Functional neural networks stratify Parkinson's disease patients across the spectrum of cognitive impairment.

INTRODUCTION: Cognitive impairment (CI) is a significant non-motor symptoms in Parkinson's disease (PD) that often precedes the emergence of motor symptoms by several years. Patients with PD hypothetically progress from stages without CI (PD-normal cognition [NC]) to stages with Mild CI (PD-MCI) and PD dementia (PDD). CI symptoms in PD are linked to different brain regions and neural pathways, in addition to being the result of dysfunctional subcortical regions. However, it is still unknown how functional dysregulation correlates to progression during the CI. Neuroimaging techniques hold promise in discriminating CI stages of PD and further contribute to the biomarker formation of CI in PD. In this study, we explore disparities in the clinical assessments and resting-state functional connectivity (FC) among three CI stages of PD. METHODS: We enrolled 88 patients with PD and 26 healthy controls (HC) for a cross sectional clinical study and performed intra- and inter-network FC analysis in conjunction with comprehensive clinical cognitive assessment. RESULTS: Our findings underscore the significance of several neural networks, namely, the default mode network (DMN), frontoparietal network (FPN), dorsal attention network, and visual network (VN) and their inter-intra-network FC in differentiating between PD-MCI and PDD. Additionally, our results showed the importance of sensory motor network, VN, DMN, and salience network (SN) in the discriminating PD-NC from PDD. Finally, in comparison to HC, we found DMN, FPN, VN, and SN as pivotal networks for further differential diagnosis of CI stages of PD. CONCLUSION: We propose that resting-state networks (RSN) can be a discriminating factor in distinguishing the CI stages of PD and progressing from PD-NC to MCI or PDD. The integration of clinical and neuroimaging data may enhance the early detection of PD in clinical settings and potentially prevent the disease from advancing to more severe stages.

The effects of cognitive, physical, and somatosensory rehabilitation after right temporo-parietal tumor resection on cognitive, motor, somatosensory, and electrophysiological parameters: A case report.

INTRODUCTION: This report examines the effects of a multimodal rehabilitation program which includes cognitive, physical, and somatosensory rehabilitation after right temporo-parietal tumor resection on cognitive, motor, somatosensory, and electrophysiological parameters. CASE DESCRIPTION: A 22-year-old patient presented with sensory loss in the dominant left hand and reduced writing ability after right temporo-parietal lobe resection. Cognitive, motor, and sensory evaluations were carried out pre and post-treatment. The patient's spontaneous electroencephalo-gram (EEG) and an EEG during application of transcutaneous electrical nerve stimulation (TENS) (TENS EEG) were recorded. As a reference for the patient's electrophysiological values, EEGs of 4 healthy individuals were also taken. Over a period of 1 year, the patient received multimodal rehabilitation which includes cognitive, physical, and somato-sensory rehabilitation on 2 days each week. OUTCOMES: An improvement of the patient's cognitive capacities, motor strength, superficial, deep and cortical sensations was achieved. After rehabilitation, an increase in parietal and occipital alpha activity as well as in frontal and parietal beta activity was seen both in spontaneous EEG and in TENS EEG. With increasing TENS intensity, alpha and beta power increased as well. CONCLUSION: Our findings suggest that a multimodal rehabilitation program may improve cognitive, sensory, and motor effects after resection due to tumor surgery.

Therapeutic Role of Repetitive Transcranial Magnetic Stimulation in Alzheimer's and Parkinson's Disease: Electroencephalography Microstate Correlates.

INTRODUCTION: The microstate analysis is a method to convert the electrical potentials on the multi-channel electrode array to topographical electroencephalography (EEG) data. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that can modulate brain networks. This study explores the pathophysiological changes through microstate analysis in two different neurodegenerative diseases, Alzheimer's (AD) and Parkinson's disease (PD), characterized by motor and cognitive symptoms and analysis the effect of rTMS on the impaired cognitive and motor functions. MATERIALS AND METHODS: We included 18 AD, 8 PD patients, and 13 age-matched controls. For both groups, we applied 5 Hz rTMS on the left pre-SMA in PD patients while 20 Hz rTMS on the left lateral parietal region in AD patients. Each patient was re-evaluated 1 week after the end of the sessions, which included a detailed clinical evaluation and measurement of EEG microstates. RESULTS: At the baseline, the common findings between our AD and PD patients were altered microstate (MS) B, MS D durations and transition frequencies between MS A-MS B, MS C-MS D while global explained variance (GEV) ratio and the extent and frequency of occurrence of MS A, MS B, and MS D were separately altered in AD patients. Although no specific microstate parameter adequately differentiated between AD and PD patients, we observed significant changes in MS B and MS D parameters in PD patients. Further, we observed that Mini-Mental State Examination (MMSE) performances were associated with the transition frequencies between MS A-MS B and MS C-MS D and GEV ratio. After left parietal rTMS application, we have observed significantly increased visual memory recognition and clock drawing scores after left parietal rTMS application associated with improved microstate conditions prominent, especially in the mean duration of MS C in AD patients. Also, pre-SMA rTMS resulted in significant improvement in motor scores and frequency of transitions from MS D to MS C in PD patients. CONCLUSION: This study shows that PD and AD can cause different and similar microstate changes that can be modulated through rTMS, suggesting the role of MS parameters and rTMS as a possible combination in monitoring the treatment effect in neurodegenerative diseases.

The Multifactorial Role of Pre-supplementary Motor Area Stimulation in the Freezing of Gait: An Alternative Strategy to the Classical Drug-Target Approach.

