Florian Kempf

High-frequency stimulation of the subthalamic nucleus suppresses oscillatory beta activity in patients with Parkinson's disease in parallel with improvement in motor performance.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinsons disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the β (13–30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local β activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP β activity for 12 s after the end of stimulation and a decrease in motor cortical–STN coherence in the β band over the same time period. The reduction in LFP β activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of β activity was associated with better task performance. These features were absent when power in the 5–12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological β activity in PD.

The subthalamic region is activated during valence-related emotional processing in patients with Parkinson's disease

Visual stimuli are judged for their emotional significance based on two fundamental dimensions, valence and arousal, and may lead to changes in neural and body functions like attention, affect, memory and heart rate. Alterations in behaviour and mood have been encountered in patients with Parkinsons disease (PD) undergoing functional neurosurgery, suggesting that electrical high‐frequency stimulation of the subthalamic nucleus (STN) may interfere with emotional information processing. Here, we use the opportunity to directly record neuronal activity from the STN macroelectrodes in patients with PD during presentation of emotionally laden and neutral pictures taken from the International Affective Picture System (IAPS) to further elucidate the role of the STN in emotional processing. We found a significant event‐related desynchronization of STN alpha activity with pleasant stimuli that correlated with the individual valence rating of the pictures. Our findings suggest involvement of the human STN in valence‐related emotional information processing that can potentially be altered during high‐frequency stimulation of the STN in PD leading to behavioural complications.

Gamma activity and reactivity in human thalamic local field potentials

Depth recordings in patients with Parkinson’s disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of ∼70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at ∼70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep–wake cycle, being suppressed during slow wave sleep and re‐emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle‐eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at ∼70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at ∼70 Hz may be involved in movement and arousal.

Deep brain stimulation of the subthalamic nucleus: A two-edged sword

Document S1. Supplemental Experimental ProceduresxDownload (.09 MB ) Document S1. Supplemental Experimental Procedures

Premovement activities in the subthalamic area of patients with Parkinson's disease and their dependence on task.

Movement preparation and execution are associated with a reduction in oscillatory synchrony over 6–35 Hz (event‐related desynchronization; ERD) and increases in oscillatory synchrony at higher frequencies (event‐related synchronization; ERS) in the human parkinsonian subthalamic nucleus (STN). The timing of the ERD < 35 Hz in STN correlates with, but precedes, the timing of voluntary movement, in line with a role in motor processing. Here, we explore how directly the synchrony manifest in local field potential (LFP) activities depends on the details of motor processing. To this end, we recorded local field potentials from the STN area of parkinsonian subjects while they performed internally paced single movements or double movements with one hand. Analysis was limited to time periods that were unequivocally premovement, so as to avoid the confounding effects of sensory afferance during movement. LFP power differed from baseline activity as early as 2.1–1.1 s prior to movement over 6–18 Hz and 56–70 Hz. However, only the early changes in LFP power in the 56–70 Hz band depended on task type. Later on, within 0.5 s of the forthcoming movement, the behaviour of both the 6–18 and 56–70 Hz bands differed according to movement type. In addition, a change was seen in LFP activity over 23–35 Hz, although the ERD in this band remained similar across movement types. The findings further implicate the human STN in the feedforward organization of movement in premotor circuits. Different aspects of this organization may be preferentially reflected in changes in synchrony at different frequencies.

Movement-related synchronization of gamma activity is lateralized in patients with dystonia

