Ventrointermediate thalamic stimulation improves motor learning in humans.

Ventrointermediate thalamic stimulation (VIM-DBS) modulates oscillatory activity in a cortical network including primary motor cortex, premotor cortex, and parietal cortex. Here we show that, beyond the beneficial effects of VIM-DBS on motor execution, this form of invasive stimulation facilitates production of sequential finger movements that follow a repeated sequence. These results highlight the role of thalamo-cortical activity in motor learning.

Enhancing Attentional Performance in Parkinson's Disease: The Impact of Combined Deep Brain Stimulation of the Substantia Nigra Pars Reticulata and the Subthalamic Nucleus.

OBJECTIVE: The concomitant stimulation of the subthalamic nucleus and the substantia nigra pars reticulata is a promising approach to improve treatment of refractory axial symptoms in Parkinson's disease. While dual stimulation of the subthalamic nucleus and the substantia nigra pars reticulata has previously shown beneficial effects on gait, the role of the substantia nigra, a crucial component of the basal ganglia circuitry, in cognitive functions such as attention and executive control remains underexplored. This study aimed to investigate the impact of selective substantia nigra pars reticulata stimulation on attentional performance in patients receiving standard deep brain stimulation of the subthalamic nucleus. METHODS: Twelve patients with bilateral subthalamic nucleus stimulation underwent computerized assessment of attention using a simple reaction time task. Reaction times were assessed under standard stimulation of the subthalamic nucleus versus simultaneous stimulation of the subthalamic nucleus and the substantia nigra pars reticulata. RESULTS: The results revealed a significant improvement in reaction times during the simple reaction time task when patients received dual stimulation compared to standard stimulation. CONCLUSIONS: Our findings provide further evidence for the pivotal role of the substantia nigra pars reticulata in cognitive functions such as attention. Despite the limitations of the study, including a small sample size, our results suggest potential benefits of simultaneous deep brain stimulation of the subthalamic nucleus and the substantia nigra pars reticulata on attentional performance in patients with Parkinson's disease. Further research with larger cohorts is warranted to confirm these findings and better understand the underlying mechanisms.

Subthalamic Nucleus Deep Brain Stimulation Restores Motor and Sensorimotor Cortical Neuronal Oscillatory Activity in the Free-Moving 6-Hydroxydopamine Lesion Rat Parkinson Model.

OBJECTIVES: Enhanced beta oscillations in cortical-basal ganglia (BG) thalamic circuitries have been linked to clinical symptoms of Parkinson's disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces beta band activity in BG regions, whereas little is known about activity in cortical regions. In this study, we investigated the effect of STN DBS on the spectral power of oscillatory activity in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) by recording via an electrocorticogram (ECoG) array in free-moving 6-hydroxydopamine (6-OHDA) lesioned rats and sham-lesioned controls. MATERIALS AND METHODS: Male Sprague-Dawley rats (250-350 g) were injected either with 6-OHDA or with saline in the right medial forebrain bundle, under general anesthesia. A stimulation electrode was then implanted in the ipsilateral STN, and an ECoG array was placed subdurally above the MCtx and SMCtx areas. Six days after the second surgery, the free-moving rats were individually recorded in three conditions: 1) basal activity, 2) during STN DBS, and 3) directly after STN DBS. RESULTS: In 6-OHDA-lesioned rats (N = 8), the relative power of theta band activity was reduced, whereas activity of broad-range beta band (12-30 Hz) along with two different subbeta bands, that is, low (12-30 Hz) and high (20-30 Hz) beta band and gamma band, was higher in MCtx and SMCtx than in sham-lesioned controls (N = 7). This was, to some extent, reverted toward control level by STN DBS during and after stimulation. No major differences were found between contacts of the electrode grid or between MCtx and SMCtx. CONCLUSION: Loss of nigrostriatal dopamine leads to abnormal oscillatory activity in both MCtx and SMCtx, which is compensated by STN stimulation, suggesting that parkinsonism-related oscillations in the cortex and BG are linked through their anatomic connections.

Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial.

