Resting-state electroencephalographic correlates of cognitive reserve: Moderating the age-related decline in cognitive function

Measurement of cognitive reserve (CR) is a matter of constant reviews and developments due to the difficulty to assess it directly, being socio-behavioral indexes used as indirect proxies. An effort to unravel the neural correlates underlying CR seems mandatory, and strongly supported by the neuroscientific literature. Neurophysiological measures through electroencephalography (EEG) have proven to be a promising, almost inexpensive method to study the CR neural correlates. In line with the recommendations of Stern et al. (2020), the aim of the present study has been to demonstrate that resting-state EEG measures may moderate the relationship between age-related brain changes and cognitive status; thus, constituting an objective neural index of CR.Our results show that two resting-state EEG measures, delta current source density in the occipital region and beta 2 connectivity between limbic and occipital regions in the right hemisphere, moderate the relation between age and cognitive performance, indexing neuroprotective effects on cognition during the aging process. These results not only shed light on the neural mechanisms involved in CR but also allow us to propose features to be taken into account in order to enhance the results of interventions to delay the onset of cognitive deficits.

Cortical morphology predicts placebo response in multiple sclerosis

Despite significant insights into the neural mechanisms of acute placebo responses, less is known about longer-term placebo responses, such as those seen in clinical trials, or their interactions with brain disease. We examined brain correlates of placebo responses in a randomized trial of a then controversial and now disproved endovascular treatment for multiple sclerosis. Patients received either balloon or sham extracranial venoplasty and were followed for 48 weeks. Venoplasty had no therapeutic effect, but a subset of both venoplasty- and sham-treated patients reported a transient improvement in health-related quality of life, suggesting a placebo response. Placebo responders did not differ from non-responders in total MRI T2 lesion load, count or location, nor were there differences in normalized brain volume, regional grey or white matter volume or cortical thickness (CT). However, responders had higher lesion activity. Graph theoretical analysis of CT covariance showed that non-responders had a more small-world-like CT architecture. In non-responders, lesion load was inversely associated with CT in somatosensory, motor and association areas, precuneus, and insula, primarily in the right hemisphere. In responders, lesion load was unrelated to CT. The neuropathological process in MS may produce in some a cortical configuration less capable of generating sustained placebo responses.

Hemispheric Lateralization of Visuospatial Attention Is Independent of Language Production on Right-Handers: Evidence From Functional Near-Infrared Spectroscopy

It is well-established that visuospatial attention is mainly lateralized to the right hemisphere, whereas language production is mainly left-lateralized. However, there is a significant controversy regarding how these two kinds of lateralization interact with each other. The present research used functional near-infrared spectroscopy (fNIRS) to examine whether visuospatial attention is indeed right-lateralized, whereas language production is left-lateralized, and more importantly, whether the extent of lateralization in the visuospatial task is correlated with that in the task involving language. Specifically, fifty-two healthy right-handed participants participated in this study. Multiple-channel fNIRS technique was utilized to record the cerebral hemodynamic changes when participants were engaged in naming objects depicted in pictures (the picture naming task) or judging whether a presented line was bisected correctly (the landmark task). The degree of hemispheric lateralization was quantified according to the activation difference between the left and right hemispheres. We found that the picture-naming task predominantly activated the inferior frontal gyrus (IFG) of the left hemisphere. In contrast, the landmark task predominantly activated the inferior parietal sulcus (IPS) and superior parietal lobule (SPL) of the right hemisphere. The quantitative calculation of the laterality index also showed a left-lateralized distribution for the picture-naming task and a right-lateralized distribution for the landmark task. Intriguingly, the correlation analysis revealed no significant correlation between the laterality indices of these two tasks. Our findings support the independent hypothesis, suggesting that different cognitive tasks may engender lateralized processing in the brain, but these lateralized activities may be independent of each other. Meanwhile, we stress the importance of handedness in understanding the relationship between functional asymmetries. Methodologically, we demonstrated the effectiveness of using the multichannel fNIRS technique to investigate the hemispheric specialization of different cognitive tasks and their lateralization relations between different tasks. Our findings and methods may have important implications for future research to explore lateralization-related issues in individuals with neural pathologies.

Revisiting Hemispheric Asymmetry in Mood Regulation: Implications for rTMS for Major Depressive Disorder

Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD.

