A simulation study of transcranial magnetoacoustic stimulation of the basal ganglia thalamic neural network to improve pathological beta oscillations in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease. Transcranial magnetoacoustic stimulation (TMAS) is a new therapy that combines a transcranial focused acoustic pressure field with a magnetic field to excite or inhibit neurons in targeted area, which suppresses the abnormally elevated beta band amplitude in PD states, with high spatial resolution and non-invasively. OBJECTIVE: To study the effective stimulation parameters of TMAS mononuclear and multinuclear stimulation for the treatment of PD with reduced beta band energy, improved abnormal synchronization, and no thermal damage. METHODS: The TMAS model is constructed based on the volunteer's computed tomography, 128 arrays of phase-controlled transducers, and permanent magnets. A basal ganglia-thalamic (BG-Th) neural network model of the PD state was constructed on the basis of the Izhikevich model and the acoustic model. An ultrasound stimulation neuron model is constructed based on the Hodgkin-Huxley model. Numerical simulations of transcranial focused acoustic pressure field, temperature field and induced electric field at single and dual targets were performed using the locations of STN, GPi, and GPe in the human brain as the main stimulation target areas. And the acoustic and electric parameters at the focus were extracted to stimulate mononuclear and multinuclear in the BG-Th neural network. RESULTS: When the stimulating effect of ultrasound is ignored, TMAS-STN simultaneously inhibits the beta-band amplitude of the GPi nucleus, whereas TMAS-GPi fails to simultaneously have an inhibitory effect on the STN. TMAS-STN&GPi can reduce the beta band amplitude. TMAS-STN&GPi&GPe suppressed the PD pathologic beta band amplitude of each nucleus to a greater extent. When considering the stimulatory effect of ultrasound, lower sound pressures of ultrasound do not affect the neuronal firing state, but higher sound pressures may promote or inhibit the stimulatory effect of induced currents. CONCLUSIONS: At 9 T static magnetic field, 0.5-1.5 MPa and 1.5-2.0 MPa ultrasound had synergistic effects on individual STN and GPi neurons. TMAS multinuclear stimulation with appropriate ultrasound intensity was the most effective in suppressing the amplitude of pathological beta oscillations in PD and may be clinically useful.

Premotor cortical beta synchronization and the network neuromodulation of externally paced finger tapping in Parkinson's disease.

Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13-30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency-range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.

Local Field Potentials Predict Motor Performance in Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment option for patients with Parkinson's disease (PD). However, clinical programming remains challenging with segmented electrodes. OBJECTIVE: Using novel sensing-enabled neurostimulators, we investigated local field potentials (LFPs) and their modulation by DBS to assess whether electrophysiological biomarkers may facilitate clinical programming in chronically implanted patients. METHODS: Sixteen patients (31 hemispheres) with PD implanted with segmented electrodes in the subthalamic nucleus and a sensing-enabled neurostimulator were included in this study. Recordings were conducted 3 months after DBS surgery following overnight withdrawal of dopaminergic medication. LFPs were acquired while stimulation was turned OFF and during a monopolar review of both directional and ring contacts. Directional beta power and stimulation-induced beta power suppression were computed. Motor performance, as assessed by a pronation-supination task, clinical programming and electrode placement were correlated to directional beta power and stimulation-induced beta power suppression. RESULTS: Better motor performance was associated with stronger beta power suppression at higher stimulation amplitudes. Across directional contacts, differences in directional beta power and the extent of stimulation-induced beta power suppression predicted motor performance. However, within individual hemispheres, beta power suppression was superior to directional beta power in selecting the contact with the best motor performance. Contacts clinically activated for chronic stimulation were associated with stronger beta power suppression than non-activated contacts. CONCLUSIONS: Our results suggest that stimulation-induced ß power suppression is superior to directional ß power in selecting the clinically most effective contact. In sum, electrophysiological biomarkers may guide programming of directional DBS systems in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cortical network formation based on subthalamic beta bursts in Parkinson's disease.

