Search bioRxiv⌕ Search

Biology subjects

Lundqvist, D.

Publications and source records attributed to Lundqvist, D..

13 recordsLinked to original sources

Comparing advanced interference suppression algorithms for OPM-MEG

On-scalp MEG using optically pumped magnetometers (OPMs) have become more widespread with the recent introduction of the first whole-head systems that offer comparable spatial sampling to conventional MEG systems. For these systems to become truly useful in neuroscience and clinically they need to be able to deal with the kind of interference seen in typical lab and hospital environments - both environmental and participant related (e.g., dental wires). Conventional MEG uses sophisticated interference suppression algorithms to deal with this, but these tend to become instable at lower sensor counts - which makes up the majority of OPM-MEG systems to date. Alternative methods for OPM-MEG are needed. Several alternative algorithms have been proposed but a clear comparison between them is lacking. Here, we test and compare 5 of the most promising candidates, namely homogenous field correction (HFC), adaptive multipole models (AMM), signal space projection (SSP), signal space separation (SSS) and its iterative implementation (SSSit) using simulations and data recorded with a whole-head system. Recorded data includes a participant with dental wire - an especially difficult to deal with source of interference. We find that all algorithms tested achieve good interference suppression with dual-axis data. With single-axis data, SSS exhibited stability problems and several algorithms showed large signal loss (up to ~25%). SSP, temporal SSS and temporal AMM were able to suppress the dental artifact. Finally, we provide recommendations for researchers to determine help decide how to deal with interference in their OPM-MEG studies.

neuroscience↗

Motor prediction reduces beta-band power and enhances cerebellar-somatosensory connectivity before self-touch to enable its attenuation

Motor control theories suggest that the brain uses forward models to predict self-generated tactile input during voluntary movements, thereby reducing the intensity of reafferent tactile sensations. When ones own body is the target, this phenomenon is called self-touch attenuation. Although self-touch attenuation is well-documented, it remains unclear how prediction-related neural mechanisms drive attenuation before the self-touch input. We used magnetoencephalography (MEG) to examine the neural correlates of self-touch prediction. 24 human participants (12 female, 12 male) performed a self-touch, and two control tasks. In one control, they received externally generated touch without movement. In the other, the touch was triggered by the participants movement, but the hands were spatially misaligned. This manipulation is known to weaken attenuation despite identical tactile input, movement, and task demands, because the sensorimotor context reduces prediction of touch at that body site. Self-touch evoked weaker somatosensory activity (M50 component) than both control conditions. A psychophysics task mirrored the pattern of neural attenuation, as the perception of self-touch was attenuated compared to the two control conditions. To isolate predictive neural mechanisms from general movement-related activity, we subtracted activity from corresponding stimulus-absent trials. Comparing self-touch with misaligned touch allowed us to refine the signal specific to predictive processing in self-touch and revealed greater pre-stimulus beta-band desynchronization and increased cerebellar-to-somatosensory connectivity before self-touch compared to misaligned touch. Our results provide the first evidence of predictive neural activity that shapes the sensory consequences of self-touch, offering insights into the mechanisms through which predictive models modulate somatosensory processing. Significance statementThe brain is thought to predict and attenuate the sensory consequences of self-generated actions, but neural evidence for prediction before sensation has been limited. Using magnetoencephalography, we show that self-touch attenuation is preceded by beta-band desynchronization and increased directed connectivity from the cerebellum to the primary somatosensory cortex. These effects cannot be attributed to movement, as they were reduced in a control condition with similar motor output but lower congruence between the action and tactile consequence, suggesting spatially specific predictive processing. Our study provides the first neural evidence of cerebellar influence on cortical sensory areas before self-touch. These pre-stimulus effects support forward models of sensorimotor control and shed new light on how the brain anticipates and modulates upcoming sensory input.

