Background: Functional outcomes in multiple sclerosis (MS) have been thoroughly investigated over the last few decades. The Frontal lobe (FL) cortex contains regions responsible for attention, memory, planning and motor functioning among others. Many efforts have been dedicated to establishing radio-functional correlates but there is an apparent paucity of information available to characterize regional specific brain changes and their correlations to functional outcomes in persons with MS (PwMS). Objectives: To investigate the association between (FL) volume and folding changes and widely used functionality measures in MS population. Methods: Forty PwMS who had comprehensive functionality assessments were randomly selected from an existing dataset (MS-CUE). Nine-Hole Peg Test (NHPT), Symbol Digit Modalities Test (SDMT) and Timed 25-Foot Walk (T25FW) were collected along with disease characteristics and demographic variables. Chart review was performed and magnetic resonance imaging (MRI) studies extracted as available from routine care. The first available MRI study was considered as their baseline imaging for this study and was used in this analysis. Baseline MRIs that were five years +/- six months away from the date of functional assessments were selected. Coronal T1 MRIs studies were chosen to assess the volume and gyrification index (GI) of the FL to two blinded experimenters using FreeSurfer software. The anterior horn of the lateral ventricle and the central sulcus were used as anatomical landmarks delineating the anterior part of the FL and the total FL, respectively. Results: Baseline total FL GI was negatively associated with performance on both the NHPT (r=-.53, p<.01) and SDMT (r=-.62, p<.01). Regional significance of this association with NHPT (r=-.42, p<.01) and SDMT (r=-.52, p<.01) was confined to the anterior part of the left FL. Furthermore, GI did not show any correlation with (T-25FW). Finally, FL volume did not show any associations with the aforementioned functionality measures. Conclusions: Reduced FL GI and hence cortical grey matter volume but not total FL volume were found to be associated with lower performance in fine motor dexterity and cognitive processing speed and not with lower extremity dysfunction . Furthermore, our data suggest that GI of the anterior part of the left FL was significantly correlated with lower performance, suggesting that these correlations may occur in a regional specific pattern.