Treatment resistance in alcohol use disorders (AUD) is a major problem for affected individuals and for society. In the search of new treatment options, few case studies using deep brain stimulation (DBS) of the nucleus accumbens have indicated positive effects in AUD. Here we report a double-blind randomized controlled trial comparing active DBS ("DBS-EARLY ON") against sham stimulation ("DBS-LATE ON") over 6 months in n = 12 AUD inpatients. This 6-month blind phase was followed by a 12-month unblinded period in which all patients received active DBS. Continuous abstinence (primary outcome), alcohol use, alcohol craving, depressiveness, anxiety, anhedonia and quality of life served as outcome parameters. The primary intention-to-treat analysis, comparing continuous abstinence between treatment groups, did not yield statistically significant results, most likely due to the restricted number of participants. In light of the resulting limited statistical power, there is the question of whether DBS effects on secondary outcomes can nonetheless be interpreted as indicative of an therapeutic effect. Analyses of secondary outcomes provide evidence for this, demonstrating a significantly higher proportion of abstinent days, lower alcohol craving and anhedonia in the DBS-EARLY ON group 6 months after randomization. Exploratory responder analyses indicated that patients with high baseline alcohol craving, depressiveness and anhedonia responded to DBS. The results of this first randomized controlled trial are suggestive of beneficial effects of DBS in treatment-resistant AUD and encourage a replication in larger samples.

Deep brain stimulation of the ventrointermediate nucleus of the thalamus to treat essential tremor improves motor sequence learning.

The network of brain structures engaged in motor sequence learning comprises the same structures as those involved in tremor, including basal ganglia, cerebellum, thalamus, and motor cortex. Deep brain stimulation (DBS) of the ventrointermediate nucleus of the thalamus (VIM) reduces tremor, but the effects on motor sequence learning are unknown. We investigated whether VIM stimulation has an impact on motor sequence learning and hypothesized that stimulation effects depend on the laterality of electrode location. Twenty patients (age: 38-81 years; 12 female) with VIM electrodes implanted to treat essential tremor (ET) successfully performed a serial reaction time task, varying whether the stimuli followed a repeating pattern or were selected at random, during which VIM-DBS was either on or off. Analyses of variance were applied to evaluate motor sequence learning performance according to reaction times (RTs) and accuracy. An interaction was observed between whether the sequence was repeated or random and whether VIM-DBS was on or off (F[1,18] = 7.89, p = .012). Motor sequence learning, reflected by reduced RTs for repeated sequences, was greater with DBS on than off (T[19] = 2.34, p = .031). Stimulation location correlated with the degree of motor learning, with greater motor learning when stimulation targeted the lateral VIM (n = 23, ρ = 0.46; p = .027). These results demonstrate the beneficial effects of VIM-DBS on motor sequence learning in ET patients, particularly with lateral VIM electrode location, and provide evidence for a role for the VIM in motor sequence learning.

Rhythmic interactions between the mediodorsal thalamus and prefrontal cortex precede human visual perception.

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition.

Deviation of the orientation angle of directional deep brain stimulation leads quantified by intraoperative stereotactic X-ray imaging.

Directional deep brain stimulation (dDBS) provides multiple programming options. Knowledge of the spatial lead orientation is useful for time-efficient programming. Recent studies demonstrated deviations of up to 90° from the intended orientation angle. We examined the deviation of dDBS-lead orientation for leads from two different manufacturers using intraoperative stereotactic (STX) X-ray images. Intraoperative 2D-X-ray images were acquired after implantation of the first lead (TP1) and the second lead (TP2) enabling the estimation of the spatial position of the first lead at TP1 and TP2 and of changes of the orientation for a defined time period. Two investigators retrospectively estimated the orientation of the directional marker for 64 patients. The mean deviation from intended spatial orientation was 40.8° ± 46.1° for all examined leads. The spatial orientation of the first lead did not significantly change within a period of approximately 1 h. The degree of deviation did not differ significantly between two lead manufacturers but depended on the lead fixation technique. Our results showed deviations from the intended orientation angle immediately after the insertion of dDBS leads. The initial spatial orientation remained stable for approximately 1 h and was not caused by technical properties of the implanted lead. Hence, it was most probably the result of unintended mechanical torsion during insertion and/or fixation. Because precise determination of the lead orientation is mandatory for target-oriented dDBS programming, the use of additional imaging suitable for precise 3D visualization of lead contacts and/or the positioning marker is recommended.

Brain biopsy in patients with CLIPPERS syndrome: why and when.

CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an inflammatory disorder of the central nervous system (CNS), predominantly involving the brainstem with a characteristic magnetic resonance imaging (MRI) appearance and clinical and radiological responsiveness to glucocorticosteroids. Yet diagnostic biomarkers are missing and other immune-mediated, (para-) infectious and malignant causes mimic CLIPPERS-like MRI presentations. We report the case of a 51-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. After 7 months, however, treatment failed, and he had a biopsy-confirmed diagnosis of a CNS B-cell lymphoma. Clinical and MRI signs of CLIPPERS include a wide spectrum of differential diagnoses which often arise only later during the course of disease. Similar to the case presented here, delayed diagnosis and specific therapy may contribute to an unfavorable outcome. Hence, we propose that in the absence of other diagnostic markers, brain biopsy should be performed as early as possible in CLIPPERS patients.

Sweets for my sweet: modulation of the limbic system drives salience for sweet foods after deep brain stimulation in Parkinson's disease.

BACKGROUND: An increase in body weight is observed in the majority of patients with Parkinson's disease (PD) who undergo deep brain stimulation (DBS) of the subthalamic nucleus (STN) although the mechanisms are unclear. OBJECTIVES: To identify the stimulation-dependent effects on reward-associated and attention-associated neural networks and to determine whether these alterations in functional connectivity are associated with the local impact of DBS on different STN parcellations. METHODS: We acquired functional task-related MRI data from 21 patients with PD during active and inactive STN DBS and 19 controls while performing a food viewing paradigm. Electrode placement in the STN was localised using a state-of-the-art approach. Based on the 3D model, the local impact of STN DBS was estimated. RESULTS: STN DBS resulted in a mean improvement of motor function of 22.6%±15.5% (on medication) and an increase of body weight of ~4 kg within 2 years of stimulation. DBS of the limbic proportion of the STN was associated with body weight gain and an increased functional connectivity within the salience network and at the same time with a decreased activity within the reward-related network in the context of sweet food images. CONCLUSIONS: Our findings indicate increased selective attention for high-caloric foods and a sweet food seeking-like behaviour after DBS particularly when the limbic proportion of the STN was stimulated.

Nucleus accumbens projections: Validity and reliability of fiber reconstructions based on high-resolution diffusion-weighted MRI.

Clinical effects of deep brain stimulation are largely mediated by the activation of myelinated axons. Hence, increasing attention has been paid in the past on targeting white matter tracts in addition to gray matter. Aims of the present study were: (i) visualization of discrete afferences and efferences of the nucleus accumbens (NAc), supposed to be a major hub of neural networks relating to mental disorders, using probabilistic fiber tractography and a data driven approach, and (ii) validation of the applied methodology for standardized routine clinical applications. MR-data from 11 healthy subjects and 7 measurement sessions each were acquired on a 3T MRI-scanner. For probabilistic fiber tracking the NAc as a seed region and the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), amygdala (AMY), hippocampus (HPC), dorsomedial thalamus (dmT) and ventral tegmental area (VTA) as target regions were segmented for each subject and both hemispheres. To quantitatively assess the reliability and stability of the reconstructions, we filtered and clustered the individual fiber-tracts (NAc to target) for each session and subject and performed a point-by-point calculation of the maximum cluster distances for intra-subject comparison. The connectivity patterns formed by the obtained fibers were in good concordance with published data from tracer and/or fiber-dissection studies. Furthermore, the reliability assessment of the (NAc to target)-fiber-tracts yielded to high correlations between the obtained clustered-tracts. Using DBS with directional lead technology, the workflow elaborated in this study may guide selective electrical stimulation of NAc projections.

Invasive Brain Stimulation in the Treatment of Psychiatric Illness­Proposed Indications and Approaches.

BACKGROUND: Drugs, psychotherapy, and other treatment modalities are effective for many patients with mental illness. Nonetheless, many patients do not achieve a total remission with the currently available interventions, and the recurrence rates are high. As part of the ongoing search for further treatment options for refractory disorders, there is renewed interest in focal neuromodulatory techniques, including invasive ones, and deep brain stimulation (DBS) in particular. METHODS: In this review article, a group consisting of neurosurgeons, psychiatrists, and one practicing ethicist/neurologist summarizes the main aspects of the use of DBS to treat mental illness and offers recommendations on its indications and practical implementation. RESULTS: The efficacy of DBS against mental illness has not been confirmed in the randomized, controlled trials (RCTs) that have been published to date. This may be because the follow-up times were too short. In contrast to the negative RCTs, case series have indeed shown a positive effect of DBS on severe depression, but this effect can only be seen several months after the operation. CONCLUSION: DBS may be a therapeutic option for selected patients with otherwise intractable mental illness. Patients should only be treated in the setting of clinical trials. RCTs with longer follow-up times must be conducted in order to substantiate, if possible, the promising evidence that has been found in case series.

