Biology subjects

Siebner, H. R.

Publications and source records attributed to Siebner, H. R..

36 records · Page 2Linked to original sources

bioRxiv2022

Linking impulsivity to activity levels in pre-supplementary motor area during sequential gambling

Impulsivity refers to the tendency to act prematurely or without forethought, and excessive impulsivity is a key problem in many neuropsychiatric disorders. Since the pre-supplementary motor area (preSMA) has been implicated in inhibitory control, this region may also contribute to impulsivity. Here, we examined whether functional recruitment of preSMA may contribute to risky choice behavior (state impulsivity) during sequential gambling and its relation to self-reported trait impulsivity. To this end, we performed task-based functional MRI (fMRI) after low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the preSMA. We expected low-frequency rTMS to modulate task-related engagement of the preSMA and hereby, tune the tendency to make risky choices. 24 healthy volunteers (12 females, 19-52 years) received real or sham rTMS on separate days in counterbalanced order. Thereafter, participants performed a sequential gambling task with concurrently increasing stakes and risk during whole-brain fMRI. In the sham-rTMS session, self-reported trait impulsivity scaled positively with state impulsivity (riskier choice behavior) during gambling. The higher the trait-impulsivity, the lower was the task-related increase in preSMA activity with increasingly risky choices. Following real-rTMS, low-impulsivity participants increased their preference for risky choices, while the opposite was true for high-impulsivity participants resulting in an overall decoupling of trait impulsivity and state impulsivity during gambling. This rTMS-induced behavioral shift was mirrored in the rTMS-induced change in preSMA activation. These results provide converging evidence for a causal link between the level of task-related preSMA activity and the propensity for impulsive risk-taking behavior in the context of sequential gambling. Significance statementImpulsivity is a personal trait characterized by a tendency to act prematurely or without forethought, and excessive impulsivity is a key problem in many neuropsychiatric disorders. The pre-supplementary motor area (preSMA) has been implicated in inhibitory control. Here, we provide evidence that this region contributes to the implementation of general impulsive tendencies (trait impulsivity) into actual behavior (state impulsivity). When healthy volunteers performed a sequential gambling task, their choice behavior (i.e., state impulsivity) correlated positively with their impulsivity score (i.e, trait impulsivity). Additionally, participants with lower trait impulsivity showed a stronger increase in task-related activity of the preSMA with increasing risk. Both of these relationships were uncoupled after perturbing the preSMA with repetitive transcranial stimulation (rTMS).

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bioRxiv2022

Multi-pulse transcranial magnetic stimulation of human motor cortex produces short-latency corticomotor facilitation via two distinct mechanisms

BackgroundSingle-pulse transcranial magnetic stimulation of the precentral hand representation (M1HAND) can elicit indirect waves in the corticospinal tract at a periodicity of ~660 Hz, called indirect or I-waves. These synchronized descending volleys are produced by transsynaptic excitation of fastconducting monosynaptic corticospinal axons in M1-HAND. Paired-pulse TMS can induce short-interval intracortical facilitation (SICF) of motor evoked potentials (MEPs) at inter-pulse intervals that match I-wave periodicity. ObjectiveTo examine whether short-latency corticospinal facilitation engages additional mechanisms independently of I-wave periodicity. MethodsIn 19 volunteers, one to four biphasic TMS pulses were applied to left M1-HAND with interpulse interval was adjusted to the first peak or first trough of the individual SICF curve. TMS was applied at different intensities to probe the intensity-response relationship. ResultsPairs, triplets, or quadruplets at individual peak-latency facilitated MEP amplitudes across a wide range of TMS intensities compared to single pulses. Multi-pulse TMSHAND at individual troughlatency also produced a consistent facilitation of MEP amplitude. Short-latency facilitation at trough-latency was less pronounced than short-latency facilitation at peak-latency, but the relative difference in facilitation decreased with increasing stimulus intensity. Increasing the number of pulses from two to four pulses had only a modest effect on MEP facilitation. ConclusionTwo mechanisms underly short-latency corticomotor facilitation caused by biphasic multi-pulse TMS. An intracortical mechanism is related to I-wave periodicity and engages fast-conducting direct projections to spinal motoneurons. A second corticospinal mechanism does not rely on I-wave rhythmicity and may be mediated by slower conducting indirect pyramidal tract projections from M1-HAND to spinal interneurons. The latter mechanism deserves more attention in TMS studies of the corticomotor system.