Recent evidence suggests that beta bursts in subthalamic nucleus (STN) play an important role in Parkinsonian pathophysiology. We studied the spatio-temporal relationship between STN beta bursts and cortical activity in 26 Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Postoperatively, we simultaneously recorded STN local field potentials (LFP) from externalized DBS leads and cortical activity using whole-brain magnetoencephalography. Event-related magnetic fields (ERF) were averaged time-locked to STN beta bursts and subjected to source localization. Our results demonstrate that ERF exhibiting activity significantly different from baseline activity were localized within areas functionally related to associative, limbic, and motor systems as well as regions pertinent for visual and language processing. Our data suggest that STN beta bursts are involved in network formation between STN and cortex. This interaction is in line with the idea of parallel processing within the basal ganglia-cortex loop, specifically within the functional subsystems of the STN (i.e., associative, limbic, motor, and the related cortical areas). ERFs within visual and language-related cortical areas indicate involvement of beta bursts in STN-cortex networks beyond the associative, limbic, and motor loops. In sum, our results highlight the involvement of STN beta bursts in the formation of multiple STN - cortex loops in patients with PD.

VIP interneurons regulate olfactory bulb output and contribute to odor detection and discrimination.

In the olfactory bulb (OB), olfactory information represented by mitral/tufted cells (M/Ts) is extensively modulated by local inhibitory interneurons before being transmitted to the olfactory cortex. While the crucial roles of cortical vasoactive-intestinal-peptide-expressing (VIP) interneurons have been extensively studied, their precise function in the OB remains elusive. Here, we identify the synaptic connectivity of VIP interneurons onto mitral cells (MCs) and demonstrate their important role in olfactory behaviors. Optogenetic activation of VIP interneurons reduced both spontaneous and odor-evoked activity of M/Ts in awake mice. Whole-cell recordings revealed that VIP interneurons decrease MC firing through direct inhibitory synaptic connections with MCs. Furthermore, inactivation of VIP interneurons leads to increased MC firing and impaired olfactory detection and odor discrimination. Therefore, our results demonstrate that VIP interneurons control OB output and play critical roles in odor processing and olfactory behaviors.

Neurophysiological responses of globus pallidus internus during the auditory oddball task in Parkinson's disease.

Parkinson's disease can be associated with significant cognitive impairment that may lead to dementia. Deep brain stimulation (DBS) of the subthalamic nucleus is an effective therapy for motor symptoms but is associated with cognitive decline. DBS of globus pallidus internus (GPi) poses less risk of cognitive decline so may be the preferred target. A research priority is to identify biomarkers of cognitive decline in this population, but efforts are hampered by a lack of understanding of the role of the different basal ganglia nuclei, such as the globus pallidus, in cognitive processing. During deep brain stimulation (DBS) surgery, we monitored single units, beta oscillatory LFP activity as well as event related potentials (ERPs) from the globus pallidus internus (GPi) of 16 Parkinson's disease patients, while they performed an auditory attention task. We used an auditory oddball task, during which one standard tone is presented at regular intervals and a second deviant tone is presented with a low probability that the subject is requested to count and report at the end of the task. All forms of neuronal activity studied were selective modulated by the attended tones. Of 62 neurons studied, the majority (51 or 82%) responded selectively to the deviant tone. Beta oscillatory activity showed an overall desynchronization during both types of attended tones interspersed by bursts of beta activity giving rise to peaks at a latency of around 200 ms after tone onset. cognitive ERPs recorded in GPi were selective to the attended tone and the right-side cERP was larger than the left side. The averages of trials showing a difference in beta oscillatory activity between deviant and standard also had a significant difference in cERP amplitude. In one block of trials, the random occurrence of 3 deviant tones in short succession silenced the activity of the GPi neuron being recorded. Trial blocks where a clear difference in LFP beta was seen were twice as likely to yield a correct tone count (25 vs 11). The data demonstrate strong modulation of GPi neuronal activity during the auditory oddball task. Overall, this study demonstrates an involvement of GPi in processing of non-motor cognitive tasks such as working memory and attention, and suggests that direct effects of DBS in non-motor GPi may contribute to cognitive changes observed post-operatively.

Correlating Beta Oscillations from Intraoperative Microelectrode and Postoperative Implanted Electrode in Patients Undergoing Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease; A Feasibility Study.