neuroscience↗

Cortex-wide topography of 1/f-exponent in Parkinson's disease

Parkinsons Disease causes progressive and debilitating changes to the brain as well as to the mind. While the diagnostic hallmark features are the characteristic movement-related symptoms, the disease also causes decline in sensory processing, cognitive, emotional performance and most patients develop dementia over time. The extent of symptoms and the brain-wide projections of neuromodulators such as dopamine suggest that many brain regions are simultaneously affected in Parkinsons disease. To characterise such disease-related and brain-wide changes in neuronal function, we performed a source level analysis of resting state magnetoencephalogram (MEG) from two groups: Parkinsons disease patients and healthy controls. Besides standard spectral analysis, we quantified the aperiodic component of the neural activity by fitting a power law ({kappa}/f {lambda}) to the MEG spectrum and then studied its relationship with age and UPDRS. Consistent with previous results, the most significant spectral changes were observed in the high theta/low alpha band (7-10 Hz) in all brain regions. Furthermore, analysis of the aperiodic part of the spectrum showed that, in all but frontal regions, {lambda} was significantly larger in Parkinsons disease patients than in control subjects. Our results indicate for the first time that Parkinsons disease is associated with significant changes in population activity across the whole neocortex. Surprisingly, even early sensory areas showed a significantly larger {lambda} in patients than in healthy controls. Moreover, {lambda} was not affected by the L-dopa medication. Finally, {lambda} was positively correlated with patient age but not with UPDRS-III (summary measure of motor symptoms clinical rating). Because {lambda} is closely associated excitationinhibition balance, our results propose new hypotheses about manifestation of Parkinsons disease in cortical networks.

neuroscience↗

On the clinical benefit of on-scalp MEG: A modeling study of on-scalp MEG epileptic activity source estimation ability

ObjectiveWhole-head on scalp magnetoencephalography (osMEG) is a novel, cutting-edge functional neuroimaging technique that positions MEG sensors closer to the cortical sources. OsMEG allows both for free head movements and improved spatial resolution compared to conventional MEG. OsMEG thus might improve clinical epilepsy evaluations. However, it remains largely unknown how osMEG characterizes epileptic activity. Here, we aimed to compare epileptic activity source estimation accuracy of osMEG, high-density EEG (hd-EEG), conventional MEG (convMEG) and subdural EEG (sbdEEG). MethodIED and seizure onset zone source estimations of osMEG, hdEEG, convMEG and sbdEEG were evaluated using equivalent current dipoles. Cancellation index of all non-invasive modalities were calculated and compared statistically. To further investigate any similarity between osMEG and sbdEEG, representational similarity analysis was used to compare IED source estimations of these two modalities. ResultsWe found that osMEG IED source estimations were significantly (p<0.05) better than both convMEG and hdEEG. Furthermore, osMEG mesial temporal lobe SOZ source estimations were superior to those of convMEG and hdEEG. OsMEG cancellation index did not differ significantly from convMEG. Interestingly, comparing osMEG and sbdEEG IED source estimation demonstrated that osMEG might be less sensitive to source directions than convMEG. ConclusionWe demonstrated that whole-head osMEG exhibited very accurate non-invasive IED and SOZ source estimations, better than both hd-EEG and convMEG. SignificanceOsMEG has a promising potential to become a safe, highly sensitive neuroimaging modality for whole head epilepsy evaluations. HighlightsO_LIAnalysis of novel on-scalp MEG (osMEG) sensors in epilepsy evaluations C_LIO_LICompares osMEG, EEG, conventional MEG & intracranial EEG epilepsy source estimations C_LIO_LIOur study demonstrates potential great clinical value of osMEG whole-head sensors C_LI

neuroscience↗

Auditory Steady-State Responses During And After A Stimulus: Cortical Sources, and the Influence of Attention and Musicality

The auditory steady-state response (ASSR) is an oscillatory brain response generated by periodic auditory stimuli and originates mainly from the temporal auditory cortices. Recent data show that while the auditory cortices are indeed strongly activated by the stimulus when it is present (ON ASSR), the anatomical distribution of ASSR sources involves also parietal and frontal cortices, indicating that the ASSR is a more complex phenomenon than previously believed. Furthermore, while the ASSR typically continues to oscillate even after the stimulus has stopped (OFF ASSR), very little is known about the characteristics of the OFF ASSR and how it compares to the ON ASSR. Here, we assessed whether the OFF and ON ASSR powers are modulated by the stimulus properties (i.e. volume and pitch), selective attention, as well as individual musical sophistication. We also investigated the cortical source distribution of the OFF ASSR using a melody tracking task, in which attention was directed between uniquely amplitude-modulated melody streams that differed in pitch. The ON and OFF ASSRs were recorded with magnetoencephalography (MEG) on a group of participants varying from low to high degree of musical sophistication. Our results show that the OFF ASSR is distinctly different from the ON ASSR in nearly every aspect. While the ON ASSR was modulated by the stimulus properties and selective attention, the OFF ASSR was not influenced by any of these factors. Furthermore, while the ON ASSR was generated primarily from temporal sources, the OFF ASSR originated mainly from the frontal cortex. These findings challenge the notion that the OFF ASSR is merely a continuation of the ON ASSR. Rather, they suggest that the OFF ASSR is an internally-driven signal that develops from an initial sensory processing state (ON ASSR), with both types of ASSRs clearly differing in cortical representation and character. Furthermore, our results show that the ON ASSR power was enhanced by selective attention at cortical sources within each of the bilateral frontal, temporal, parietal and insular lobes. Finally, the ON ASSR proved sensitive to musicality, demonstrating positive correlations between musical sophistication and ASSR power, as well as with the degree of attentional ASSR modulation at the left and right parietal cortices. Taken together, these results show new aspects of the ASSR response, and demonstrate its usefulness as an effective tool for analysing how selective attention interacts with individual abilities in music perception.

