Beyond Emotions: Oscillations of the Amygdala and Their Implications for Electrical Neuromodulation

The amygdala is a structure involved in emotions, fear, learning and memory and is highly interconnected with other brain regions, for example the motor cortex and the basal ganglia that are often targets of treatments involving electrical stimulation. Deep brain stimulation of the basal ganglia is successfully used to treat movement disorders, but can carry along non-motor side effects. The origin of these non-motor side effects is not fully understood yet, but might be altered oscillatory communication between specific motor areas and the amygdala. Oscillations in various frequency bands have been detected in the amygdala during cognitive and emotional tasks, which can couple with oscillations in cortical regions or the hippocampus. However, data on oscillatory coupling between the amygdala and motor areas are still lacking. This review provides a summary of oscillation frequencies measured in the amygdala and their possible functional relevance in different species, followed by evidence for connectivity between the amygdala and motor areas, such as the basal ganglia and the motor cortex. We hypothesize that the amygdala could communicate with motor areas through coherence of low frequency bands in the theta-alpha range. Furthermore, we discuss a potential role of the amygdala in therapeutic approaches based on electrical stimulation

Longitudinal Recordings Reveal Transient Increase of Alpha/Low-Beta Power in the Subthalamic Nucleus Associated With the Onset of Parkinsonian Rest Tremor

Functional magnetic resonance imaging studies suggest that different subcortico-cortical circuits control different aspects of Parkinsonian rest tremor. The basal ganglia were proposed to drive tremor onset, and the cerebellum was suggested to be responsible for tremor maintenance (“dimmer-switch” hypothesis). Although several electrophysiological correlates of tremor have been described, it is currently unclear whether any of these is specific to tremor onset or maintenance. In this study, we present data from a single patient measured repeatedly within 2 years after implantation of a deep brain stimulation (DBS) system capable of recording brain activity from the target. Local field potentials (LFPs) from the subthalamic nucleus and the scalp electroencephalogram were recorded 1 week, 3 months, 6 months, 1 year, and 2 years after surgery. Importantly, the patient suffered from severe rest tremor of the lower limbs, which could be interrupted voluntarily by repositioning the feet. This provided the unique opportunity to record many tremor onsets in succession. We found that tremor onset and tremor maintenance were characterized by distinct modulations of subthalamic oscillations. Alpha/low-beta power increased transiently immediately after tremor onset. In contrast, beta power was continuously suppressed during tremor maintenance. Tremor maintenance was additionally associated with subthalamic and cortical power increases around individual tremor frequency. To our knowledge, this is the first evidence of distinct subthalamic LFP modulations in tremor onset and tremor maintenance. Our observations suggest the existence of an acceleration signal for Parkinsonian rest tremor in the basal ganglia, in line with the “dimmer-switch” hypothesis

A direct relationship between oscillatory subthalamic nucleus-cortex coupling and rest tremor in Parkinson's disease

Electrophysiological studies suggest that rest tremor in Parkinson's disease is associated with an alteration of oscillatory activity. Although it is well known that tremor depends on cortico-muscular coupling, it is unclear whether synchronization within and between brain areas is specifically related to the presence and severity of tremor. To tackle this longstanding issue, we took advantage of naturally occurring spontaneous tremor fluctuations and investigated cerebral synchronization in the presence and absence of rest tremor. We simultaneously recorded local field potentials from the subthalamic nucleus, the magnetoencephalogram and the electromyogram of forearm muscles in 11 patients with Parkinson's disease (all male, age: 52-74 years). Recordings took place the day after surgery for deep brain stimulation, after withdrawal of anti-parkinsonian medication. We selected epochs containing spontaneous rest tremor and tremor-free epochs, respectively, and compared power and coherence between subthalamic nucleus, cortex and muscle across conditions. Tremor-associated changes in cerebro-muscular coherence were localized by Dynamic Imaging of Coherent Sources. Subsequently, cortico-cortical coupling was analysed by computation of the imaginary part of coherency, a coupling measure insensitive to volume conduction. After tremor onset, local field potential power increased at individual tremor frequency and cortical power decreased in the beta band (13-30 Hz). Sensor level subthalamic nucleus-cortex, cortico-muscular and subthalamic nucleus-muscle coherence increased during tremor specifically at tremor frequency. The increase in subthalamic nucleus-cortex coherence correlated with the increase in electromyogram power. On the source level, we observed tremor-associated increases in cortico-muscular coherence in primary motor cortex, premotor cortex and posterior parietal cortex contralateral to the tremulous limb. Analysis of the imaginary part of coherency revealed tremor-dependent coupling between these cortical areas at tremor frequency and double tremor frequency. Our findings demonstrate a direct relationship between the synchronization of cerebral oscillations and tremor manifestation. Furthermore, they suggest the feasibility of tremor detection based on local field potentials and might thus become relevant for the design of closed-loop stimulation systems