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bioRxiv2022

Corticospinal excitability is influenced by the recent history of electrical digital stimulation: implications for the relative magnitude of short-latency afferent inhibition

BackgroundElectrical stimulation of the hand can suppress the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) of the primary motor hand area (M1-HAND) when the afferent stimulus arrives in M1-HAND at the time of TMS. The magnitude of short-latency afferent inhibition (SAI) is expressed as the ratio between the conditioned and unconditioned MEP and is widely used to probe sensorimotor interactions in human physiological studies. Objective/HypothesisWe hypothesized that corticospinal excitability and SAI are influenced by the recent history of peripheral electrical stimulation. MethodsIn twenty healthy participants, we recorded MEPs from the right first dorsal interosseus muscle. MEPs were evoked by single-pulse TMS of the left M1-HAND alone (unconditioned TMS) or by TMS preceded by electrical stimulation of the right index finger ("homotopic" conditioning) or little finger ("heterotopic" conditioning). The three conditions were pseudo-randomly intermixed or delivered in blocks in which a single condition was repeated five or ten times. MEP amplitudes and SAI magnitudes were compared using linear mixed effect models. ResultsAll stimulation protocols consistently produced SAI, which was stronger after homotopic stimulation. Randomly intermingling the three stimulation conditions reduced the relative magnitude of homotopic and heterotopic SAI as opposed to blocked stimulation. The apparent attenuation of SAI was caused by a suppression of the unconditioned but not the conditioned MEP amplitude during the randomly intermixed condition. Conclusion(s)The recent history of afferent stimulation modulates corticospinal excitability. This "history effect" impacts on the relative magnitude of SAI depending on how conditioned and unconditioned responses are intermixed and needs to be taken into consideration when probing afferent inhibition and corticospinal excitability.

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bioRxiv2022

Short periods of bipolar anodal TDCS induce no instantaneous dose-dependent increase in cerebral blood flow in the targeted human motor cortex

BackgroundAnodal transcranial direct current stimulation (aTDCS) of primary motor hand area (M1-HAND) can enhance corticomotor excitability. Yet, it is still unknown which current intensity produces the strongest effect on regional neural activity. Magnetic resonance imaging (MRI) combined with pseudo-continuous Arterial Spin Labeling (pc-ASL MRI) can map regional cortical blood flow (rCBF) and may thus be useful to probe the relationship between current intensity and neural response at the individual level. ObjectiveHere we employed pc-ASL MRI to map acute rCBF changes during short-duration aTDCS of left M1-HAND. Using the rCBF response as a proxy for regional neuronal activity, we investigated if short-duration aTDCS produces an instantaneous dose-dependent rCBF increase in the targeted M1-HAND that may be useful for individual dosing. MethodsNine healthy right-handed participants received 30 seconds of aTDCS at 0.5, 1.0, 1.5, and 2.0 mA with the anode placed over left M1-HAND and cathode over the right supraorbital region. Concurrent pc-ASL MRI at 3 T probed TDCS-related rCBF changes in the targeted M1-HAND. Movement-induced rCBF changes were also assessed. ResultsApart from a subtle increase in rCBF at 0.5 mA, short-duration aTDCS did not modulate rCBF in the M1-HAND relative to no-stimulation periods. None of the participants showed a dose-dependent increase in rCBF during aTDCS, even after accounting for individual differences in TDCS-induced electrical field strength. In contrast, finger movements led to robust activation of left M1-HAND before and after aTDCS. ConclusionShort-duration bipolar aTDCS does not produce instantaneous dose-dependent rCBF increases in the targeted M1-HAND at conventional intensity ranges. Therefore, the regional hemodynamic response profile to short-duration aTDCS may not be suited to inform individual dosing of TDCS intensity. HighlightsO_LIArterial spin labeling (ASL) MRI probed regional cerebral blood flow (rCBF) during anodal TDCS. C_LIO_LIShort-duration anodal TDCS was applied to left motor hand area (M1-HAND) at 0.5, 1.0, 1.5 and 2.0 mA. C_LIO_LIAnodal TDCS produced no instantaneous dose-dependent rCBF increase in left M1-HAND. C_LIO_LIApart from a subtle increase at 0.5 mA, rCBF was not modified in M1-HAND during anodal TDCS. C_LI

