TRANSCRANIAL DIRECT STIMULATION IN THE NEUROMODULATION OF CONTROLLING MAIN SYMPTOMS OF PARKINSON’S DISEASE: A CASE STUDY

Parkinson’s disease (PD) is a central nervous system neurodegenerative disorder that primarily affects the motor system, decreasing motor coordination, balance and generating tremors, and a progressive loss of everyday mobility, including walking. This study was conducted to verify the effects of Transcranial Direct Current Stimulation (tDCS) on balance, motor control, and the quality of life in Parkinson’s disease patients. The patient received three treatments consisting of 10 sessions of 20 minutes each and a one-week interval between treatments. Active stimulation was applied on the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the dorsolateral prefrontal cortex (D Sham-tDCS. DLPFC stimulation produced the best improvements in terms of motor control, balance, gait, and overall PD symptoms, as evaluated by different scales and questionnaires. As a result, active stimulation of the DLPFC produced superior outcomes and may contribute to treating Parkinson’s disease.

Alterations in pain processing circuitries in episodic migraine

Background The precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli. Methods Functional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity. Results Despite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons. Conclusions These data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.

Transcranial direct current stimulation (tDCS) to dorsolateral prefrontal cortex influences perceived pleasantness of food

The ability to regulate the intake of unhealthy foods is critical in modern, calorie dense food environments. Frontal areas of the brain, such as the dorsolateral prefrontal cortex (DLPFC), are thought to play a central role in cognitive control and emotional regulation. Therefore, increasing activity in the DLPFC may enhance these functions which could improve the ability to reappraise and resist consuming highly palatable but unhealthy foods. One technique for modifying brain activity is transcranial direct current stimulation (tDCS), a non-invasive technique for modulating neuronal excitability that can influence performance on a range of cognitive tasks. We tested whether tDCS targeting the DLPFC would influence how people perceived highly palatable foods. In the present study, 98 participants were randomly assigned to receive a single session of active tDCS or sham stimulation. While receiving active or sham stimulation, participants viewed images of highly palatable foods and reported how pleasant it would be to eat each food (liking) and how strong their urge was to eat each food (wanting). We found that participants who received active versus sham tDCS stimulation perceived food as less pleasant, but there was no difference in how strong their urge was to eat the foods. Our findings suggest that modulating excitability in the DLPFC influences “liking” but not “wanting” of highly palatable foods. Non-invasive brain stimulation might be a useful technique for influencing the hedonic experience of eating and might have implications for changing food consumption.

High-Frequency Repetitive Transcranial Magnetic Stimulation Over the Left Dorsolateral Prefrontal Cortex Shortly Alleviates Fatigue in Patients With Multiple System Atrophy: A Randomized Controlled Trial

Background: Fatigue is a common symptom in patients with Multiple system atrophy (MSA), but effective treatments remain elusive. The present study aims to investigate whether high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) could relieve fatigue in patients with MSA.Methods: This is a single-center, randomized and double-blind trial. Twenty-two patients with MSA and fatigue were randomly allocated to receive 10 sessions of either active (N = 11) or sham (N = 11) 10 Hz rTMS over the left DLPFC. The participants were assessed at baseline (T0), after the last session of treatment (T1), and at 2-week (T2), and 4-week (T3) follow-up timepoints. The primary outcomes were Fatigue Severity Scale-9 (FSS-9) scores, with Unified Multiple System Atrophy Rating Scale (UMSARS), 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) as secondary outcomes.Results: Two-way repeated ANOVAs revealed significant group × time interactions for FSS-9 scores (p < 0.001), HAMD-17 scores (p = 0.01), HAMA scores (p = 0.01), and UMRSA part II (p = 0.05). Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FSS-9 and UMRSA part II scores at T1 and T2, but not at T3, and also in HAMD-17 and HAMA scores at T1, T2, and T3. No significant improvement was found in the sham group.Conclusion: High-frequency rTMS over the left DLPFC could provide short-term improvements for alleviating fatigue in patients with MSA, but the beneficial effects last no more than 4 weeks.

Functional dissection of neural connectivity in generalized anxiety disorder

Differences in the correlated activity of networked brain regions have been reported in individuals with generalized anxiety disorder (GAD) but an overreliance on the null-hypothesis significance testing (NHST) framework limits the identification and characterization of disorder-relevant relationships. In this preregistered study, we applied a Bayesian statistical framework as well as NHST to the analysis of resting-state fMRI scans from females with GAD and demographically matched healthy comparison females. Eleven a-priori hypotheses about functional correlativity (FC) were evaluated using Bayesian (multilevel model) and frequentist (t-test) inference. Reduced FC between the ventromedial prefrontal cortex (vmPFC) and the posterior-mid insula (PMI) was confirmed by both statistical approaches. FC between the vmPFC-anterior insula, the amygdala-PMI, and the amygdala-dorsolateral prefrontal cortex (dlPFC) region pairs did not survive multiple comparison correction using the frequentist approach. However, the Bayesian model provided evidence for these region pairs having decreased FC in the GAD group. Leveraging Bayesian modeling, we demonstrate decreased FC of the vmPFC, insula, amygdala, and dlPFC in females with GAD. Exploiting the Bayesian framework revealed FC abnormalities between region pairs excluded by the frequentist analysis, as well as other previously undescribed regions, demonstrating the benefits of applying this statistical approach to resting state FC data.

