BackgroundIn Parkinson disease (PD), enhanced beta frequency band activity in cortico-basal ganglia networks has been proposed as a possible biomarker for adaptive deep brain stimulation (DBS). Previous studies demonstrated enhanced beta frequency peaks both in the acute Haloperidol (HALO) and the chronic 6-hydroxydopamine (6-OHDA) rat models of parkinsonism. Beta peaks decreased after apomorphine (APO) injection or with DBS of the subthalamic nucleus (STN).ObjectiveWe investigate changes in motor cortical oscillatory activity using fractal dimension (FD) in the HALO and the 6-OHDA rat models of PD. Additionally, we test a support vector machine (SVM) model to predict neuronal dynamics in the 6-OHDA PD model which has been used earlier in an acute rat model of PD.MethodsIn the HALO model, electrocorticogram (ECoG) was recorded from the motor cortex (MCtx) (1) during basal activity, (2) after injection of HALO (0.5 mg/kg), and (3) after subsequent APO injection (1 mg/kg). For the chronic 6-OHDA model, MCtx-ECoG recordings were obtained (1) during basal activity, and (2) during STN DBS. Higuchi's FD algorithm and SVM-based classification were utilized for analysis.ResultsAverage FD values in the MCtx were higher in both PD models compared to controls (P < 0.001). APO injection (P < 0.001) and STN DBS (P < 0.05) reduced average FD values in both models. The SVM model achieved 80% classification accuracy and an AUC of 0.86 in the 6-OHDA rat model.ConclusionThe non-linear analysis of FD reveals changes in cortical oscillatory patterns in rodent models of PD. SVM-based predictions demonstrate potential for classifying altered neural activity, which may offer future strategies for adaptive DBS.

BACKGROUND:In rodent models of intracranial tumor development, evaluating the actual burden experienced by animals beyond procedural severity is essential for ethical and legal compliance. This study examined whether voluntary wheel running (VWR) could serve as a sensitive indicator of post-surgical burden following subcutaneous transmitter implantation, tumor cell injection, and tumor resection. It also assessed whether VWR supports the detection of humane endpoints. VWR outcomes were compared with body weight, clinical scores, heart rate, and activity levels recorded via telemetry. METHODS:Fourteen male BDIX rats were housed individually in cages equipped with a running wheel. Under general anesthesia, telemetric devices to monitor heart rate and activity were subcutaneously implanted. After recovery, glioblastoma BT4Ca cells were stereotaxically injected into the right frontal cortex. Eight days later, the resulting tumors were microsurgically resected. Body weight, VWR, heart rate, and general activity were continuously monitored until the animals reached humane endpoint criteria, indicated by sudden weight loss and clinical deterioration. RESULTS:On average, body weight and VWR declined significantly after all surgical procedures, with tumor resection causing the most pronounced effect. As animals approached the endpoint, a marked drop in these parameters was observed, along with an increased clinical score (p < 0.05). Activity measures supported these findings, though less consistently than weight and VWR. CONCLUSIONS:Monitoring body weight and VWR enables an effective assessment of the actual postoperative burden experienced by rats undergoing surgeries of different procedural complexity. Moreover, VWR is a valuable supplementary tool for identifying humane endpoints alongside body weight and clinical scoring.

In humans, the auditory three-class oddball paradigm probes neural markers of target detection among rare distractors and frequent standard stimuli, critically involving the thalamic centromedian-parafascicular (CM-Pf) complex. Rodents are widely used in translational research but differ from humans in auditory perception and learning. We tested whether rats can be trained with human-relevant stimuli and effects on CM-Pf event-related potentials (ERPs). Male Sprague Dawley rats (n = 11) were trained to respond to a rare target tone (5 kHz, high-tone subgroup, or 1.5 kHz, low-tone subgroup) while ignoring a rare distractor (1.5 or 5 kHz) and a frequent standard tone (3 kHz). During behavioral testing, ERPs were recorded using stereotaxically implanted electrodes in the CM-Pf. During training, reaction times to target tones were initially randomly distributed, but became increasingly locked to stimulus onset as accuracy improved (p < 0.01). In contrast, false responses to sequentially introduced standard and distractor tones were initially stimulus-locked, but later became sparse and randomly distributed (p < 0.05) as rats learned to ignore these tones. CM-Pf ERP amplitudes were highest for target tones (p < 0.01), while standard and distractor tones did not differ, indicating neglect of both stimulus types (p = 0.15). Training with 1.5 or 5 kHz target tones produced no major behavioral or neural differences. These findings support the use of rats as a translational model for auditory discrimination and deviance processing using human-relevant tone frequencies, while highlighting the need to consider learning dynamics involved when comparing rats and humans.