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bioRxiv2021

Relationship between high-frequency activity in the sensory and the motor hand areas, and regional myelin content

BackgroundThe human primary sensory (S1) and primary motor (M1) hand areas feature high-frequency neuronal responses. Electrical nerve stimulation evokes high-frequency oscillations (HFO) at around 650 Hz in the contralateral S1. Likewise, transcranial magnetic stimulation (TMS) of M1 can evoke a series of descending volleys in the corticospinal pathway that can be detected non-invasively with a paired-pulse TMS protocol, called short interval intracortical facilitation (SICF). SICF features several peaks of facilitation of motor evoked potentials in contralateral hand muscles, which are separated by inter-peak intervals resembling HFO rhythmicity. HypothesisIn this study, we tested the hypothesis that the individual expressions of HFO and SICF are tightly related to each other and to the regional myelin content in the sensorimotor cortex. MethodsIn 24 healthy volunteers, we recorded HFO and SICF, and, in a subgroup of 20 participants, we mapped the cortical myelin content using the ratio between the T1- and T2-weighted MRI signal as read-out. ResultsThe individual frequencies and magnitudes of HFO and SICF curves were tightly correlated: the intervals between the first and second peak of cortical HFO and SICF showed a positive linear relationship (r= 0.703, p< 0.001), while their amplitudes were inversely related (r= -0.613, p= 0.001). The rhythmicity, but not the magnitude of the high-frequency responses, was related to the cortical myelin content: the higher the cortical myelin content, the shorter the inter-peak intervals of HFO and SICF. ConclusionThe results confirm a tight functional relationship between high-frequency responses in S1 (i.e., HFO) and M1 (i.e., as measured with SICF). They also establish a link between the degree of regional cortical myelination and the expression of high-frequency responses in the human sensorimotor cortex, giving further the opportunity to infer their generators.

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bioRxiv2021

Only females show a stable association between neuroticism and microstructural asymmetry of the cingulum across childhood and adolescence: A longitudinal DTI study

Neuroticism is characterized by a tendency to experience negative and anxious emotions. This personality trait is linked to an increased risk of anxiety and mood disorders. In a cross-sectional 3T diffusion tensor imaging (DTI) study in children and adolescents, we found an association between neuroticism and a relative imbalance between left and right (i.e., asymmetry) fractional anisotropy (FA) in the cingulum and white matter underlying the ventromedial prefrontal cortex with opposite directions in females and males. Here we analyzed the longitudinal follow-up DTI data, which was acquired in 76 typically-developing 7- to 18-year-olds, including up to 11 scans per subject. Neuroticism was assessed up to four times. Our longitudinal DTI measurements substantiate robust associations between higher neuroticism scores and increased left relative to right cingulum FA in females and decreased left relative to right cingulum FA in males. In females, the association was already present in late childhood and with a stable expression across childhood and adolescence. In males, the association gradually emerged during adolescence. Future longitudinal studies should clarify which neurobiological factors (e.g., genetic variation, prenatal stress, sex hormones) contribute to the sex-specific associations in the relationship between neuroticism and interhemispheric microstructural asymmetry of the cingulum. HighlightO_LIWe analyzed a unique longitudinal DTI dataset covering late childhood and adolescence. C_LIO_LIIn the cingulum, left-right fractional anisotropy (FA) asymmetry scaled with neuroticism. C_LIO_LIFemales displayed a stable association of neuroticism with increased cingulum asymmetry. C_LIO_LIMales showed an association between neuroticism and decreased cingulum FA asymmetry. C_LIO_LIThe association in males became more accentuated during adolescence C_LI

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bioRxiv2021

On the Reconstruction of Magnetic ResonanceCurrent Density Images of the Human Brain:Pitfalls and Perspectives

