Neuroimaging-Guided Transcranial Magnetic and Direct Current Stimulation in MCI: Toward an Individual, Effective and Disease-Modifying Treatment.

The therapeutic approaches currently applied in Alzheimer's disease (AD) and similar neurodegenerative diseases are essentially based on pharmacological strategies. However, despite intensive research, the effectiveness of these treatments is limited to transient symptomatic effects, and they are still far from exhibiting a true therapeutic effect capable of altering prognosis. The lack of success of such pharmacotherapy-based protocols may be derived from the cases in the majority of trials being too advanced to benefit significantly in therapeutic terms at the clinical level. For neurodegenerative diseases, mild cognitive impairment (MCI) may be an early stage of the disease continuum, including Alzheimer's. Noninvasive brain stimulation (NIBS) techniques have been developed to modulate plasticity in the human cortex in the last few decades. NIBS techniques have made it possible to obtain unique findings concerning brain functions, and design novel approaches to treat various neurological and psychiatric conditions. In addition, its synaptic and cellular neurobiological effects, NIBS is an attractive treatment option in the early phases of neurodegenerative diseases, such as MCI, with its beneficial modifying effects on cellular neuroplasticity. However, there is still insufficient evidence about the potential positive clinical effects of NIBS on MCI. Furthermore, the huge variability of the clinical effects of NIBS limits its use. In this article, we reviewed the combined approach of NIBS with various neuroimaging and electrophysiological methods. Such methodologies may provide a new horizon to the path for personalized treatment, including a more individualized pathophysiology approach which might even define new specific targets for specific symptoms of neurodegenerations.

Comparison of Electrophysiological and Radiological Subthalamic Nucleus Length and Volume.

AIM: To investigate the surgical value of MER recordings and improve surgical technique by demonstrating the consistency between preoperative radiological STN volume and intraoperative neurophysiological STN length. MATERIAL AND METHODS: Sixty-one patients with PD were enrolled. The volumes of the STN were measured using magnetic resonance images 3-dimensional volume reconstructions of stereotactic magnetic resonance images. MER were performed in all patient and the maximal electrophysiologic length of the STN was recorded each patient. In the postoperative period, the permanent electrode was modeled and reconstructed in 3D, and the longest distance traveled in the STN was calculated. RESULTS: A total of 61 patients who underwent surgery between 2012-2022 were included in the study. Thirty-six (59%) of the patients were male, and 25 (41%) were female. A total of 122 STNs were performed with 166 electrodes. The most common end alignment used was center with 86. STN length averaged 4.9 mm (0-10.5 mm). The mean STN volume was 0.11 cm3. The STN Volume of men were significantly higher than women. The STN Length, Volume, and the target MER length showed a positive correlation significantly. CONCLUSION: With radiological advances, it is possible to better visualize the target points and define the boundaries better, and direct methods can be used more in making targeting plans. MER records obtained during surgery and STN dimensions in presurgical planning show compatibility, and it is seen that there may be differences between the right and left sides because of brain shifting. Although radiology is increasingly providing better support, electrophysiological recordings provides real-time information on the electrodes? locations and give the opportunity to surgical team choosing alternative target.

The therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in parkinsonian visual hallucinations: Electrophysiological correlates.

We have evaluated an 82 years old PD patient who has acutely developed VH secondary to acute visual loss that was associated with increased electroencephalographic activity in the gamma range over the parietal, occipital and frontal regions. In this respect, we have tested the therapeutic effect of occipital lobe oriented rTMS application and its electrophysiological correlates that led to significant improvement in the hallucinatory symptomatology of the patient after two weeks. We have revealed that the improved hallucinatory symptoms after rTMS application resolved completely after switching from the pramipexole treatment to L-Dopa indicating that there could be a combined therapeutic effect of L-Dopa and rTMS. Furthermore, Quantitative-Electroencephalography analysis has shown that the therapeutic effects of rTMS and L-Dopa were seen with the improvement of impaired gamma power spectrum. Although the main limitation of this report is that this a single case study and that these findings need to be replicated in a larger sample, e.g., as part of a controlled trial, our present findings help us to enlighten the unknown pathophysiological overlapping between the visual hallucinations in PD and Charles Bonnet Syndrome. Finally, our study revealed increased gamma coherence and power spectrum which is seen with visual hallucinations and improved after the application of 1 Hz rTMS on the occipital lobe. These findings together suggest that rTMS could be used as a therapeutic tool for parkinsonian complex VH and probably due affecting gamma coherence and power spectrum.

