Aberrant oscillatory dynamics during somatosensory processing in HIV-infected adults

Abstract

While the arrival of combination antiretroviral therapy significantly decreased the prevalence of HIV-associated dementia, between 35 and 70% of all infected adults continue to develop some form of cognitive impairment. These deficits appears to affect multiple neural subsystems, but the mechanisms and extent of damage are not fully understood. In the current study, we utilized magnetoencephalography (MEG), advanced oscillatory analysis methods, and a paired-pulse somatosensory stimulation paradigm to interrogate pre-attentive inhibitory processing in 43 HIV-infected adults and 28 demographically-matched uninfected controls. MEG responses were imaged using a beamformer, and time series data were extracted from the peak voxel in grand-averaged functional brain images to quantify the dynamics of sensory gating, oscillatory power, spontaneous power, and other neural indices. We found a significantly weakened response to the second stimulation compared to the first across groups, indicating significant sensory gating irrespective of HIV-infection. Interestingly, HIV-infected participants exhibited reduced neural responses in the 20–75 Hz gamma range to each somatosensory stimulation compared to uninfected controls, and exhibited significant alterations in peak gamma frequency in response to the second stimulation. Finally, HIV-infected participants also had significantly stronger spontaneous activity in the gamma range (i.e., 20–75 Hz) during the baseline period before stimulation onset. In conclusion, while HIV-infected participants had the capacity to efficiently gate somatosensory input, their overall oscillatory responses were weaker, spontaneous baseline activity was stronger, and their response to the second stimulation had an altered peak gamma frequency. We propose that this pattern of deficits suggests dysfunction in the somatosensory cortices, which is potentially secondary to accelerated aging.

High‐definition transcranial direct current stimulation dissociates fronto‐visual theta lateralization during visual selective attention

“…For each comparison, at least 10,000 permutations were computed to build a distribution of cluster values. Further details of this method and our processing pipeline can be found in recent papers Spooner et al 2018aSpooner et al ,b, 2020McDermott et al 2019).…”

Methodological considerations for a better somatosensory gating paradigm: The impact of the inter-stimulus interval

“…In line with the most recent studies of somatosensory gating, we evaluated the effect of ISI on the dynamics of high-frequency gamma (>30 Hz) oscillations in response to the first and second stimulation ( Cheng et al, 2016b ; Kurz et al, 2017 ; Spooner et al, 2018 , 2019 ; Wiesman et al, 2017 ). Critically, we found that the gating of somatosensory input was optimal (i.e., smaller gating ratios) when stimulations were presented 200 ms apart from one another, irrespective of whether this ratio was calculated using peak oscillatory power or peak frequency.…”

“…This weakened response to stimuli presented in rapid succession is thought to reflect the brain’s capacity to filter irrelevant information to preserve neural resources for more behaviorally relevant stimuli ( Adler et al, 1982 , 1998 ; Cromwell et al, 2008 ; Nagamoto et al, 1989 , 1991 ; Venables, 1964 ). SG has been examined in many clinical populations and across multiple sensory modalities (e.g., auditory and somatosensory) and broadly is known to be aberrant in aging, as well as many psychiatric and neurological conditions (e.g., schizophrenia, bipolar disorder, cerebral palsy, neuroHIV ( Brinkman and Stauder, 2007 ; Cheng et al, 2015a ; Cheng et al, 2016a ; Cheng et al, 2015b ; Cheng and Lin, 2013 ; Kisley et al, 2003 ; Kurz et al, 2017 ; Light and Braff, 1999 ; Spooner et al, 2018 ; Spooner et al, 2019 ; Thoma et al, 2017 )). Historically, SG paradigms have used a paired-stimulus presentation design, whereby pairs of auditory tones or electrical stimulations are administered in close temporal proximity to evaluate gating in the auditory or somatosensory domain, respectively.…”

“…The ratio approach is the most common as it is less affected by individual differences in response amplitude across both stimulations. Importantly, regardless of the tested modality or clinical population, aberrations in SG are thought to reflect alterations in functional inhibitory processing ( Cheng et al, 2016b ; Cromwell et al, 2008 ; Gao et al, 2013 ; Spooner et al, 2018 , 2019 ), making the application of such protocols in human neurophysiology extremely desirable.…”

“…However, several recent studies of SG have employed advanced oscillatory analysis methods and found rich, multi-spectral recruitment of neural populations following the paired stimuli. For example, in the context of the somatosensory system, recent studies have shown that electrical stimulation of the median nerve elicits robust oscillatory activity up to 90 Hz (e.g., 20–90 Hz; ( Cheng et al, 2016b ; Spooner et al, 2018 ; Spooner et al, 2019 ; Wiesman et al, 2017 ). These high-frequency or gamma oscillations (>30 Hz) are critical to the basic processing of fine stimulus features across modalities and may ultimately provide mechanistic insight into intracortical inhibitory processing.…”