COVID-19 vaccination-related exacerbation of seizures in persons with epilepsy.

Although vaccines are generally safe in persons with epilepsy (PWE), seizures can be associated with vaccination, including COVID-19. This study assessed the occurrence of COVID-19 vaccination-related seizure exacerbations in PWE. Adult PWE who had received a COVID-19 vaccine were consecutively recruited at a tertiary epilepsy clinic between June 2021 and April 2022. Patient demographics, including epilepsy history, vaccination details, and reported adverse effects were recorded. Seizure exacerbation, defined as occurring within one week of vaccination, was assessed. Five hundred and thirty PWE received the COVID-19 vaccine. 75 % received the Comirnaty (Pfizer) vaccine as their initial dose. Most patients (72 %) were taking ≥ 2 antiseizure medications (ASM) and had focal epilepsy (73 %). One-third were 12 months seizure free at their first vaccination. 13 patients (2.5 %) reported a seizure exacerbation following their first vaccination, three of whom required admission. None were seizure-free at baseline. Six of these patients (46 %) had a further exacerbation of seizures with their second vaccine. An additional four patients reported increased seizures only with the second vaccine dose. Seizure exacerbations are infrequently associated with COVID-19 vaccination, mainly in patients with ongoing seizures. The likelihood of COVID-19 infection complications in PWE outweighs the risk of vaccination-related seizure exacerbations.

Neuroanatomical features in soldiers with post-traumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD), an anxiety disorder that can develop after exposure to psychological trauma, impacts up to 20 % of soldiers returning from combat-related deployment. Advanced neuroimaging holds diagnostic and prognostic potential for furthering our understanding of its etiology. Previous imaging studies on combat-related PTSD have focused on selected structures, such as the hippocampi and cortex, but none conducted a comprehensive examination of both the cerebrum and cerebellum. The present study provides a complete analysis of cortical, subcortical, and cerebellar anatomy in a single cohort. Forty-seven magnetic resonance images (MRIs) were collected from 24 soldiers with PTSD and 23 Control soldiers. Each image was segmented into 78 cortical brain regions and 81,924 vertices using the corticometric iterative vertex based estimation of thickness algorithm, allowing for both a region-based and a vertex-based cortical analysis, respectively. Subcortical volumetric analyses of the hippocampi, cerebellum, thalamus, globus pallidus, caudate, putamen, and many sub-regions were conducted following their segmentation using Multiple Automatically Generated Templates Brain algorithm. RESULTS: Participants with PTSD were found to have reduced cortical thickness, primarily in the frontal and temporal lobes, with no preference for laterality. The region-based analyses further revealed localized thinning as well as thickening in several sub-regions. These results were accompanied by decreased volumes of the caudate and right hippocampus, as computed relative to total cerebral volume. Enlargement in several cerebellar lobules (relative to total cerebellar volume) was also observed in the PTSD group. CONCLUSIONS: These data highlight the distributed structural differences between soldiers with and without PTSD, and emphasize the diagnostic potential of high-resolution MRI.

Atypical spatiotemporal signatures of working memory brain processes in autism.

Working memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM-related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed.

Low-frequency connectivity is associated with mild traumatic brain injury.

Mild traumatic brain injury (mTBI) occurs from a closed-head impact. Often referred to as concussion, about 20% of cases complain of secondary psychological sequelae, such as disorders of attention and memory. Known as post-concussive symptoms (PCS), these problems can severely disrupt the patient's quality of life. Changes in local spectral power, particularly low-frequency amplitude increases and/or peak alpha slowing have been reported in mTBI, but large-scale connectivity metrics based on inter-regional amplitude correlations relevant for integration and segregation in functional brain networks, and their association with disorders in cognition and behaviour, remain relatively unexplored. Here, we used non-invasive neuroimaging with magnetoencephalography to examine functional connectivity in a resting-state protocol in a group with mTBI (n = 20), and a control group (n = 21). We observed a trend for atypical slow-wave power changes in subcortical, temporal and parietal regions in mTBI, as well as significant long-range increases in amplitude envelope correlations among deep-source, temporal, and frontal regions in the delta, theta, and alpha bands. Subsequently, we conducted an exploratory analysis of patterns of connectivity most associated with variability in secondary symptoms of mTBI, including inattention, anxiety, and depression. Differential patterns of altered resting state neurophysiological network connectivity were found across frequency bands. This indicated that multiple network and frequency specific alterations in large scale brain connectivity may contribute to overlapping cognitive sequelae in mTBI. In conclusion, we show that local spectral power content can be supplemented with measures of correlations in amplitude to define general networks that are atypical in mTBI, and suggest that certain cognitive difficulties are mediated by disturbances in a variety of alterations in network interactions which are differentially expressed across canonical neurophysiological frequency ranges.