INTRODUCTION: The pre-supplementary motor area (Pre-SMA) plays a pivotal role in the control of voluntary motor control and freezing of gait (FOG) pathophysiological mechanism. Here, we aimed to modulate if the pre-SMA would have beneficial effects on motor and behavioural outcomes in freezing of gait. To test this hypothesis, we examined the left pre-SMA stimulating effect of repetitive Transcranial Magnetic Stimulation (rTMS) on motor, cognitive and behavioural parameters in Parkinson's patients with FOG. METHODS: The study included 20 Parkinson's patients with FOG (3 females, 17 males) who received the left Pre-SMA rTMS procedure. The clinical assessments were performed on all patients at the baseline and the patients were re-evaluated under the same clinical conditions one week after the end of the sessions. RESULTS & DISCUSSION: We found significant improvements in motor, cognitive and behavioural symptoms (p<0.05). The main finding of our study is that Pre-SMA is an attractive stimulation area leading to critical improvement of symptoms of Parkinson's patients with FOG. CONCLUSION: The high-frequency rTMS stimulation over the left preSMA has a restorative effect on the motor, cognitive and behavioural symptoms of Parkinson's patients with FOG.

The correlation of non-motor symptoms and sleep on balance in Parkinson's disease patients with normal cognition and mild cognitive impairment.

BACKGROUND: Parkinson's disease (PD) is characterized by non-motor symptoms (NMS) as well as by motor symptoms. Together with the impairment of cognitive functions, NMS and sleep also affect motor symptoms negatively. The aim of our study is to examine the correlation of NMS and sleep on balance in PD patients with normal cognition (PD-NC) and with mild cognitive impairment (PD-MCI). METHODS: A total of 69 patients were included in our study. Using the Standardized Mini-Mental State Examination, participants were divided into 2 groups, PD-NC and PD-MCI. Patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Berg Balance Scale (BBS), the Tinetti Balance Assessment Tool (TBAT), the Non-Motor Symptoms Questionnaire (NMSQ), and the Parkinson's Disease Questionnaire (PDQ-39). RESULTS: PD-MCI patients had statistically significant worse motor symptoms and more balance disorder compared to PD-NC (UPDRS: p = 0.009; BBS: p = 0.010; TBAT: p = 0.004). PD-MCI patients had greater severity of non-motor symptoms and worse sleep quality than the PD-NC group (NMSQ-total: p = 0.02; NMSQ-sleep total: p = 0.01). The evaluation has shown that with a diagnosis of MCI, NMS, and sleeping problems were correlated, and the correlation was associated with impairment of the balance function. While being more pronounced in the PD-MCI group, quality of life was affected in both groups (p < 0.05). CONCLUSION: Our data demonstrate a negative effect on the balance function in patients with cognitive impairment suffering increased NMS and sleeping disorders. Treatment of these patients needs to concentrate on NMS and cognitive functions as much as on motor symptoms.

The Relationship Between Pain, and Freezing of Gait and Falls in Parkinson's Disease.

INTRODUCTION: To investigate the relationship between pain, freezing of gait (FOG) and falls in Parkinson's Disease (PD). METHODS: The study included 110 PD patients. The Unified PD Rating Scale (UPDRS) and Hoehn and Yahr Scale were used to evaluate disease severity. The patients self-reported occurrence of FOG and falls, and the FOG Questionnaire was administered to evaluate the severity of FOG. A visual analog scale (VAS) was used to measure the severity of pain and pain localization was self-reported by the patients. RESULTS: Fifty-eight of the patients had FOG and 43 experienced falls. Among the patients, 42 had no pain, whereas 35 had lower extremity pain. Higher UPDRS motor and FOG scores, and advanced-stage disease were noted in significantly more of the patients with FOG and falls. VAS scores were not affected by the presence of FOG or falls. There was a positive correlation between the severity of FOG and VAS score in the male patients (r=0.308; p=0.010). More patients with falls had lower extremity pain than those without falls (r=0.308; p=0.010). DISCUSSION: Patients with FOG and falls had more severe motor findings. Pain is correlated with both FOG and falls. Further investigations should be done to understand the mechanism of this relationship to prevent the motor complications in advanced PD.

Preliminary findings on the role of high-frequency (5Hz) rTMS stimulation on M1 and pre-SMA regions in Parkinson's disease.

It has been already shown that the motor symptoms of the Parkinson's Disease (PD) have been improved with high frequency rTMS although there is no consensus on the most suitable target brain localization for a maximal therapeutic efficacy. Here, we aimed to compare the therapeutic effect of high frequency (5Hz) rTMS stimulation on primary motor cortex (M1) and pre-supplementary (pre SMA) regions in patients with PD who were still on pharmacological treatment. The study included right-hand dominant16 patients with PD (5 females, 11 males) with demographically and clinically similar characteristics which were randomly assigned to group 1 (n=8) and group 2 (n=8) and received left M1 and the left pre-SMA rTMS procedure, respectively. Total and sequential motor scores of the Unified Parkinson's Disease Rating Scale (UPDRSmotor) were applied to all patients at the baseline and the patients were re-evaluated under the same clinical conditions one week after the end of the sessions. Comparisons of the UPDRS-motor scores between two groups yielded significant improvements after the rTMS on pre-SMA compared to M1 (M1 p=0.14; pre-SMA p=0.01). which were especially significant for the bradykinesia (p=0.04) and axial score related items (p=0.01). This is the first study that shows the effect of rTMS on pre-SMA and it appears to be a promising option in the treatment of PD.