Introspection of UBNIN and Modified-UBNIN Algorithms for Structural MRI. Reply to Kelly et al. A Comparison of Brain-State Representations of Binary Neuroimaging Connectivity Data. Comment on "Samantaray et al. Unique Brain Network Identification Number for Parkinson's and Healthy Individuals Using Structural MRI. Brain Sci. 2023, 13, 1297".

The purpose of this reply is to address the comments given by Kelly et al. on our original paper "Unique Brain Network Identification Number for Parkinson's and Healthy Individuals using Structural MRI". We agree to the inadvertent rounding pitfall in our original paper due to the non-inclusion of symbolic math toolbox (MATLAB). We now provide the actual ranges (with decimal values) of the UBNIN values of healthy individuals and those with Parkinson's disease and further observations. Upon further introspection, we propose another variant, called Modified-UBNIN (UBNIN-MT,MN) which is highly weighted on the node with the highest network degree (i.e., connections). The italicized sentences within inverted commas are statements from Kelly et al.'s comment paper.

Brain connectivity for subtypes of parkinson's disease using structural MRI.

Objective. Delineating Parkinson's disease (PD) into distinct subtypes is a major challenge. Most studies use clinical symptoms to label PD subtypes while our work uses an imaging-based data-mining approach to subtype PD. Our study comprises two major objectives - firstly, subtyping Parkinson's patients based on grey matter information from structural magnetic resonance imaging scans of human brains; secondly, comparative structural brain connectivity analysis of PD subtypes derived from the former step.Approach. Source-based-morphometry decomposition was performed on 131 Parkinson's patients and 78 healthy controls from PPMI dataset, to derive at components (regions) with significance in disease and high effect size. The loading coefficients of significant components were thresholded for arriving at subtypes. Further, regional grey matter maps of subtype-specific subjects were separately parcellated and employed for construction of subtype-specific association matrices using Pearson correlation. These association matrices were binarized using sparsity threshold and leveraged for structural brain connectivity analysis using network metrics.Main results. Two distinct Parkinson's subtypes (namely A and B) were detected employing loadings of two components satisfying the selection criteria, and a third subtype (AB) was detected, common to these two components. Subtype A subjects were highly weighted in inferior, middle and superior frontal gyri while subtype B subjects in inferior, middle and superior temporal gyri. Network metrics analyses through permutation test revealed significant inter-subtype differences (p < 0.05) in clustering coefficient, local efficiency, participation coefficient and betweenness centrality. Moreover, hubs were obtained using betweenness centrality and mean network degree.Significance. MRI-based data-driven subtypes show frontal and temporal lobes playing a key role in PD. Graph theory-driven brain network analyses could untangle subtype-specific differences in structural brain connections showing differential network architecture. Replication of these initial results in other Parkinson's datasets may be explored in future. Clinical Relevance- Investigating structural brain connections in Parkinson's disease may provide subtype-specific treatment.

Unique Brain Network Identification Number for Parkinson's and Healthy Individuals Using Structural MRI.

We propose a novel algorithm called Unique Brain Network Identification Number (UBNIN) for encoding the brain networks of individual subjects. To realize this objective, we employed structural MRI on 180 Parkinson's disease (PD) patients and 70 healthy controls (HC) from the National Institute of Mental Health and Neurosciences, India. We parcellated each subject's brain volume and constructed an individual adjacency matrix using the correlation between the gray matter volumes of every pair of regions. The unique code is derived from values representing connections for every node (i), weighted by a factor of 2-(i-1). The numerical representation (UBNIN) was observed to be distinct for each individual brain network, which may also be applied to other neuroimaging modalities. UBNIN ranges observed for PD were 15,360 to 17,768,936,615,460,608, and HC ranges were 12,288 to 17,733,751,438,064,640. This model may be implemented as a neural signature of a person's unique brain connectivity, thereby making it useful for brainprinting applications. Additionally, we segregated the above datasets into five age cohorts: A: ≤32 years (n1 = 4, n2 = 5), B: 33-42 years (n1 = 18, n2 = 14), C: 43-52 years (n1 = 42, n2 = 23), D: 53-62 years (n1 = 69, n2 = 22), and E: ≥63 years (n1 = 46, n2 = 6), where n1 and n2 are the number of individuals in PD and HC, respectively, to study the variation in network topology over age. Sparsity was adopted as the threshold estimate to binarize each age-based correlation matrix. Connectivity metrics were obtained using Brain Connectivity toolbox (Version 2019-03-03)-based MATLAB (R2020a) functions. For each age cohort, a decreasing trend was observed in the mean clustering coefficient with increasing sparsity. Significantly different clustering coefficients were noted in PD between age-cohort B and C (sparsity: 0.63, 0.66), C and E (sparsity: 0.66, 0.69), and in HC between E and B (sparsity: 0.75 and above 0.81), E and C (sparsity above 0.78), E and D (sparsity above 0.84), and C and D (sparsity: 0.9). Our findings suggest network connectivity patterns change with age, indicating network disruption may be due to the underlying neuropathology. Varying clustering coefficients for different cohorts indicate that information transfer between neighboring nodes changes with age. This provides evidence of age-related brain shrinkage and network degeneration. We also discuss limitations and provide an open-access link to software codes and a help file for the entire study.

Sparsity Dependent Metrics Depict Alteration of Brain Network Connectivity in Parkinson's Disease.

To date, regional brain atrophy unfolded using neuroimaging methods is observed to be the signature of Parkinson's disease (PD). In addition, graph theory-based studies are proving altered structural connectivity in PD. This motivated us to employ regional grey matter volume of PD patients (N=70) for comparative network analysis with an equal number of age- and gender-matched healthy controls (HC). In the current study, normalized grey matter maps obtained from structural magnetic resonance imaging (sMRI) were parcellated into 56 ROI (regions of interest) for construction of symmetric matrix using partial correlation between every pair of regional grey matter volumes. Sparsity thresholding was used to binarize the matrices and MATLAB functions from brain connectivity toolbox were employed to obtain the connectivity metrics. We observed PD with a significantly lower clustering coefficient as well as local efficiency at higher sparsities (above 0.9 and 0.84, respectively) with p<0.05. The right fusiform gyrus was found to be the conserved hub, besides disruption of four hubs and regeneration of five other hubs. Lower clustering coefficient and local efficiency were indicative of reduced local integration and information processing, respectively. Hence, we suggest that global clustering coefficient and local efficiency could have a pivotal role in evaluating network topology. Thereby, our findings confirmed impairment of normal structural brain network topology reflecting disconnectivity mechanisms in PD. Clinical Relevance - Analyzing structural brain connectivity in Parkinson's disease might provide the researchers and clinicians with a signature pattern of the disease to discriminate patients from normal controls.