The effect of one left-sided dorsolateral prefrontal sham-controlled HF-rTMS session on approach and withdrawal related emotional neuronal processes

Objective

Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotional changes in healthy volunteers, it remains largely unknown how rTMS is able to influence emotion.

Methods

In this sham-controlled, single-blind crossover study using fMRI, we examined in 20 right-handed healthy females whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces.

Results

While positive information was being processed, we observed after one active HF-rTMS session enhanced neuronal activity in the left superior frontal cortex and right inferior parietal cortex. After sham HF-rTMS, we found significant decreases in neuronal activity in the left superior frontal cortex, the left inferior prefrontal cortex, as well as in the right posterior cingulate gyrus. When negative information was processed, one active stimulation attenuated neuronal activity in the right insula only.

Conclusions

Our findings suggest that during the processing of positive information one active session enhanced the ability to empathize with the depicted emotional stimuli, while during the processing of negative information it resulted in decreased psychophysiological reactions.

Significance

These results provide new information on the working mechanism of left-sided HF-rTMS.     

Pathways to change in one-session exposure with and without cognitive intervention: an exploratory study in spider phobia

It is well established that exposure therapy is an effective treatment for anxiety disorders. It is less clear, however, which mechanisms are crucial in explaining its success. In previous studies, cognitive change has been identified as a mediating variable. Several theorists have argued that the addition of cognitive interventions will, therefore, result in enhanced treatment effects. We tested this hypothesis by examining cognitive mediation of treatment in a purely behavioral versus a cognitive–behavioral exposure format. Thirty-one spider phobics were randomly assigned to either behavioral exposure or to exposure as a test for maladaptive cognitions (i.e., behavioral experiments). Both treatment formats showed large treatment effects and strong cognitive mediation of these effects. This indicates that, even when cognitions are not explicitly targeted, exposure effects are cognitively mediated. This challenges the idea that cognitions have to be explicitly challenged to elicit cognitive change in exposure treatment.     

Magnetoencephalography in epilepsy patients carrying a vagus nerve stimulator

Due to technical constraints, magnetoencephalography (MEG) is challenging in vagus nerve stimulation (VNS) patients. This study evaluates (1) the feasibility of MEG in VNS patients and (2) the added value of MEG in their presurgical evaluation (PE). Ten VNS patients were studied by MEG using the spatiotemporal signal space separation (tSSS) method. Equivalent current dipoles (ECD) were classified "clustered"/"scattered". It was evaluated whether MEG (1) confirmed localisation of the hypothesized epileptogenic zone (HEZ), (2) improved delineation of the HEZ, or (3) identified 1 out of multiple HEZs. Finally it was evaluated whether adding MEG to the PE improved patient management by changing or supporting the hypothesis. In 7/10 patients, tSSS allowed to obtain interpretable MEG data, with interictal epileptiform discharges in 6/7. ECD clustered within 1 lobe in 4/6; confirming the localisation of the HEZ in 2/4 and improving delineation of the HEZ in 2/4. When ECD clustered within 2 lobes (1/6) or were scattered (1/6), MEG could not identify 1 out of multiple HEZs. In 2 patients, MEG changed management to invasive video-EEG monitoring (IVEM) and resective surgery (RS). In 4 patients, MEG further supported the management; IVEM in 2/4 and unsuitability for RS in 2/4. So far IVEM, performed in 2, resulted into RS. This study demonstrates the feasibility of MEG in VNS patients. MEG changed management in 20% and further supported the proposed management in 40% illustrating the clinical value of MEG in the PE of VNS patients.     