The three-class auditory oddball paradigm is used to study sensory processing, attention, and decision-making. In this paradigm, a rare behaviorally relevant target is presented among frequent behaviorally irrelevant standard and rare distractor tones. The Tone Approach Paradigm (TAP) was designed as a variation of this paradigm in which task difficulty increases as the target and distractor frequencies sequentially approach the frequency of the standard tone to investigate neurocognitive aspects of processing behaviorally relevant auditory stimuli under challenging hearing conditions in rats. Male Sprague-Dawley rats (n = 10) were trained to respond to target (5000 Hz), while ignoring distractor (1500 Hz) and standard tones (3000 Hz) in baseline (BSL) condition. After training, electrodes were implanted in the medial prefrontal cortex (mPFC) for local field potential recording during behavioral testing. Starting from BSL, the frequency differences between target and distractor to standard tones in the TAP sessions were reduced by 500 Hz per session. Hit ratios for targets declined with increasing difficulty of TAP sessions (p < 0.05). Cumulative distributions of reaction times shifted from a sigmoidal profile with stimulus-locked behavior to a more linear profile, suggesting less temporally clustered responding. Event-related potential amplitudes increased at low and moderate TAP difficulty, indicating higher processing effort, but decreased at the highest difficulty, suggesting impaired processing. Our findings show that manipulating task difficulty via frequency changes directly affects behavior and neural processing within the mPFC. TAP provides a translational framework for investigating neurophysiological mechanisms of attention and stimulus evaluation, with relevance for models of attention-related dysfunction.

Background The three-class oddball paradigm allows to investigate the processing of behaviorally relevant and irrelevant auditory stimuli. In humans, event-related potentials (ERPs) are used as neural correlate of behavior. We recorded local field potentials (LFPs) within the medial prefrontal cortex (mPFC) in rats during three-class and passive two-class oddball paradigms and analyzed the ERPs focusing on similarities to human recordings. New method Rats were trained in a three-class auditory oddball paradigm to respond by nose poke to an infrequent Target tone that was rewarded, while ignoring an infrequent Distractor and frequent Standard tone of different frequencies. After reaching a success criterion of correct responses to the Target and correct rejection of the Standard and Distractor (80%,each), electrodes were stereotaxically implanted into the mPFC. The recording of the neuronal activity took place in the three-class oddball paradigm as well as in a passive two-class oddball paradigm with unfamiliar frequencies. Results Correct responding to the Target tone was accompanied by a higher amplitude of the ERP in comparison to the Standard and Distractor tones (p<0.05). Target Miss, or incorrect responding to Distractor or Standard led to reduced, respectively enhanced peak latency. In the two-class oddball paradigm, the amplitude of the Distractor ERP was enhanced as compared to that after Standard (p<0.05). Conclusion ERPs derived from mPFC LFPs of rats show key characteristics similar to that derived from human EEGs. This model allows to investigate the processing of behaviorally important and irrelevant auditory stimuli in subcortical brain regions in a translational approach.

Background/Objectives: Cerebellar cognitive affective syndrome (CCAS) is a well-recognized postoperative complication in children following resection of brain tumors involving cerebellar midline structures. The fastigial nucleus is regarded as relevant, but the underlying neural mechanisms remain incompletely understood. This study uses an oddball paradigm designed to model attentional and learning processes relevant to CCAS to investigate how early-life lesions of the fastigial nucleus in rats affect cognitive performance and neural information processing in the medial prefrontal cortex (mPFC) in adulthood. Methods: Fastigial lesions were induced stereotaxically in 23-day-old male Sprague Dawley rats [n = 9]. Naïve [n = 9] and sham-lesioned rats [n = 6] served as controls. As adults, all rats were trained in an oddball paradigm requiring discrimination of a rare target tone from a rare distractor and a frequent standard tone. Local field potentials (LFPs) were recorded from electrodes implanted in the mPFC during oddball testing and event-related potentials (ERPs) were analyzed. Results: Rats with fastigial lesions required significantly more training days to reach ≥70% correct performance criterion. In fully trained rats, analysis of neural recordings during behavioral testing revealed reduced ERP amplitudes and prolonged latencies of late ERP components after target stimuli. Developmental fastigial lesions lead to lasting deficits in cognitive learning capacity and neural mPFC processing, highlighting the integrative role of cerebellar midline structures in higher-order cognitive function and sensory discrimination. Conclusions: This rodent model provides a valuable translational platform for further investigating the neural basis of CCAS and may inform neurosurgical strategies aimed at minimizing cognitive sequelae in children undergoing cerebellar tumor resection.