Magnetic resonance current density imaging (MRCDI) of the human brain aims to reconstruct the current density distribution caused by transcranial electric stimulation from MR-based measurements of the current-induced magnetic fields. The reconstruction problem is challenging due to a low signal-to-noise ratio and a limited volume coverage of the MR-based measurements, the lack of data from the scalp and skull regions and because MRCDI is only sensitive to the component of the current-induced magnetic field parallel to the scanner field. Most existing reconstruction approaches have been validated using simulation studies and measurements in phantoms with simplified geometries. Only one reconstruction method, the projected current density algorithm, has been applied to human in-vivo data so far, however resulting in blurred current density estimates even when applied to noise-free simulated data. We analyze the underlying causes for the limited performance of the projected current density algorithm when applied to human brain data. In addition, we compare it with an approach that relies on the optimization of the conductivities of a small number of tissue compartments of anatomically detailed head models reconstructed from structural MR data. Both for simulated ground truth data and human in-vivo MRCDI data, our results indicate that the estimation of current densities benefits more from using a personalized volume conductor model than from applying the projected current density algorithm. In particular, we introduce a hierarchical statistical testing approach as a principled way to test and compare the quality of reconstructed current density images that accounts for the limited signal-to-noise ratio of the human in-vivo MRCDI data and the fact that the ground truth of the current density is unknown for measured data. Our results indicate that the statistical testing approach constitutes a valuable framework for the further development of accurate volume conductor models of the head. Our findings also highlight the importance of tailoring the reconstruction approaches to the quality and specific properties of the available data.

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bioRxiv2021

Profiling the transcallosal response of rat motor cortex evoked by contralateral optogenetic stimulation of glutamatergic cortical neurons

BackgroundEfficient interhemispheric integration of neural activity between left and right primary motor cortex (M1) is critical for inter-limb motor control. ObjectiveWe employed optogenetic stimulation to establish a framework for probing transcallosal M1-M1 interactions in rats. MethodsIn male rats, we optogenetically stimulated glutamatergic neurons in right M1 and recorded the transcallosally evoked potential with chronically implanted electrodes in contralateral left M1 during dexmedetomidine anesthesia. We systematically varied the stimulation intensity and duration to characterize the relationship between stimulation parameters in right M1 and the characteristics of the evoked intracortical potentials in left M1. ResultsOptogenetic stimulation of right M1 consistently evoked a transcallosal response in left M1 with a consistent negative peak (N1) that sometimes was preceded by a smaller positive peak (P1). Higher stimulation intensity or longer stimulation duration gradually increased N1 amplitude and reduced N1 variability across trials. Median N1 latencies remained stable, once stimulation elicited a reliable N1 peak and did not display a systematic shortening with increasing stimulation intensity or duration. ConclusionsOptogenetically stimulated glutamatergic neurons in M1 can reliably evoke a transcallosal response in anesthetized rats and can be used to characterize the relationship between "stimulation dose" and "response magnitude" (i.e., the gain function) of transcallosal M1-to-M1 glutamatergic connections. Detailed knowledge of the stimulus-response relationship is needed to optimize the efficacy of optogenetic stimulation. Since transcallosal M1-M1 interactions can also be probed non-invasively with transcranial magnetic stimulation in humans, our optogenetic stimulation approach bears translational potential for studying how unilateral M1 stimulation can induce interhemispheric plasticity.

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bioRxiv2021

Sensitivity and resolution improvement for in-vivo magnetic resonance current density imaging (MRCDI) of the human brain

PurposeMagnetic resonance current density imaging (MRCDI) combines MR brain imaging with the injection of time-varying weak currents (1-2 mA) to assess the current flow pattern in the brain. However, the utility of MRCDI is still hampered by low measurement sensitivity and poor image quality. MethodsWe recently introduced a multi-gradient-echo-based MRCDI approach that has the hitherto best documented efficiency. We now advanced our MRCDI approach in three directions and performed phantom and in-vivo human brain experiments for validation: First, we verified the importance of enhanced spoiling and optimize it for imaging of the human brain. Second, we improved the sensitivity and spatial resolution by using acquisition weighting. Third, we added navigators as a quality control measure for tracking physiological noise. Combining these advancements, we tested our optimized MRCDI method by using 1 mA transcranial electrical stimulation (TES) currents injected via two different electrode montages in five subjects. ResultsFor a session duration of 4:20 min, the new MRCDI method was able to detect magnetic field changes caused by the TES current flow at a sensitivity level of 84 pT, representing in a twofold increase relative to our original method. Comparing both methods to current flow simulations based on personalized head models demonstrated a consistent increase in the coefficient of determination of {Delta}R2=0.12 for the current-induced magnetic fields and {Delta}R2=0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite of the strongly improved measurement quality. This suggests that MRCDI can reveal useful information for the improvement of head models used for current flow simulations. ConclusionThe advanced method strongly improves the sensitivity and robustness of MRCDI and is an important step from proof-of-concept studies towards a broader application of MRCDI in clinical and basic neuroscience research.