Resting-state hippocampal connectivity correlates with symptom severity in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a serious mental health injury which can manifest after experiencing a traumatic life event. The disorder is characterized by symptoms of re-experiencing, avoidance, emotional numbing and hyper-arousal. Whilst its aetiology and resultant symptomology are better understood, relatively little is known about the underlying cortical pathophysiology, and in particular whether changes in functional connectivity may be linked to the disorder. Here, we used non-invasive neuroimaging with magnetoencephalography to examine functional connectivity in a resting-state protocol in the combat-related PTSD group (n = 23), and a military control group (n = 21). We identify atypical long-range hyperconnectivity in the high-gamma-band resting-state networks in a combat-related PTSD population compared to soldiers who underwent comparable environmental exposure but did not develop PTSD. Using graph analysis, we demonstrate that apparent network connectivity of relevant brain regions is associated with cognitive-behavioural outcomes. We also show that left hippocampal connectivity in the PTSD group correlates with scores on the well-established PTSD Checklist (PCL). These findings indicate that atypical synchronous neural interactions may underlie the psychological symptoms of PTSD, whilst also having utility as a potential biomarker to aid in the diagnosis and monitoring of the disorder.

Colour or shape: examination of neural processes underlying mental flexibility in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a mental disorder that stems from exposure to one or more traumatic events. While PTSD is thought to result from a dysregulation of emotional neurocircuitry, neurocognitive difficulties are frequently reported. Mental flexibility is a core executive function that involves the ability to shift and adapt to new information. It is essential for appropriate social-cognitive behaviours. Magnetoencephalography (MEG), a neuroimaging modality with high spatial and temporal resolution, has been used to track the progression of brain activation during tasks of mental flexibility called set-shifting. We hypothesized that the sensitivity of MEG would be able to capture the abnormal neurocircuitry implicated in PTSD and this would negatively impact brain regions involved in set-shifting. Twenty-two soldiers with PTSD and 24 matched control soldiers completed a colour-shape set-shifting task. MEG data were recorded and source localized to identify significant brain regions involved in the task. Activation latencies were obtained by analysing the time course of activation in each region. The control group showed a sequence of activity that involved dorsolateral frontal cortex, insula and posterior parietal cortices. The soldiers with PTSD showed these activations but they were interrupted by activations in paralimbic regions. This is consistent with models of PTSD that suggest dysfunctional neurocircuitry is driven by hyper-reactive limbic areas that are not appropriately modulated by prefrontal cortical control regions. This is the first study identifying the timing and location of atypical neural responses in PTSD with set-shifting and supports the model that hyperactive limbic structures negatively impact cognitive function.

fMRI and MEG in the study of typical and atypical cognitive development.

The tremendous changes in brain structure over childhood are critical to the development of cognitive functions. Neuroimaging provides a means of linking these brain-behaviour relations, as task protocols can be adapted for use with young children to assess the development of cognitive functions in both typical and atypical populations. This paper reviews some of our research using magnetoencephalography (MEG) and functional MRI (fMRI) in the study of cognitive development, with a focus on frontal lobe functions. Working memory for complex abstract patterns showed clear development in terms of the recruitment of frontal regions, seen with fMRI, with indications of strategy differences across the age range, from 6 to 35 years of age. Right hippocampal involvement was also evident in these n-back tasks, demonstrating its involvement in recognition in simple working memory protocols. Children born very preterm (7 to 9 years of age) showed reduced fMRI activation particularly in the precuneus and right hippocampal regions relative to control children. In a large normative n-back study (n=90) with upright and inverted faces, MEG data also showed right hippocampal activation that was present across the age range; frontal sources were evident only from 10 years of age. Other studies have investigated the development of set shifting, an executive function that is often deficit in atypical populations. fMRI showed recruitment of frontal areas, including the insula, that have significantly different patterns in children (7 to 14 years of age) with autism spectrum disorder compared to typically developing children, indicating that successful performance implicated differing strategies in these two groups of children. These types of studies will help our understanding of both normal brain-behaviour development and cognitive dysfunction in atypically developing populations.

Recognising upright and inverted faces: MEG source localisation.