FDG-PET Scanning Shows Distributed Changes in Cortical Activity Associated with Visual Hallucinations in Eye Disease.

BACKGROUND AND OBJECTIVE: Charles Bonnet Syndrome (CBS) has been defined as complex visual hallucinations (CVH) due to visual loss. The underlying mechanism of CBS is not clear and the underlying pathophysiology of the visual hallucinations in CBS patients and pure visually impaired patients is still not clear. METHODS: In our study, we have scanned three patients with eye disease and CBS (VH+) and three patients with eye disease without CBS (VH-) using FDG-PET. RESULTS: Our results showed underactivity in the pons and overactivity in primary right left visual cortex and inferior parietal cortex in VH- patients and underactivity in left Broca, left inf frontal primary visual cortex and anterior and posterior cingulate cortex in VH+ patients relative to the normative 18FFDG PET data that was taken from the database consisting of 50 age-matched healthy adults without neuropsychiatric disorders. CONCLUSION: From this distributed pattern of activity changes, we conclude that the generation of visual hallucination in CBS is associated with bottom-up and top-down mechanism rather than the generally accepted visual deafferentation-related hyperexcitability theory.

Anterior cerebral artery infarcts; two years follow-up study.

BACKGROUND AND PURPOSE: Anterior cerebral infarct (ACA) infarcts are reported very rare that is due to the compensatory collateral circulation provided by the anterior communicating artery. There are very few studies reporting the long-term follow-up results of ACA infarcts regarding their aetiology, clinical features and prognosis. Most studies reported in the literature vary between several months to one year. METHODS: A total of 27 patients with ACA infarcts were registered (14 women and 13 men). The mean age of the patients was 68.5 (age range: 45-89 years). RESULTS: Bilateral ACA infarcts were reported in four patients (14.8%), right ACA infarct in 11 (40%) patients and left ACA infarct in 12 patients (44%). During the initial examination 15 patients (55.5%) were found to have apathy, 13 patients (48%) had incontinence, nine patients (33.3%) had primitive reflexes, 11 patients (40.7%) had aphasia, while six patients (22.2%) were found to suffer from neglect. At the end of one-year follow-up, five patients (22.7%) were reported to have apathy, 6 patients (27.2%) had incontinence, one patient (4.5%) had primitive reflexes, while one patient (4.5%) was found to have permanent aphasia, and no patients was found to suffer from neglect. CONCLUSION: Here we present our clinical data regarding the aetiology, specific clinical characteristics (including the speech disorders) and prognosis of 27 patients with ACA infarcts during a relatively longer follow-up period (3 months - 30 months) in compared to previous literature. We show that there are differences in the etiological factors of ACA infarcts between the Asian and European communities. Regarding speech disorders which are frequently reported during ACA infarcts, our study results are in agreement with other studies suggesting that this clinical picture is more than a real aphasia and associated with general hypokinesia and reduction in psychomotor activity.

Beyond The Therapeutic Effect of rTMS in Alzheimer's Disease: A Possible Neuroprotective Role of Hippocampal BDNF? : A Minireview.

Repetitive transcranial magnetic stimulation (rTMS) is a well known non-invasive brain stimulation procedure which is capable of inducing the expression of the hippocampal BDNF that has been already shown to exert significant neuroprotective and pro-cognitive effects in AD. However, it is nearly impossible directly to evaluate the BDNF expression in humans after rTMS application. Here we summarized the underlying mechanisms of the neuroprotective and procognitive effect of BDNF that can be induced through a region-specific rTMS approach. Additionally, we have also evaluated the role of Magnetic Resonance Spectroscopy in monitoring the BDNF response after rTMS application in Alzheimer's Disease. We have provided strong evidence that rTMS exerts significant neuroprotective and pro-cognitive effects through the expression of hippocampal BDNF. Furthermore, Magnetic Resonance Spectroscopy might play a critical role in monitoring the BDNF response after rTMS application in AD patients. Such a sophisticated approach might be able to enlighten us on the time-dependent cognitive and neuroprotective correlates of the rtMS application in AD patients.