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Karsten Witt

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5 papers

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YNICL Journal 2021 Journal Article

Abnormal effective connectivity in the sensory network in writer’s cramp

Inken Tödt
Alexander Baumann
Arne Knutzen
Oliver Granert
Elinor Tzvi
Julia Lindert
Stephan Wolff
Karsten Witt

BACKGROUND: Writer's cramp (WC), a task specific form of dystonia, is considered to be a motor network disorder, but abnormal sensory tactile processing has also been acknowledged. The sensory spatial discrimination threshold (SDT) can be determined with a spatial acuity test (JVP domes). In addition to increased SDT, patients with WC exhibited dysfunctional sensory processing in the sensory cortex, insula, basal ganglia and cerebellum in a functional magnetic resonance imaging (fMRI) study while performing the spatial acuity test. OBJECTIVES: To assess whether effective connectivity (EC) in the sensory network including cortical, basal ganglia, thalamic and cerebellar regions of interest in WC patients is abnormal. METHODS: We used fMRI and applied a block design, while 19 WC patients and 13 age-matched healthy controls performed a spatial discrimination task. Before we assessed EC using dynamic causal modelling, we compared three model structures based on the current literature. We enclosed regions of interest that are established for sensory processing during right hand stimulation: Left thalamus, somatosensory, parietal and insular cortex, posterior putamen, and right cerebellum. RESULTS: The EC analysis revealed task-dependent decreased unidirectional connectivity between the insula and the posterior putamen. The connectivity involving the primary sensory cortex, parietal cortex and cerebellum were not abnormal in WC. The two groups showed no differences in their behavioural data. CONCLUSIONS: Perception and integration of sensory information requires the exchange of information between the insula cortex and the putamen, a sensory process that was disturbed in WC patients.

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YNICL Journal 2018 Journal Article

Dynamic causal modeling revealed dysfunctional effective connectivity in both, the cortico-basal-ganglia and the cerebello-cortical motor network in writers' cramp

Inken Rothkirch
Oliver Granert
Arne Knutzen
Stephan Wolff
Felix Gövert
Anya Pedersen
Kirsten E. Zeuner
Karsten Witt

Writer's cramp (WC) is a focal task-specific dystonia characterized by sustained or intermittent muscle contractions while writing, particularly with the dominant hand. Since structural lesions rarely cause WC, it has been assumed that the disease might be caused by a functional maladaptation within the sensory-motor system. Therefore, our objective was to examine the differences between patients suffering from WC and a healthy control (HC) group with regard to the effective connectivity that describes causal influences one brain region exerts over another within the motor network. The effective connectivity within a network including contralateral motor cortex (M1), supplementary motor area (SMA), globus pallidus (GP), putamen (PU) and ipsilateral cerebellum (CB) was investigated using dynamic causal modeling (DCM) for fMRI. Eight connectivity models of functional motor systems were compared. Fifteen WC patients and 18 age-matched HC performed a sequential, five-element finger-tapping task with the non-dominant and non-affected left hand within a 3 T MRI-scanner as quickly and accurately as possible. The task was conducted in a fixed block design repeated 15 times and included 30 s of tapping followed by 30 s of rest. DCM identified the same model in WC and HC as superior for reflecting basal ganglia and cerebellar motor circuits of healthy subjects. The M1-PU, as well as M1-CB connectivity, was more strongly influenced by tapping in WC, but the intracortical M1-SMA connection was more facilitating in controls. Inhibiting influences originating from GP to M1 were stronger in controls compared to WC patients whereby facilitating influences the PU exerts over CB and CB exerts over M1 were not as strong. Although the same model structure explains the given data best, DCM confirms previous research demonstrating a malfunction in effective connectivity intracortically (M1-SMA) and in the cortico-basal ganglia circuitry in WC. In addition, DCM analysis demonstrates abnormal reciprocal excitatory connectivity in the cortico-cerebellar circuitry. These results highlight the dysfunctional cerebello-cortical as well as basalganglio-cortical interaction in WC.