Face recognition is a complex cognitive task that involves a distributed network of neural sources. While some components of this network have been identified, the temporal sequence of these components is not well understood. Magnetoencephalography (MEG), analyzed with a spatial filtering source localisation algorithm, was used to determine frontal contributions to face recognition. We tested 22 adults (mean age 26.3 years; 10 females). Upright and inverted faces were presented in counter-balanced blocks and subjects identified repetitions in a 1-back protocol. MEG data were recorded continuously from a 151 channel CTF machine and source localised to each participant's MRI. The classic face components, M100 and M170, were seen for upright and inverted faces with M100 localizing to bilateral occipital areas and M170 to bilateral fusiform areas. A third component, M240, showed high global field power to correctly recognised repeated faces and localised to right middle frontal and insula sources at 240 ms for upright faces and bilateral mid-frontal sources for inverted faces. The effect of repetition was examined and a source identified at 250 ms in the cingulate, for inverted faces. These results provide timing information on frontal lobe activation, seen reliably in fMRI memory studies; the immediate recognition of repeated faces activates the right frontal sources at 240-250 ms, with bilateral activation to repeated inverted faces, perhaps due to increased task difficulty.

Magnetoencephalography for clinical pediatrics: the effect of head positioning on measurement of somatosensory-evoked fields.

OBJECTIVE: At present, whole-head MEG systems are designed to accommodate adult heads, thereby introducing a technical issue unique to pediatric MEG. It is known that magnetic field strength decreases as a function of 1/distance(2). For pediatric patients, we questioned whether re-positioning the head to minimize the distance between the expected source location and the MEG sensor array would significantly improve source measurement. METHODS: Somatosensory-evoked fields (SEFs) were recorded in 17 children (mean=4.96 years) with their head placed centrally in the MEG, and then re-positioned laterally to reduce the distance between the cortical source and sensors. Equivalent current dipole (ECD) source models were evaluated for changes in residual variance (RV), signal-to-noise ratio (SNR), moment (strength), and location. RESULTS: Re-positioning the head closer to the sensors resulted in a significant shift in the mediolateral dipole coordinate location, accompanied by a significant increase in the SNR, decrease in the dipole RV, and a reduction in size of ECD confidence volumes. CONCLUSIONS: We conclude that for clinical pediatric measurement of the SEF, repositioning of the head to minimize the distance between the expected SEF source location and the sensor array will significantly improve SEF source measurement and concomitant ECD source modeling. SIGNIFICANCE: These issues are relevant to all pediatric MEG settings involving healthy or clinical populations and underscores the need for future development of a MEG helmet specifically designed for pediatric populations.

Face processing in adolescents with and without epilepsy.

Children with temporal lobe epilepsy frequently suffer memory deficits, often marked in face processing. To determine the neural correlates of this dysfunction, we investigated face processing in adolescents with intractable epilepsy compared to typically developing controls. The M170 and M220 MEG event-related fields (ERFs) were recorded while the adolescents completed an n-back task on blocks of upright and inverted faces. Source analyses of the ERF data were performed using an event-related beamforming technique that allowed the detection of multiple sources. The control adolescents showed the expected waveforms and inversion effects, although there were differences in source localization, compared to the adult literature. The participants with epilepsy had poor performance on the tasks. The adolescents with extra-temporal lobe epilepsy showed both the M170 and M220 but the source localizations were highly atypical. The patients with right temporal lobe epilepsy had an absent or highly atypical M220, a component related to face recognition processes. We hypothesize that the children with extra-temporal lobe epilepsy have difficulty with face encoding processes while the patients with right temporal lobe epilepsy have specific difficulty with face recognition.

Affordable measurement of human total energy expenditure and body composition using one-tenth dose doubly labelled water.

BACKGROUND: The doubly labelled water (DLW) method is the technique of choice for measurement of free-living total energy expenditure (TEE) in humans. A major constraint on the clinical applicability of the method has been the expense of the (18)O isotope. METHOD: We have used a reduced-dose (one-tenth of the currently recommended standard dose) of DLW for the measurement of TEE and body composition in nine healthy adult male volunteers. RESULTS: TEE measured by reduced-dose DLW was positively correlated with resting energy expenditure measured by metabolic cart (r=0.87, P<0.01). Isotope-derived fat mass and body mass index were strongly correlated (r=0.86, P<0.01). In four subjects in whom we performed a complementary evaluation using standard-dose isotope enrichment, the TEE measurements were satisfactorily comparable (mean+/-s.d.: reduced dose 2586+/-155 kcal/day vs standard dose 2843+/-321 kcal/day; mean difference 257+/-265 kcal/day). CONCLUSION: These data indicate that DLW measurements of human energy expenditure and body composition can be performed at a substantially reduced dose (and cost) of isotope enrichment than is currently employed.

Tracking the development of the N1 from age 3 to adulthood: an examination of speech and non-speech stimuli.

