Functional Brain Abnormalities During Finger-Tapping in HIV-Infected Older Adults: A Magnetoencephalography Study

Abstract

Despite the availability of combination antiretroviral therapy, at least mild cognitive dysfunction is commonly observed in HIV-infected patients, with an estimated prevalence of 35-70%. Neuropsychological studies of these HIV-associated neurocognitive disorders (HAND) have documented aberrations across a broad range of functional domains, although the basic pathophysiology remains unresolved. Some of the most common findings have been deficits in fine motor control and reduced psychomotor speed, but to date no neuroimaging studies have evaluated basic motor control in HAND. In this study, we used magnetoencephalography (MEG) to evaluate the neurophysiological processes that underlie motor planning in older HIV-infected adults and a matched, uninfected control group. MEG is a noninvasive and direct measure of neural activity with good spatiotemporal precision. During the MEG recording, participants fixated on a central crosshair and performed a finger-tapping task with the dominant hand. All MEG data was corrected for head movements, preprocessed, and imaged in the time-frequency domain using beamforming methodology. All analyses focused on the pre-movement beta desynchronization, which is known to be an index of movement planning. Our results demonstrated that HIV-1-infected patients have deficient beta desynchronization relative to controls within the left/right precentral gyri, and the supplementary motor area. In contrast, HIV-infected persons showed abnormally strong beta responses compared to controls in the right dorsolateral prefrontal cortex and medial prefrontal areas. In addition, the amplitude of beta activity in the primary and supplementary motor areas correlated with scores on the Grooved Pegboard test in HIV-infected adults. These results demonstrate that primary motor and sensory regions may be particularly vulnerable to HIV-associated damage, and that prefrontal cortices may serve a compensatory role in maintaining motor performance levels in infected patients.

Circadian modulation of motor-related beta oscillatory responses

“…These results are consistent with many prior studies of beta activity in healthy adults and children (Gaetz et al, 2010; Hall et al, 2011; Heinrichs-Graham et al, in press; Jurkiewicz et al, 2006; Tzagarakis et al, 2010; Wilson et al, 2010, 2011, 2013), which have characterized this response as a marker of movement planning (Doyle et al, 2005; Kaiser et al, 2001). Interestingly, we found that the amplitude of the beta ERD significantly increased from morning to afternoon in recognized regions of the motor network, which has not been previously reported.…”

“…During the movement task, participants were instructed to fixate on a centrally-presented cross hair and to perform a single flexion-extension of the second metacarpus phalangeal (i.e., index finger) of the right hand each time a dot reached the 12 o’clock position. This dot completed one full rotation around a clock-like circle without tick marks or numbers every 6 s, and was meant to serve as a pacing device (Heinrichs-Graham et al, in press; Wilson et al, 2013). The precise timing of movement onset was determined by a fiber optic switch, whereby a signal was emitted from one side of a groove that functioned as the finger rest area.…”

Neuroimaging with magnetoencephalography: A dynamic view of brain pathophysiology

“…For example, an MEG study of motor control demonstrated that HIV-infected patients had reduced beta responses (14-28 Hz) prior to movement onset in the supplementary motor area and bilateral primary motor cortices (stronger on the side contralateral to movement) relative to demographically-matched controls. 82 HIV-infected patients also had increased activity in bilateral prefrontal cortices, which likely reflected compensatory processes serving movement planning, as significant correlations were observed between the amplitude of such activity and performance on the Trail Making Test (A+B). 82 An MEG study of visual attention also found abnormal activity in the right prefrontal cortices, as well as the frontal eye-fields of HIV-infected older adults compared with matched uninfected controls.…”

“…82 HIV-infected patients also had increased activity in bilateral prefrontal cortices, which likely reflected compensatory processes serving movement planning, as significant correlations were observed between the amplitude of such activity and performance on the Trail Making Test (A+B). 82 An MEG study of visual attention also found abnormal activity in the right prefrontal cortices, as well as the frontal eye-fields of HIV-infected older adults compared with matched uninfected controls. 83 Consistent with the motor control study, the magnitude of neural responses in these areas correlated with neuropsychological performance in the HIV-infected patients.…”

Aging with HIV-1 Infection: Motor Functions, Cognition, and Attention – A Comparison with Parkinson’s Disease

“…HIV-infected individuals exhibit deficits in motor functioning, particularly on tasks requiring fine motor movement (Wilson et al 2013), gait (Robertson et al 2006), and postural stability (Bernard et al 2013; Sullivan et al 2011). Impaired motor functioning in HIV-infected individuals was a prominent symptom before the introduction of HAART and comprised a unique diagnostic category before the revision of neurocognitive disorders criteria in 2007 (Antinori et al 2007).…”