Alex I. Wiesman

Quiet connections: Reduced fronto‐temporal connectivity in nondemented Parkinson's Disease during working memory encoding

Parkinsons disease (PD) is a common neurodegenerative disorder characterized primarily by motor symptoms such as bradykinesia, muscle rigidity, and resting tremor. It is now broadly accepted that these motor symptoms frequently co‐occur with cognitive impairments, with deficits in working memory and attention being among the most common cognitive sequelae associated with PD. While these cognitive impairments are now recognized, the underlying neural dynamics and precise regions involved remain largely unknown. To this end, we examined the oscillatory dynamics and interregional functional connectivity that serve working memory processing in a group of unmedicated adults with PD and a matched group without PD. Each participant completed a high‐load, Sternberg‐type working memory task during magnetoencephalography (MEG), and we focused on the encoding and maintenance phases. All data were transformed into the time–frequency domain and significant oscillatory activity was imaged using a beamforming approach. Phase‐coherence (connectivity) was also computed among the brain subregions exhibiting the strongest responses. Our most important findings were that unmedicated patients with PD had significantly diminished working memory performance (i.e., accuracy), and reduced functional connectivity between left inferior frontal cortices and left supramarginal–superior temporal cortices compared to participants without PD during the encoding phase of working memory processing. We conclude that patients with PD have reduced neural interactions between left prefrontal executive circuits and temporary verbal storage centers in the left supramarginal/superior temporal cortices during the stimulus encoding phase, which may underlie their diminished working memory function. Hum Brain Mapp 37:3224–3235, 2016.

Spatiotemporal oscillatory dynamics of visual selective attention during a flanker task

&NA; The flanker task is a test of visual selective attention that has been widely used to probe error monitoring, response conflict, and related constructs. However, to date, few studies have focused on the selective attention component of this task and imaged the underlying oscillatory dynamics serving task performance. In this study, 21 healthy adults successfully completed an arrow‐based version of the Eriksen flanker task during magnetoencephalography (MEG). All MEG data were pre‐processed and transformed into the time‐frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach, and voxel time series were extracted from the peak responses to identify the temporal dynamics. Across both congruent and incongruent flanker conditions, our results indicated robust decreases in alpha (9–12 Hz) activity in medial and lateral occipital regions, bilateral parietal cortices, and cerebellar areas during task performance. In parallel, increases in theta (3–7 Hz) oscillatory activity were detected in dorsal and ventral frontal regions, and the anterior cingulate. As per conditional effects, stronger alpha responses (i.e., greater desynchronization) were observed in parietal, occipital, and cerebellar cortices during incongruent relative to congruent trials, whereas the opposite pattern emerged for theta responses (i.e., synchronization) in the anterior cingulate, left dorsolateral prefrontal, and ventral prefrontal cortices. Interestingly, the peak latency of theta responses in these latter brain regions was significantly correlated with reaction time, and may partially explain the amplitude difference observed between congruent and incongruent trials. Lastly, whole‐brain exploratory analyses implicated the frontal eye fields, right temporoparietal junction, and premotor cortices. These findings suggest that regions of both the dorsal and ventral attention networks contribute to visual selective attention processes during incongruent trials, and that such differential processes are transient and fully completed shortly after the behavioral response in most trials. HighlightsHealthy adults performed a visual selective attention task while undergoing MEG.Participants exhibited significant theta and alpha oscillations during the task.These responses were imaged with a beamformer and voxel time series were extracted.Results showed occipital and parietal alpha activity and theta in prefrontal cortex.Oscillatory dynamics within attention networks distinguished attention conditions.

Oscillatory dynamics and functional connectivity during gating of primary somatosensory responses

Sensory gating is important for preventing excessive environmental stimulation from overloading neural resources. Gating in the human somatosensory cortices is a critically understudied topic, particularly in the lower extremities. We utilize the unique capabilities of magnetoencephalographic neuroimaging to quantify the normative neural population responses and dynamic functional connectivity of somatosensory gating in the lower extremities of healthy human participants. We show that somatosensory processing is subserved by a robust gating effect in the oscillatory domain, as well as a dynamic effect on interhemispheric functional connectivity between primary sensory cortices. These results provide novel insight into the dynamic neural mechanisms that underlie the processing of somatosensory information in the human brain, and will be vital in better understanding the neural responses that are aberrant in gait‐related neurological disorders (e.g. cerebral palsy).