OBJECTIVE: We sought to investigate the feasibility of intraoperative local field potential (LFP) recording from the microelectrode during deep brain stimulation surgery for patients with Parkinson disease. METHODS: Sixteen subthalamic nucleus recordings from 10 Parkinson disease patients who underwent deep brain stimulation surgery were included in this study. Signals from microelectrodes were amplified and differently filtered to display real-time single-unit neuronal activity and LFP simultaneously during surgery. LFP recordings were also recorded postoperatively from the implanted macroelectrodes and, power spectral density and peak frequency of beta oscillation of LFP (beta LFP) between 2 conditions were compared. RESULTS: Stable intraoperative beta LFP were observed in 68.75% (11 of 16) cases. There was no significant difference of peak frequency between intraoperative and postoperative beta-LFP but significant difference of mean percentage of beta LFP was noted between 2 conditions. CONCLUSIONS: Despite low signal-to-noise ratio and susceptibility to noises from external sources, this study shows that intraoperative recording of beta LFP using microelectrode is feasible. And, given that no significant difference in peak frequency of beta LFP between intraoperative and postoperative LFP was found, we suggest that not only intraoperative beta LFP can be used as a reliable surrogate for postoperative beta LFP, but it can also provide us an information for estimating the location with maximal power of beta oscillation within the subthalamic nucleus.

Threat imminence modulates neural gain in attention and motor relevant brain circuits in humans.

Different levels of threat imminence elicit distinct computational strategies reflecting how the organism interacts with its environment in order to guarantee survival. Thereby, parasympathetically driven orienting and inhibition of on-going behavior in post-encounter situations and defense reactions in circa-strike conditions associated with sympathetically driven action preparation are typically observed across species. Here, we show that healthy humans are characterized by markedly variable individual orienting or defense response tendencies as indexed by differential heart rate (HR) changes during the passive viewing of unpleasant pictures. Critically, these HR response tendencies predict neural gain modulations in cortical attention and preparatory motor circuits as measured by neuromagnetic steady-state visual evoked fields (ssVEFs) and induced beta-band (19-30 Hz) desynchronization, respectively. Decelerative HR orienting responses were associated with increased ssVEF power in the parietal cortex and reduced beta-band desynchronization in pre-motor and motor areas. However, accelerative HR defense response tendencies covaried with reduced ssVEF power in the parietal cortex and lower beta-band desynchronization in cortical motor circuits. These results show that neural gain in attention- and motor-relevant brain areas is modulated by HR indexed threat imminence during the passive viewing of unpleasant pictures. The observed mutual ssVEF and beta-band power modulations in attention and motor brain circuits support the idea of two prevalent response tendencies characterized by orienting and motor inhibition or reduced stimulus processing and action initiation tendencies at different perceived threat imminence levels.

Oscillatory and structural signatures of language plasticity in brain tumor patients: A longitudinal study.

Recent evidence suggests that damage to the language network triggers its functional reorganization. Yet, the spectro-temporal fingerprints of this plastic rearrangement and its relation to anatomical changes is less well understood. Here, we combined magnetoencephalographic recordings with a proxy measure of white matter to investigate oscillatory activity supporting language plasticity and its relation to structural reshaping. First, cortical dynamics were acquired in a group of healthy controls during object and action naming. Results showed segregated beta (13-28 Hz) power decreases in left ventral and dorsal pathways, in a time-window associated to lexico-semantic processing (~250-500 ms). Six patients with left tumors invading either ventral or dorsal regions performed the same naming task before and 3 months after surgery for tumor resection. When longitudinally comparing patients' responses we found beta compensation mimicking the category-based segregation showed by controls, with ventral and dorsal damage leading to selective compensation for object and action naming, respectively. At the structural level, all patients showed preoperative changes in white matter tracts possibly linked to plasticity triggered by tumor growth. Furthermore, in some patients, structural changes were also evident after surgery and showed associations with longitudinal changes in beta power lateralization toward the contralesional hemisphere. Overall, our findings support the existence of anatomo-functional dependencies in language reorganization and highlight the potential role of oscillatory markers in tracking longitudinal plasticity in brain tumor patients. By doing so, they provide valuable information for mapping preoperative and postoperative neural reshaping and plan surgical strategies to preserve language function and patient's quality of life.

Single unit and beta oscillatory activities in subthalamic nucleus are modulated during visual choice preference.