Background: In children, hearing loss has been associated with hyperactivity, disturbed social interaction, and risk of cognitive disturbances. Mechanistic explanations of these relations sometimes involve language. To investigate the effect of hearing loss on behavioral deficits in the absence of language, we tested the impact of hearing loss in juvenile rats on motor, social, and cognitive behavior and on physiology of prefrontal cortex. Methods: Hearing loss was induced in juvenile (postnatal day 14) male Sprague-Dawley rats by intracochlear injection of neomycin under general anesthesia. Sham-operated and non-operated hearing rats served as controls. One week after surgery auditory brainstem response (ABR) measurements verified hearing loss or intact hearing in sham-operated and non-operated controls. All rats were then tested for locomotor activity (open field), coordination (Rotarod), and for social interaction during development in weeks 1, 2, 4, 8, 16, and 24 after surgery. From week 8 on, rats were trained and tested for spatial learning and memory (4-arm baited 8-arm radial maze test). In a final setting, neuronal activity was recorded in the medial prefrontal cortex (mPFC). Results: In the open field deafened rats moved faster and covered more distance than sham-operated and non-operated controls from week 8 on (both p < 0.05). Deafened rats showed significantly more play fighting during development (p < 0.05), whereas other aspects of social interaction, such as following, were not affected. Learning of the radial maze test was not impaired in deafened rats (p > 0.05), but rats used less next-arm entries than other groups indicating impaired concept learning (p < 0.05). In the mPFC neuronal firing rate was reduced and enhanced irregular firing was observed. Moreover, oscillatory activity was altered, both within the mPFC and in coherence of mPFC with the somatosensory cortex (p < 0.05). Conclusions: Hearing loss in juvenile rats leads to hyperactive behavior and pronounced play-fighting during development, suggesting a causal relationship between hearing loss and cognitive development. Altered neuronal activities in the mPFC after hearing loss support such effects on neuronal networks outside the central auditory system. This animal model provides evidence of developmental consequences of juvenile hearing loss on prefrontal cortex in absence of language as potential confounding factor.

Age-related hearing loss in humans has been associated with cognitive decline, though the underlying mechanisms remain unknown. We investigated the long-term effects of hearing loss on attention, impulse control, social interaction, and neural activity within medial prefrontal cortex (mPFC) subregions. Hearing loss was induced in adult rats via intracochlear neomycin injection (n = 13), with non-operated rats as controls (n = 10). Rats were tested for motor activity (open field), coordination (Rotarod), and social interaction (including ultrasonic vocalization, USV) before surgery and at weeks 1, 2, 4, 8, 16, and 24 post-surgery. From week 8 on, rats were trained in the five-choice serial reaction time task (5-CSRTT) to assess visuospatial attention and impulse control. Finally, oscillatory neuronal activity in mPFC subregions was recorded with multielectrode arrays during anesthesia, followed by immunohistological staining for NeuN+ and Parvalbumin+ cells. Deafened rats were more active than controls, whereas social interaction and USV were temporarily reduced. They also had difficulties to learn the concept of the 5-CSRTT paradigm and made more incorrect responses. Electrophysiology showed decreased power in theta, alpha, and beta frequency, and enhanced high gamma band in the mPFC in deafened rats, which was most pronounced in the cingulate subregion (Cg1). The number of NeuN+ and Parvalbumin+ cells, however, did not differ between groups. The behavioral deficits together with the altered neuronal activity found in the Cg1 subregion of the mPFC in adult deafened rats may be used as an endophenotype to elucidate the mechanisms behind the cognitive decline seen in older patients with hearing loss.