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YNICL Journal 2016 Journal Article

Altered brain activation in a reversal learning task unmasks adaptive changes in cognitive control in writer's cramp

Kirsten E. Zeuner
Arne Knutzen
Oliver Granert
Simone Sablowsky
Julia Götz
Stephan Wolff
Olav Jansen
Dirk Dressler

Previous receptor binding studies suggest dopamine function is altered in the basal ganglia circuitry in task-specific dystonia, a condition characterized by contraction of agonist and antagonist muscles while performing specific tasks. Dopamine plays a role in reward-based learning. Using fMRI, this study compared 31 right-handed writer's cramp patients to 35 controls in reward-based learning of a probabilistic reversal-learning task. All subjects chose between two stimuli and indicated their response with their left or right index finger. One stimulus response was rewarded 80%, the other 20%. After contingencies reversal, the second stimulus response was rewarded in 80%. We further linked the DRD2/ANKK1-TaqIa polymorphism, which is associated with 30% reduction of the striatal dopamine receptor density with reward-based learning and assumed impaired reversal learning in A + subjects. Feedback learning in patients was normal. Blood-oxygen level dependent (BOLD) signal in controls increased with negative feedback in the insula, rostral cingulate cortex, middle frontal gyrus and parietal cortex (pFWE < 0.05). In comparison to controls, patients showed greater increase in BOLD activity following negative feedback in the dorsal anterior cingulate cortex (BA32). The genetic status was not correlated with the BOLD activity. The Brodmann area 32 (BA32) is part of the dorsal anterior cingulate cortex (dACC) that plays an important role in coordinating and integrating information to guide behavior and in reward-based learning. The dACC is connected with the basal ganglia-thalamo-loop modulated by dopaminergic signaling. This finding suggests disturbed integration of reinforcement history in decision making and implicate that the reward system might contribute to the pathogenesis in writer's cramp.

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YNIMG Journal 2015 Journal Article

Striatal–cerebellar networks mediate consolidation in a motor sequence learning task: An fMRI study using dynamic causal modelling

Elinor Tzvi
Anne Stoldt
Karsten Witt
Ulrike M. Krämer

The fast and slow learning stages of motor sequence learning are suggested to be realized through plasticity in a distributed cortico-striato-cerebellar network. To better understand the causal interactions within this network in the different phases of motor sequence learning, we investigated the effective connectivity within this network during encoding (Day 1) and after consolidation (Day 2) of a serial reaction time task. Using Dynamic Causal Modelling of fMRI data, we found general changes in network connections reflected in altered input nodes and endogenous connections when comparing the early and fast learning session to the late and slow learning session. Whereas encoding of a motor memory early on modulated several connections in a distributed network, slow learning resulted in a pruned network. More specifically, we found a negative modulation of connections from left M1 to right cerebellum, right premotor cortex to left cerebellum, as well as backward connections from putamen to cerebellum bilaterally in the encoding session. While connections during pre-sleep were significantly modulated by learning per se (i. e. , specifically modulated by performance on sequence conditions), the connections observed after sleep were rather modulated by general performance (i. e. , modulated by performance on both sequence and random conditions). A forward connection from left cerebellum to right putamen was found to be consistent across participants for the sequence condition only during slow learning. Together these findings suggest that whereas encoding in the fast learning phase requires plasticity in several connections implementing both motor and perceptual learning components, slow learning is mediated through connectivity from left cerebellum to right putamen.

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YNIMG Journal 2009 Journal Article

Rotated alphanumeric characters do not automatically activate frontoparietal areas subserving mental rotation

Michael M. Weiss
Thomas Wolbers
Martin Peller
Karsten Witt
Lisa Marshall
Christian Buchel
Hartwig R. Siebner

Functional neuroimaging studies have identified a set of areas in the intraparietal sulcus and dorsal precentral cortex which show a linear increase in activity with the angle of rotation across a variety of mental rotation tasks. This linear increase in activity with angular disparity suggests that these frontoparietal regions compute rotational transformations. An open question is whether rotated target stimuli automatically activate these frontoparietal regions, even if the task does not require rotational transformations. To address this question, we performed functional MRI while healthy male volunteers made two-choice reaction-time judgements on canonical or mirror images of two-dimensional alphanumeric characters presented at various angles of rotation. Participants had either to decide whether characters were normal or mirror-reversed (i. e. , mental rotation) or judge whether the stimulus was a letter or a number (i. e. , stimulus categorization). Reaction times and error rates linearly increased with the angle of rotation for mirror-reversed judgements but not for number–letter judgements, showing that only the mental rotation task required rotational transformations of the characters. The mental rotation task was associated with a linear increase in neuronal activity with angular disparity in a bilateral set of frontoparietal areas, comprising the rostral dorsal premotor cortex, frontal eye field, ventral and medial intraparietal sulcus. Neuronal activity in these regions was neither increased nor modulated by angular disparity during the stimulus categorization task. These results suggest that at least for alphanumerical characters, areas implicated in mental rotation will only be called into action if the task requires a rotational transformation.

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