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bioRxiv2020

Does pericentral mu-rhythm power corticomotor excitability? A matter of EEG perspective

BackgroundElectroencephalography (EEG) and single-pulse transcranial magnetic stimulation (spTMS) of the primary motor hand area (M1-HAND) have been combined to explore whether the instantaneous expression of pericentral mu-rhythm drives fluctuations in corticomotor excitability, but this line of research has yielded diverging results. ObjectivesTo re-assess the relationship between the mu-rhythm power expressed in left pericentral cortex and the amplitude of motor potentials (MEP) evoked with spTMS in left M1-HAND. Methods15 non-preselected healthy young participants received spTMS to the motor hot spot of left M1-HAND. Regional expression of mu-rhythm was estimated online based on a radial source at motor hotspot and informed the timing of spTMS which was applied either during epochs belonging to the highest or lowest quartile of regionally expressed mu-power. Using MEP amplitude as dependent variable, we computed a linear mixed-effects model, which included mu-power and mu-phase at the time of stimulation and the inter-stimulus interval (ISI) as fixed effects and subject as a random effect. Mu-phase was estimated by post-hoc sorting of trials into four discrete phase bins. We performed a follow-up analysis on the same EEG-triggered MEP data set in which we isolated mu-power at the sensor level using a Laplacian montage centered on the electrode above the M1-HAND. ResultsPericentral mu-power traced as radial source at motor hot spot did not significantly modulate the MEP, but mu-power determined by the surface Laplacian did, showing a positive relation between mu-power and MEP amplitude. In neither case, there was an effect of mu-phase on MEP amplitude. ConclusionThe relationship between cortical oscillatory activity and cortical excitability is complex and minor differences in the methodological choices may critically affect sensitivity.

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bioRxiv2020

Maturational trajectories of white matter microstructure underlying the right presupplementary motor area reflect individual improvements in motor response cancellation in children and adolescents

The ability to effectively suppress motor response tendencies is essential for focused and goal-directed behavior. Here, we tested the hypothesis that developmental improvement in the ability to cancel a motor response is reflected by maturational changes in the white matter underlying the right presupplementary motor area (preSMA) and posterior inferior frontal gyrus (IFG), two cortical key areas of the fronto-basal ganglia "stopping" network. Eighty-eight typically-developing children and adolescents, aged 7-19 years, were longitudinally assessed with the stop-signal task (SST) and diffusion tensor imaging (DTI) of the brain over a period of six years. Participants were examined from two to nine times with an average of 6.6 times, resulting in 576 SST-DTI datasets. We applied tract-based spatial statistics to extract mean fractional anisotropy (FA) from regions-of-interest in the white matter underlying the right IFG (IFGFA) and right preSMA (preSMAFA) at each time point. Motor response cancelation performance, estimated with the stop-signal reaction time (SSRT), improved with age. Initially well performing children plateaued around the age of 11 years, while initially poor performers caught up at the age of 13-14 years. White matter microstructure continued to mature across the investigated age range. Males generally displayed linear maturational trajectories, while females displayed more curvilinear trajectories that leveled off around 12-14 years of age. Maturational increases in right preSMAFA but not right IFGFA were associated with developmental improvements in SSRT. This association differed depending on the mean right preSMAFA across the individual maturational trajectory. Children with lower mean right preSMAFA exhibited poorer SSRT performance at younger ages but steeper developmental trajectories of SSRT improvement. Children with higher mean right preSMAFA exhibited flatter trajectories of SSRT improvement along with faster SSRT already at the first assessments. The results suggest that no further improvement in motor response cancellation is achieved once a certain level of maturity in the white matter underlying the right preSMA is reached. Similar dynamics may apply to other behavioral read-outs and brain structures and, thus, need to be considered in longitudinal MRI studies designed to map brain structural correlates of behavioral changes during development. HighlightsO_LIMotor response cancellation, i.e. SSRT, improvement plateaued at 13-14 years of age C_LIO_LIFractional anisotropy (FA) captured maturation of white matter (WM) microstructure C_LIO_LIFA in the WM underlying right preSMA (preSMAFA) reflected SSRT improvement with age C_LIO_LIIndividual SSRT improvement depended on mean right preSMAFA across all DTI sessions C_LIO_LIChildren with lower mean right preSMAFA had the steepest improvements in SSRT C_LI

