Immediate effects of deep brain stimulation of anterior thalamic nuclei on executive functions and emotion–attention interaction in humans

Hartikainen, Kaisa M.; Sun, Lihua; Polvivaara, Markus; Brause, Maarja; Kai, Li; Haapasalo, Joonas; Möttönen, Timo; Väyrynen, Kirsi; Ogawa, Keith H.; Öhman, Juha; Peltola, Jukka

doi:10.1080/13803395.2014.913554

Cited by 67 publications

(64 citation statements)

References 46 publications

(58 reference statements)

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“…Better understanding of emotion–attention interaction in healthy individuals provides insights into its alterations in affective disorders, in attentional deficits, and in treatments that directly influence limbic and associative circuitries behind this interaction, such as deep brain stimulation 29. The current study points to the intricate interplay between emotion and attention with clinical relevance in treatment and rehabilitation of patients with emotion–attention dysfunction.…”

Section: Discussionmentioning

confidence: 71%

Low attentional engagement makes attention network activity susceptible to emotional interference

et al. 2014

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Section: Discussionmentioning

confidence: 71%

Low attentional engagement makes attention network activity susceptible to emotional interference

et al. 2014

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“…However, patients diagnosed with other forms of epilepsy who do not benefit sufficiently from medication may be eligible for (cerebellar) DBS 47. Currently, the options for applying DBS are limited; only the anterior thalamic nucleus is currently described in the US Food and Drug Administration guidelines to treat intractable epilepsy, and although promising, the outcome is limited and can result in cognitive and emotional problems 72, 73. Given the powerful impact of CN stimulation on thalamocortical activity that is shown in the present study, we hypothesize that CN stimulation may also exert very positive effects in these other, more severe kinds of epilepsies.…”

Section: Discussionmentioning

confidence: 99%

Cerebellar output controls generalized spike‐and‐wave discharge occurrence

Kros

Rooda

Spanke

et al. 2015

Annals of Neurology

119

138

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ObjectiveDisrupting thalamocortical activity patterns has proven to be a promising approach to stop generalized spike‐and‐wave discharges (GSWDs) characteristic of absence seizures. Here, we investigated to what extent modulation of neuronal firing in cerebellar nuclei (CN), which are anatomically in an advantageous position to disrupt cortical oscillations through their innervation of a wide variety of thalamic nuclei, is effective in controlling absence seizures.MethodsTwo unrelated mouse models of generalized absence seizures were used: the natural mutant tottering, which is characterized by a missense mutation in Cacna1a, and inbred C3H/HeOuJ. While simultaneously recording single CN neuron activity and electrocorticogram in awake animals, we investigated to what extent pharmacologically increased or decreased CN neuron activity could modulate GSWD occurrence as well as short‐lasting, on‐demand CN stimulation could disrupt epileptic seizures.ResultsWe found that a subset of CN neurons show phase‐locked oscillatory firing during GSWDs and that manipulating this activity modulates GSWD occurrence. Inhibiting CN neuron action potential firing by local application of the γ‐aminobutyric acid type A (GABA‐A) agonist muscimol increased GSWD occurrence up to 37‐fold, whereas increasing the frequency and regularity of CN neuron firing with the use of GABA‐A antagonist gabazine decimated its occurrence. A single short‐lasting (30–300 milliseconds) optogenetic stimulation of CN neuron activity abruptly stopped GSWDs, even when applied unilaterally. Using a closed‐loop system, GSWDs were detected and stopped within 500 milliseconds.InterpretationCN neurons are potent modulators of pathological oscillations in thalamocortical network activity during absence seizures, and their potential therapeutic benefit for controlling other types of generalized epilepsies should be evaluated. Ann Neurol 2015;77:1027–1049

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“…Due to the reports of cognitive difficulties after anterior thalamic stimulation for epilepsy control (Fisher et al, 2010; Hartikainen et al, 2014), we also evaluated the effects of chemogenetic silencing on cognitive function in our rats. We found that spontaneous alternation performance (as a measure of working memory (Dudchenko, 2004) was unimpaired by CNO treatment.…”

Section: Discussionmentioning

confidence: 99%

“…However, a limitation to thalamic DBS are the reports of cognitive side-effects in a subset of patients (Fisher et al, 2010; Hartikainen et al, 2014). DBS is also limited by issues such as current spread and activation of fibers of passage (Yousif and Liu, 2007).…”

Section: Introductionmentioning

confidence: 99%

Chemogenetic silencing of the midline and intralaminar thalamus blocks amygdala-kindled seizures

Wicker

Forcelli

2016

Experimental Neurology

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Temporal lobe epilepsy is the most common form of medically-intractable epilepsy. While seizures in TLE originate in structures such as hippocampus, amygdala, and temporal cortex, they propagate through a crucial relay: the midline/intralaminar thalamus. Prior studies have shown that pharmacological inhibition of midline thalamus attenuates limbic seizures. Here, we examined a recently developed technology, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), as a means of chemogenetic silencing to attenuate limbic seizures. Adult, male rats were electrically kindled from the amygdala, and injected with virus coding for inhibitory (hM4Di) DREADDs into the midline/intralaminar thalamus. When treated with the otherwise inert ligand Clozapine-N-Oxide (CNO) at doses of 2.5, 5, and 10 mg/kg, electrographic and behavioral seizure manifestations were suppressed in comparison to vehicle. At higher doses, we found complete blockade of seizure activity in a subset of subjects. CNO displayed a sharp time-response profile, with significant seizure attenuation seen 20-30 mins post injection, in comparison to 10 and 40 mins post injection. Seizures in animals injected with a control vector (i.e., no DREADD) were unaffected by CNO administration. These data underscore the crucial role of the midline/intralaminar thalamus in the propagation of seizures, specifically in the amygdala kindling model, and provide validation of chemogenetic silencing of limbic seizures.

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Immediate effects of deep brain stimulation of anterior thalamic nuclei on executive functions and emotion–attention interaction in humans

Cited by 67 publications

References 46 publications

Low attentional engagement makes attention network activity susceptible to emotional interference

Low attentional engagement makes attention network activity susceptible to emotional interference

Cerebellar output controls generalized spike‐and‐wave discharge occurrence

Chemogenetic silencing of the midline and intralaminar thalamus blocks amygdala-kindled seizures

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