Parkinson's disease is a neurodegenerative disease affecting the supply of dopamine to basal ganglia nuclei, leading to pathological beta band (13-35 Hz) oscillations in the subthalamic nucleus (STN). STN and beta activity are recognized in motoric functions but their role in cognitive functions remains elusive. We examined single unit and beta local field potential (LFP) activity in the STN during a visual choice preference task in PD patients (n = 12) undergoing deep brain stimulation surgery. Patients viewed 2 of 5 possible animal picture-pairs and were instructed to choose their favorite ("fav") picture by clicking the left or right mouse key. A block of trials consisted of 50-75 picture-pair presentations. Single unit histograms and LFP spectrograms were aligned to picture presentation and point of decision for pairs that included the fav and non-fav pictures, respectively. A total of 58 neurons from 26 blocks of trials were analyzed. Thirty of 58 neurons showed a selective change in spiking activity 0.20-0.65 s to fav picture presentation, which preceded the shortest recorded reaction time (=0.7 s), and 17/58 neurons showed no significant response in our task. Beta LFP significantly desynchronized in response to fav but not non-fav pictures in all trials, and in 14/26 blocks of trials, the desynchronization was followed by a "beta burst" and ramp-up to baseline activity. Neurons with choice preference responses were found throughout the dorsoventral extent of the STN. STN single units and beta activity are modulated during visual choice preference, and this suggests a role for STN beta activity in cognitive processing.

Neuromodulation effects of deep brain stimulation on beta rhythm: A longitudinal local field potential study.

BACKGROUND: Deep brain stimulation (DBS) holds great promise in treating various brain diseases but its chronic therapeutic mechanisms are unclear. OBJECTIVE: To explore the immediate and chronic effects of DBS on brain oscillations, and understand how different sub-bands of oscillations may be related to symptom improvement in Parkinson's patients. METHODS: We carried out a longitudinal study to examine the effects of DBS on local field potentials recorded by sensing-enabled neurostimulators in the subthalamic nuclei of Parkinson's patients, using a novel block-design stimulation paradigm. RESULTS: DBS significantly suppressed beta activity (13-35Hz) but the suppression effect appeared to gradually attenuate during a 6-month follow-up period after surgery (p = 0.002). However, beta suppression did not attenuate after repeated stimulation over several minutes (p > 0.110), suggesting that the changes in beta suppression may reflect a slow reconfiguration of neural pathways instead of habituation. Suppression of beta was also associated with clinical symptom improvement across subjects. Importantly, symptom-relevant features fell within the high beta band at month 1 but shifted to the low beta band at month 6, indicating that the high beta and the low beta oscillations may play different functional roles and respond differently to stimulation over the long-term treatment. CONCLUSION: These data may advance understanding of chronic DBS effects on beta oscillations and their association with clinical improvement, offering novel insights to the therapeutic mechanisms of DBS.

Stress Assessment by Combining Neurophysiological Signals and Radio Communications of Air Traffic Controllers.

Air Traffic Control (ATC) has been classified as the fourth most stressful job. In this regard, sixteen controllers were asked to perform ecological ATC simulation during which behavioral (Radio Communications with pilots - RCs), subjective (stress perception) and neurophysiological signals (brain activity and skin conductance - SC) were collected. All the considered parameters reported significant changes under high stress conditions. In particular, the theta, alpha, and beta brain rhythms increased significantly (all p<0.05) all over the brain areas, and both the SC components exhibited higher values (p<0.01). Additionally, the number of speech under high stress decreased significantly (p<10-4) while both the mean and median value of the F0 component of the RC increased (p<0.01). The results can be employed to objectively measure and track the controller's stress level while dealing with ATC activities to better tailoring the workshift and maintaining high safety levels.

Parkinson's disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input in vivo.

Abnormally sustained beta-frequency synchronisation between the motor cortex and subthalamic nucleus (STN) is associated with motor symptoms in Parkinson's disease (PD). It is currently unclear whether STN neurons have a preference for beta-frequency input (12-35 Hz), rather than cortical input at other frequencies, and how such a preference would arise following dopamine depletion. To address this question, we combined analysis of cortical and STN recordings from awake human PD patients undergoing deep brain stimulation surgery with recordings of identified STN neurons in anaesthetised rats. In these patients, we demonstrate that a subset of putative STN neurons is strongly and selectively sensitive to magnitude fluctuations of cortical beta oscillations over time, linearly increasing their phase-locking strength with respect to the full range of instantaneous amplitude in the beta-frequency range. In rats, we probed the frequency response of STN neurons in the cortico-basal-ganglia-network more precisely, by recording spikes evoked by short bursts of cortical stimulation with variable frequency (4-40 Hz) and constant amplitude. In both healthy and dopamine-depleted rats, only beta-frequency stimulation led to a progressive reduction in the variability of spike timing through the stimulation train. This suggests, that the interval of beta-frequency input provides an optimal window for eliciting the next spike with high fidelity. We hypothesize, that abnormal activation of the indirect pathway, via dopamine depletion and/or cortical stimulation, could trigger an underlying sensitivity of the STN microcircuit to beta-frequency input.