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bioRxiv2020

Multimodal finger-printing of the human precentral cortex forming the motor hand knob

Transcranial magnetic stimulation (TMS) of the precentral hand knob can evoke motor evoked potentials (MEP) in contralateral hand muscles. Biophysical modelling points to the dorsal premotor cortex (PMd) in the superficial crown-lip region as primary site of TMS-induced neuronal excitation. Here, we used a sulcus-aligned MRI-informed TMS mapping approach to determine the optimal site (hotspot) for evoking MEPs in the precentral hand knob. Individual precentral hotspot location varied along the rostro-caudal axis. Individuals with a more rostral location had longer MEP latencies. Spatiotemporal "hotspot rostrality" was associated with higher precentral myelin-related signals, stronger movement-related activation of PMd in the precentral crown, and higher temporal precision during paced finger tapping. Together, our multimodal mapping approach provides first-time evidence for behaviourally relevant, structural and functional phenotypic variation in the crown of human precentral motor hand knob. The results have important implications for physiological and interventional TMS studies targeting the precentral hand knob.

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bioRxiv2019

No trace of phase: Corticomotor excitability is not tuned by phase of pericentral mu-rhythm

BackgroundThe motor potentials evoked by transcranial magnetic stimulation (TMS) over the motor hand area (M1-HAND) show substantial inter-trial variability. Pericentral mu-rhythm oscillations, might contribute to inter-trial variability. Recent studies targeting mu-activity based on real-time electroencephalography (EEG) reported an influence of mu-power and mu-phase on the amplitude of motor evoked potentials (MEPs) in a preselected group with strong pericentral mu-activity. Other studies that determined mu-power or mu-phase based on post-hoc trial sorting according in non-preselected individuals were largely negative.\n\nObjectivesTo reassess if cortico-spinal activity is modulated by the mu-rhythm, we applied single-pulse TMS to the M1-HAND conditional on the phase of the intrinsically expressed pericentral mu-rhythm in 14 non-preselected healthy young participants.\n\nMethodsTMS was given at 0, 90, 180, and 270 degrees of the mu-phase. Based on the absence of effects of mu-phase or mu-power when analyzing the mean MEP amplitudes, we also computed a linear mixed effects model, which included mu-phase, mu-power, inter-stimulus interval (ISIs) as fixed effects, treating the subject factor as a random effect.\n\nResultsMixed model analysis revealed a significant effect of mu-power and ISI, but no effect of mu-phase and no interactions. MEP amplitude scaled linearly with lower mu-power or longer ISIs, but these modulatory effects were very small relative to inter-trial MEP variability.\n\nConclusionOur largely negative results are in agreement with previous offline TMS-EEG studies and point to a possible influence of ISI. Future research needs to clarify under which circumstances the responsiveness of human the M1-HAND to TMS depends on the synchronicity with mu-power and mu-phase.\n\nHighlightsO_LIPhase-triggered TMS at four distinct phases of the ongoing mu-oscillations is technically feasible in non-preselected young volunteers\nC_LIO_LITargeting the ongoing mu-activity did not reveal consistent modulatory effect of mu-phase on corticospinal excitability in a non-preselected group\nC_LIO_LIMixed-effects analysis revealed a weak but significant effect of pre-stimulus mu-power and ISI on corticospinal excitability\nC_LI

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bioRxiv2018

Individuals with 22q11.2 deletion syndrome show intact prediction but reduced adaptation in responses to repeated sounds: evidence from Bayesian mapping