The role of the anterior nuclei of the thalamus in human memory processing.

Extensive neuroanatomical connectivity between the anterior thalamic nuclei (ATN) and hippocampus and neocortex renders them well-placed for a role in memory processing, and animal, lesion, and neuroimaging studies support such a notion. The deep location and small size of the ATN have precluded their real-time electrophysiological investigation during human memory processing. However, ATN electrophysiological recordings from patients receiving electrodes implanted for deep brain stimulation for pharmacoresistant focal epilepsy have enabled high temporal resolution study of ATN activity. Theta frequency synchronization of ATN and neocortical oscillations during successful memory encoding, enhanced phase alignment, and coupling between ATN local gamma frequency activity and frontal neocortical and ATN theta oscillations provide evidence of an active role for the ATN in memory encoding, potentially integrating information from widespread neocortical sources. Greater coupling of a broader gamma frequency range with theta oscillations at rest than during memory encoding provides additional support for the hypothesis that the ATN play a role in selecting local, task-relevant high frequency activity associated with particular features of a memory trace.

Deep Brain Stimulation for Refractory Focal Epilepsy: Unraveling the Insertional Effect up to Five Months Without Stimulation.

INTRODUCTION: Following electrode implantation, a subgroup of patients treated with deep brain stimulation (DBS) for focal epilepsy exhibits a reduction of seizure frequency before stimulation is initiated. Microlesioning of the target structure has been postulated to be the cause of this "insertional" effect (IE). We examined the occurrence and duration of this IE in a group of patients with focal epilepsy following electrode implantation in the anterior nuclei of the thalamus (ANT) and/or nucleus accumbens (NAC) for DBS treatment. MATERIALS AND METHODS: Changes in monthly seizure frequency compared to preoperative baseline were assessed one month (14 patients) and five months (four patients) after electrode implantation. A group analysis between patients with implantation of bilateral ANT-electrodes (four patients), NAC-electrodes (one patient) as well as ANT and NAC-electrodes (nine patients) was performed. RESULTS: In this cohort, seizure frequency decreased one month after electrode implantation by 57.1 ± 30.1%, p ≤ 0.001 (compared to baseline). No significant difference within stimulation target subcohorts was found (p > 0.05). Out of the four patients without stimulation for five months following electrode insertion, three patients showed seizure frequency reduction lasting two to three months, while blinded to their stimulation status. CONCLUSION: An IE might explain seizure frequency reduction in our cohort. This effect seems to be independent of the number of implanted electrodes and of the target itself. The time course of the blinded subgroup of epilepsy patients suggests a peak of the lesional effect at two to three months after electrode insertion.

Neuromodulation of the subthalamic nucleus in Parkinson's disease: the effect of fiber tract stimulation on tremor control.

BACKGROUND: Therapeutic effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) may in parts be attributed to the stimulation of white matter near the targeted structure. The dentato-rubro-thalamic (DRT) tract supposed to improve tremor control in patients with essential tremor could be one candidate structure. The aim of this study was to investigate the effect of stimulation proximity to the DRT on tremor control in PD patients treated with STN-DBS. METHODS: For this retrospective analysis, we included 36 consecutive patients (median age 65.5 years) treated with STN-DBS for disabling motor symptoms including tremor. Stereotactic implantation of DBS electrodes into the motor area of the STN was performed using direct MRI-based targeting and intraoperative microelectrode recording. Tremor severity was assessed preoperatively and at regular intervals postoperatively (Unified Parkinson's Disease Rating Scale III). The DRT was visualized in 60 hemispheres after probabilistic fiber tracking (3-T MRI). The position of active electrode contacts was verified on intraoperative stereotactic X-rays and postoperative CT images after co-registration with 3D treatment planning MRI/CT images. We determined the shortest distance of active contacts to the ipsilateral DRT tracts on perpendicular view slices and correlated this value with tremor change percentage. RESULTS: Twelve patients had unilateral tremor only, and accordingly, 12 hemispheres were excluded from further imaging analysis. The remaining 60 hemispheres were associated with contralateral resting tremor. Active brain electrode contacts leading to resting tremor improvement (46 hemispheres) had a significantly shorter distance to the DRT (1.6 mm (0.9-2.1) [median (25th-75th percentiles)]) compared with contacts of non-responders (14 hemispheres, distance: 2.8 mm (2-4.6), p < 0.001). CONCLUSION: This retrospective analysis suggests that in STN-DBS, better tremor control in PD patients correlates with the distance of active electrode contacts to the DRT. Tractography may optimize both individually DBS targeting and postoperative adjustment of stimulation parameters.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Neuronal oscillations of the pedunculopontine nucleus in progressive supranuclear palsy: Influence of levodopa and movement.

