Category Archives: understanding the brain

Cerebellar output controls generalized spike-and-wave discharge occurrence

Cerebellar output controls generalized spike-and-wave discharge occurrence.



Disrupting 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.


Two 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 (ECoG) in awake animals, we investigated to what extent pharmacologically increased or decreased CN neuron activity could modulate GSWD occurrence and short-lasting on-demand CN stimulation could disrupt epileptic seizures.


We found that a subset of CN neurons shows 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 GABAA -agonist muscimol increased GSWD occurrence up to 37-fold, whereas increasing the frequency and regularity of CN neuron firing with the use of gabazine decimated its occurrence. A single short-lasting (30-300 ms) 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 ms.


CN 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.

This article is protected by copyright. All rights reserved.

© 2015 American Neurological Association.

PMID: 25762286
[PubMed – as supplied by publisher]

Building a Bionic Nervous System

Electroceuticals Inside!

“It’s an electrifying time to be in neuroscience. Using implanted devices that send pulses of electricity through the nervous system, physicians are learning how to influence the neural systems that control people’s bodies and minds. These devices give neurologists new ways to treat patients with a wide range of disorders, including epilepsy, chronic pain, depression, and Parkinson’s disease. So far, these stimulators have been oneway devices that deliver a steady sequence of pulses to the nervous system but can’t react to changes in the patient’s body. Now, at last, medical device companies are coming out with dynamic neural stimulators that have a bit of “brain” themselves. These smart systems can detect changes in a physiological signal and then respond by delivering a therapy or adjusting the patient’s treatment in real time.”

Abstract of a paper by Tim Denison, Milton Morris and Felice Sun in IEEE Spectrum, Febr. 2015, DOI: 10.1109/MSPEC.2015.7024509.

Laagfrequente tinnitus

Foto en artwork: Marleen Serdijn

Foto en artwork: Marleen Serdijn

Vandaag ontving ik een email van een lezer van de Bioelectronics weblog, met daarin de vraag of neuromodulatie ook zin heeft in de behandeling van laagfrequente tinnitus, d.w.z., tinnitus die zich manifesteert als een gebrom of gezoem in plaats van een hoge (fluit-) toon.

Hieronder een deel van mijn reactie aan deze lezer, in de hoop dat het ook nuttig kan zijn voor andere mensen die lijden onder tinnitus.

Beste [afzender van de email],


Voor zover ik heb begrepen is tinnitus potentieel goed te behandelen indien het zijn oorsprong vindt in de gehoorschors en zich nog niet erg lang manifesteert (minder dan een paar jaren). [Prof.] Dirk de Ridder [verbonden aan het St. Augustinus Ziekenhuis in Antwerpen] en zijn team onderzoeken hoe ze de structurele verandering van de gehoorschors, bijv. ontstaan als gevolg van een gehoortrauma (bijvoorbeeld luid geluid), ongedaan kunnen maken door neuromodulatie, al of niet vergezeld van andere vormen van stimulatie. Of de tinnitus hoog- of laag-frequent is maakt volgens mij niet fundamenteel uit. Het kan wel betekenen dat de tinnitus een andere oorzaak heeft en dus anders “in de hersenen geprogrammeerd” en daarmee minder goed te behandelen is. Er is bijvoorbeeld een vaak voorkomende relatie tussen gehoorverlies en het optreden van tinnitus.

Als technisch wetenschapper probeer ik verbeterde technologie te ontwikkelen die de neurowetenschappers en neurochirurgen in staat stelt betere behandelingen te ontwikkelen, die minder invasief is en zich automatisch aanpast aan de therapeutische behoeften patient.

Ik hoop dat u iets aan het bovenstaande heeft.