Intraarterial anti-leptin therapy via ICA protects ipsilateral CA1 neurons subjected to ischemia and reperfusion

Background Brain reperfusion following an ischemic event is essential for tissue viability, however, it also involves processes that promote neuronal cell death. We have recently shown that local expression of the hormone leptin in cardiovascular organs drives deleterious remodeling. As cerebral ischemia-reperfusion (IR) lesions derive expression of both the leptin hormone and its receptor, we hypothesized that blocking leptin activity in the injured brain area will reduce the deleterious effects of IR injury. Methods C57BL6 male mice underwent bilateral common carotid artery and external carotid artery ligation. The right hemisphere was reperfused after 12 minutes, followed by intraarterial injection of either a low-dose leptin antagonist or saline solution via the ipsilateral ICA. The left common carotid artery remained ligated. Fifteen IR/leptin antagonist-injected and fourteen IR/saline-injected mice completed the experiment. Five days after surgery brains were collected and samples of the hippocampal CA1 region were analyzed for cell viability (H&E) and apoptosis (TUNEL and caspase3), for neuroinflammation (Iba1), and for signaling pathways of pSTAT3 and pSmad2. Results The right hemisphere hippocampal CA1 region subjected to IR and saline injection exhibited increased apoptosis and necrosis of pyramidal cells. Also, increased density of activated microglia/macrophages was evident around the CA1 region. Comparatively, leptin antagonist treatment at reperfusion reduced apoptosis and necrosis of pyramidal cells, as indicated by increased number of viable cells (p < 0.01), and reduced TUNEL (p < 0.001) and caspase3-positive cells (p<0.05). Furthermore, this treatment reduced the density of activated microglia/macrophages (p < 0.001) in the CA1 region. Signaling pathway analysis revealed that while pSTAT3 and pSmad2-positive cells were found surrounding the stratum pyramidal in saline-treated animals, pSTAT3 signal was undetected and pSmad2 was greatly reduced in this territory following leptin antagonist treatment (p < 0.01). Conclusions Inhibition of leptin activity in hemispheric IR injury preserved the viability of ipsilateral hippocampal CA1 neurons, likely by preventing apoptosis and local inflammation. These results indicate that intraarterial anti-leptin therapy may have clinical potential in reducing hemispheric brain IR injury.

Acoustic-level and language-specific processing of native and non-native phonological sequence onsets in the low gamma and theta-frequency bands

Acoustic structures associated with native-language phonological sequences are enhanced within auditory pathways for perception, although the underlying mechanisms are not well understood. To elucidate processes that facilitate perception, time–frequency (T–F) analyses of EEGs obtained from native speakers of English and Polish were conducted. Participants listened to same and different nonword pairs within counterbalanced attend and passive conditions. Nonwords contained the onsets /pt/, /pət/, /st/, and /sət/ that occur in both the Polish and English languages with the exception of /pt/, which never occurs in the English language in word onset. Measures of spectral power and inter-trial phase locking (ITPL) in the low gamma (LG) and theta-frequency bands were analyzed from two bilateral, auditory source-level channels, created through source localization modeling. Results revealed significantly larger spectral power in LG for the English listeners to the unfamiliar /pt/ onsets from the right hemisphere at early cortical stages, during the passive condition. Further, ITPL values revealed distinctive responses in high and low-theta to acoustic characteristics of the onsets, which were modulated by language exposure. These findings, language-specific processing in LG and acoustic-level and language-specific processing in theta, support the view that multi scale temporal processing in the LG and theta-frequency bands facilitates speech perception.

Magnetoencephalography resting-state correlates of executive and language components of verbal fluency

Verbal fluency (VF) is a heterogeneous cognitive function that requires executive as well as language abilities. The purpose of this study was to elucidate the specificity of the resting state MEG correlates of the executive and language components. To this end, we administered a VF test, another verbal test (Vocabulary), and another executive test (Trail Making Test), and we recorded 5-min eyes-open resting-state MEG data in 28 healthy participants. We used source-reconstructed spectral power estimates to compute correlation/anticorrelation MEG clusters with the performance at each test, as well as with the advantage in performance between tests, across individuals using cluster-level statistics in the standard frequency bands. By obtaining conjunction clusters between verbal fluency scores and factor loading obtained for verbal fluency and each of the two other tests, we showed a core of slow clusters (delta to beta) localized in the right hemisphere, in adjacent parts of the premotor, pre-central and post-central cortex in the mid-lateral regions related to executive monitoring. We also found slow parietal clusters bilaterally and a cluster in the gamma 2 and 3 bands in the left inferior frontal gyrus likely associated with phonological processing involved in verbal fluency.

