Oscillatory activity in the basal ganglia and deep brain stimulation

Professor Peter Brown is Professor of Experimental Neurology and Director of the Medical Research Council Brain Network Dynamics Unit at the University of Oxford. Prior to 2010 he was a Professor of Neurology at University College London.For decades we have had cardiac pacemakers that adjust their pacing according to demand and yet therapeutic adaptive stimulation approaches for the central nervous system are still not clinically available. Instead, to treat patients with advanced Parkinson’s disease we stimulate the basal ganglia with fixed regimes, unvarying in frequency or intensity. Although effective, this comes with side-effects and in terms of sophistication this treatment approach could be compared to having central heating system on all the time, regardless of temperature. This talk will describe recent steps being taken to define the underlying circuit dysfunction in Parkinson’s and to improve deep brain stimulation by controlling its delivery according to the state of pathological activity.Evidence is growing that motor symptoms in Parkinson’s disease are due, at least in part, to excessive synchronisation between oscillating neurons. Recordings confirm bursts of oscillatory synchronisation in the basal ganglia centred around 20 Hz. The bursts of 20 Hz activity are prolonged in patients withdrawn from their usual medication and the dominance of these long duration bursts negatively correlates with motor impairment. Longer bursts attain higher amplitudes, indicative of more pervasive oscillatory synchronisation within the neural circuit. In contrast, in heathy primates and in treated Parkinson’s disease bursts tend to be short. Accordingly, it might be best to use closed-loop controlled deep brain stimulation to selectively terminate longer, bigger, pathological beta bursts to both save power and to spare the ability of underlying neural circuits to engage in more physiological processing between long bursts. It is now possible to record and characterise bursts on-line during stimulation of the same site and trial adaptive stimulation. Thus far, this has demonstrated improvements in efficiency and side-effects over conventional continuous stimulation, with at least as good symptom control in Parkinsonian patients.

Download Full-text

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia

IEEE Transactions on Neural Systems and Rehabilitation Engineering ◽

10.1109/tnsre.2017.2712418 ◽

2017 ◽

Vol 25 (11) ◽

pp. 2188-2195 ◽

Cited By ~ 12

Author(s):

Shivakeshavan Ratnadurai-Giridharan ◽

Chung C. Cheung ◽

Leonid L. Rubchinsky

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Brain Stimulation ◽

Oscillatory Activity ◽

Deep Brain

Download Full-text

Effects of high-frequency stimulation of the internal pallidal segment on neuronal activity in the thalamus in parkinsonian monkeys

Journal of Neurophysiology ◽

10.1152/jn.00104.2016 ◽

2016 ◽

Vol 116 (6) ◽

pp. 2869-2881 ◽

Cited By ~ 15

Author(s):

Stefan Kammermeier ◽

Damien Pittard ◽

Ikuma Hamada ◽

Thomas Wichmann

Keyword(s):

Electrical Stimulation ◽

Deep Brain Stimulation ◽

Basal Ganglia ◽

Brain Stimulation ◽

Oscillatory Activity ◽

Internal Globus Pallidus ◽

Ventral Thalamus ◽

Deep Brain ◽

Stimulation Of ◽

Spiking Activity

Deep brain stimulation of the internal globus pallidus (GPi) is a major treatment for advanced Parkinson's disease. The effects of this intervention on electrical activity patterns in targets of GPi output, specifically in the thalamus, are poorly understood. The experiments described here examined these effects using electrophysiological recordings in two Rhesus monkeys rendered moderately parkinsonian through treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after sampling control data in the same animals. Analysis of spontaneous spiking activity of neurons in the basal ganglia-receiving areas of the ventral thalamus showed that MPTP-induced parkinsonism is associated with a reduction of firing rates of segments of the data that contained neither bursts nor decelerations, and with increased burst firing. Spectral analyses revealed an increase of power in the 3- to 13-Hz band and a reduction in the γ-range in the spiking activity of these neurons. Electrical stimulation of the ventrolateral motor territory of GPi with macroelectrodes, mimicking deep brain stimulation in parkinsonian patients (bipolar electrodes, 0.5 mm intercontact distance, biphasic stimuli, 120 Hz, 100 μs/phase, 200 μA), had antiparkinsonian effects. The stimulation markedly reduced oscillations in thalamic firing in the 13- to 30-Hz range and uncoupled the spiking activity of recorded neurons from simultaneously recorded local field potential (LFP) activity. These results confirm that oscillatory and nonoscillatory characteristics of spontaneous activity in the basal ganglia receiving ventral thalamus are altered in MPTP-induced parkinsonism. Electrical stimulation of GPi did not entrain thalamic activity but changed oscillatory activity in the ventral thalamus and altered the relationship between spikes and simultaneously recorded LFPs.

