Whole brain and deep gray matter structure segmentation: Quantitative comparison between MPRAGE and MP2RAGE sequences.

OBJECTIVE: T1-weighted MRI images are commonly used for volumetric assessment of brain structures. Magnetization prepared 2 rapid gradient echo (MP2RAGE) sequence offers superior gray (GM) and white matter (WM) contrast. This study aimed to quantitatively assess the agreement of whole brain tissue and deep GM (DGM) volumes obtained from MP2RAGE compared to the widely used MP-RAGE sequence. METHODS: Twenty-nine healthy participants were included in this study. All subjects underwent a 3T MRI scan acquiring high-resolution 3D MP-RAGE and MP2RAGE images. Twelve participants were re-scanned after one year. The whole brain, as well as DGM segmentation, was performed using CAT12, volBrain, and FSL-FAST automatic segmentation tools based on the acquired images. Finally, contrast-to-noise ratio between WM and GM (CNRWG), the agreement between the obtained tissue volumes, as well as scan-rescan variability of both sequences were explored. RESULTS: Significantly higher CNRWG was detected in MP2RAGE vs. MP-RAGE (Mean ± SD = 0.97 ± 0.04 vs. 0.8 ± 0.1 respectively; p<0.0001). Significantly higher total brain GM, and lower cerebrospinal fluid volumes were obtained from MP2RAGE vs. MP-RAGE based on all segmentation methods (p<0.05 in all cases). Whole-brain voxel-wise comparisons revealed higher GM tissue probability in the thalamus, putamen, caudate, lingual gyrus, and precentral gyrus based on MP2RAGE compared with MP-RAGE. Moreover, significantly higher WM probability was observed in the cerebellum, corpus callosum, and frontal-and-temporal regions in MP2RAGE vs. MP-RAGE. Finally, MP2RAGE showed a higher mean percentage of change in total brain GM compared to MP-RAGE. On the other hand, MP-RAGE demonstrated a higher overtime percentage of change in WM and DGM volumes compared to MP2RAGE. CONCLUSIONS: Due to its higher CNR, MP2RAGE resulted in reproducible brain tissue segmentation, and thus is a recommended method for volumetric imaging biomarkers for the monitoring of neurological diseases.

Differential changes in visual and auditory event-related oscillations in dementia with Lewy bodies.

OBJECTIVE: Aside from the cognitive impairment, patients with dementia with Lewy bodies (DLB) have a high frequency of visual hallucinations and a number of other vision-related symptoms, whereas auditory hallucinations are less frequent. To better understand the differential dysfunction of the visual network in DLB, we compared auditory and visual event-related potentials and oscillations in patients with DLB. METHODS: Event-related potentials elicited by visual and auditory oddball tasks were recorded in 23 patients with DLB and 22 healthy controls and analyzed in time and time-frequency domain. RESULTS: DLB patients had decreased theta band activity related to both early sensory and later cognitive processing in the visual, but not in the auditory task. Patients had lower delta and higher alpha and beta bands power related to later cognitive processing in both auditory and visual tasks. CONCLUSIONS: In DLB visual event-related oscillations are characterized by a decrease in theta and lack of inhibition in alpha bands. SIGNIFICANCE: Decreased theta and a lack of inhibition in alpha band power might be an oscillatory underpinning of some classical DLB symptoms such as fluctuations in attention and high-level visual disturbances and a potential marker of dysfunction of the visual system in DLB.

Changes in event-related potentials during dual task walking in aging and Parkinson's disease.

OBJECTIVE: To investigate EEG changes during an auditory odd-ball task while walking (dual-task) in young adults, older adults, and patients with Parkinson's disease. METHODS: 11 young adults, 10 older adults, and 10 patients with Parkinson's disease (PD) performed an auditory oddball task during standing and walking on a treadmill, while wearing a wireless EEG cap. The amplitude and latency of P300 were compared between groups and within conditions using linear mix model analysis. Gait was evaluated using wearable sensors and cognition was assessed using the Color Trail Test. RESULTS: P300 latency became longer during walking in all groups (p = 0.005). During walking, older adults (p = 0.005) and patients with PD (p = 0.001) showed prolonged P300 latency compared to young adults. Significant task by group interaction was found in P300 amplitude (p = 0.008). Patients with PD demonstrated reduced P300 amplitude during walking compared to standing (p = 0.023). Among all subjects, better motor and cognitive performance correlated with shorter P300 latency (r = 0.457, p = 0.014 and r = 0.431, p = 0.040, respectively). CONCLUSIONS: These findings provide direct evidence of the physiological recruitment of attentional networks during walking and their impact by ageing and disease. SIGNIFICANCE: This study is the first to report on changes in P300 latency and amplitude during dual-task oddball walking in older adults and patients with PD.

Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson's Disease and Their First-Degree Unaffected Relatives.

Cerebral atrophy has been detected in patients with Parkinson's disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program. All participants were cognitively intact based on a computerized cognitive assessment battery. Fifty-seven idiopathic PD patients, 9 LRRK2-PD, 12 GBA-PD, 49 NMNC, 41 LRRK2-NMC and 14 GBA-NMC participated in this study. Lower volumes among patients with PD compared to unaffected participants were detected in bilateral hippocampus, nucleus accumbens, caudate, thalamus, putamen and amygdala and the right pallidum (p = 0.016). PD patients demonstrated lower cortical thickness indexes in a majority of regions assessed compared with non-manifesting participants. No differences in cortical thickness and subcortical volumes were detected within each of the groups of participants based on genetic status. Mutations in the GBA and LRRK2 genes are not important determinants of cortical thickness and subcortical volumes in both patients with PD and non-manifesting participants. PD is associated with a general reduction in cortical thickness and sub-cortical atrophy even in cognitively intact patients.