Age-related trends in neuromagnetic transient beta burst characteristics during a sensorimotor task and rest in the Cam-CAN open-access dataset.

Non-invasive neurophysiological recordings, such as those measured by magnetoencelography (MEG), provide insight into the behaviour of neural networks and how these networks change with factors such as task performance, disease state, and age. Recently, there has been a trend in describing neurophysiological recordings as a series of transient bursts of neural activity rather than averaged sustained oscillations as burst characteristics may be more directly correlated with the neurological generators of brain activity. In this work, we investigate how beta burst characteristics change with age in a large open access dataset. The objectives are (1) to detect and characterize transient beta bursts over the ipsilateral and contralateral primary sensorimotor cortices during a unilateral motor task performance and during wakeful resting, and (2) to identify age-related changes in beta burst characteristics, in the context of earlier reports of age-related changes in beta suppression and the post-movement beta rebound. MEG data, acquired at the Cambridge Centre for Ageing and Neuroscience, of roughly 600 participants with a nearly uniform distribution of ages between 18 and 88 years old was used for analysis. We found that burst rate is the predominant factor related to age-related changes in the amplitude of the induced beta rhythm responses associated with a button press task. Furthermore, we present a cross-validation of burst parameters detected at the sensor- (peak sensor and sensor ROI) and source-level (beamformer spatial filter). This work is as an important step in characterizing transient bursts in neuromagnetic signals in the temporal domain, towards a better understanding of the healthy aging human brain.

Patients with fibromyalgia show increased beta connectivity across distant networks and microstates alterations in resting-state electroencephalogram.

Fibromyalgia (FM) is a chronic condition characterized by widespread pain of unknown etiology associated with alterations in the central nervous system. Although previous studies demonstrated altered patterns of brain activity during pain processing in patients with FM, alterations in spontaneous brain oscillations, in terms of functional connectivity or microstates, have been barely explored so far. Here we recorded the EEG from 43 patients with FM and 51 healthy controls during open-eyes resting-state. We analyzed the functional connectivity between different brain networks computing the phase lag index after group Independent Component Analysis, and also performed an EEG microstates analysis. Patients with FM showed increased beta band connectivity between different brain networks and alterations in some microstates parameters (specifically lower occurrence and coverage of microstate class C). We speculate that the observed alterations in spontaneous EEG may suggest the dominance of endogenous top-down influences; this could be related to limited processing of novel external events and the deterioration of flexible behavior and cognitive control frequently reported for FM. These findings provide the first evidence of alterations in long-distance phase connectivity and microstate indices at rest, and represent progress towards the understanding of the pathophysiology of fibromyalgia and the identification of novel biomarkers for its diagnosis.

Synchrony Drives Motor Cortex Beta Bursting, Waveform Dynamics, and Phase-Amplitude Coupling in Parkinson's Disease.

Several lines of inquiry have separately identified beta oscillations, synchrony, waveform shape, and phase-amplitude coupling as important but sometimes inconsistent factors in the pathophysiology of Parkinson's disease. What has so far been lacking is a means by which these neurophysiological parameters are interrelated and how they relate to clinical symptomatology. To clarify the relationship among oscillatory power, bursting, synchrony, and phase-amplitude coupling, we recorded local field potentials/electrocorticography from hand motor and premotor cortical area in human subjects with c (N = 10) and Parkinson's disease (N = 22) during deep brain stimulator implantation surgery (14 females, 18 males). We show that motor cortical high beta oscillations in Parkinson's disease demonstrate increased burst durations relative to essential tremor patients. Notably, increased corticocortical synchrony between primary motor and premotor cortices precedes motor high beta bursts, suggesting a possible causal relationship between corticocortical synchrony and localized increases in beta power. We further show that high beta bursts are associated with significant changes in waveform shape and that beta-encoded phase-amplitude coupling is more evident during periods of high beta bursting. These findings reveal a deeper structure to the pathologic changes identified in the neurophysiology of Parkinson's disease, suggesting mechanisms by which the treatment may be enhanced using targeted network synchrony disruption approaches.SIGNIFICANCE STATEMENT Understanding Parkinson's disease pathophysiology is crucial for optimizing symptom management. Present inconsistencies in the literature may be explained by temporal transients in neural signals driven by transient fluctuations in network synchrony. Synchrony may also act as a unifying phenomenon for the pathophysiological observations reported in Parkinson's disease. Here, simultaneous recordings from motor cortices show that increases in network beta synchrony anticipate episodes of beta bursting. We furthermore identify beta bursting as being associated with changes in waveform shape and increases in phase-amplitude coupling. Our results identify network synchrony as a driver of various pathophysiological observations reported in the literature and account for inconsistencies in the literature by virtue of the temporally variable nature of the phenomenon.