Background: One of the most common copy number variants, the 22q11.2 microdeletion, confers a increased risk for schizophrenia. Since schizophrenia has been associated with an aberrant neural response to repeated stimuli through both reduced adaptation and prediction, we here hypothesized that this may also be the case in nonpsychotic individuals with a 22q11.2 deletion. Methods: We recorded high-density EEG from 19 individuals with 22q11.2 deletion syndrome (12-25 years), as well as 27 healthy volunteers with comparable age and sex distribution, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Using posterior probability maps and dynamic causal modelling we tested three different models accounting for repetition dependent changes in cortical responses as well as in effective connectivity; namely an adaptation model, a prediction model, and a model including both adaptation and prediction. Results: Repetition-dependent changes were parametrically modulated by a combination of adaptation and prediction and were apparent in both cortical responses and in the underlying effective connectivity. This effect was reduced in individuals with a 22q11.2 deletion and was negatively correlated with negative symptom severity. Follow-up analysis showed that the reduced effect of the combined adaptation and prediction model seen in individuals with 22q11.2 deletion was driven by reduced adaptation rather than prediction failure. Conclusions: Our findings suggest that adaptation is reduced in individuals with a 22q11.2 deletion, which can be interpreted in light of the framework of predictive coding as a failure to suppress prediction errors.

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bioRxiv2018

Altered orbitofrontal sulcogyral patterns in gambling disorder: a multicenter study

Gambling disorder is a serious psychiatric condition characterized by decision-making and reward processing impairments that are associated with dysfunctional brain activity in the orbitofrontal cortex (OFC). However, it remains unclear whether OFC functional abnormalities in gambling disorder are accompanied by structural abnormalities. We addressed this question by examining the organization of sulci and gyri in the OFC. This organization is in place very early and stable across life, such that OFC sulcogyral patterns (classified into Type I, II and III) can be regarded as potential pre-morbid markers of pathological conditions. We gathered structural brain data from nine existing studies, reaching a total of 165 individuals with gambling disorder and 159 healthy controls. Our results, supported by both frequentist and Bayesian statistics, show that the distribution of OFC sulcogyral patterns is skewed in individuals with gambling disorder, with an increased prevalence of Type II pattern compared with healthy controls. Examination of gambling severity did not reveal any significant relationship between OFC sulcogyral patterns and disease severity. Altogether, our results provide evidence for a skewed distribution of OFC sulcogyral patterns in gambling disorder, and suggest that pattern Type II might represent a pre-morbid structural brain marker of the disease. It will be important to investigate more closely the functional implications of these structural abnormalities in future work.

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bioRxiv2018

The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies

Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud \"click\" sound, the TMS-evoked EEG potential (TEP) not only reflects neural activity induced by transcranial neuronal excitation but also neural activity reflecting somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the study design to enable a dissociation between truly transcranial and non-transcranial components of TEPs.

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bioRxiv2018

The Homeostatic Logic of Reward

Energy homeostasis depends on behavior to predictively regulate metabolic states within narrow bounds. Here we review three theories of homeostatic control and ask how they provide insight into the circuitry underlying energy homeostasis. We offer two contributions. First, we detail how control theory and reinforcement learning are applied to homeostatic control. We show how these schemes rest on implausible assumptions; either via circular definitions, unprincipled drive functions, or by ignoring environmental volatility. We argue active inference can elude these shortcomings while retaining important features of each model. Second, we review the neural basis of energetic control. We focus on a subset of arcuate subpopulations that project directly to, and are thus in a privileged position to opponently modulate, dopaminergic cells as a function of energetic predictions over a spectrum of time horizons. We discuss how this can be interpreted under these theories, and how this can resolve paradoxes that have arisen. We propose this circuit constitutes a homeostatic-reward interface that underwrites the conjoint optimisation of physiological and behavioural homeostasis.

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bioRxiv2017

Use-dependent plasticity in human primary motor hand area:Synergistic interplay between training and immobilisation

Training and immobilization are powerful drivers of use-dependent plasticity in human primary motor hand area (M1HAND). Here we used transcranial magnetic stimulation to clarify how training and immobilisation of a single finger interact within M1HAND. Healthy volunteers trained to track a moving target with a finger for one week. The tracking skill acquired with the trained finger was transferred to a non-trained finger of the same hand. The cortical representations of the trained and non-trained finger muscle converged in proportion with skill transfer. Finger immobilisation alone attenuated the corticomotor representation and pre-existing tracking skill of the immobilized finger. The detrimental effects of finger immobilization were blocked by concurrent training of the non-immobilized finger. Conversely, immobilization of the non-trained fingers accelerated learning during the first two days of training. The results provide novel insight into use-dependent cortical plasticity, revealing synergistic rather than competitive interaction patterns within M1HAND.

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