Oscillations during observations: Dynamic oscillatory networks serving visuospatial attention

The dynamic allocation of neural resources to discrete features within a visual scene enables us to react quickly and accurately to salient environmental circumstances. A network of bilateral cortical regions is known to subserve such visuospatial attention functions; however the oscillatory and functional connectivity dynamics of information coding within this network are not fully understood. Particularly, the coding of information within prototypical attention‐network hubs and the subsecond functional connections formed between these hubs have not been adequately characterized. Herein, we use the precise temporal resolution of magnetoencephalography (MEG) to define spectrally specific functional nodes and connections that underlie the deployment of attention in visual space. Twenty‐three healthy young adults completed a visuospatial discrimination task designed to elicit multispectral activity in visual cortex during MEG, and the resulting data were preprocessed and reconstructed in the time–frequency domain. Oscillatory responses were projected to the cortical surface using a beamformer, and time series were extracted from peak voxels to examine their temporal evolution. Dynamic functional connectivity was then computed between nodes within each frequency band of interest. We find that visual attention network nodes are defined functionally by oscillatory frequency, that the allocation of attention to the visual space dynamically modulates functional connectivity between these regions on a millisecond timescale, and that these modulations significantly correlate with performance on a spatial discrimination task. We conclude that functional hubs underlying visuospatial attention are segregated not only anatomically but also by oscillatory frequency, and importantly that these oscillatory signatures promote dynamic communication between these hubs. Hum Brain Mapp 38:5128–5140, 2017.

Veterans with post-traumatic stress disorder exhibit altered emotional processing and attentional control during an emotional Stroop task

BACKGROUND Post-traumatic stress disorder (PTSD) is often associated with attention allocation and emotional regulation difficulties, but the brain dynamics underlying these deficits are unknown. The emotional Stroop task (EST) is an ideal means to monitor these difficulties, because participants are asked to attend to non-emotional aspects of the stimuli. In this study, we used magnetoencephalography (MEG) and the EST to monitor attention allocation and emotional regulation during the processing of emotionally charged stimuli in combat veterans with and without PTSD. METHOD A total of 31 veterans with PTSD and 20 without PTSD performed the EST during MEG. Three categories of stimuli were used, including combat-related, generally threatening and neutral words. MEG data were imaged in the time-frequency domain and the network dynamics were probed for differences in processing threatening and non-threatening words. RESULTS Behaviorally, veterans with PTSD were significantly slower in responding to combat-related relative to neutral and generally threatening words. Veterans without PTSD exhibited no significant differences in responding to the three different word types. Neurophysiologically, we found a significant three-way interaction between group, word type and time period across multiple brain regions. Follow-up testing indicated stronger theta-frequency (4-8 Hz) responses in the right ventral prefrontal (0.4-0.8 s) and superior temporal cortices (0.6-0.8 s) of veterans without PTSD compared with those with PTSD during the processing of combat-related words. CONCLUSIONS Our data indicated that veterans with PTSD exhibited deficits in attention allocation and emotional regulation when processing trauma cues, while those without PTSD were able to regulate emotion by directing attention away from threat.

Children with Cerebral Palsy Hyper-Gate Somatosensory Stimulations of the Foot

We currently have a substantial knowledge gap in our understanding of the neurophysiological underpinnings of the sensory perception deficits often reported in the clinic for children with cerebral palsy (CP). In this investigation, we have begun to address this knowledge gap by using magnetoencephalography (MEG) brain imaging to evaluate the sensory gating of neural oscillations in the somatosensory cortices. A cohort of children with CP (Gross Motor Function Classification System II-III) and typically developing children underwent paired-pulse electrical stimulation of the tibial nerve during MEG. Advanced beamforming methods were used to image significant oscillatory responses, and subsequently the time series of neural activity was extracted from peak voxels. Our experimental results showed that somatosensory cortical oscillations (10-75 Hz) were weaker in the children with CP for both stimulations. Despite this reduction, the children with CP actually exhibited a hyper-gating response to the second, redundant peripheral stimulation applied to the foot. These results have further established the nexus of the cortical somatosensory processing deficits that are likely responsible for the degraded sensory perceptions reported in the clinic for children with CP.