Disparate effects of training on brain activation in Parkinson disease.

OBJECTIVE: To compare the effects of 2 forms of exercise, i.e., a 6-week trial of treadmill training with virtual reality (TT + VR) that targets motor and cognitive aspects of safe ambulation and a 6-week trial of treadmill training alone (TT), on brain activation in patients with Parkinson disease (PD). METHODS: As part of a randomized controlled trial, patients were randomly assigned to 6 weeks of TT (n = 17, mean age 71.5 ± 1.5 years, disease duration 11.6 ± 1.6 years; 70% men) or TT + VR (n = 17, mean age 71.2 ± 1.7 years, disease duration 7.9 ± 1.4 years; 65% men). A previously validated fMRI imagery paradigm assessed changes in neural activation pretraining and post-training. Participants imagined themselves walking in 2 virtual scenes projected in the fMRI: (1) a clear path and (2) a path with virtual obstacles. Whole brain and region of interest analyses were performed. RESULTS: Brain activation patterns were similar between training arms before the interventions. After training, participants in the TT + VR arm had lower activation than the TT arm in Brodmann area 10 and the inferior frontal gyrus (cluster level familywise error-corrected [FWEcorr] p < 0.012), while the TT arm had lower activation than TT + VR in the cerebellum and middle temporal gyrus (cluster level FWEcorr p < 0.001). Changes in fall frequency and brain activation were correlated in the TT + VR arm. CONCLUSIONS: Exercise modifies brain activation patterns in patients with PD in a mode-specific manner. Motor-cognitive training decreased the reliance on frontal regions, which apparently resulted in improved function, perhaps reflecting increased brain efficiency.

Virtual reality and motor imagery: promising tools for assessment and therapy in Parkinson's disease.

Motor imagery (MI) and virtual reality (VR) are two evolving therapeutic approaches that make use of cognitive function to study and enhance movement, in particular, balance and mobility of people with Parkinson's disease (PD). This review examines the literature on the use of VR and MI in the assessment of mobility and as a therapeutic intervention to improve balance and gait in patients with PD. A study was eligible for inclusion if MI or VR were used to assess motor or cognitive function to improve gait, balance, or mobility in patients with PD. Data were extracted on the following categories: participants; study design; intervention (type, duration, and frequency); and outcomes. Intervention studies were evaluated for quality using the Physiotherapy Evidence Database scale. Sixteen studies were identified; 4 articles used MI and 12 used VR for assessment and treatment of gait impairments in PD. The studies included small samples and were diverse in terms of methodology. Quality of the intervention trials varied from fair for VR to good for MI. The benefits of using MI and VR for assessment and treatment were noted. Encouraging findings on the potential benefits of using MI and VR in PD were found, although further good-quality research is still needed. Questions remain on the optimal use, content of interventions, and generalizability of findings across the different stages of the disease. The possible mechanisms underlying MI and VR and recommendations for future research and therapy are also presented.

Appreciation of humor is decreased among patients with Parkinson's disease.

OBJECTIVE: To test whether appreciation of humor might be a non-motor function affected by Parkinson's disease (PD). METHODS: Thirty-nine PD patients and 38 healthy controls participated in this study. Appreciation of humor and effect of the presentation method utilized were assessed. Sense of humor was evaluated by the sense of humor questionnaire (SHQ-6). Humor appreciation was tested using three methods of presentation: videos, audio sketches and pictorial cartoons, each portraying both obvious and non-obvious humor content. Depression, anxiety, cognition, disease severity and quality of life were measured by standardized questionnaires and correlated with humor outcomes. RESULTS: Patients with PD rated humor content lower than controls on every method of presentation as well as on the SHQ-6 (p = 0.004). The greatest between-group difference was noted when the material was presented visually via pictorial cartoons (p < 0.0001). In addition, obvious humor content was rated higher than non-obvious content by the PD group in all three presentation methods (p < 0.05). The degree of depression and anxiety did not influence these results. CONCLUSIONS: Patients with PD have a decreased sense of humor compared to healthy controls. Utilizing audio methods of presentation and humor in an obvious mode appears to be the preferred approach for eliciting responses to humor in a PD population.

Audio-biofeedback training for posture and balance in patients with Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease (PD) suffer from dysrhythmic and disturbed gait, impaired balance, and decreased postural responses. These alterations lead to falls, especially as the disease progresses. Based on the observation that postural control improved in patients with vestibular dysfunction after audio-biofeedback training, we tested the feasibility and effects of this training modality in patients with PD. METHODS: Seven patients with PD were included in a pilot study comprised of a six weeks intervention program. The training was individualized to each patient's needs and was delivered using an audio-biofeedback (ABF) system with headphones. The training was focused on improving posture, sit-to-stand abilities, and dynamic balance in various positions. Non-parametric statistics were used to evaluate training effects. RESULTS: The ABF system was well accepted by all participants with no adverse events reported. Patients declared high satisfaction with the training. A significant improvement of balance, as assessed by the Berg Balance Scale, was observed (improvement of 3% p = 0.032), and a trend in the Timed up and go test (improvement of 11%; p = 0.07) was also seen. In addition, the training appeared to have a positive influence on psychosocial aspects of the disease as assessed by the Parkinson's disease quality of life questionnaire (PDQ-39) and the level of depression as assessed by the Geriatric Depression Scale. CONCLUSIONS: This is, to our knowledge, the first report demonstrating that audio-biofeedback training for patients with PD is feasible and is associated with improvements of balance and several psychosocial aspects.