Antiepileptic drugs modulate P-glycoproteins in the brain: a mice study with (11)C-desmethylloperamide

P-glycoprotein transporters (P-gp) located at the blood-brain barrier (BBB) are likely to play a role in refractory epilepsy. In vitro studies already pointed out that several antiepileptic drugs (AEDs) are substrate of P-gp. This study proposes a new in vivo approach to investigate the interaction between some AEDs and P-gp located at the BBB. (11)C-desmethylloperamide ((11)C-dLop), a radiolabelled substrate of P-gp, was intravenously administrated after pretreatment with saline or AEDs (sodium valproate, levetiracetam, topiramate and phenytoin) at their human therapeutic and four times their therapeutic dose. The effect of the different pretreatment on the intracerebral concentration of (11)C-dLop was determined to indirectly investigate possible in vivo interactions between AEDs and P-gp. Pretreatment with levetiracetam, topiramate and phenytoin at therapeutic doses significantly decreased intracerebral concentration of (11)C-dLop. Pretreatment with a therapeutic dose of sodium valproate did not influence brain uptake of (11)C-dLop. In case of pretreatment with supratherapeutic doses of AED, (11)C-dLop brain uptake was not different compared to pretreatment with saline. The metabolisation rate of (11)C-dLop in plasma was unaltered, indicating that observed differences in brain uptake of the tracer were not due to pharmacokinetic changes. The following conclusion can be made: levetiracetam, topiramate and phenytoin demonstrate biphasic modulation of the BBB P-gp. At therapeutic doses they act as inducers of efflux, at supratherapeutic doses they have no effect on the efflux rate. Sodium valproate does not interact with P-gp at therapeutic nor at higher doses.     

The effects of high frequency rTMS on negative attentional bias are influenced by baseline state anxiety

High frequency (HF) repetitive Transcranial Magnetic Stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been shown to induce an attentional bias towards threatening information in healthy adults, associated with decreased activation in the right DLPFC and increased activation in the right amygdala. Additionally, it has been shown that healthy individuals with higher state anxiety portray similar negative attentional biases and cortico-subcortical activation patterns to those induced by HF-rTMS of the right DLPFC. Therefore, the aim of this study is to investigate whether inter-individual differences in state anxiety levels prior to the administration of HF-rTMS of the right DLPFC might be related to the degree to which rTMS induces such a negative attentional bias in healthy volunteers. We administered HF-rTMS of the right DLPFC to a group of 28 healthy female individuals. In line with previous research, a single session of HF-rTMS of the right DLPFC induced an attentional bias towards threatening information. Moreover, self-report measures of state anxiety (STAI-State) prior to stimulation correlated positively with the magnitude of the induced attentional bias. More specifically, we found that healthy individuals who scored higher on self-reports of state anxiety acquired more attentional bias towards negative information after HF-rTMS. Therefore, the effects of a single placebo-controlled rTMS session of the right DLPFC is consistent with the effects of a disrupted prefrontal-amygdala circuitry. The effects on attentional bias are largest in those participants reporting higher state anxiety scores, possibly because underlying amygdala activation is highest.     

Radiation of the rat brain suppresses seizure-induced neurogenesis and transiently enhances excitability during kindling acquisition

PURPOSE: Adult hippocampal neurogenesis is enhanced in several models for temporal lobe epilepsy (TLE). In this study, we used low-dose whole brain radiation to suppress hippocampal neurogenesis and then studied the effect of this treatment on epileptogenesis in a kindling model for TLE. METHODS: Half of the rats were exposed to a radiation dose of 8 Gy one day before the initiation of a rapid kindling protocol. Afterdischarge threshold (ADT), afterdischarge duration (ADD), clinical seizure severity, and inflammation were compared between groups. On the first and third day after radiation, rats were injected with 5'-bromo-2'-deoxyuridine (BrdU) to evaluate neurogenesis. Seven and 21 days after radiation, numbers of doublecortin (DCX) positive neuroblasts in subgranular zone and granule cell layer were compared between groups. RESULTS: We showed that radiation significantly suppressed neurogenesis and neuroblast production during kindling acquisition. Radiation prevented an increase in ADT that became significantly lower in radiated rats. On the third and fourth kindling acquisition day radiated rats developed more severe seizures more rapidly, which resulted in a significantly higher mean severity score on these days. Differences in ADD could not be demonstrated. DISCUSSION: Our results demonstrate that brain radiation with a relatively low dose effectively suppressed the generation of new granule cells and transiently enhanced excitability during kindling acquisition. Although seizure-induced neurogenesis was lower in the radiated rats we could not detect a strong effect on the final establishment of the permanent fully kindled state, which argues against a prominent role of seizure-induced neurogenesis in epileptogenesis.