A prospective pilot trial for pallidal deep brain stimulation in Huntington's Disease

BACKGROUND: Movement disorders in Huntington's disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial. METHODS: In a controlled double-blind phase six patients (four chorea-dominant, two Westphal-variant) with predominant movement disorder were randomly assigned to either the sequence of 6-week internal- or 6-week external-pallidal stimulation, or vice versa, followed by further 3 months chronic pallidal stimulation at the target with best effect-side-effect ratio. Primary endpoints were changes in the Unified Huntington's Disease Rating Scale motor-score, chorea subscore, and total motor-score 4 (blinded-video ratings), comparing internal- versus external-pallidal stimulation, and 6 months versus baseline. Secondary endpoints assessed scores on dystonia, hypokinesia, cognition, mood, functionality/disability, and quality-of-life. RESULTS: Intention-to-treat analysis of all patients (n = 3 in each treatment sequence): Both targets were equal in terms of efficacy. Chorea subscores decreased significantly over 6 months (-5.3 (60.2%), p = 0.037). Effects on dystonia were not significant over the group due to it consisting of three responders (>50% improvement) and three non-responders. Westphal patients did not improve. Cognition was stable. Mood and some functionality/disability and quality-of-life scores improved significantly. Eight adverse events and two additional serious adverse events - mostly internal-pallidal stimulation-related - resolved without sequalae. No procedure-related complications occurred. CONCLUSION: Pallidal deep brain stimulation was demonstrated to be a safe treatment option for the reduction of chorea in Huntington's disease. Their effects on chorea and dystonia and on quality-of-life should be examined in larger controlled trial

Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation

Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds

Non-epileptic seizures in autonomic dysfunction as the initial symptom of COVID-19

Objective!#!Vestibular evoked myogenic potentials (VEMPs) have been suggested as biomarkers in the differential diagnosis of Menière's disease (MD) and vestibular migraine (VM). The aim of this study was to compare the degree of asymmetry for ocular (o) and cervical (c) VEMPs in large cohorts of patients with MD and VM and to follow up the responses.!##!Study design!#!Retrospective study in an interdisciplinary tertiary center for vertigo and balance disorders.!##!Methods!#!cVEMPs to air-conducted sound and oVEMPs to bone-conducted vibration were recorded in 100 patients with VM and unilateral MD, respectively. Outcome parameters were asymmetry ratios (ARs) of oVEMP n10p15 and cVEMP p13n23 amplitudes, and of the respective latencies (mean ± SD).!##!Results!#!The AR of cVEMP p13n23 amplitudes was significantly higher for MD (0.43 ± 0.34) than for VM (0.26 ± 0.24; adjusted p = 0.0002). MD-but not VM-patients displayed a higher AR for cVEMP than for oVEMP amplitudes (MD 0.43 ± 0.34 versus 0.23 ± 0.22, p < 0.0001; VM 0.26 ± 0.14 versus 0.19 ± 0.15, p = 0.11). Monitoring of VEMPs in single patients indicated stable or fluctuating amplitude ARs in VM, while ARs in MD appeared to increase or remain stable over time. No differences were observed for latency ARs between MD and VM.!##!Conclusions!#!These results are in line with (1) a more common saccular than utricular dysfunction in MD and (2) a more permanent loss of otolith function in MD versus VM. The different patterns of o- and cVEMP responses, in particular their longitudinal assessment, might add to the differential diagnosis between MD and VM