Biology subjects

Hirschmann, J.

Publications and source records attributed to Hirschmann, J..

8 recordsLinked to original sources

bioRxiv2025

Beyond beta: Aperiodic broadband power reflects Parkinson's disease severity - a multicenter study

Parkinsons disease is linked to increased beta oscillations in the subthalamic nucleus, which correlate with motor symptoms. However, findings across studies have varied. Our standardized analysis of multicenter datasets shows that small sample sizes contributed to these discrepancies--a challenge we address by pooling datasets into one large cohort (n=119). Moving beyond beta power, we disentangled spectral components reflecting distinct neural processes. Combining aperiodic offset, low beta, and low gamma oscillations explained significantly more variance in symptom severity than beta alone. Moreover, interhemispheric within-patient analyses showed that, unlike beta oscillations, aperiodic broadband power-likely reflecting spiking activity-was increased in the more affected hemisphere. These findings identify aperiodic broadband power as a potential biomarker for adaptive deep brain stimulation and provide novel insights into the relationship between subthalamic hyperactivity and motor symptoms in human Parkinsons disease.

neuroscience↗

bioRxiv2025

Modulations of thalamo-cortical coupling during voluntary movement in patients with essential tremor

The ventral intermediate nucleus of the thalamus (VIM) is the main thalamic hub for processing cerebellar inputs and the main deep brain stimulation target for the treatment of essential tremor (ET). As such, it presumably plays a critical role in motor control. So far, however, this structure has been rarely investigated in humans, and almost all of the existing studies focus on tremor. Here, we set out to study neural oscillations in the VIM and their coupling to cortical oscillations during voluntary movement. We investigated thalamo-cortical coupling by means of simultaneous recordings of thalamic local field potentials and magnetoencephalography in 10 ET patients with externalized deep brain stimulation electrodes. Brain activity was measured while patients were pressing a button repeatedly in response to a visual cue. In a whole-brain analysis of coherence between VIM and cortex, we contrasted activity around a pre-movement baseline and button pressing. Button pressing was associated with a bilateral decrease of thalamic power in the alpha (8- 12 Hz) and beta (13-21 Hz) band and a contralateral power increase in the gamma (35- 90 Hz) band. Moreover, changes in VIM-cortex coherence were observed. Alpha/low beta (8- 20 Hz) coherence decreased before and during movement, and the effect localized to the supplementary motor area and premotor cortex. A rebound of high beta (21-35 Hz) coherence occurred in the same region, but was more focal than the suppression. Pre-movement levels of thalamo-cortex low-beta coherence correlated with reaction time. Our results demonstrate that voluntary movement is associated with modulations of behaviourally relevant thalamic coupling, primarily to premotor areas. We observed a clear distinction between low- and high-beta frequencies and our results suggest that the concept of "antikinetic" beta oscillations, originating from research on Parkinsons disease, is transferable to ET.

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bioRxiv2024

Oscillatory coupling between thalamus, cerebellum and motor cortex in essential tremor

BackgroundEssential tremor is hypothesized to emerge from synchronized oscillatory activity within the cerebello-thalamo-cortical circuit. However, this hypothesis has not yet been tested using local field potentials directly recorded from the thalamus alongside signals from both the cortex and cerebellum, leaving a gap in the understanding of essential tremor. ObjectivesTo clarify the importance of cerebello-thalamo-cortical oscillatory coupling for essential tremor. MethodsWe investigated oscillatory coupling between thalamic local field potentials and simultaneously recorded magnetoencephalography in 19 essential tremor patients with externalized deep brain stimulation electrodes. Brain activity was measured while patients repeatedly adopted a tremor-provoking posture and while pouring rice from one cup to another. In a whole-brain analysis of coherence between the ventral intermediate nucleus of the thalamus and cortex, we contrasted epochs containing tremor and epochs lacking tremor. ResultsBoth postural and kinetic tremor were associated with an increase of thalamic power and thalamo-cortex coherence at individual tremor frequency in the bilateral cerebellum and primary sensorimotor cortex contralateral to tremor. These areas also exhibited an increase in corticomuscular coherence in the presence of tremor. The coupling of motor cortex to both thalamus and muscle correlated with tremor amplitude during postural tremor. ConclusionsThese results demonstrate that essential tremor is indeed associated with increased oscillatory coupling at tremor frequency within a cerebello-thalamo-cortical network, with coupling strength directly reflecting tremor severity.

