Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI

Abstract

The substantia nigra pars reticulata (SNr) and external globus pallidus (GPe) constitute the two major output targets of the rodent striatum. Both the SNr and GPe converge upon thalamic relay nuclei (directly or indirectly, respectively), and are traditionally modeled as functionally antagonistic relay inputs. However, recent anatomical and functional studies have identified unanticipated circuit connectivity in both the SNr and GPe, demonstrating their potential as far more than relay nuclei. In the present study, we employed simultaneous deep brain stimulation and functional magnetic resonance imaging (DBS-fMRI) with cerebral blood volume (CBV) measurements to functionally and unbiasedly map the circuit- and network level connectivity of the SNr and GPe. Sprague-Dawley rats were implanted with a custom-made MR-compatible stimulating electrode in the right SNr (n = 6) or GPe (n = 7). SNr- and GPe-DBS, conducted across a wide range of stimulation frequencies, revealed a number of surprising evoked responses, including unexpected CBV decreases within the striatum during DBS at either target, as well as GPe-DBS-evoked positive modulation of frontal cortex. Functional connectivity MRI revealed global modulation of neural networks during DBS at either target, sensitive to stimulation frequency and readily reversed following cessation of stimulation. This work thus contributes to a growing literature demonstrating extensive and unanticipated functional connectivity among basal ganglia nuclei.

Monitoring deep brain stimulation by measuring regional brain oxygen responses in freely moving mice

“…Although average results suggested a small increase, no significant short-term (up to 9 min; Fig.6a) or long-term (up to 60 min; Fig.6b) effects were observed of turning on the stimulation. This is in apparent contrast to our previous results with cFos and also to a number of previously reported increases in BOLD or CBV responses in brain areas distant from various DBS (Albough et al, 2016;Chao et al, 2014;Lai et al, 2013;Van Den Berge et al, 2017;Young et al, 2011). However, we must…”

Full activation pattern mapping by simultaneous deep brain stimulation and fMRI with graphene fiber electrodes

“…The BOLD signal time courses were calculated for each ROI. One-way repeated measures ANOVA tests with Tukey post hoc analysis were conducted to evaluate frequency-dependent responses 10 . Significance level was set at *p < 0.05; **p < 0.01; ***p < 0.001.…”

“…Functional magnetic resonance imaging (fMRI) represents a powerful tool for mapping brain activity on a whole-brain scale. Simultaneous DBS and fMRI (DBS-fMRI) thus could provide us with valuable insights into brain function and connectivity patterns, as well as modulatory effects and therapeutic mechanisms of functional electrical stimulation in various neurological disorders [8][9][10] .…”

“…A close examination of the signal time traces revealed a clear "double peak" feature of the BOLD signal in certain regions, including the motor cortex, somatosensory cortex, cingulate cortex, and STN ( Fig. 5), possibly due to the involvement of two different circuitries or a delayed neurotransmission effect 10 . It is worth noting that, for 10 Hz STN-DBS, the three cortex and caudate putamen regions first produced a small negative BOLD signal followed by a positive BOLD response during the stimulation epoch, a feature that is distinct from other regions and other frequencies.…”

Functional networks and network perturbations in rodents

“…Rodent models provide a good way to elucidate the mechanisms involved and to optimize the stimulation target and paradigm. Using deep brain stimulation, it has been shown that high frequency (130Hz) stimulation in the external globus pallidus, substantia nigra or nucleus accumbens can transiently modulate brain-wide FC, particularly in downstream regions not directly activated by the stimulation (Albaugh et al, 2016;Van Den Berge et al, 2017). This indicates that high frequency neural oscillation could alter RSNs and the potential roles of those subcortical nuclei in shaping RSN activity.…”