Neurodegenerative diseases (NDs) such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are devastating conditions that can develop without noticeable symptoms, causing irreversible damage to neurons before any signs become clinically evident. NDs are a major cause of disability and mortality worldwide. Currently, there are no cures or treatments to halt their progression. Therefore, the development of early detection methods is urgently needed to delay neuronal loss as soon as possible. Despite advancements in Medtech, the early diagnosis of NDs remains a challenge at the intersection of medical, IT, and regulatory fields. Thus, this review explores “digital biomarkers” (tools designed for remote neurocognitive data collection and AI analysis) as a potential solution. The review summarizes that recent studies combining AI with digital biomarkers suggest the possibility of identifying pre-symptomatic indicators of NDs. For instance, research utilizing convolutional neural networks for eye tracking has achieved significant diagnostic accuracies. ROC-AUC scores reached up to 0.88, indicating high model performance in differentiating between PD patients and healthy controls. Similarly, advancements in facial expression analysis through tools have demonstrated significant potential in detecting emotional changes in ND patients, with some models reaching an accuracy of 0.89 and a precision of 0.85. This review follows a structured approach to article selection, starting with a comprehensive database search and culminating in a rigorous quality assessment and meaning for NDs of the different methods. The process is visualized in 10 tables with 54 parameters describing different approaches and their consequences for understanding various mechanisms in ND changes. However, these methods also face challenges related to data accuracy and privacy concerns. To address these issues, this review proposes strategies that emphasize the need for rigorous validation and rapid integration into clinical practice. Such integration could transform ND diagnostics, making early detection tools more cost-effective and globally accessible. In conclusion, this review underscores the urgent need to incorporate validated digital health tools into mainstream medical practice. This integration could indicate a new era in the early diagnosis of neurodegenerative diseases, potentially altering the trajectory of these conditions for millions worldwide. Thus, by highlighting specific and statistically significant findings, this review demonstrates the current progress in this field and the potential impact of these advancements on the global management of NDs.

Recurrent projections comprise a universal feature of cerebral organization. Here, we show that the corticofugal projections from the striate cortex (V1) to the lateral geniculate nucleus (LGN) robustly and multiplicatively enhance the responses of parvocellular neurons, stimulated by gratings restricted to the classical receptive field and modulated in luminance, by over two-fold in a contrast-independent manner at all but the lowest contrasts. In the equiluminant plane, wherein stimuli are modulated in chromaticity with luminance held constant, such enhancement is strongly contrast dependent. These projections also robustly enhance the responses of magnocellular neurons but contrast independently only at high contrasts. Thus, these results have broad functional significance at both network and neuronal levels by providing the experimental basis and quantitative constraints for a wide range of models on recurrent projections and the control of contrast gain.

Subfield analysis of the receptive fields (RFs) of parafoveal V4 complex cells demonstrates directly that most RFs are tiled by overlapping second-order excitatory inputs that for any given V4 cell are predominantly selective to the same preferred values of spatial frequency and orientation. These results extend hierarchical principles of RF organization in the spatial, orientation and spatial frequency domains, first recognized in V1, to an intermediate extrastriate cortex. Spatial interaction studies across subfields demonstrate that the responses of V4 neurons to paired stimuli may either decrease or increase as a function of inter-stimulus distance across the width axis. These intra-RF suppressions and facilitations vary independently in magnitude and spatial extent from cell to cell. These results taken together with the relatively large RF sizes of V4 neurons — as compared with RF sizes of their afferent inputs — lead us to hypothesize a novel property, namely that classes of stimulus configurations that enhance areal summation while reducing suppressive interactions between excitatory inputs will evoke especially robust responses. We tested, and found support for, this hypothesis by presenting stimuli consisting of optimally tuned sine-wave gratings visible only within an annular region and found that such stimuli vigorously activate V4 neurons at firing rates far higher than those evoked by comparable stimuli to either the full-field or central core. On the basis of these results we propose a framework for a new class of neural network models for the spatial RF organizations of prototypic V4 neurons.

Humans are a vision-dominated species; what we perceive depends on where we look. Therefore, eye movements (EMs) are essential to our interactions with the environment, and experimental findings show EMs are affected in neurodegenerative disorders (ND). This could be a reason for some cognitive and movement disorders in ND. Therefore, we aim to establish whether changes in EM-evoked responses can tell us about the progression of ND, such as Alzheimer’s (AD) and Parkinson’s diseases (PD), in different stages. In the present review, we have analyzed the results of psychological, neurological, and EM (saccades, antisaccades, pursuit) tests to predict disease progression with machine learning (ML) methods. Thanks to ML algorithms, from the high-dimensional parameter space, we were able to find significant EM changes related to ND symptoms that gave us insights into ND mechanisms. The predictive algorithms described use various approaches, including granular computing, Naive Bayes, Decision Trees/Tables, logistic regression, C-/Linear SVC, KNC, and Random Forest. We demonstrated that EM is a robust biomarker for assessing symptom progression in PD and AD. There are navigation problems in 3D space in both diseases. Consequently, we investigated EM experiments in the virtual space and how they may help find neurodegeneration-related brain changes, e.g., related to place or/and orientation problems. In conclusion, EM parameters with clinical symptoms are powerful precision instruments that, in addition to their potential for predictions of ND progression with the help of ML, could be used to indicate the different preclinical stages of both diseases.

We still do not know how the brain and its computations are affected by nerve cell deaths and their compensatory learning processes, as these develop in neurodegenerative diseases (ND). Compensatory learning processes are ND symptoms usually observed at a point when the disease has already affected large parts of the brain. We can register symptoms of ND such as motor and/or mental disorders (dementias) and even provide symptomatic relief, though the structural effects of these are in most cases not yet understood. It is very important to obtain early diagnosis, which can provide several years in which we can monitor and partly compensate for the disease’s symptoms, with the help of various therapies. In the case of Parkinson’s disease (PD), in addition to classical neurological tests, measurements of eye movements are diagnostic. We have performed measurements of latency, amplitude, and duration in reflexive saccades (RS) of PD patients. We have compared the results of our measurement-based diagnoses with standard neurological ones. The purpose of our work was to classify how condition attributes predict the neurologist’s diagnosis. For n = 10 patients, the patient age and parameters based on RS gave a global accuracy in predictions of neurological symptoms in individual patients of about 80%. Further, by adding three attributes partly related to patient ‘well-being’ scores, our prediction accuracies increased to 90%. Our predictive algorithms use rough set theory, which we have compared with other classifiers such as Naïve Bayes, Decision Trees/Tables, and Random Forests (implemented in KNIME/WEKA). We have demonstrated that RS are powerful biomarkers for assessment of symptom progression in PD.