There is evidence for synchronization at frequencies both under 30 Hz and over 60–80 Hz in the so‐called gamma frequency band in patients with Parkinsons disease (PD). Gamma activity increases after dopaminergic therapy and during voluntary movement, suggesting that it might be physiological and relate to motor processing in the basal ganglia (BG). We recorded local field potential (LFP) activity during a choice reaction time task in 11 patients with dystonia undergoing implantation of the internal globus pallidus for therapeutic stimulation. The spectral content of the LFP was averaged with respect to movement onset over 6–11 Hz, 18–25 Hz and 60–80 Hz, separately for responses ipsilateral and contralateral to movement. There was a perimovement increase in 60–80 Hz activity in the LFP, but only contralateral to movement. In contrast, low‐frequency LFP activity decreased symmetrically during movement. This occurred earlier in the 18–25 Hz band than in the 6–11 Hz band, and was followed by a postmovement increase in oscillatory activity in the 18–25 Hz band that was contralateral to movement. The presence of a lateralized movement‐related increase in gamma activity in the BG of patients with dystonia, similar to that recorded in patients with treated PD, suggests that this may be a residual feature of normal BG function. Moreover, the results provide further support for functional distinctions between BG oscillatory activities of different frequency.

Amplitude modulation of oscillatory activity in the subthalamic nucleus during movement.

Depth recordings in patients with Parkinsons disease (PD) have demonstrated exaggerated local field potential (LFP) activity at frequencies between 10 and 30 Hz in the subthalamic nucleus (STN). This activity is modulated prior to single phasic movements, possibly as part of the feedforward organization of incipient voluntary movement, and after single phasic movements, as a consequence of afferent feedback processes. Here we test the hypothesis that this activity is also modulated during repetitive movements, reflecting a role in ongoing performance. Accordingly, we recorded LFP activity from the contralateral STN of seven patients with PD withdrawn from anti‐parkinsonian medication while they performed repetitive index finger to thumb taps. Cross‐correlograms of LFP activity at different frequencies in the 10–30 Hz band with finger position showed that LFP activity was modulated in amplitude by finger tapping. The modulation was higher at the beginning of each recording when tapping performance was better, and diminished as tapping became more bradykinetic over time. The best modulations were seen over those frequencies that were maximal in the power spectrum of the corresponding LFP, and for a given side were most marked at the contact pair that exhibited the highest power at these frequencies. In conclusion, subthalamic activity in the 10–30‐Hz band is amplitude modulated during movement. This process fails as bradykinesia increases.

144. Movement-related gamma synchronization is lateralized to the contralateral ventral intermediate nucleus (VIM) of the thalamus in tremor patients

widespread degradation of fractional anisotropy (FA) in main fibre tracts not limited to the respective temporal lobe. Main fibre-tracts as the uncinate fasciculus, the fronto-occipital fasciculus, the corpus callosum and the corticospinal tract on the respective side are also affected. FA is also decreased in the ipsilateral posterior cingulate gyrus. Patients with left-hemispheric surgery additionally show affections of the contralateral temporal lobe, mainly localized in the inferior longitudinal fasciculus. Conclusions: Medial temporal lobe surgery leads to widespread degradation of fibre tracts consistent with downstream wallerian degeneration, which is likely after surgical resection of mesial temporal lobe structures. Left-sided surgery seems to have stronger impact on white matter tracts, which is in line with the larger and more widespread neuropsychological effects of left-sided medial temporal lobe epilepsy and surgery. Because of the cohort-design of this study, the side and date of the surgery may not completely explain the results, as the underlying disease itself might also cause a part of the detected white matter changes. Further, longitudinal studies are needed to dissect the influence of the epilepsy and the surgery, respectively (Fig. 1).

The human subthalamic nucleus is activated earlier during internally paced single and sequential movements compared to externally paced movements

new scrambled pictures displayed a more right-lateralized activation. Picture Paradigm: the activation of new vs. old pictures was bilateral with the maximum in the right hippocampus. The contrast of new pictures vs. new scrambled pictures revealed also bilateral hippocampal activation with the maximum in the left hippocampus. Conclusions: The present study revealed a strong left-lateralized activation for the encoding of verbal stimuli, while faces as well as pictures exhibited a more bilateral activation. The aim of these paradigms is the clinical application during the presurgical evaluation of patients with temporal lobe epilepsy and hippocampal sclerosis (HS) to enable a prediction of a post-surgical memory outcome. To apply this paradigm to individual patients, the activation on the individual subject-level and the degree of lateralization has to be calculated.