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bioRxiv2024

A role for acetylcholine in reinforcement learning and decision making under uncertainty

The neuromodulator acetylcholine has been suggested to govern learning under uncertainty. Here, we investigated the role of muscarinic acetylcholine receptors in reward-guided learning and decision making under different degrees of uncertainty. We administered the muscarinic antagonist biperiden (4 mg) to healthy male participants (n = 43) in a within-subjects, placebo-controlled design. Participants performed a gambling and a learning task involving different levels of uncertainty, while magnetoencephalography (MEG) was recorded. We show that biperiden did not affect decision making in the gambling task, where no learning was required. However, in the learning task, where option values were associated with uncertainty, biperiden reduced the sensitivity to probabilities, particularly when choice-outcome-contingencies switched frequently. Reinforcement learning models revealed that the change in behaviour was caused by noisier estimates of probabilities resulting from increased learning rates for rewarded choices under biperiden. These behavioural findings were paralleled by elimination of the lateral prefrontal representation of learnt reward probability in high-beta (20 - 30 Hz) power under biperiden. Together, these findings suggest that muscarinic acetylcholine transmission controls learning in highly uncertain contexts, when the demand for carefully calibrated adjustments is highest.

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bioRxiv2024

Beta Waves in Action: Context-Dependent Modulations of Subthalamo-Cortical Synchronization during Rapid Reversals of Movement Direction

The role of beta band activity in cortico-basal ganglia interactions during motor control has been studied extensively in resting-state and for simple movements, such as button pressing. However, little is known about how beta oscillations change and interact in more complex situations involving rapid changes of movement in various contexts. To close this knowledge gap, we combined magnetoencephalography (MEG) and local field potential recordings from the subthalamic nucleus (STN) in Parkinsons disease patients to study beta dynamics during initiation, stopping, and rapid reversal of rotational movements. The action prompts were manipulated to be predictable vs. unpredictable. We observed movement-related beta suppression at motor sequence start, and a beta rebound after motor sequence stop in STN power, motor cortical power, and STN-cortex coherence. Despite involving a brief stop of movement, no clear rebound was observed during reversals of turning direction. On the cortical level, beta power decreased bilaterally following reversals, but more so in the hemisphere ipsilateral to movement, due to a floor effect on the contralateral side. In the STN, power modulations varied across patients, with patients revealing brief increases or decreases of high-beta power. Importantly, cue predictability affected these modulations. Event-related increases of STN-cortex beta coherence were generally stronger in the unpredictable than in the predictable condition. In summary, this study reveals the influence of movement context on beta oscillations in basal ganglia-cortex loops when humans change ongoing movements according to external cues. We find that movement scenarios requiring higher levels of caution involve enhanced modulations of subthalamo-cortical beta synchronization. Further, our results confirm that beta oscillations reflect the start and end of motor sequences better than movement changes within a sequence. Significance StatementBeta synchrony between motor cortex and the subthalamic nucleus is intensified when instructional cues within a continuous motor sequence become less predictable, calling for more cautious behavior.

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bioRxiv2024

Altered Cortical Network Dynamics during Observing and Preparing Action in Patients with Corticobasal Syndrome

