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1. A multimodal magnetoencephalography 7 T fMRI and 7 T proton MR spectroscopy study in first episode psychosis

   https://doi.org/10.1038/s41537-020-00113-4  

   Gawne, Timothy J. ; Overbeek, Gregory J. ; Killen, Jeffery F. ; Reid, Meredith A. ; Kraguljac, Nina V. ; Denney, Thomas S. ; Ellis, Charles A. ; Lahti, Adrienne C. ( September 2020 , npj Schizophrenia)

   We combined magnetoencephalography (MEG), 7 T proton magnetic resonance spectroscopy (MRS), and 7 T fMRI during performance of a task in a group of 23 first episode psychosis (FEP) patients and 26 matched healthy controls (HC). We recorded both the auditory evoked response to 40 Hz tone clicks and the resting state in MEG. Neurometabolite levels were obtained from the anterior cingulate cortex (ACC). The fMRI BOLD response was obtained during the Stroop inhibitory control task. FEP showed a significant increase in resting state low frequency theta activity (p < 0.05; Cohend= 0.69), but no significant difference in the 40 Hz auditory evoked response compared to HC. An across-groups whole brain analysis of the fMRI BOLD response identified eight regions that were significantly activated during task performance (p < 0.01, FDR-corrected); the mean signal extracted from those regions was significantly different between the groups (p = 0.0006;d = 1.19). In the combined FEP and HC group, there was a significant correlation between the BOLD signal during task performance and MEG resting state low frequency activity (p < 0.05). In FEP, we report significant alteration in resting state low frequency MEG activity, but no alterations in auditory evoked gamma band response, suggesting that the former is a more robust biomarker of early psychosis. There weremore »no correlations between gamma oscillations and GABA levels in either HC or FEP. Finally, in this study, each of the three imaging modalities differentiated FEP from HC; fMRI with good and MEG and MRS with moderate effect size.

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2. Epidural cerebellar stimulation drives widespread neural synchrony in the intact and stroke perilesional cortex.

   https://doi.org/10.1186/s12984-021-00881-9  

   Abbasi, A. ; Danielsen, N.P. ; Leung, J. ; Muhammad, A.K.M.G. ; Patel, S. ; Gulati, T. ( May 2021 , Journal of neuroengineering and rehabilitation)

   Manto, Mario (Ed.)

   Background Cerebellar electrical stimulation has shown promise in improving motor recovery post-stroke in both rodent and human studies. Past studies have used motor evoked potentials (MEPs) to evaluate how cerebellar stimulation modulates ongoing activity in the cortex, but the underlying mechanisms are incompletely understood. Here we used invasive electrophysiological recordings from the intact and stroke-injured rodent primary motor cortex (M1) to assess how epidural cerebellar stimulation modulates neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics. Methods We recorded single unit spiking and local field potentials (LFPs) in both the intact and acutely stroke-injured M1 contralateral to the stimulated cerebellum in adult Long-Evans rats under anesthesia. We analyzed changes in the firing rates of single units, the extent of synchronous spiking and power spectral density (PSD) changes in LFPs during and post-stimulation. Results Our results show that post-stimulation, the firing rates of a majority of M1 neurons changed significantly with respect to their baseline rates. These firing rate changes were diverse in character, as the firing rate of some neurons increased while others decreased. Additionally, these changes started to set in during stimulation. Furthermore, cross-correlation analysis showed a significant increase in coincidentmore »firing amongst neuronal pairs. Interestingly, this increase in synchrony was unrelated to the direction of firing rate change. We also found that neuronal ensembles derived through principal component analysis were more active post-stimulation. Lastly, these changes occurred without a significant change in the overall spectral power of LFPs post-stimulation. Conclusions Our results show that cerebellar stimulation caused significant, long-lasting changes in the activity patterns of M1 neurons by altering firing rates, boosting neural synchrony and increasing neuronal assemblies’ activation strength. Our study provides evidence that cerebellar stimulation can directly modulate cortical dynamics. Since these results are present in the perilesional cortex, our data might also help explain the facilitatory effects of cerebellar stimulation post-stroke.« less
3. Role of cerebellar GABAergic dysfunctions in the origins of essential tremor

   https://doi.org/10.1073/pnas.1817689116  

   Zhang, Xu ; Santaniello, Sabato ( July 2019 , Proceedings of the National Academy of Sciences)