Disruptions of the Human Connectome Associated With Hemispatial Neglect

Background and ObjectivesHemispatial neglect is a heterogeneous and complex disorder that can be classified by frame of reference for “left” vs “right,” including viewer-centered neglect (VCN, affecting the contralesional side of the view), stimulus-centered neglect (SCN, affecting the contralesional side of the stimulus, irrespective of its location with respect to the viewer), or both. We investigated the effect of acute stroke lesions on the connectivity of neural networks that underlie VCN or SCN.MethodsA total of 174 patients within 48 hours of acute right hemispheric infarct underwent a detailed hemispatial neglect assessment that included oral reading, scene copy, line cancellation, gap detection, horizontal line bisection tests, and MRI. Each patient's connectivity map was generated. We performed a linear association analysis between network connectivity strength and continuous measures of neglect to identify lesion-induced disconnections associated with the presence or severity of VCN and SCN. Results were corrected for multiple comparisons.ResultsAbout 42% of the participants with right hemisphere stroke had at least one type of neglect. The presence of any type of neglect was associated with lesions to tracts connecting the right inferior parietal cortex, orbitofrontal cortex, and right thalamus to other right-hemispheric structures. VCN only was strongly associated with tracts connecting the right putamen to other brain regions and tracts connecting right frontal regions with other brain regions. The presence of both types of neglect was most strongly associated with tracts connecting the right inferior and superior parietal cortex to other brain regions and those connecting left or right mesial temporal cortex to other brain regions.DiscussionOur study provides new evidence for the specific white matter tracts where disruption can cause hemispatial neglect in a relatively large number of participants and homogeneous time after onset. We obtained MRI and behavioral testing acutely, before the opportunity for rehabilitation or substantial recovery.Classification of EvidenceThis study provides Class II evidence that damage to specific white matter tracts identified on MRI are associated with the presence of neglect following right hemispheric stroke.

The Study of Face Processing in Social Anxiety Disorder Based on Face-Specific N170 Component

Although previous studies showed that social anxiety disorder (SAD) exhibits the attentional bias for angry faces, few studies investigated effective face recognition combined with event-related potential (ERP) technique in SAD patients, especially the treatment effect. This study examines the differences in face processing in SAD patients before and after treatment and healthy control people (H-group). High-density EEG scans were registered in response to emotional schematic faces, particularly interested in the face processing N170 component. Analysis of N170 amplitude revealed a larger N170 for P-group-pre in response to inverted and upright stimuli than H-group in the right hemisphere. The result of the intragroup t-test showed that N170 was delayed for inverted relative to upright faces only in P-group-post and H-group but not in P-group-pre. Remarkably, the results of ANOVAs manifested that emotional expression cannot modulate N170 for SAD patients. Besides, the N170-based asymmetry index (AI) was introduced to analyze the left- and right-hemisphere dominance of N170 for three groups. It was found that, with the improvement of patients’ treatment, the value of A I N 170 − b a s e d presented a decreasing trend. These results together suggested that there was no inversion effect observed for patients with SAD. The change in the value of A I N 170 − b a s e d can be used as potential electrophysiological markers for the diagnosis and treatment effects on patients with SAD.

Computer-Based Assessment: Dual-Task Outperforms Large-Screen Cancellation Task in Detecting Contralesional Omissions

Objective: Traditionally, asymmetric spatial processing (i.e., hemispatial neglect) has been assessed with paper-and-pencil tasks, but growing evidence indicates that computer-based methods are a more sensitive assessment modality. It is not known, however, whether simply converting well-established paper-and-pencil methods into a digital format is the best option. The aim of the present study was to compare sensitivity in detecting contralesional omissions of two different computer-based methods: a “digitally converted” cancellation task was compared with a computer-based Visual and Auditory dual-tasking approach, which has already proved to be very sensitive.Methods: Participants included 40 patients with chronic unilateral stroke in either the right hemisphere (RH patients, N = 20) or the left hemisphere (LH patients, N = 20) and 20 age-matched healthy controls. The cancellation task was implemented on a very large format (173 cm × 277 cm) or in a smaller (A4) paper-and-pencil version. The computer-based dual-tasks were implemented on a 15′′ monitor and required the detection of unilateral and bilateral briefly presented lateralized targets.Results: Neither version of the cancellation task was able to show spatial bias in RH patients. In contrast, in the Visual dual-task RH patients missed significantly more left-sided targets than controls in both unilateral and bilateral trials. They also missed significantly more left-sided than right-sided targets only in the bilateral trials of the Auditory dual-task.Conclusion: The dual-task setting outperforms the cancellation task approach even when the latter is implemented on a (large) screen. Attentionally demanding methods are useful for revealing mild forms of contralesional visuospatial deficits.