Functional MRI during hippocampal deep brain stimulation in the healthy rat brain

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS

EEG source connectivity to localize the seizure onset zone in patients with drug resistant epilepsy

Visual inspection of the EEG to determine the seizure onset zone (SOZ) in the context of the presurgical evaluation in epilepsy is time-consuming and often challenging or impossible. We offer an approach that uses EEG source imaging (ESI) in combination with functional connectivity analysis (FC) to localize the SOZ from ictal EEG. Ictal low-density-scalp EEG from 111 seizures in 27 patients who were rendered-seizure free after surgery was analyzed. For every seizure, ESI (LORETA) was applied on an artifact-free epoch selected around the seizure onset. Additionally, FC was applied on the reconstructed sources. We estimated the SOZ in two ways: (i)the source with highest power after ESI and (ii)the source with the most outgoing connections after ESI and FC. For both approaches, the distance between the estimated SOZ and the resected zone (RZ) of the patient were calculated. Using ESI alone, the SOZ was estimated inside the RZ in 31% of the seizures and within 10mm from the border of the RZ in 42%. For 18.5% of the patients, all seizures were estimated within 10mm of the RZ. Using ESI and FC, 72% of the seizures were estimated inside the RZ, and 94% within 10mm. For 85% of the patients, all seizures were estimated within 10mm of the RZ. FC provided a significant added value to ESI alone (p<0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy

Multiple-look effects on temporal discrimination within sound sequences

The multiple-look notion holds that the difference limen (DL) decreases with multiple observations. We investigated this notion for temporal discrimination in isochronous sound sequences. In Experiment 1, we established a multiple-look effect when sequences comprised nine standard time intervals (S) followed by an increasing number of comparison time intervals (C), but no multiple-look effect when one trailing C interval was preceded by an increasing number of S intervals. In Experiment 2, we extended the design. There were four sequential conditions: (a) 9 leading S intervals followed by 1, 2, …, or 9 C-intervals; (b) 9 leading C intervals followed by 1, 2, …, or 9 S intervals; (c) 9 trailing C-intervals preceded by 1, 2, …, or 9 S-intervals; and (d) 9 trailing S-intervals preceded by 1, 2, …, or 9 C-intervals. Both the interval accretions before and after the tempo change caused multiple-look effects, irrespective of the time order of S and C. Complete deconfounding of the number of intervals before and after the tempo change was accomplished in Experiment 3. The multiple-look effect of interval accretion before the tempo change was twice as big as that after the tempo change. The diminishing returns relation between the DL and interval accretion could be described well by a reciprocal function

The impact of patient advocacy: the case of innovative breast cancer drug reimbursement

Current research into patient advocacy focuses on attempts of patient groups to mobilise resources and to influence researchers, pharmaceutical companies and policy-makers. This paper adopts a ‘framing political opportunities’ approach to draw attention to other kinds of advocacy strategies. In a case study of breast cancer patient advocacy of Herceptin reimbursement, it is shown how patient groups tried to gain access to policy-making by means of three different opportunity-framing strategies. Articulation aims at creating awareness through public-agenda building. Negotiation aims at frame alignment between interdependent stakeholders by arranging meetings. Politicisation is a strategy to influence the agendas of political arenas. Patient organisations succeeded in creating awareness and support, which had a considerable impact on other stakeholders. These impacts in turn aided the politicisation of the issue. However, the final impact on reimbursement procedures was only partially achieved due to depoliticising counterstrategies based on persistent ideas buttressing a particular division of responsibilities in the organisation of healthcare. According to these ideas cost control in healthcare is a medical responsibility, not a political one

The impact of patient advocacy: the case of innovative breast cancer drug reimbursement

Abstract Current research into patient advocacy focuses on attempts of patient groups to mobilise resources and to influence researchers, pharmaceutical companies and policy-makers. This paper adopts a &apos;framing political opportunities&apos; approach to draw attention to other kinds of advocacy strategies. In a case study of breast cancer patient advocacy of Herceptin reimbursement, it is shown how patient groups tried to gain access to policy-making by means of three different opportunity-framing strategies. Articulation aims at creating awareness through public-agenda building. Negotiation aims at frame alignment between interdependent stakeholders by arranging meetings. Politicisation is a strategy to influence the agendas of political arenas. Patient organisations succeeded in creating awareness and support, which had a considerable impact on other stakeholders. These impacts in turn aided the politicisation of the issue. However, the final impact on reimbursement procedures was only partially achieved due to depoliticising counterstrategies based on persistent ideas buttressing a particular division of responsibilities in the organisation of healthcare. According to these ideas cost control in healthcare is a medical responsibility, not a political one