neuroscience↗

Interictal epileptiform discharges in focal epilepsy are preceded by a gradual increase in low-frequency oscillations

Epilepsy is characterized by recurrent seizures and may also have negative influence on cognitive function. In addition to ictal activity, the epileptic brain also gives rise to interictal epileptiform discharges (IEDs). These IEDs constitute the diagnostic hallmark of epilepsy, and have been linked to impaired memory formation and negative effects on neurodevelopment. The neurophysiological dynamics underlying IED generation seem to resemble those underlying seizure development. Understanding the neurophysiological characteristics surrounding and preceding IED development would hence provide valuable insights into the pathophysiology of the epileptic brain. In order to improve this understanding, we aimed to characterize the dynamical activity changes that occurs immediately prior to an IED onset. We used magnetoencephalography (MEG) recordings from nine focal epilepsy patients to characterize the oscillatory activity preceding IED onsets. Our results showed a systematic and gradual increase in oscillatory delta and theta band activity (1-4 Hz and 4-8 Hz, respectively) during this pre-IED interval, reaching a maximum power at IED onset. These results indicate that the pre-IED brain state is characterized by a gradual synchronization that culminates in the neuronal hypersynchronization underlying IEDs. We discuss how IED generation might resemble seizure development, where physiological brain activity similarly undergoes a gradual synchronization that terminates in seizure onset.

neuroscience↗

Attentional Modulation of the Auditory Steady-State Response across the Cortex

Selective auditory attention allows us to focus on relevant sounds within noisy or complex auditory environments, and is essential for the processing of speech and music. The auditory steady-state response (ASSR) has been proposed as a neural measure for tracking selective auditory attention, even within continuous and complex soundscapes. However, the current literature is inconsistent on how the ASSR is influenced by selective attention, with findings based primarily on attention being directed to either ear rather than to sound content. In this experiment, a mixture of melody streams was presented to both ears identically (diotically) as we examined if selective auditory attention to sound content influences the ASSR. Using magnetoencephalography (MEG), we assessed the stream-specific ASSRs from three frequency-tagged melody streams when attention was directed between each melody stream, based on their respective pitch and timing. Our main results showed that selective attention enhances the ASSR power of an attended melody stream by 15 % at a general sensor level. This ability to readily capture attentional changes in a stimuli-precise manner makes the ASSR a useful tool for studying selective auditory attention, especially in complex auditory environments. Furthermore, as a secondary aim, we explored the distribution of cortical ASSR sources and their respective attentional modulation. A novel finding using distributed source modelling revealed that the ASSR is modulated by attention in many areas across the cortex, with frontal regions experiencing the strongest enhancement of up to ~ 80 %. ASSRs in the temporal and parietal cortices were enhanced by approximately 20 - 25 %. For future studies, this work can serve as a template to narrow-down possible sites of ASSR attentional modulation for further investigation.

neuroscience↗

Detection of interictal epileptiform discharges:A comparison of on-scalp MEG and conventional MEGmeasurements