The efficacy of electrodes that are chronically implanted and used in the context of deep brain stimulation (DBS) for the treatment of neurological disorders critically depends on stable impedance. Platinum–iridium electrodes were coated with laser-generated platinum nanoparticle colloids (PtNPs) via electrophoretic deposition using pulsed direct currents (DC-EPD). Uncoated electrodes were used as controls. In vitro, electrodes were stimulated for four weeks in a 0.9% NaCl solution. For the in vivo (rats) study, coated electrodes were implanted in the left and uncoated control electrodes in the right subthalamic nucleus (STN). After two weeks of recovery, electrodes were stimulated for four weeks. Impedance measurements were conducted after each week of stimulation, both in vivo and in vitro. NP-coating resulted in a significant and long-lasting reduction in electrode impedance (p < 0.05) over four weeks of in vitro stimulation. Despite an initial increase in impedance after intracranial implantation, the impedance of the NP-coated electrodes was also reduced during in vivo stimulation over four weeks. NP-coated electrodes had a lower fluctuation of impedance during stimulation compared to uncoated electrodes both in vitro and in vivo (p < 0.05). Laser-generated PtNPs applied to electrodes by pulsed DC-EPD lead to lower and more stable electrode impedance during chronic stimulation, with the potential to enhance the performance of DBS systems during chronic use.

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.

Autism spectrum disorder is discussed in the context of altered neural oscillations and imbalanced cortical excitation-inhibition of cortical origin. We studied here whether developmental changes in peripheral auditory processing, while preserving basic hearing function, lead to altered cortical oscillations. Local field potentials (LFPs) were recorded from auditory, visual, and prefrontal cortices and the hippocampus of BdnfPax2 KO mice. These mice develop an autism-like behavioral phenotype through deletion of BDNF in Pax2+ interneuron precursors, affecting lower brainstem functions, but not frontal brain regions directly. Evoked LFP responses to behaviorally relevant auditory stimuli were weaker in the auditory cortex of BdnfPax2 KOs, connected to maturation deficits of high-spontaneous rate auditory nerve fibers. This was correlated with enhanced spontaneous and induced LFP power, excitation-inhibition imbalance, and dendritic spine immaturity, mirroring autistic phenotypes. Thus, impairments in peripheral high-spontaneous rate fibers alter spike synchrony and subsequently cortical processing relevant for normal communication and behavior. Scheme for high-spontaneous low-threshold fiber loss resulting in unsharp auditory processing and disturbed cortical network dynamics. (i) Developmental changes due to BDNF deletion in Pax2-positive inhibitory interneurons result in partly dysfunctional high-SR fibers in the cochlea. (ii) Spike synchronization of ANFs fails, impairing spectral and temporal resolution. (iii) The missing drive for cortical excitatory input to pyramidal neurons and inhibitory interneurons leads to altered intracortical network dynamics within AC and across areas (PFC/HC). Increased spontaneous but reduced evoked responsiveness in oscillatory frequency bands doesn't allow for the necessary context- and stimulus-specific pattern segregation of sensory inputs.image

INTRODUCTION:Evidence-based grading of the impact of intracranial surgery on rat's well-being is important for ethical and legal reasons. We assessed the severity of complex and repeated intracranial surgery in a 6-hydroxydopamine (6-OHDA) Parkinson's rat model with subsequent intracranial electrode implantation and in an intracranial tumor model with subsequent resection.METHODS:Stereotactic surgery was performed in adult male rats with the same general anesthesia and perioperative pain management. In Parkinson's model, Sprague Dawley rats received unilateral injection of 6-OHDA (n = 11) or vehicle (n = 7) into the medial forebrain bundle as first operation (1st OP). After four weeks, neural electrodes were implanted in all rats as second operation (2nd OP). For tumor formation, BDIX/UlmHanZtm rats (n = 8) received frontocortical injection of BT4Ca cells as 1st OP, followed by tumor resection as 2nd OP after one week. Multiple measures severity assessment was done two days before and four days after surgery in all rats, comprising clinical scoring, body weight, and detailed behavioral screening. To include a condition with a known burden, rats with intracranial tumors were additionally assessed up to a predefined humane endpoint that has previously been classified as "moderate".RESULTS:After the 1st OP, only 6-OHDA injection resulted in transient elevated clinical scores, a mild long-lasting weight reduction, and motor disturbances. After the second surgery, body weight was transiently reduced in all groups. All other parameters showed variable results. Principal component analysis showed a separation from the preoperative state driven by motor-related parameters after 6-OHDA injection, while separation after electrode implantation and more clearly after tumor resection was driven by pain-related parameters, although not reaching the level of the humane endpoint of our tumor model.CONCLUSION:Overall, cranial surgery of different complexity only transiently and rather mildly affects rat's well-being. Multiple measures assessment allows the differentiation of model-related motor disturbances in Parkinson's model from potentially pain-related conditions after tumor resection and electrode implantation.