Met vriendelijke groet,

Wouter Serdijn

Wouter A. Serdijn, PhD, F-IEEE, DL-IEEE Head Section Bioelectronics

Delft University of Technology Faculty of Electrical Engineering, M&CS Mekelweg 4, 2628 CD Delft The Netherlands Phone/Fax: +31-15-278-1715/5922 Email:

Quote from Michael Merzenich

While reading, correcting and enjoying the essay of Jose Manuel Rosas Escobar, I stumbled on a quote from Michael Merzenich, which I think you should read and comtemplate on.
So here goes…
“The success with any complicated prosthetic device relates as much to how the brain adjusts to it, accepts it and controls its use as it does to the device itself. If we can figure out how to engage the brain to do its part, it can make a merely adequate neural prosthetic device work marvelously.”


Does enriched acoustic environment in humans abolish chronic tinnitus clinically and electrophysiologically?

Animal research has shown that loss of normal acoustic stimulation can increase spontaneous firing in the central auditory system and induce cortical map plasticity. Enriched acoustic environment after noise trauma prevents map plasticity and abolishes neural signs of tinnitus. In humans, the tinnitus spectrum overlaps with the area of hearing loss. Based on these findings it can be hypothesized that stimulating the auditory system by presenting music compensating specifically for the hearing loss might also suppress chronic tinnitus. To verify this hypothesis, a study was conducted in three groups of tinnitus patients. One group listened just to unmodified music (i.e. active control group), one group listened to music spectrally tailored to compensate for their hearing loss, and a third group received music tailored to overcompensate for their hearing loss, associated with one (in presbycusis) or two notches (in audiometric dip) at the edge of hearing loss. Our data indicate that applying overcompensation to the hearing loss worsens the patients’ tinnitus loudness, the tinnitus annoyance and their depressive feelings.
No significant effects were obtained for the control group or for the compensation group. These clinical findings were associated with an increase in current density within the left dorsal anterior cingulate cortex in the alpha2 frequency band and within the left pregenual anterior cingulate cortex in beta1 and beta2 frequency band. In addition, a region of interest analysis also demonstrated an associated increase in gamma band activity in the auditory cortex after overcompensation in comparison to baseline measurements. This was, however, not the case for the control or the compensation groups. In conclusion, music therapy compensating for hearing loss is not beneficial in suppressing tinnitus, and overcompensating hearing loss actually worsens tinnitus, both clinically and electrophysiologically.

2012 Published by Elsevier B.V, in Hearing Research, Hear Res. 2012 Oct 23. pii: S0378-5955(12)00244-4. doi: 10.1016/j.heares.2012.10.003. Authors: Vanneste Svan Dongen MDe Vree BHiseni Svan der Velden EStrydis CKathleen JNorena ASerdijn WDe Ridder D

First implantation of a vestibular implant

Today it was reported in ‘De Volkskrant’ that doctors of Maastricht University Medical Center have succeeded in, for the first time ever, implanting an artificial balance organ, a vestibular implant, in two patients. A vestibular implant is more or less a cochlear implant that relays information on orientation and accelleration onto the hair cells in the vestibula, the small organ attached to the cochlea that assists in preserving balance. According to Prof. Robert Stokroos of UMCM, the first measurements after the surgery showed positive results. Very important, as far as I understand, will be whether the vestibular implant will allow for perfect integration of the balance information delivered by the implant and the balance perceived by the eyes.

Despite all this, I believe we have exciting times ahead for the application of novel neurostimulating devices.


Motivation 2.0

Today, it was announced in the news that the Netherlands is again facing, now for the third time, a case of severe fraud in science. A professor in Consumer Behavior at the Erasmus University Rotterdam has resigned from his duties and two of his articles will be withdrawn from the journals they were published in.

Mark my words. We’re not dealing with intrinsically bad people here and before you raise your fingers at the scapegoats, read this [taken from the Book ‘Drive’ by Daniel H. Pink]: "Goals may cause systematic problems for organizations due to narrowed focus, unethical behavior, increased risk taking, decreased cooperation and decreased intrinsic motivation. Use care when applying goals in your organization."

It makes me wonder to what extent the universities are falling into the pits they digged themselves.