A controlled clinical crossover trial of exercise training to improve cognition and neural communication in pediatric brain tumor survivors.

OBJECTIVE: To assess the efficacy of aerobic exercise training to improve controlled attention, information processing speed and neural communication during increasing task load and rest in pediatric brain tumor survivors (PBTS) treated with cranial radiation. METHODS: Participants completed visual-motor Go and Go/No-Go tasks during magnetoencephalography recording prior to and following the completion of 12-weeks of exercise training. Exercise-related changes in response accuracy and visual-motor latency were evaluated with Linear Mixed models. The Phase Lag Index (PLI) was used to estimate functional connectivity during task performance and rest. Changes in PLI values after exercise training were assessed using Partial Least Squares analysis. RESULTS: Exercise training predicted sustained (12-weeks) improvement in response accuracy (p<0.05) during No-Go trials. Altered functional connectivity was detected in theta (4-7Hz) alpha (8-12Hz) and high gamma (60-100Hz) frequency bands (p<0.001) during Go and Go/No-Go trials. Significant changes in response latency and resting state connectivity were not detected. CONCLUSION: These findings support the efficacy of aerobic exercise to improve controlled attention and enhance functional mechanisms under increasing task load in participants. SIGNIFICANCE: It may be possible to harness the beneficial effects of exercise as therapy to promote cognitive recovery and enhance brain function in PBTS.

Valoración del cociente Theta/Beta en el electroencefalograma cuantificado de los trastornos por déficit de atención e hiperactividad / Measurement of the theta / beta ratio with the quantified electroencephalogram in attention-deficit hyperactivity disorders

El cociente Theta-Beta (T/B) del electroencefalograma cuantificado (EEGQ) de los pacientes con trastorno por déficit de atención e hiperactividad (TDAH) constituye una variable del EEG característica del trastorno primario con una precisión global del 89%. El objetivo de este estudio es medir el cociente T/B de una población de con TDAH y los efectos del tratamiento farmacológico con psicoestimulantes y no psicoestimulantes sobre el cociente T/B. La muestra estaba formada por 85 sujetos de entre 6 y los 18 años (68 niños y 17 niñas) con el diagnóstico de TDAH de subtipo inatento y combinado, según los criterios del DSM-V. Se les realizó un EEGQ con medición del cociente T/B antes y después de 6 meses de tratamiento con fármacos psicoestimulantes y no psicoestimulantes. Se compararon ambos grupos mediante la prueba de rangos con signo de Wilcoxon para muestras relacionadas. En el 86% de los casos el cociente T/B fue elevado respecto de los valores normales para la edad. La reducción en el cociente T/B fue significativa en el grupo tratado con psicoestimulantes aunque la reducción con los no psicoestimulantes no fue significativa. En conclusión, se confirma la elevación del cociente T/B en los pacientes con TDAH. Los fármacos psicoestimulantes disminuyen de forma significativa el cociente T/B elevado en los pacientes con TDAH tras 6 meses de tratamiento.