OBJECTIVE: The pedunculopontine nucleus (PPN) has been proposed as a new deep brain stimulation (DBS) target for the treatment in idiopathic Parkinson's syndrome (IPS) and progressive supranuclear palsy (PSP). In IPS, levodopa has been shown to induce alpha activity in the PPN, indicating a possible physiological role for these oscillations in movement control. Despite shared clinical features, the PPN is more severely affected in PSP than IPS. Here we investigated neuronal oscillations in the PPN in PSP and the influence of levodopa and movement. METHODS: Local field potentials were recorded bilaterally from the PPN of 4 PSP patients at rest, with levodopa and during self-paced leg movements. RESULTS: During rest, levodopa administration was associated with significantly increased alpha and reduced gamma activity in the PPN. Without levodopa, continuous movements were associated with reduced alpha and beta power. These differences between oscillatory power during movement and resting state were not observed with levodopa administration. CONCLUSION: In PSP the changes in neuronal oscillations in the PPN region on levodopa administration are similar to those reported in IPS. The enhancement of lower frequency oscillations in the PPN is possibly influenced by a dopaminergic activation of the striatal pathway and a reduced pallidal inhibition. SIGNIFICANCE: Levodopa influences neuronal oscillations at low and high frequencies in the PPN region in Parkinsonian disorders.

Cerebello-striatal interaction mediates effects of subthalamic nucleus deep brain stimulation in Parkinson's disease.

BACKGROUND: In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) go beyond DRT effects including highly beneficial tremor suppression. OBJECTIVES: Here, we aimed to determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN DBS. METHODS: In a repeated-measurement design, 26 medicated PD patients (60.9 years (SD 8.9)) were investigated using resting state fMRI while bipolar STN stimulation was (i) active or (ii) switched off, and dynamic causal modelling was subsequently performed. RESULTS: DBS improved the MDS-UPDRS-III score by 26.4% (DBS ON/Med ON vs. DBS OFF/Med ON). Active stimulation resulted in an increased effective connectivity from cerebellum to putamen (p = 0.00118). In addition, there was a stronger coupling from PFC to cerebellum (p = 0.021), as well as from cerebellum to SMA (p = 0.043) on an uncorrected level. Coupling strength from PFC to cerebellum correlated with the DBS-related change of the resting tremor subscore (r = 0.54, p = 0.031). Self-connections increased as a function of DBS in the right PFC, PMC, SMA, M1, thalamus and left cerebellum. CONCLUSIONS: DBS-related improvement of Parkinsonian signs appears to be driven by an interaction between the cerebellum and the putamen. Resting tremor suppression may be related to an enhanced prefronto-cerebellar network. Activation of the mesial premotor loop (PFC-SMA) as seen in DRT may thus be secondary due to the primary modulation of cerebellar networks.

Deep Brain Stimulation of the Subthalamic Nucleus Selectively Modulates Emotion Recognition of Facial Stimuli in Parkinson's Patients.