Oscillatory dynamics in the dorsal and ventral attention networks during the reorienting of attention

The ability to reorient attention within the visual field is central to daily functioning, and numerous fMRI studies have shown that the dorsal and ventral attention networks (DAN, VAN) are critical to such processes. However, despite the instantaneous nature of attentional shifts, the dynamics of oscillatory activity serving attentional reorientation remain poorly characterized. In this study, we utilized magnetoencephalography (MEG) and a Posner task to probe the dynamics of attentional reorienting in 29 healthy adults. MEG data were transformed into the time‐frequency domain and significant oscillatory responses were imaged using a beamformer. Voxel time series were then extracted from peak voxels in the functional beamformer images. These time series were used to quantify the dynamics of attentional reorienting, and to compute dynamic functional connectivity. Our results indicated strong increases in theta and decreases in alpha and beta activity across many nodes in the DAN and VAN. Interestingly, theta responses were generally stronger during trials that required attentional reorienting relative to those that did not, while alpha and beta oscillations were more dynamic, with many regions exhibiting significantly stronger responses during non‐reorienting trials initially, and the opposite pattern during later processing. Finally, stronger functional connectivity was found following target presentation (575‐700 ms) between bilateral superior parietal lobules during attentional reorienting. In sum, these data show that visual attention is served by multiple cortical regions within the DAN and VAN, and that attentional reorienting processes are often associated with spectrally‐specific oscillations that have largely distinct spatiotemporal dynamics.

Rhythmic Spontaneous Activity Mediates the Age-Related Decline in Somatosensory Function

Sensory gating is a neurophysiological process whereby the response to a second stimulus in a pair of identical stimuli is attenuated, and it is thought to reflect the capacity of the CNS to preserve neural resources for behaviorally relevant stimuli. Such gating is observed across multiple sensory modalities and is modulated by age, but the mechanisms involved are not understood. In this study, we examined somatosensory gating in 68 healthy adults using magnetoencephalography (MEG) and advanced oscillatory and time-domain analysis methods. MEG data underwent source reconstruction and peak voxel time series data were extracted to evaluate the dynamics of somatosensory gating, and the impact of spontaneous neural activity immediately preceding the stimulation. We found that gating declined with increasing age and that older adults had significantly reduced gating relative to younger adults, suggesting impaired local inhibitory function. Most importantly, older adults had significantly elevated spontaneous activity preceding the stimulation, and this effect fully mediated the impact of aging on sensory gating. In conclusion, gating in the somatosensory system declines with advancing age and this effect is directly tied to increased spontaneous neural activity in the primary somatosensory cortices, which is likely secondary to age-related declines in local GABA inhibitory function.

Aberrant occipital dynamics differentiate HIV-infected patients with and without cognitive impairment

The population-level neural dynamics underlying HIV-associated neurocognitive disorders (HAND) are poorly understood. Wiesman et al. report that spontaneous and oscillatory neural activity in occipital cortices distinguish HIV-infected patients from uninfected controls, and patients by HAND status. This is the first neuroimaging evidence to dissociate HIV-infected patients with and without HAND.

Endocytosis sustains release at photoreceptor ribbon synapses by restoring fusion competence

Endocytosis is an essential process at sites of synaptic release. Not only are synaptic vesicles recycled by endocytosis, but the removal of proteins and lipids by endocytosis is needed to restore release site function at active zones after vesicle fusion. Synaptic exocytosis from vertebrate photoreceptors involves synaptic ribbons that serve to cluster vesicles near the presynaptic membrane. In this study, we hypothesize that this clustering increases the likelihood that exocytosis at one ribbon release site may disrupt release at an adjacent site and therefore that endocytosis may be particularly important for restoring release site competence at photoreceptor ribbon synapses. To test this, we combined optical and electrophysiological techniques in salamander rods. Pharmacological inhibition of dynamin-dependent endocytosis rapidly inhibits release from synaptic ribbons and slows recovery of ribbon-mediated release from paired pulse synaptic depression. Inhibiting endocytosis impairs the ability of second-order horizontal cells to follow rod light responses at frequencies as low as 2 Hz. Inhibition of endocytosis also increases lateral membrane mobility of individual Ca2+ channels, showing that it changes release site structure. Visualization of single synaptic vesicles by total internal reflection fluorescence microscopy reveals that inhibition of endocytosis reduces the likelihood of fusion among vesicles docked near ribbons and increases the likelihood that they will retreat from the membrane without fusion. Vesicle advance toward the membrane is also reduced, but the number of membrane-associated vesicles is not. Endocytosis therefore appears to be more important for restoring later steps in vesicle fusion than for restoring docking. Unlike conventional synapses in which endocytic restoration of release sites is evident only at high frequencies, endocytosis is needed to maintain release from rod ribbon synapses even at modest frequencies.