Farid Salih

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.

Corticospinal excitability in human sleep as assessed by transcranial magnetic stimulation

The excitability of the corticospinal system was studied in 23 healthy subjects in sleep stages NREM2, NREM4, REM, and wakefulness using transcranial magnetic stimulation. Assessment of motor thresholds, stimulus-response curves, and latencies of motor evoked potentials shows activation of the fast-conducting corticospinal fibers in all sleep stages and a neuronal recruitment pattern similar to wakefulness, however, at a lower level of excitability and with significant differences between sleep stages.

Inhibitory and excitatory intracortical circuits across the human sleep–wake cycle using paired-pulse transcranial magnetic stimulation

Studies using single‐pulse transcranial magnetic stimulation (TMS) have shown that excitability of the corticospinal system is systematically reduced in natural human sleep as compared to wakefulness with significant differences between sleep stages. However, the underlying excitatory and inhibitory interactions on the corticospinal system across the sleep–wake cycle are poorly understood. Here, we specifically asked whether in the motor cortex short intracortical inhibition (SICI) and facilitation (ICF) can be elicited at all in sleep using the paired‐pulse TMS protocol, and if so, how SICI and ICF vary across sleep stages. We studied 28 healthy subjects at interstimulus intervals of 3 ms (SICI) and 10 ms (ICF), respectively. Magnetic stimulation was performed over the hand area of the motor cortex using a focal coil and evoked motor potentials were recorded from the contralateral first dorsal interosseus muscle (1DI). Relevant data was obtained from 13 subjects (NREM 2: n= 7; NREM 3/4: n= 7; REM: n= 7). Results show that both SICI and ICF were present in NREM sleep. SICI was significantly enhanced in NREM 3/4 as compared to wakefulness and all other sleep stages whereas in NREM 2 neither SICI nor ICF differed from wakefulness. In REM sleep SICI was in the same range as in wakefulness, but ICF was entirely absent. These results in humans support the hypothesis derived from animal experiments which suggests that intracortical inhibitory mechanisms are involved in the control of neocortical pyramidal cells in NREM and REM sleep, but along different intraneuronal circuits. Further, our findings suggest that cortical mechanisms may additionally contribute to the inhibition of spinal motoneurones in REM sleep.

A Hypothesis for How Non-REM Sleep Might Promote Seizures in Partial Epilepsies: A Transcranial Magnetic Stimulation Study

Summary:  Purpose: To investigate alterations of inhibitory and excitatory cortical circuits during non–rapid eye movement (NREM) sleep in drug‐naive patients with partial epilepsies and sleep‐bound seizures only.

Excitability and recruitment patterns of spinal motoneurons in human sleep as assessed by F-wave recordings

This study examines the excitability and recruitment of spinal motoneurons in human sleep. The main objective was to assess whether supraspinal inhibition affects the different subpopulations of the compound spinal motoneuron pool in the same way or rather in a selective fashion in the various sleep stages. To this end, we studied F-conduction velocities (FCV) and F-tacheodispersion alongside F-amplitudes and F-persistence in 22 healthy subjects in sleep stages N2, N3 (slow-wave sleep), REM and in wakefulness. Stimuli were delivered on the ulnar nerve, and F-waves were recorded from the first dorsal interosseus muscle. Repeated sets of stimuli were stored to obtain at least 15 F-waves for each state of vigilance. F-tacheodispersion was calculated based on FCVs using the modified Kimura formula. Confirming the only previous study, excitability of spinal motoneurons was generally decreased in all sleep stages compared with wakefulness as indicated by significantly reduced F-persistence and F-amplitudes. More importantly, F-tacheodispersion showed a narrowed range of FCV in all sleep stages, most prominently in REM. In non-REM, this narrowed range was associated with a shift towards significantly decreased maximal FCV and mean FCV as well as with a trend towards lower minimal FCV. In REM, the lowering of mean FCV was even more pronounced, but contrary to non-REM sleep without a shift of minimal and maximal FCV. Variations in F-tacheodispersion between sleep stages suggest that different supraspinal inhibitory neuronal circuits acting on the spinal motoneuron pool may contribute to muscle hypotonia in human non-REM sleep and to atonia in REM sleep.

Functional connectivity between motor cortex and globus pallidus in human non-REM sleep.

