Ultrasonic thalamic stimulation modulates neural activity of thalamus and motor cortex in the mouse

Objective. Previous studies have demonstrated that ultrasound thalamic stimulation (UTS) can treat disorders of consciousness. However, it is still unclear how UTS modulates neural activity in the thalamus and cortex. Approach. In this study, we performed UTS in mice and recorded the neural activities including spike and local field potential (LFP) of the thalamus and motor cortex. We analyzed the firing rate of spikes and the power spectrum of LFPs and evaluated the coupling relationship between LFPs from the thalamus and motor cortex with Granger causality. Main results. Our results clearly indicate that UTS can directly induce neural activity in the thalamus and indirectly induce neural activity in the motor cortex. We also found that there is a strong connection relationship of neural activity between thalamus and motor cortex under UTS. Significance. These results demonstrate that UTS can modulate the neural activity of the thalamus and motor cortex in mice. It has the potential to provide guidance for the ultrasound treatment of thalamus-related diseases.

Similarities Between Somatosensory Cortical Responses Induced via Natural Touch and Microstimulation in the Ventral Posterior Lateral Thalamus in Macaques

Lost sensations, such as touch, could be restored by microstimulation (MiSt) along the sensory neural substrate. Such neuroprosthetic sensory information can be used as feedback from an invasive brain-machine interface (BMI) to control a robotic arm/hand, such that tactile and proprioceptive feedback from the sensorized robotic arm/hand is directly given to the BMI user. Microstimulation in the human somatosensory thalamus (Vc) has been shown to produce somatosensory perceptions. However, until recently, systematic methods for using thalamic stimulation to evoke naturalistic touch perceptions were lacking. We have recently presented rigorous methods for determining a mapping between ventral posterior lateral thalamus (VPL) MiSt, and neural responses in the somatosensory cortex (S1), in a rodent model (Choi et al., 2016; Choi and Francis, 2018). Our technique minimizes the difference between S1 neural responses induced by natural sensory stimuli and those generated via VPL MiSt. Our goal is to develop systems that know what MiSt will produce a given neural response and possibly a more natural "sensation." To date, our optimization has been conducted in the rodent model and simulations. Here we present data from simple non-optimized thalamic MiSt during peri-operative experiments, where we MiSt in the VPL of macaques with a somatosensory system more like humans. We implanted arrays of microelectrodes across the hand area of the macaque S1 cortex as well as in the VPL thalamus. Multi and single-unit recordings were used to compare cortical responses to natural touch and thalamic MiSt in the anesthetized state. Post stimulus time histograms were highly correlated between the VPL MiSt and natural touch modalities, adding support to the use of VPL MiSt towards producing a somatosensory neuroprosthesis in humans.

A functional network target for tic reduction during thalamic stimulation for Tourette Syndrome

ABSTRACTBackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for severe, treatment-refractory Tourette syndrome (TS). It remains unanswered which functionally connected networks need to be modulated to obtain optimal treatment results.MethodsWe assessed treatment response of 15 patients with TS untergoing thalamic DBS six and twelve months postoperatively using the Yale Global Tic Severity Scale (YGTSS) tic score. For each time point, functional connectivity maps seeding from stimulation sites were calculated based on a normative functional connectome derived from 1000 healthy subjects. Resulting maps were analyzed in a voxel-wise mixed model for repeated measurements to identify patterns of connectivity associated with tic reduction.ResultsConnectivity of stimulation to the medial frontal cortex, bilateral insulae and sensorimotor cortex was associated with tic reduction. Connectivity with the temporal lobe, cerebellum, ventral striatum and orbitofrontal cortex was negatively associated. The overall connectivity pattern was robust to leave-one-out cross-validation, explaining 25 % of outcome variance (R = 0.500; p = 0.005).ConclusionsWe delineated a functional connectivity profile seeding from stimulation sites associated with TS-DBS outcome. This pattern comprised areas linked to the processing of premonitory urges and tic execution, thereby extending our current understanding of effective neuromodulation for TS.