Theta-Beta (T / B) ratio of the quantified electroencephalogram (EEGQ) in patients with attention deficit hyperactivity disorder (ADHD) constitutes a characteristic EEG variable of the primary disorder with an overall accuracy of 89%. The objective of this study was to measure the T/B ratio in a sample of patients with ADHD and the effects of the treatment with psychostimulants and non-psychostimulants on the T/B ratio. The sample consisted of 85 children between 6 and 18 years (68 males and 17 females) with the diagnosis of the inattentive and combined subtype of ADHD, according to the criteria of the DSM-V. An EEGQ was performed with measurement of the T/B ratio before and after 6 months of treatment with psychostimulant and non-psychostimulant drugs. Both groups were compared using the Wilcoxon signed range test for related samples. The results showed that 86% of the cases had a T/B ratio above the normal values for the age of them. The reduction in the T/B ratio was statistically significant in the group of patients treated with psychostimulants. The reduction of non-psychostimulants was not significant. In conclusion, we confirmed the high T/B ratio in patients with ADHD. Psychostimulant drugs decrease the elevated T/B ratio in patients with ADHD after 6 months of treatment.

Sevoflurane and Parkinson's Disease: Subthalamic Nucleus Neuronal Activity and Clinical Outcome of Deep Brain Stimulation.

BACKGROUND: General anesthetics-induced changes of electrical oscillations in the basal ganglia may render the identification of the stimulation targets difficult. The authors hypothesized that while sevoflurane anesthesia entrains coherent lower frequency oscillations, it does not affect the identification of the subthalamic nucleus and clinical outcome. METHODS: A cohort of 19 patients with Parkinson's disease with comparable disability underwent placement of electrodes under either sevoflurane general anesthesia (n = 10) or local anesthesia (n = 9). Microelectrode recordings during targeting were compared for neuronal spiking characteristics and oscillatory dynamics. Clinical outcomes were compared at 5-yr follow-up. RESULTS: Under sevoflurane anesthesia, subbeta frequency oscillations predominated (general vs. local anesthesia, mean ± SD; delta: 13 ± 7.3% vs. 7.8 ± 4.8%; theta: 8.4 ± 4.1% vs. 3.9 ± 1.6%; alpha: 8.1 ± 4.1% vs. 4.8 ± 1.5%; all P < 0.001). In addition, distinct dorsolateral beta and ventromedial gamma oscillations were detected in the subthalamic nucleus solely in awake surgery (mean ± SD; dorsal vs. ventral beta band power: 20.5 ± 6.6% vs. 15.4 ± 4.3%; P < 0.001). Firing properties of subthalamic neurons did not show significant difference between groups. Clinical outcomes with regard to improvement in motor and psychiatric symptoms and adverse effects were comparable for both groups. Tract numbers of microelectrode recording, active contact coordinates, and stimulation parameters were also equivalent. CONCLUSIONS: Sevoflurane general anesthesia decreased beta-frequency oscillations by inducing coherent lower frequency oscillations, comparable to the pattern seen in the scalp electroencephalogram. Nevertheless, sevoflurane-induced changes in electrical activity patterns did not reduce electrode placement accuracy and clinical effect. These observations suggest that microelectrode-guided deep brain stimulation under sevoflurane anesthesia is a feasible clinical option.

The Cumulative Effect of Transient Synchrony States on Motor Performance in Parkinson's Disease.

Bursts of beta frequency band activity in the basal ganglia of patients with Parkinson's disease (PD) are associated with impaired motor performance. Here we test in human adults whether small variations in the timing of movement relative to beta bursts have a critical effect on movement velocity and whether the cumulative effects of multiple beta bursts, both locally and across networks, matter. We recorded local field potentials from the subthalamic nucleus (STN) in 15 PD patients of both genders OFF-medication, during temporary lead externalization after deep brain stimulation surgery. Beta bursts were defined as periods exceeding the 75th percentile amplitude threshold. Subjects performed a visual cued joystick reaching task, with the visual cue being triggered in real time with different temporal relationships to bursts of STN beta activity. The velocity of actions made in response to cues prospectively triggered by STN beta bursts was slower than when responses were not time-locked to recent beta bursts. Importantly, slow movements were those that followed multiple bursts close to each other within a trial. In contrast, small differences in the delay between the last burst and movement onset had no significant impact on velocity. Moreover, when the overlap of bursts between the two STN was high, slowing was more pronounced. Our findings suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, may impact on motor performance.SIGNIFICANCE STATEMENT Bursts of beta frequency band activity in the basal ganglia are associated with slowing of voluntary movement in patients with Parkinson's disease. We show that slow movements are those that follow multiple bursts close to each other and bursts that are coupled across regions. These results suggest that the cumulative, but recent, history of beta bursting, both locally and across basal ganglia networks, impacts on motor performance in this condition. The manipulation of burst dynamics may be a means of selectively improving motor impairment.