   Essential tremor (ET) is among the most prevalent movement disorders, but its origins are elusive. The inferior olivary nucleus (ION) has been hypothesized as the prime generator of tremor because of the pacemaker properties of ION neurons, but structural and functional changes in ION are unlikely under ET. Abnormalities have instead been reported in the cerebello-thalamo-cortical network, including dysfunctions of the GABAergic projections from the cerebellar cortex to the dentate nucleus. It remains unclear, though, how tremor would relate to a dysfunction of cerebellar connectivity. To address this question, we built a computational model of the cortico-cerebello-thalamo-cortical loop. We simulated the effects of a progressive loss of GABA A α 1 -receptor subunits and up-regulation of α 2/3 -receptor subunits in the dentate nucleus, and correspondingly, we studied the evolution of the firing patterns along the loop. The model closely reproduced experimental evidence for each structure in the loop. It showed that an alteration of amplitudes and decay times of the GABAergic currents to the dentate nucleus can facilitate sustained oscillatory activity at tremor frequency throughout the network as well as a robust bursting activity in the thalamus, which is consistent with observations of thalamic tremor cells in ET patients.more »Tremor-related oscillations initiated in small neural populations and spread to a larger network as the synaptic dysfunction increased, while thalamic high-frequency stimulation suppressed tremor-related activity in thalamus but increased the oscillation frequency in the olivocerebellar loop. These results suggest a mechanism for tremor generation under cerebellar dysfunction, which may explain the origin of ET.« less
4. Stress degrades working memory-related frontostriatal circuit function

   https://doi.org/10.1093/cercor/bhad084  

   Berridge, Craig W. ; Devilbiss, David M. ; Martin, Andrea J. ; Spencer, Robert C. ; Jenison, Rick L. ( March 2023 , Cerebral Cortex)

   Goal-directed behavior is dependent on neuronal activity in the prefrontal cortex (PFC) and extended frontostriatal circuitry. Stress and stress-related disorders are associated with impaired frontostriatal-dependent cognition. Our understanding of the neural mechanisms that underlie stress-related cognitive impairment is limited, with the majority of prior research focused on the PFC. To date, the actions of stress across cognition-related frontostriatal circuitry are unknown. To address this gap, the current studies examined the effects of acute noise-stress on the spiking activity of neurons and local field potential oscillatory activity within the dorsomedial PFC (dmPFC) and dorsomedial striatum (dmSTR) in rats engaged in a test of spatial working memory. Stress robustly suppressed responses of both dmPFC and dmSTR neurons strongly tuned to key task events (delay, reward). Additionally, stress strongly suppressed delay-related, but not reward-related, theta and alpha spectral power within, and synchrony between, the dmPFC and dmSTR. These observations provide the first demonstration that stress disrupts the neural coding and functional connectivity of key task events, particularly delay, within cognition-supporting dorsomedial frontostriatal circuitry. These results suggest that stress-related degradation of neural coding within both the PFC and striatum likely contributes to the cognition-impairing effects of stress.
5. N100 as a generic cortical electrophysiological marker based on decomposition of TMS-evoked potentials across five anatomic locations

   https://doi.org/doi:10.1007/s00221-016-4773-7  

   Xiaoming Du, Fow-Sen Choa ( January 2017 , Experimental brain research)

   N100, the negative peak of electrical response occurring around 100 ms, is present in diverse functional paradigms including auditory, visual, somatic, behavioral and cognitive tasks. We hypothesized that the presence of the N100 across different paradigms may be indicative of a more general property of the cerebral cortex regardless of functional or anatomic specificity. To test this hypothesis, we combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to measure cortical excitability by TMS across cortical regions without relying on specific sensory, cognitive or behavioral modalities. The five stimulated regions included left prefrontal, left motor, left primary auditory cortices, the vertex and posterior cerebellum with stimulations performed using supra- and subthreshold intensities. EEG responses produced by TMS stimulation at the five locations all generated N100s that peaked at the vertex. The amplitudes of the N100s elicited by these five diverse cortical origins were statistically not significantly different (all uncorrected p > 0.05). No other EEG response components were found to have this global property of N100. Our findings suggest that anatomy- and modality-specific interpretation of N100 should be carefully evaluated, and N100 by TMS may be used as a bio-marker for evaluating local versus general cortical properties across the brain.