the interhemispheric development of mirror subcortical structures in the brain. Seven subcortical structures in each hemisphere were automatically segmented in a large sample of 3312 magnetic resonance imaging (MRI) studies of elderly individuals in their 70s and 80s. We performed Eigenvalue analysis, and found that anatomic volumes in the limbic system and basal ganglia show similar statistical dependency whether considered in the same hemisphere (intrahemispherically) or different hemispheres (interhemispherically). Our results indicate that anatomic bilaterality of subcortical volumes is preserved in the aging human brain, supporting the hypothesis that coupling between non-adjacent subcortical structures might act as a mechanism to compensate for the deleterious effects of aging.

Cortical Thickness and Serum NfL Explain Cognitive Dysfunction in Newly Diagnosed Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: To determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS). METHODS: Thirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment. RESULTS: Compared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R2 = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT. DISCUSSION: Thalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS.

A ventromedial prefrontal dysrhythmia in obsessive-compulsive disorder is attenuated by nucleus accumbens deep brain stimulation.

BACKGROUND: Obsessive-compulsive disorder (OCD) has consistently been linked to abnormal frontostriatal activity. The electrophysiological disruption in this circuit, however, remains to be characterized. OBJECTIVE/HYPOTHESIS: The primary goal of this study was to investigate the neuronal synchronization in OCD patients. We predicted aberrant oscillatory activity in frontal regions compared to healthy control subjects, which would be alleviated by deep brain stimulation (DBS) of the nucleus accumbens (NAc). METHODS: We compared scalp EEG recordings from nine patients with OCD treated with NAc-DBS with recordings from healthy controls, matched for age and gender. Within the patient group, EEG activity was compared with DBS turned off vs. stimulation at typical clinical settings (3.5 V, frequency of stimulation 130 Hz, pulse width 60 µs). In addition, intracranial EEG was recorded directly from depth macroelectrodes in the NAc in four OCD patients. RESULTS: Cross-frequency coupling between the phase of alpha/low beta oscillations and amplitude of high gamma was significantly increased over midline frontal and parietal electrodes in patients when stimulation was turned off, compared to controls. Critically, in patients, beta (16-25 Hz) -gamma (110-166 Hz) phase amplitude coupling source localized to the ventromedial prefrontal cortex, and was reduced when NAc-DBS was active. In contrast, intracranial EEG recordings showed no beta-gamma phase amplitude coupling. The contribution of non-sinusoidal beta waveforms to this coupling are reported. CONCLUSION: We reveal an increased beta-gamma phase amplitude coupling in fronto-central scalp sensors in patients suffering from OCD, compared to healthy controls, which may derive from ventromedial prefrontal regions implicated in OCD and is normalized by DBS of the nucleus accumbens. This aberrant cross-frequency coupling could represent a biomarker of OCD, as well as a target for novel therapeutic approaches.

Nucleus Accumbens Stimulation Modulates Inhibitory Control by Right Prefrontal Cortex Activation in Obsessive-Compulsive Disorder.

Inhibitory control is considered a compromised cognitive function in obsessive-compulsive (OCD) patients and likely linked to corticostriatal circuitry disturbances. Here, 9 refractory OCD patients treated with deep brain stimulation (DBS) were evaluated to address the dynamic modulations of large-scale cortical network activity involved in inhibitory control after nucleus accumbens (NAc) stimulation and their relationship with cortical thickness. A comparison of DBS "On/Off" states showed that patients committed fewer errors and exhibited increased intraindividual reaction time variability, resulting in improved goal maintenance abilities and proactive inhibitory control. Visual P3 event-related potentials showed increased amplitudes during Go/NoGo performance. Go and NoGo responses increased cortical activation mainly over the right inferior frontal gyrus and medial frontal gyrus, respectively. Moreover, increased cortical activation in these areas was equally associated with a higher cortical thickness within the prefrontal cortex. These results highlight the critical role of NAc DBS for preferentially modulating the neuronal activity underlying sustained speed responses and inhibitory control in OCD patients and show that it is triggered by reorganizing brain functions to the right prefrontal regions, which may depend on the underlying cortical thinning. Our findings provide updated structural and functional evidence that supports critical dopaminergic-mediated frontal-striatal network interactions in OCD.

Predicting Neuropsychological Impairment in Relapsing Remitting Multiple Sclerosis: The Role of Clinical Measures, Treatment, and Neuropsychiatry Symptoms.