OBJECTIVES: To examine developmental changes in the N1a, N1b and N1c evoked by a tone and a speech consonant (/da/). METHODS: Subjects (n=70 for tones; n=69 for /da/) were grouped into 2 year intervals (age 3-16) and adults. They listened to a tone (2 kHz; 36 ms; 77 dB SL; ISI=600 ms; n=346) or a speech consonant /da/ (female voice recording; 7 ms VOT; 212 ms; 72 dB SL; ISI=600 ms; n=349) while watching a Disney((R)) screensaver. EEG was recorded from 26 electrodes referenced to Cz. An averaged reference was computed off-line. Amplitude and latency data were analyzed with repeated-measures ANOVAs for agexelectrode, and agexN1 component, respectively. RESULTS: Left hemisphere N1a was mature before age 3 whereas the right hemisphere N1a matured around 7-8 years. The vertex N1b showed a parietal distribution which shifted anteriorly with age. The N1c showed age- and stimulus-related changes. The N1c measured over the left hemisphere matured earlier than the N1c over the right hemisphere. The N1c to /da/ matured earlier than that to tones. CONCLUSIONS: Auditory processing undergoes steady and subtle developmental changes. These changes follow different maturational patterns depending on the type of stimuli. The evidence suggests earlier development of the left hemisphere and earlier development of the generators underlying speech processing.

Developmental changes in early cognitive processes.

The three paradigms presented in this paper demonstrate the value of ERPs in examining the development of early cognitive processes. Although we have presented only three examples, early cognitive processing could be investigated in a wide range of paradigms using ERPs, in normal as well as clinical populations. Clearly, a next step in understanding the age-related changes in these cognitive processes is to employ dipole source localization to examine the involvement of different generators and their maturation. The final conclusion is that developmental studies are important as they can contribute to our understanding of models of processing and of the generators of ERPs, in terms of cognition as well as neuroanatomy. Hence, the models of cognitive processes in adults should include the development of those processes through childhood.

Dissociation of the mismatch negativity and processing negativity attentional waveforms with nitrous oxide.

In Näätänen's model of early attention, the role of arousal in influencing the permanent feature detection system (indexed by mismatch negativity [MMN]) and the temporary feature-detection system (indexed by processing negativity [PN]) is unclear. To address this question, we investigated the effects of the anesthetic gas nitrous oxide (N2O) on the MMN and PN. Ten subjects performed a dichotic listening task in which discrimination difficulty and breathing mixture (air or 25% N2O) were manipulated factorially. MMN, PN, N1 and P300 at Fz, Cz, and Pz, as well as reaction time (RT), were measured. N2O had no effect on the PN, but decreased MMN amplitude. As expected, N2O decreased the amplitude of the N1 and P300 and increased the latency of the P300 and RT. The dissociation of MMN and PN by N2O suggests that this agent decreases the ability to detect automatic stimulus change without affecting voluntary selective attention. We interpret these results as indicating that arousal has multidimensional effects on early attentional mechanisms. These dimensions can be differentiated chemically by neurotransmitters in the reticular formation of the brain.

Mismatch negativity to speech stimuli in 8-month-old infants and adults.

The mismatch negativity (MMN) was measured in 15 normal awake 8-month-old infants and 10 adults to the speech consonants /da/ and /ta/. ERPs were analyzed at 11 electrodes (Fz, Cz, Pz, C3, C4, T3, T4, T5, T6, P3, P4). Four-hundred trials were presented: the /da/ standards with 80% probability and the /ta/ deviants with 20% probability. The ISI was 600 ms. An MMN was observed for both adults and infants but with different scalp distributions. A clear infant MMN was observed only at C3 and T3 electrodes, whereas the adult MMN was present at Fz, Cz, C3, C4 and Pz. A repeated-measures ANOVA on the normalized summed area between 200 and 250 ms revealed an age (adult vs. infant) x electrode interaction. Paired t-tests indicated that adults and infants showed significant differences at the C3, Cz, T3, Pz and T6 electrodes. The adult MMN was largest at Cz and C3 whereas the infant MMN was largest at T3. These data are discussed in terms of possible maturational changes in the MMN.

Use of nitrous oxide to dissociate the non-specific and specific components of the human auditory N1.

The components of the N1 are thought to be related to sensory functioning (Components 1 and 2) and arousal (Component 3). To provide direct evidence for the involvement of Component 3 in arousal, we hypothesized that it should be more sensitive to the anesthetic gas nitrous oxide (N2O) than Component 1. Using the technique of selective adaptation, 30 blocks of 5 tones were presented at 1 min intervals to 9 subjects who breathed air, 25% and 35% N2O. As hypothesized, the amplitude of Component 3 was significantly reduced in a dose-dependent manner by N2O, but the amplitude of Component 1 was not, although the latter showed some evidence of a decrease at 25% N2O.