In neurological and neuropsychiatric disorders neuronal oscillatory activity between basal ganglia and cortical circuits are altered, which may be useful as biomarker for adaptive deep brain stimulation. We investigated whether changes in the spectral power of oscillatory activity in the motor cortex (MCtx) and the sensorimotor cortex (SMCtx) of rats after injection of the dopamine (DA) receptor antagonist haloperidol (HALO) would be similar to those observed in Parkinson disease. Thereafter, we tested whether a convolutional neural network (CNN) model would identify brain signal alterations in this acute model of parkinsonism. A sixteen channel surface micro-electrocorticogram (ECoG) recording array was placed under the dura above the MCtx and SMCtx areas of one hemisphere under general anaesthesia in rats. Seven days after surgery, micro ECoG was recorded in individual free moving rats in three conditions: (1) basal activity, (2) after injection of HALO (0.5 mg/kg), and (3) with additional injection of apomorphine (APO) (1 mg/kg). Furthermore, a CNN-based classification consisting of 23,530 parameters was applied on the raw data. HALO injection decreased oscillatory theta band activity (4–8 Hz) and enhanced beta (12–30 Hz) and gamma (30–100 Hz) in MCtx and SMCtx, which was compensated after APO injection (P ¡ 0.001). Evaluation of classification performance of the CNN model provided accuracy of 92%, sensitivity of 90% and specificity of 93% on one-dimensional signals. The CNN proposed model requires a minimum of sensory hardware and may be integrated into future research on therapeutic devices for Parkinson disease, such as adaptive closed loop stimulation, thus contributing to more efficient way of treatment.

BackgroundHearing loss was proposed as a factor affecting development of cognitive impairment in elderly. Deficits cannot be explained primarily by dysfunctional neuronal networks within the central auditory system. We here tested the impact of hearing loss in adult rats on motor, social, and cognitive function. Furthermore, potential changes in the neuronal activity in the medial prefrontal cortex (mPFC) and the inferior colliculus (IC) were evaluated.Materials and methodsIn adult male Sprague Dawley rats hearing loss was induced under general anesthesia with intracochlear injection of neomycin. Sham-operated and naive rats served as controls. Postsurgical acoustically evoked auditory brainstem response (ABR)-measurements verified hearing loss after intracochlear neomycin-injection, respectively, intact hearing in sham-operated and naive controls. In intervals of 8 weeks and up to 12 months after surgery rats were tested for locomotor activity (open field) and coordination (Rotarod), for social interaction and preference, and for learning and memory (4-arms baited 8-arms radial maze test). In a final setting, electrophysiological recordings were performed in the mPFC and the IC.ResultsLocomotor activity did not differ between deaf and control rats, whereas motor coordination on the Rotarod was disturbed in deaf rats (P < 0.05). Learning the concept of the radial maze test was initially disturbed in deaf rats (P < 0.05), whereas retesting every 8 weeks did not show long-term memory deficits. Social interaction and preference was also not affected by hearing loss. Final electrophysiological recordings in anesthetized rats revealed reduced firing rates, enhanced irregular firing, and reduced oscillatory theta band activity (4–8 Hz) in the mPFC of deaf rats as compared to controls (P < 0.05). In the IC, reduced oscillatory theta (4–8 Hz) and gamma (30–100 Hz) band activity was found in deaf rats (P < 0.05).ConclusionMinor and transient behavioral deficits do not confirm direct impact of long-term hearing loss on cognitive function in rats. However, the altered neuronal activities in the mPFC and IC after hearing loss indicate effects on neuronal networks in and outside the central auditory system with potential consequences on cognitive function.