Effects of transcranial alternating current stimulation over right-DLPFC on vigilance tasks depend on the arousal level

Current theoretical accounts on the oscillatory nature of sustained attention predict that entrainment via transcranial alternating current stimulation (tACS) at alpha and theta frequencies on specific areas of the prefrontal cortex could prevent the drops in vigilance across time-on-task. Nonetheless, most previous studies have neglected both the fact that vigilance comprises two dissociable components (i.e., arousal and executive vigilance) and the potential role of differences in arousal levels. We examined the effects of theta- and alpha-tACS over the right dorsolateral prefrontal cortex in both components of vigilance and in participants who differed in arousal level according to their chronotype and time of testing. Intermediate-types performed the vigilance tasks when their arousal level was optimal, whereas evening-types performed the vigilance tasks when their arousal levels were non-optimal. Both theta- and alpha-tACS improved arousal vigilance in the psychomotor vigilance task (PVT), whereas alpha-tACS, but not theta-tACS, improved executive vigilance in the sustained attention to response task (SART), and counteracted the typical vigilance decrement usually observed in this task. Importantly, these stimulation effects were only found when arousal was low (i.e., with evening-types performing the tasks at their non-optimal time of day). The results support the multicomponent view of vigilance, the relevance of heeding individual differences in arousal, and the role of alpha oscillations as a long-range cortical scale synchronization mechanism that compensates the decrements in performance as a function of time-on-task by exerting and maintaining cognitive control attributed to activation of the right dorsolateral prefrontal cortex.

Progressive Prefrontal Cortex Dysfunction in Parkinson's Disease With Probable REM Sleep Behavior Disorder: A 3-Year Longitudinal Study

This study aimed to explore the disrupted prefrontal cortex activity specific to patients with Parkinson's disease (PD) with rapid eye movement sleep behavior disorder (RBD) compared with those without and to further examine the associations between these alterations and neuropsychological measurements. Ninety-six patients with early PD underwent both structural and functional MRI, and also neuropsychological assessments in the Parkinson's Progression Markers Initiative (PPMI) database. Of these, 46 patients who completed 1- and 3-year fMRI follow-up examinations were categorized as PD with probable RBD (PD-pRBD+) and without (PD-pRBD−). The left dorsolateral prefrontal cortex (DLPFC) seed-to-voxel functional connectivity analysis was conducted to evaluate the progressive neural alterations specific to PD-pRBD+ compared with PD-pRBD− over time. Furthermore, relationships between these alterations and neuropsychological performance were examined. Compared with patients with PD-pRBD−, patients with PD-pRBD+ initially exhibited connectivity deficits between the left DLPFC and the medial frontopolar cortex. Moreover, these patients further exhibited disrupted DLPFC connectivity in the lateral frontopolar cortex at the 3-year follow-up evaluation. Correlation analysis revealed that connectivity between the left DLPFC and frontopolar cortex was positively related to executive function in PD-pRBD+ after adjusting for nuisance variables. Progressive prefrontal cortex dysfunction associated with RBD in early PD may provide an effective subtype-specific biomarker of neurodegenerative progression, which may shed light on the neuropathological mechanisms underlying the clinical heterogeneity of this disease.

Multiplexed and flexible neural coding in sensory, parietal, and frontal cortices during goal-directed virtual navigation

We do not understand how neural nodes operate within the recurrent action-perception loops that characterize naturalistic self-environment interactions, nor how brain networks reconfigure during changing computational demands. Here, we record local field potentials (LFPs) and spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and dorsolateral prefrontal cortex (dlPFC) as monkeys navigate in virtual reality to “catch fireflies”. This task requires animals to actively sample from a closed-loop visual environment while concurrently computing latent variables: the evolving distance and angle to a memorized firefly. We observed mixed selectivity in all areas, with even a traditionally sensory area (MSTd) tracking latent variables. Strikingly, global encoding profiles and unit-to-unit coupling suggested a functional subnetwork between MSTd and dlPFC, and not between these areas and 7a, as anatomy would suggest. When sensory evidence was rendered scarce, lateral connectivity through neuron-to-neuron coupling within MSTd strengthened but its pattern remained fixed, while neuronal coupling adaptively remapped within 7a and dlPFC. The larger the remapping in 7a/dlPFC and the greater the stability within MSTd, the less was behavior impacted by loss of sensory evidence. These results highlight the distributed nature of neural coding during closed-loop action-perception naturalistic behaviors and suggest internal models may be housed in the pattern of fine-grain lateral connectivity within parietal and frontal cortices.