Download Full-text

Patterned low-frequency deep brain stimulation induces motor deficits and modulates cortex-basal ganglia neural activity in healthy rats

Journal of Neurophysiology ◽

10.1152/jn.00929.2017 ◽

2018 ◽

Vol 120 (5) ◽

pp. 2410-2422 ◽

Cited By ~ 5

Author(s):

Chintan S. Oza ◽

David T. Brocker ◽

Christina E. Behrend ◽

Warren M. Grill

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Brain Stimulation ◽

Movement Disorders ◽

Neural Activity ◽

Low Frequency ◽

Oscillatory Activity ◽

Motor Deficits ◽

Motor Symptoms ◽

Deep Brain

Deep brain stimulation (DBS) is an effective therapy for movement disorders, including Parkinson’s disease (PD), although the mechanisms of action remain unclear. Abnormal oscillatory neural activity is correlated with motor symptoms, and pharmacological or DBS treatment that alleviates motor symptoms appears to suppress abnormal oscillations. However, whether such oscillatory activity is causal of motor deficits such as tremor remains unclear. Our goal was to generate abnormal oscillatory activity in the cortex-basal ganglia loop using patterned subthalamic nucleus DBS and to quantify motor behavior in awake healthy rats. Stimulation patterns were designed via model-based optimization to increase power in the low-frequency (7–11 Hz) band because these oscillations are associated with the emergence of motor symptoms in the 6-hydroxydopamine lesioned rat model of parkinsonism. We measured motor activity using a head-mounted accelerometer, as well as quantified neural activity in cortex and globus pallidus (GP), in response to 5 stimulation patterns that generated a range of 7- to 11-Hz spectral power. Stimulation patterns induced oscillatory activity in the low-frequency band in the cortex and GP and caused tremor, whereas control patterns and regular 50-Hz DBS did not generate any such effects. Neural and motor-evoked responses observed during stimulation were synchronous and time-locked to stimulation bursts within the patterns. These results identified elements of irregular patterns of stimulation that were correlated with tremor and tremor-related neural activity in the cortex and basal ganglia and may lead to the identification of the oscillatory activity and structures associated with the generation of tremor activity. NEW & NOTEWORTHY Subthalamic nucleus deep brain stimulation is a promising therapy for movement disorders such as Parkinson’s disease. Several groups reported correlation between suppression of abnormal oscillatory activity in the cortex-basal ganglia and motor symptoms, but it remains unclear whether such oscillations play a causal role in the emergence of motor symptoms. We demonstrate generation of tremor and pathological oscillatory activity in otherwise healthy rats by stimulation with patterns that produced increases in low-frequency oscillatory activity.

Download Full-text

Thalamic oscillatory activity may predict response to deep brain stimulation of the anterior nuclei of the thalamus

Epilepsia ◽

10.1111/epi.16883 ◽

2021 ◽

Author(s):

Barbora Deutschová ◽

Petr Klimeš ◽

Zsofia Jordan ◽

Pavel Jurák ◽

Lorand Erőss ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Oscillatory Activity ◽

Deep Brain ◽

Stimulation Of

Download Full-text

Effects of repetitive transcranial magnetic and deep brain stimulation on long‐range synchrony of oscillatory activity in a rat model of developmental schizophrenia

European Journal of Neuroscience ◽

10.1111/ejn.15125 ◽

2021 ◽

Author(s):

Benjamin Lippmann ◽

Gleb Barmashenko ◽

Klaus Funke

Keyword(s):

Deep Brain Stimulation ◽

Long Range ◽

Brain Stimulation ◽

Rat Model ◽

Oscillatory Activity ◽

Deep Brain

Download Full-text

Deep brain stimulation of the subthalamic nucleus reestablishes neuronal information transmission in the 6-OHDA rat model of parkinsonism

Journal of Neurophysiology ◽

10.1152/jn.00713.2013 ◽

2014 ◽

Vol 111 (10) ◽

pp. 1949-1959 ◽

Cited By ~ 29

Author(s):

Alan D. Dorval ◽

Warren M. Grill

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Information Transmission ◽

Brain Stimulation ◽

Rat Model ◽

Information Transfer ◽

Firing Pattern ◽

Signal Propagation ◽

Neuronal Firing ◽

Deep Brain

Pathophysiological activity of basal ganglia neurons accompanies the motor symptoms of Parkinson's disease. High-frequency (>90 Hz) deep brain stimulation (DBS) reduces parkinsonian symptoms, but the mechanisms remain unclear. We hypothesize that parkinsonism-associated electrophysiological changes constitute an increase in neuronal firing pattern disorder and a concomitant decrease in information transmission through the ventral basal ganglia, and that effective DBS alleviates symptoms by decreasing neuronal disorder while simultaneously increasing information transfer through the same regions. We tested these hypotheses in the freely behaving, 6-hydroxydopamine-lesioned rat model of hemiparkinsonism. Following the onset of parkinsonism, mean neuronal firing rates were unchanged, despite a significant increase in firing pattern disorder (i.e., neuronal entropy), in both the globus pallidus and substantia nigra pars reticulata. This increase in neuronal entropy was reversed by symptom-alleviating DBS. Whereas increases in signal entropy are most commonly indicative of similar increases in information transmission, directed information through both regions was substantially reduced (>70%) following the onset of parkinsonism. Again, this decrease in information transmission was partially reversed by DBS. Together, these results suggest that the parkinsonian basal ganglia are rife with entropic activity and incapable of functional information transmission. Furthermore, they indicate that symptom-alleviating DBS works by lowering the entropic noise floor, enabling more information-rich signal propagation. In this view, the symptoms of parkinsonism may be more a default mode, normally overridden by healthy basal ganglia information. When that information is abolished by parkinsonian pathophysiology, hypokinetic symptoms emerge.

Download Full-text