Deep brain stimulation (DBS) of the bed nucleus of the stria terminalis/anterior limb of the internal capsule (BNST/ALIC) is successfully used for treatment of patients with obsessive-compulsive disorder (OCD). Clinical and experimental studies have suggested that enhanced network synchronization in the theta band is correlated with severity of symptoms. The mechanisms of action of DBS remain unclear in OCD. We here investigate the effect of acute stimulation of the BNCT/ALIC on oscillatory neuronal activity in patients with OCD implanted with DBS electrodes. We recorded the oscillatory activity of local field potentials (LFPs) from DBS electrodes (contact + 0/− 3; bipolar configuration; both hemispheres) from the BNST/ALIC parallel with frontal cortical electroencephalogram (EEG) one day after DBS surgery in four patients with OCD. BNST/ALIC and frontal EEG oscillatory activities were analysed before stimulation as baseline, and after three periods of stimulation with different voltage amplitudes (1 V, 2 V and 3.5 V) at 130 Hz. Overall, acute high frequency DBS reduced oscillatory theta band (4-8 Hz; p < 0.01) but increased other frequency bands in BNST/ALIC and the frontal cortex (p < 0.01). We show that stimulation of the BNST/ALIC in OCD modulates oscillatory activity in brain regions that are involved in the pathomechanisms of OCD. Our findings confirm and extend the findings that enhanced theta oscillatory activity in neuronal networks may be a biomarker for OCD.

BACKGROUND:Obsessive compulsive disorder (OCD) is a severe disabling disease, and around 10% of patients are considered to be treatment-resistant (tr) in spite of guideline-based therapy. Deep brain stimulation (DBS) has been proposed as a promising treatment for patients with trOCD. However, the optimal site for stimulation is still a matter of debate, and clinical long-term follow-up observations including data on quality of life are sparse. We here present six trOCD patients who underwent DBS with electrodes placed in the bed nucleus of the stria terminalis/anterior limb of the internal capsule (BNST/ALIC), followed for four to eight years after lead implantation.MATERIALS AND METHODS:In this prospective observational study, six patients (four men, two women) aged 32-51 years and suffering from severe to extreme trOCD underwent DBS of the BNST/ALIC. Symptom severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and quality of life using the World Health Organization Quality of Life assessment scale (WHO-QoL BREF). Follow-up was obtained at least for four years in all patients.RESULTS:With chronic DBS for four to eight years, four of the six patients had sustained improvement. Two patients remitted and two patients responded (defined as >35% symptom reduction), while the other two patients were considered nonresponders on long-term. Quality of life markedly improved in remitters and responders. We did not observe peri-interventional side effects or adverse effects of chronic stimulation.CONCLUSIONS:Chronic DBS of ALIC provides long-term benefit up to four to eight years in trOCD, although not all patients take profit. Targeting the BNST was not particularly relevant since no patient appeared to benefit from direct stimulation of the BNST. Quality of life improved in DBS responders, documented by improved QoL scores and, even more important, by regaining of autonomy and improving psychosocial functioning.

The cerebellar cognitive affective syndrome may result from various cerebellar injuries. Although it is not exactly known which anatomical structures are involved, the fastigial nucleus has been thought to play a pivotal role according to recent studies. Here we investigate whether bilateral fastigial nucleus lesions in juvenile rats affect cognitive-associative and limbic related functions in adulthood. Furthermore, potential effects on the neuronal activity in the medial prefrontal cortex (mPFC) and local field coherence with the sensorimotor cortex (SMCtx) were evaluated. The fastigial nucleus was lesioned bilaterally by thermocoagulation via stereotaxically inserted electrodes in 23-day old male Sprague Dawley rats. Naïve and sham-lesioned rats (electrodes inserted above the nucleus and no electrical current applied) served as controls. As adults, all groups were tested for cognitive-associative function, social behavior, and anxiety. Thereafter, electrophysiological recordings were obtained under urethane anesthesia. Finally, lesions and recording sites were histologically verified. Spatial learning in a radial maze test and learning in an operant learning paradigm was disturbed in rats with fastigial lesions. Furthermore, in the elevated plus maze anxiety was enhanced, whereas social behavior was not affected. Electrophysiological recordings showed enhanced local field coherence between mPFC and SMCtx across all frequency bands. Impaired cognitive and affective functions together with enhanced coherence between mPFC and SMCtx after bilateral fastigial nucleus lesions indicate that the fastigial nucleus contribute to the development of the cerebellar cognitive affective syndrome and associated motor behavior.