OBJECTIVE: This retrospective observational study aimed to define neuropsychological impairment (NI) profiles and determine the influence of clinical, demographic, and neuropsychiatric measures in specific cognitive domains in a cohort of relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: Ninety-one RRMS patients underwent a neurological examination and a brief neuropsychological assessment. Patients were classified according to the disease-modifying therapies (DMTs) received (platform or high-efficacy). Differences between groups and multiple regression analyses were performed to determine the predictive value of the assessed measures in cognitive performance. RESULTS: More than two-thirds of the patients showed NI. Specifically, mild to moderate NI was presented in approximately half of the participants. Paced Auditory Serial Addition Test (PASAT-3) and Symbol Digit Modalities Test (SDMT) were the most frequently impaired cognitive tests (45.3% and 41.3%, respectively) followed by phonemic verbal fluency (PVF) (27.8%). Expanded Disability Status Scale (EDSS), age, depressive symptoms, and disease duration were the best predictors of SDMT (R2 = .34; p < .01), whereas disease duration, EDSS, and anxiety-state levels predicted PASAT-3 (R2 = .33, p < .01). Educational level, age, EDSS, and depressive symptoms demonstrated the strongest association with PVF (R2 = .31, p < .01). CONCLUSIONS: Our results indicated a significant prevalence of NI in RRMS patients that was not dependent on the DMT type. In addition to the meaningful working memory (PASAT-3) and information processing speed (SDMT) impairments found, PVF deficits may also be an important marker of cognitive impairment in RRMS patients. This study supports the relevance of standard clinical measures and reinforces the importance of quantifying clinical and neuropsychiatric symptoms to predict subsequent cognitive performance on a similar multiple sclerosis phenotype and disease stage.

Individual test-retest reliability of evoked and induced alpha activity in human EEG data.

Diverse psychological mechanisms have been associated with modulations of different EEG frequencies. To the extent of our knowledge, there are few studies of the test-retest reliability of these modulations in the human brain. To assess evoked and induced alpha reliabilities related to cognitive processing, EEG data from twenty subjects were recorded in 58 derivations in two different sessions separated by 49.5 ± 48.9 (mean ± standard deviation) days. A visual oddball was selected as the cognitive task, and three main parameters were analyzed for evoked and induced alpha modulations (latency, amplitude and topography). Latency and amplitude for evoked and induced modulations showed stable behavior between the two sessions. The correlation between sessions for alpha evoked and induced topographies in the grand average (group level) was r = 0.923, p<0.001; r = 0.962, p<0.001, respectively. The within-subject correlation values for evoked modulation ranged from 0.472 to 0.974 (mean: 0.766), whereas induced activity showed a different range, 0.193 to 0.892 (mean: 0.655). Individual analysis of the test-retest reliability showed a higher heterogeneity in the induced modulation, probably due to the heterogeneous phases found in the second case. However, despite this heterogeneity in phase values for induced activity relative to the onset of the stimuli, an excellent correlation score was obtained for group topography, with values that were better than those of the grand average evoked topography. As a main conclusion, induced alpha activity can be observed as a stable and reproducible response in the cognitive processing of the human brain.

Attentional Differences as a Function of Rock Climbing Performance.

The purpose of this study was to investigate the relationship between attention (using two different attention tasks) and self-reported climbing ability while considering potential confounding factors (sex, age, climbing experience, and cardiorespiratory fitness) in a group of experienced climbers. Accuracy of response (AC) and reaction time (RT) from two different attention tasks using the Vienna Test System, along with self-reported on-sight and red-point climbing ability, were assessed in 35 climbers. Linear regression revealed that climbers with the highest self-reported on-sight grade had better AC during the attention task. Linear regression models revealed, after controlling for potential confounders, that AC, measured using two attention tasks, was positively related to climbers' highest self-reported on-sight climbing ability (ß = 0.388; p = 0.031). No significant differences were found between AC and self-reported red-point climbing ability (ß = 0.286; p = 0.064). No significant relationship was found between RT and climbing ability (ß = -0.102 to 0.020; p = 0.064). In conclusion, higher-level rock climbers appear to have an enhanced attention, which is related to on-sight lead climbing style, and thus, it may be an important component of climbing performance. Coaches should consider incorporating techniques to train attention based on on-sight climbing style in climbers.

Plasma Neurofilament Light Chain in Primary Progressive Aphasia and Related Disorders: Clinical Significance and Metabolic Correlates.

BACKGROUND: Primary progressive aphasia (PPA) is a heterogeneous syndrome that is difficult to diagnose at early stages. Plasma neurofilament light chain (NFL) has been proposed as a potential biomarker for PPA. OBJECTIVE: To examine the diagnostic properties of plasma NFL in PPA and to evaluate its association with clinical stages of the disease and brain metabolism. METHODS: Our study included 80 participants (13 with non-fluent, 12 with semantic, and 16 with logopenic variant PPA; 13 with amnestic Alzheimer's disease [AD]; 13 with behavioral variant frontotemporal dementia; and 13 healthy controls). Plasma NFL concentration was measured using a high-sensitivity enzyme-linked immunosorbent assay (ELISA) kit. PET imaging was performed in a subgroup of patients. RESULTS: NFL discriminated patients from controls with an area under the curve of 0.914 (95% CI, 0.843-0.984; p < 0.001) (cut-off: 76.46 pg/mL; 94% sensitivity, 76.9% specificity). There were no significant differences between clinical syndromes (PPA subtypes), the main clinical forms of dementia (frontotemporal dementia and AD), or the expected pathological groups (frontotemporal lobar degeneration-tau [FTLD-tau], FTLD-TDP43, and AD). NFL levels showed weak to moderate correlations with age and functional scale score. We found no significant correlation with the extent of hypometabolism observed on FDG-PET images. CONCLUSION: Plasma NFL is a non-specific marker of neurodegeneration, and may be helpful in the diagnosis of PPA. However, NFL does not permit differential diagnosis between PPA subtypes and is not correlated with the extent of neurodegeneration.