Recent evidence suggests that the motor system undergoes very specific modulation in its functional state during the different sleep stages. Here we test the hypothesis that changes in the functional organization of the motor system involve both cortical and subcortical levels and that these distributed changes are interrelated in defined frequency bands. To this end we evaluated functional connectivity between motor and non‐motor cortical sites (fronto‐central, parieto‐occipital) and the globus pallidus (GP) in human non‐REM sleep in seven patients undergoing deep brain stimulation (DBS) for dystonia using a variety of spectral measures (power, coherence, partial coherence and directed transfer function (DTF)). We found significant coherence between GP and fronto‐central cortex as well as between GP and parieto‐occipital cortex in circumscribed frequency bands that correlated with sleep specific oscillations in ‘light sleep’ (N2) and ‘slow‐wave sleep’ (N3). These sleep specific oscillations were also reflected in significant coherence between the two cortical sites corroborating previous studies. Importantly, we found two different physiological activities represented within the broad band of significant coherence between 9.5 and 17 Hz. One component occurred in the frequency range of sleep spindles (12.5–17 Hz) and was maximal in the coherence between fronto‐central and parieto‐occipital cortex as well as between GP and both cortical sites during N2. This component was still present between fronto‐central and parieto‐occipital cortex in N3. Functional connectivity in this frequency band may be due to a common input to both GP and cortex. The second component consisted of a spectral peak over 9.5–12.5 Hz. Coherence was elevated in this band for all topographical constellations in both N2 and N3, but especially between GP and fronto‐central cortex. The DTF suggested that the 9.5–12.5 Hz activity consisted of a preferential drive from GP to the fronto‐central cortex in N2, whereas in N3 the DTF between GP and fronto‐central cortex was symmetrical. Partial coherence supported distinctive patterns for the 9.5–12.5 and 12.5 and 17 Hz component, so that only coherence in the 9.5–12.5 Hz band was reduced when the effects of GP were removed from the coherence between the two cortical sites. The data suggest that activities in the GP and fronto‐central cortex are functionally connected over 9.5–12.5 Hz, possibly as a specific signature of the motor system in human non‐REM sleep. This finding is pertinent to the longstanding debate about the nature of alpha–delta sleep as a physiological or pathological feature of non‐REM sleep.

Intracranial pressure and cerebral perfusion pressure in patients developing brain death

PURPOSE We investigated whether a critical rise of intracranial pressure (ICP) leading to a loss of cerebral perfusion pressure (CPP) could serve as a surrogate marker of brain death (BD). MATERIALS AND METHODS We retrospectively analyzed ICP and CPP of patients in whom BD was diagnosed (n = 32, 16-79 years). Intracranial pressure and CPP were recorded using parenchymal (n = 27) and ventricular probes (n = 5). Data were analyzed from admission until BD was diagnosed. RESULTS Intracranial pressure was severely elevated (mean ± SD, 95.5 ± 9.8 mm Hg) in all patients when BD was diagnosed. In 28 patients, CPP was negative at the time of diagnosis (-8.2 ± 6.5 mm Hg). In 4 patients (12.5%), CPP was reduced but not negative. In these patients, minimal CPP was 4 to 18 mm Hg. In 1 patient, loss of CPP occurred 4 hours before apnea completed the BD syndrome. CONCLUSIONS Brain death was universally preceded by a severe reduction of CPP, supporting loss of cerebral perfusion as a critical step in BD development. Our data show that a negative CPP is neither sufficient nor a prerequisite to diagnose BD. In BD cases with positive CPP, we speculate that arterial blood pressure dropped below a critical closing pressure, thereby causing cessation of cerebral blood flow.

Der erhöhte intrakranielle Druck – Multimodales Neuromonitoring – Indikationen und Methoden

Managing patients after severe traumatic brain injury and aneurysmal subarachnoid hemorrhage is a challenging task of modern intensive care. Most patients do require sedation for mechanical ventilation due to respiratory distress or treatment of increased intracranial pressure. Besides standard ICP monitoring, a variety of continuous monitoring technologies for bedside use exists. The paper discusses the 5 methods most frequently used and their significance for multimodal neuromonitoring.

A syndrome of the dentate nucleus mimicking psychogenic ataxia

To date, cerebellar involvement in control of non-motor functions like cognition and emotion is increasingly well established. Current models suggest that motor and non-motor networks connecting the cerebellum with cortical areas operate independently in closed and segregated loops. Here, we report a 59-year-old female patient with a small cerebellar lesion that shows that cognitive activation can significantly influence cerebellar motor control. Surprisingly, this led to a clinical picture mimicking a psychogenic disorder. Similar to non-human primates, this case suggests that the human dentate nucleus consists of distinct cognitive and motor domains with additional somatotopical arrangement of the latter. Extending current models of cerebro-cerebellar interaction, this case further illustrates that there can be significant functional cross-talk between motor and cognitive cerebellar networks.

Complete loss of F-waves during cataplectic attacks in patients with narcolepsy

Cataplexy is one of the hallmark symptoms of patients diagnosed with narcolepsy type 1 (N1 = narcolepsy with cataplexy). Our pathophysiologic understanding of cataplexy has been based on the hypothesis that the loss of muscle tone characteristic for cataplectic attacks (CA) is identical to muscle atonia in REM sleep.1 However, this hypothesis has not been proved in humans since cataplexy can hardly be provoked experimentally. Recently, F-waves have been shown to be a valuable marker for spinal inhibition in REM sleep.2 We present F-wave recordings in 3 patients with N1 before, during, and after a CA (figure) to test whether the level of spinal excitability in cataplexy equals that in REM sleep.