Magnetoencephalography (MEG) is an important part of epilepsy evaluations because of its unsurpassed ability to detect interictal epileptiform discharges (IEDs). This ability may be improved by next-generation MEG sensors, where sensors are placed directly on the scalp instead of in a fixed-size helmet, as in todays conventional MEG systems. In order to investigate the usefulness of on-scalp MEG measurements we performed the first-ever measurements of on-scalp MEG on an epilepsy patient. The measurement was conducted as a benchmarking study, with special focus on IED detection. An on-scalp high-temperature SQUID system was utilized alongside a conventional low-temperature "in-helmet" SQUID system. EEG was co-registered during both recordings. Visual inspection of IEDs in the raw on-scalp MEG data was unfeasible why a novel machine learning-based IED-detection algorithm was developed to guide IED detection in the on-scalp MEG data. A total of 24 IEDs were identified visually from the conventional in-helmet MEG session (of these, 16 were also seen in the EEG data; eight were detected only by MEG). The on-scalp MEG data contained a total of 47 probable IEDs of which 16 IEDs were co-registered by the EEG, and 31 IEDs were on-scalp MEG-unique IEDs found by the IED detection algorithm. We present a successful benchmarking study where on-scalp MEG are compared to conventional in-helmet MEG in a temporal lobe epilepsy patient. Our results demonstrate that on-scalp MEG measurements are feasible on epilepsy patients, and indicate that on-scalp MEG might capture IEDs not seen by other non-invasive modalities.

neuroscience↗

Reduction of spontaneous cortical beta bursts in Parkinson’s disease is linked to symptom severity

Parkinsons disease is characterized by a gradual loss of dopaminergic neurons, which are associated with altered neuronal activity in the beta band (13-30 Hz). Assessing beta band activity typically involves transforming the time-series to get the power of the signal in the frequency-domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine-and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical features in the beta band activity--for example, that the beta band exhibits transient bursts of high-amplitude activity.\n\nIn an exploratory study we used magnetoencephalography (MEG) to record cortical beta band activity to characterize how spontaneous cortical beta bursts manifest in Parkinsons patients ON and OFF dopaminergic medication, and compare this to matched healthy controls. From three minutes of MEG data, we extracted the time-course of beta band activity from the sensorimotor cortex and characterized high-amplitude epochs in the signal to test if they exhibited burst like properties. We then compared the rate, duration, inter-burst interval, and peak amplitude of the high-amplitude epochs between the Parkinsons patients and healthy controls.\n\nOur results show that Parkinsons patients OFF medication had a 6-17% lower beta bursts rate compared to healthy controls, while both the duration and the amplitude of the bursts were the same for Parkinsons patients and healthy controls and medicated state of the Parkinsons patients. These data thus support the view that beta bursts are fundamental underlying features of beta band activity, and show that changes in cortical beta band power in PD can be explained primarily by changes in the underlying burst rate. Importantly, our results also revealed a relationship between beta bursts rate and motor symptom severity in PD: a lower burst rate scaled with increased in severity of bradykinesia and postural/kinetic tremor. Beta burst rate might thus serve as neuromarker for Parkinsons disease that can help in the assessment of symptom severity in Parkinsons disease or evaluate treatment effectiveness.

neuroscience↗

On-scalp MEG SQUIDs are sensitive to early somatosensory activity unseen by conventional MEG

Magnetoencephalography (MEG) has a unique capacity to resolve the spatio-temporal development of brain activity from non-invasive measurements. Conventional MEG, however, relies on sensors that sample from a distance (20-40 mm) to the head due to thermal insulation requirements (the MEG sensors function at 4 K in a helmet). A gain in signal strength and spatial resolution may be achieved if sensors are moved closer to the head. Here, we report a study comparing measurements from a seven-channel on-scalp SQUID MEG system to those from a conventional (in-helmet) SQUID MEG system.\n\nWe compared spatio-temporal resolution between on-scalp and conventional MEG by comparing the discrimination accuracy for neural activity patterns resulting from stimulating five different phalanges of the right hand. Because of proximity and sensor density differences between on-scalp and conventional MEG, we hypothesized that on-scalp MEG would allow for a more high-resolved assessment of these activity patterns, and therefore also a better classification performance in discriminating between neural activations from the different phalanges.\n\nWe observed that on-scalp MEG provided better classification performance during an early post-stimulus period (15-30 ms). This corresponded to electroencephalographic (EEG) response components N16 and P23, and was an unexpected observation as these components are usually not observed in conventional MEG. They indicate that on-scalp MEG opens up for a richer registration of the cortical signal, allowing for sensitivity to what are potentially sources in the thalamo-cortical radiation and to quasi-radial sources.\n\nWe had originally expected that on-scalp MEG would provide better classification accuracy based on activity in proximity to the P60m component compared to conventional MEG. This component indeed allowed for the best classification performance for both MEG systems (60-75%, chance 50%). However, we did not find that on-scalp MEG allowed for better classification than conventional MEG at this latency. We believe this may be due to the limited sensor coverage in the recording, in combination with our strategy for positioning the on-scalp MEG sensors. We discuss how sensor density and coverage as well as between-phalange source field dissimilarities may influence our hypothesis testing, which we believe to be useful for future benchmarking measurements.