: Background: Diminished emotion recognition is a known symptom in Parkinson (PD) patients and subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to further deteriorate the processing of especially negative emotions. While emotion recognition generally refers to both, implicit and explicit processing, demonstrations of DBS-influences on implicit processing are sparse. In the present study, we assessed the impact of STN-DBS on explicit and implicit processing for emotional stimuli. METHODS: Under STN-DBS ON and OFF, fourteen PD patients performed an implicit as well as an explicit emotional processing task. To assess implicit emotional processing, patients were tested with a lexical decision task (LTD) combined with an affective priming paradigm, which provides emotional content through the facial eye region. To assess explicit emotional processing, patients additionally explicitly rated the emotional status of eyes and words used in the implicit task. RESULTS: DBS affected explicit emotional processing more than implicit processing with a more pronounced effect on error rates than on reaction speed. STN-DBS generally worsened implicit and explicit processing for disgust stimulus material but improved explicit processing of fear stimuli. CONCLUSIONS: This is the first study demonstrating influences of STN-DBS on explicit and implicit emotion processing in PD patients. While STN stimulation impeded the processing of disgust stimuli, it improved explicit discrimination of fear stimuli.

Long-term outcomes of semi-implantable functional electrical stimulation for central drop foot.

BACKGROUND: Central drop foot is a common problem in patients with stroke or multiple sclerosis (MS). For decades, it has been treated with orthotic devices, keeping the ankle in a fixed position. It has been shown recently that semi-implantable functional electrical stimulation (siFES) of the peroneal nerve can lead to a greater gait velocity increase than orthotic devices immediately after being switched on. Little is known, however, about long-term outcomes over 12 months, and the relationship between quality of life (QoL) and gait speed using siFES has never been reported applying a validated tool. We provide here a report of short (3 months) and long-term (12 months) outcomes for gait speed and QoL. METHODS: Forty-five consecutive patients (91% chronic stroke, 9% MS) with central drop foot received siFES (Actigait®). A 10 m walking test was carried out on day 1 of stimulation (T1), in stimulation ON and OFF conditions, and repeated after 3 (T2) and 12 (T3) months. A 36-item Short Form questionnaire was applied at all three time points. RESULTS: We found a main effect of stimulation on both maximum (p < 0.001) and comfortable gait velocity (p < 0.001) and a main effect of time (p = 0.015) only on maximum gait velocity. There were no significant interactions. Mean maximum gait velocity across the three assessment time points was 0.13 m/s greater with stimulation ON than OFF, and mean comfortable gait velocity was 0.083 m/s faster with stimulation ON than OFF. The increase in maximum gait velocity over time was 0.096 m/s, with post hoc testing revealing a significant increase from T1 to T2 (p = 0.012), which was maintained but not significantly further increased at T3. QoL scores showed a main effect of time (p < 0.001), with post hoc testing revealing an increase from T1 to T2 (p < 0.001), which was maintained at T3 (p < 0.001). Finally, overall absolute QoL scores correlated with the absolute maximum and comfortable gait speeds at T2 and T3, and the increase in overall QoL scores correlated with the increase in comfortable gait velocity from T1 to T3. Pain was reduced at T2 (p < 0.001) and was independent of gait speed but correlated with overall QoL (p < 0.001). CONCLUSIONS: Peroneal siFES increased maximal and comfortable gait velocity and QoL, with the greatest increase in both over the first three months, which was maintained at one year, suggesting that 3 months is an adequate follow-up time. Pain after 3 months correlated with QoL and was independent of gait velocity, suggesting pain as an independent outcome measure in siFES for drop foot.

Electric stimulation of the medial forebrain bundle influences sensorimotor gaiting in humans.

BACKGROUND: Prepulse inhibition (PPI) of the acoustic startle response, a measurement of sensorimotor gaiting, is modulated by monoaminergic, presumably dopaminergic neurotransmission. Disturbances of the dopaminergic system can cause deficient PPI as found in neuropsychiatric diseases. A target specific influence of deep brain stimulation (DBS) on PPI has been shown in animal models of neuropsychiatric disorders. In the present study, three patients with early dementia of Alzheimer type underwent DBS of the median forebrain bundle (MFB) in a compassionate use program to maintain cognitive abilities. This provided us the unique possibility to investigate the effects of different stimulation conditions of DBS of the MFB on PPI in humans. RESULTS: Separate analysis of each patient consistently showed a frequency dependent pattern with a DBS-induced increase of PPI at 60 Hz and unchanged PPI at 20 or 130 Hz, as compared to sham stimulation. CONCLUSIONS: Our data demonstrate that electrical stimulation of the MFB modulates PPI in a frequency-dependent manner. PPI measurement could serve as a potential marker for optimization of DBS settings independent of the patient or the examiner.