Iris Sommer, Professor in psychiatry at the UMC Utrecht describes in a video at a schizophrenic man who told her about the terrible voices in his head. To figure out what happened in his brain during these hallucinations, she made several MRI (magnetic resonance imaging) scans. It turned out that in patients with hallucinations also the language areas in the right half of the brain become active. In healthy people usually only those areas in the left half of the brain are active.

She further explains that these areas and the voices in the head can be influenced in a variety of ways, e.g., by means of TMS, transcranial (through-the-skull) magnetic stimulation. Unfortunately, TMS is not always effective and psychiatrists are on the lookout for alternatives. 

I would say that this is another area where neurostimulation can come to the rescue. In the (often successful) treatment of tinnitus, patients are first exposed to TMS to check whether neurostimulation, in this case, electrical stimulation of the auditory cortex, can possibly be an effective treatment for them. Once indeed the level/severity of tinnitus can be influenced by TMS, neurostimulation becomes a logical next step for permanent treatment of the tinnitus.

Now it is just a matter of convincing the other voices in my head that this is indeed the right way…


Lecture “Chips voor het Brein” in Het Paard van Troje, Den Haag, March 14, 20:00 hrs

My best guess is that the following presentation will be in Dutch. 

Unfortunately, they forgot to invite us to participate in the presentation, as we are the only groep in the Netherlands that actually does research on Chips for the Brain.



Lezing door Nick Ramsey, UMCU
Paard van Troje
Prinsegracht 12
2512 GA Den Haag
Woensdag, 14 maart 2012, 20:00 uur
Grote Zaal
[Hieronderstaande tekst is afkomstig van:]

Op vertoon van je studentenpas is de toegang gratis.

Volledig verlamd en gezond van verstand, je hersenen zijn intact maar
je kunt niet communiceren. En niemand die je kan helpen.
Neurowetenschapper Nick Ramsey heeft een plan, hij werkt met zijn team
aan een miniatuur computer die direct met de hersenen in verbinding
staat. Hij wil die neuroprothese gaan implanteren bij verlamden zodat ze
kunnen twitteren, en apparaten kunnen aanzetten met alleen hun
gedachten. Tijdens de NIHC-publiekslezing geeft Ramsey de belofte van
hersenimplantaten prijs. Hij is er klaar voor, bent u dat ook?

Nick Ramsey is als hoogleraar cognitieve psychologie verbonden aan
het Rudolf Magnus Instituut en aan de afdeling neurochirurgie van het
Universitair Medisch Centrum Utrecht. Hij brengt de specifieke
hersenfuncties in kaart. In 2006 ontving hij voor zijn onderzoek een
prestigieuze ‘Vici-subsidie’ ter grootte van 1,25 miljoen Euro. Sinds
2009 is hij coördinator van de onderzoekspijler Gezondheid van het
NIHC-onderzoeksprogramma Hersenen en Cognitie: Maatschappelijke

Het Nationaal Initiatief Hersenen en
Cognitie (NIHC) is een regieorgaan waarbinnen onder anderen
taalwetenschappers, ICT-ers, psychiaters, neurologen, biologen,
psychologen en pedagogen samen wetenschappelijk onderzoek doen naar de
hersenen en hun invloed op menselijk gedrag en de maatschappij. Het NIHC
streeft naar excellent onderzoek voor een beter begrip van hersenen en
gedrag, maar ook naar toepassing van die onderzoeksresultaten binnen
concrete maatschappelijke vraagstukken. Het Nationaal Initiatief wordt
ondersteund en gecoördineerd door de Nederlandse Organisatie voor
Wetenschappelijk Onderzoek (NWO). Meer over NIHC op 

Future treatment of Neurological disorders: Neuromodulation through Deep Brain Stimulation

In recent years, neuromodulation has proved to be a feasible alternative in the treatment of the increasingly common neurological conditions. This essay describes deep brain stimulation as a treatment option for neurological disorders. First, a brief history of brain stimulation is presented followed by a description of the mechanisms of action and the surgical procedure. The current technology is not perfect and many of the complications which arise from deep brain stimulation are hardware related. These complications can be addressed by the further development of intelligent leads, new power generation methods and a less invasive technique.