neuroscience↗

Sensor localization using magnetic dipole-like coils: A method for highly accurate co-registration in on-scalp MEG

Source modelling in magnetoencephalography (MEG) requires precise co-registration of the sensor array and the anatomical structure of the measured individuals head. In conventional MEG, positions and orientations of the sensors relative to each other are fixed and known beforehand, requiring only localization of the head relative to the sensor array. Since the sensors in on-scalp MEG are positioned on the scalp, locations of the individual sensors depend on the subjects head shape and size. The positions and orientations of on-scalp sensors must therefore be measured at every recording. This can be achieved by inverting conventional head localization, localizing the sensors relative to the head - rather than the other way around.\n\nIn this study we present a practical method for localizing sensors using magnetic dipole-like coils attached to the subjects head. We implement and evaluate the method in a set of on-scalp MEG recordings using a 7-channel on-scalp MEG system based on high critical temperature superconducting quantum interference devices (high-Tc SQUIDs). The method provides accurate estimates of individual sensor positions and orientations with short averaging time ([&le;] 2 mm and < 3 degrees, respectively, with 1-second averaging), enabling continuous sensor localization. Calibrating and jointly localizing the sensor array can further improve the localization accuracy (< 1 mm and < 2.5 degrees, respectively, with 1-second coil recordings).\n\nWe demonstrate source localization of on-scalp recorded somatosensory evoked activity based on co-registration with our method. Equivalent current dipole fits of the evoked responses corresponded well (within 5.3 mm) with those based on a commercial, whole-head MEG system.

neuroscience↗

Somatosensory responses to nothing: an MEG study of expectations during omission of tactile stimulations

The brain builds up expectations to future events based on the patterns of past events. This function has been studied extensively in the auditory and visual domains using various oddball paradigms, but only little exploration of this phenomenon has been done in the somatosensory domain. In this study, we explore how expectations of somatosensory stimulations are established and expressed in neural activity as measured with magnetoencephalography. Using tactile stimulations to the index finger, we compared conditions with actual stimulation to conditions with omitted stimulations, both of which were either expected or unexpected.\n\nOur results show that when a stimulation is expected but omitted, a time-locked response occurs [~]135 ms subsequent to the expected stimulation. This somatosensory response to \"nothing\" was source localized to the secondary somatosensory cortex and to the insula. This provides novel evidence of the capability of the brain of millisecond time-keeping of somatosensory patterns across intervals of 3000 ms.\n\nOur results also show that when stimuli are repeated and expectations are established, there is associated activity in the theta and beta bands. These theta and beta band expressions of expectation were localized to the primary somatosensory area, inferior parietal cortex and cerebellum. Furthermore, there was gamma band activity in the right insula for the first stimulation after an omission, which indicates the detection of a new stimulation event after an expected pattern has been broken.\n\nFinally, our results show that cerebellum play a crucial role in predicting upcoming stimulation and in predicting when stimulation may begin again.

neuroscience↗

Attenuated post-movement beta rebound in Parkinson’s disease to proprioceptive afferent feedback

Motor symptoms are defining traits in the diagnosis of Parkinsons disease (PD). A crucial component in motor function and control of movements is the integration of efferent signals from the motor network to the peripheral motor system, and afferent proprioceptive sensory feedback. Previous studies have indicated abnormal movement-related cortical oscillatory activity in PD, but the role of the proprioceptive afference on abnormal oscillatory activity in PD has not been elucidated. In the present study, we examine the role of proprioception by studying the cortical processing of proprioceptive stimulation in PD patients, ON/OFF levodopa medication, as compared to that of healthy controls (HC). We used a proprioceptive stimulator that generated precisely controlled passive movements of the index finger and measured the induced cortical oscillatory responses following the proprioceptive stimulation using magnetoencephalography (MEG). Both PD patients and HC showed a typical initial mu/beta-band (8-30 Hz) desynchronization during the passive movement. However, the subsequent beta rebound after the passive movement that was apparent in HC was much attenuated and almost absent in PD patients. Furthermore, we found no difference in the degree of beta rebound attenuation between patients ON and OFF levodopa medication. Our results hence demonstrate a disease-related deterioration in cortical processing of proprioceptive afference in PD, and further suggest that such disease-related loss of proprioceptive function is due to processes outside the dopaminergic system affected by levodopa medication.

neuroscience↗