Reorganization of Thalamic Inputs to Lesioned Cortex Following Experimental Traumatic Brain Injury

Traumatic brain injury (TBI) disrupts thalamic and cortical integrity. The effect of post-injury reorganization and plasticity in thalamocortical pathways on the functional outcome remains unclear. We evaluated whether TBI causes structural changes in the thalamocortical axonal projection terminals in the primary somatosensory cortex (S1) that lead to hyperexcitability. TBI was induced in adult male Sprague Dawley rats with lateral fluid-percussion injury. A virus carrying the fluorescent-tagged opsin channel rhodopsin 2 transgene was injected into the ventroposterior thalamus. We then traced the thalamocortical pathways and analyzed the reorganization of their axonal terminals in S1. Next, we optogenetically stimulated the thalamocortical relays from the ventral posterior lateral and medial nuclei to assess the post-TBI functionality of the pathway. Immunohistochemical analysis revealed that TBI did not alter the spatial distribution or lamina-specific targeting of projection terminals in S1. TBI reduced the axon terminal density in the motor cortex by 44% and in S1 by 30%. A nematic tensor-based analysis revealed that in control rats, the axon terminals in layer V were orientated perpendicular to the pial surface (60.3°). In TBI rats their orientation was more parallel to the pial surface (5.43°, difference between the groups p < 0.05). Moreover, the level of anisotropy of the axon terminals was high in controls (0.063) compared with TBI rats (0.045, p < 0.05). Optical stimulation of the sensory thalamus increased alpha activity in electroencephalography by 312% in controls (p > 0.05) and 237% (p > 0.05) in TBI rats compared with the baseline. However, only TBI rats showed increased beta activity (33%) with harmonics at 5 Hz. Our findings indicate that TBI induces reorganization of thalamocortical axonal terminals in the perilesional cortex, which alters responses to thalamic stimulation.

Thalamic but Not Subthalamic Neuromodulation Simplifies Word Use in Spontaneous Language

Several investigations have shown language impairments following electrode implantation surgery for Deep Brain Stimulation (DBS) in movement disorders. The impact of the actual stimulation, however, differs between DBS targets with further deterioration in formal language tests induced by thalamic DBS in contrast to subtle improvement observed in subthalamic DBS. Here, we studied speech samples from interviews with participants treated with DBS of the thalamic ventral intermediate nucleus (VIM) for essential tremor (ET), or the subthalamic nucleus (STN) for Parkinson’s disease (PD), and healthy volunteers (each n = 13). We analyzed word frequency and the use of open and closed class words. Active DBS increased word frequency in case of VIM, but not STN stimulation. Further, relative to controls, both DBS groups produced fewer open class words. Whereas VIM DBS further decreased the proportion of open class words, it was increased by STN DBS. Thus, VIM DBS favors the use of relatively common words in spontaneous language, compatible with the idea of lexical simplification under thalamic stimulation. The absence or even partial reversal of these effects in patients receiving STN DBS is of interest with respect to biolinguistic concepts suggesting dichotomous thalamic vs. basal ganglia roles in language processing.

Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation

The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little or no spiking activity, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation ‘awakened’ anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.

Neural circuitry for maternal oxytocin release induced by infant cries

SummaryOxytocin is a neuropeptide important for maternal physiology and childcare, including parturition and milk ejection during nursing. Suckling triggers oxytocin release, but other sensory cues- specifically infant cries- can elevate oxytocin levels in new human mothers, indicating that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit routing auditory information about infant vocalizations to the oxytocin system of the mouse brain. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice presented with pup calls. We found that oxytocin neurons responded to pup vocalizations via input from the posterior intralaminar thalamus, and repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. Suppression of this pathway impaired maternal behavior and playing pup calls led to central oxytocin release in vivo. This circuit provides a mechanism for transforming acoustic input into hormonal output to ensure modulation of brain state required for successful parenting.