Besides parkinsonism, higher order cortical dysfunctions such as apraxia are hallmarks of the corticobasal syndrome (CBS). To date, little is known about the electrophysiological underpinnings of these symptoms. To shed more light on the pathophysiology of CBS, we recorded the magnetoencephalogram of 17 CBS patients and 20 age-matched controls engaged in an observe-to-imitate task. The task involved the display of a tool-use video in first person view (action observation), a written instruction to withhold movement until the presentation of a Go cue (movement preparation), and unilateral tool-use imitation. We investigated modulations of spectral power on the source level. Action observation was associated with an event-related desynchronization in the beta-band (13-30Hz), which was weaker in CBS patients than in healthy controls. The group effect localized to superior parietal, primary motor, premotor and inferior frontal cortex bilaterally. While participants awaited the Go cue, beta power was again suppressed in the hemisphere contralateral to movement, and the rate of suppression correlated with reaction time. This modulation, too, was weaker in the CBS group. Immediately before movement onset, however, beta power was similar in both groups. Our results reveal that action observation triggers beta suppression, likely reflecting motor cortical disinhibition, which is reduced in CBS patients. This pathological alteration might be a neural correlate of a selective deficit in the embedding of observed action into a motor representation (visuo-motor mapping). The suboptimal timing of the beta-power suppression to the upcoming Go cue presumably reflects a deficit in learning the trials temporal structure rather than a deficit in movement initialization. HighlightsO_LIAction observation elicits a suppression of cortical beta power. C_LIO_LIThis suppression is diminished in CBS patients relative to controls. C_LIO_LIThe timing of beta desynchronization to an upcoming Go cue is impaired in CBS patients. C_LIO_LINo evidence for an alteration of movement initialization in CBS patients. C_LI

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bioRxiv2022

Slowing of Frontocentral Beta Oscillations in Atypical Parkinsonism

Diagnosis of atypical parkinsonian syndromes mostly relies on clinical presentation as well as structural and molecular brain imaging. It has not been investigated whether cortical oscillatory activity exhibits features distinguishing these syndromes. Therefore, we measured resting-state magnetoencephalography in 13 patients with corticobasal syndrome, 10 patients with progressive supranuclear palsy, 23 patients with idiopathic Parkinsons disease and 23 healthy controls. We compared spectral power as well as amplitude and frequency of power peaks between the groups. Atypical Parkinsonism was associated with spectral slowing, distinguishing both corticobasal syndrome and progressive supranuclear palsy from age-matched healthy controls and Parkinsons disease. Patients with atypical Parkinsonism showed a shift of beta peaks (13-30 Hz) towards lower frequencies in frontal and central areas bilaterally. A concomitant increase in theta/alpha power relative to controls was observed in both atypical parkinsonian syndromes and in Parkinsons disease. Our results demonstrate that slowing of frontocentral beta oscillations is characteristic of atypical Parkinsonism. Spectral slowing with a different topography has previously been observed in other neurodegenerative disorders, such as Alzheimers disease, suggesting that spectral slowing might be an electrophysiological marker of cortical neurodegeneration. As such, it might support differential diagnosis of parkinsonian syndromes in the future. HighlightsO_LISlowing of beta oscillations distinguishes atypical parkinsonian syndromes from healthy controls and idiopathic Parkinsons disease C_LIO_LISpectral slowing is most pronounced in frontocentral areas C_LIO_LIBeta oscillations are shifted towards lower frequencies independent of their amplitude C_LI

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bioRxiv2018

Spontaneous network activity accounts for variability in stimulus-induced gamma responses

Gamma range activity in human visual cortex is believed to play a major role in cognitive functions, such as selective attention. Although recent studies have revealed substantial variability in gamma activity, its origins are still unclear.\n\nWe investigated whether variability in stimulus-induced gamma activity is related to the spontaneous dynamics of resting-state networks using Hidden Markov Modelling. The magnetoencephalogram (MEG) of 15 healthy participants was recorded at rest and while they were performing a task involving a visual stimulus inducing strong, narrow-band gamma activity. Brain states were inferred from the tasks baseline periods and from resting-state recordings, respectively.\n\nOur results show how network states are related to the amplitude of stimulus-induced gamma responses. Across trials, we found an association between the amplitude of gamma responses and the brain state occurring immediately prior to stimulus presentation. Strong gamma responses followed a state characterized by prominent delta/theta oscillations in parieto-occipital regions and comparably weak alpha activity. Across subjects, the overall probability of visiting this state in the baseline period, i.e. the individual preference for this state, correlated positively with the amplitude of the trial-averaged gamma response. Remarkably, this relationship persisted when states were inferred from resting-state recordings rather than the tasks baseline.\n\nIn summary, both within- and across-subject variability in stimulus-induced gamma activity can in part be explained by the ongoing dynamics of whole-brain network states. Fast, pre-stimulus modulations of brain states account for differences between trials while stable, individual state preferences account for differences between subjects.

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