The ability to learn sequential contingencies of actions for predicting future outcomes is indispensable for flexible behavior in many daily decision-making contexts. It remains open whether such ability may be enhanced by transcranial direct current stimulation. The present study combined tDCS with functional near-infrared spectroscopy to investigate potential tDCS-induced effects on sequential decision-making and the neural mechanisms underlying such modulations. Offline tDCS and sham stimulation were applied over the left and right dorsolateral prefrontal cortex in young male adults (...) in a double-blind between-subject design using a three-state Markov decision task. The results showed an enhanced dlPFC hemodynamic response during the acquisition of sequential state transitions that is consistent with the findings from a previous functional magnetic resonance imaging study; a tDCS-induced increase of the hemodynamic response in the dlPFC, but without accompanying performance-enhancing effects at the behavioral level; and a greater tDCS-induced upregulation of hemodynamic responses in the delayed reward condition that seems to be associated with faster decision speed. Taken together, these findings provide empirical evidence for fNIRS as a suitable method for investigating hemodynamic correlates of sequential decision-making as well as functional brain correlates underlying tDCS-induced modulation. Future research with larger sample sizes for carrying out subgroup analysis is necessary in order to decipher interindividual differences in tDCS-induced effects on sequential decision-making process at the behavioral and brain levels. (shrink)

Patients requiring deep brain stimulation due to intracerebral metallic foreign substances have not been reported elsewhere in the world. Additionally, the long-term effects of metallic foreign bodies on deep brain stimulation are unknown. A 79-year-old man with a 5-year history of Parkinson's disease reported that, 40 years ago, while playing with a pistol, a metallic bullet was accidentally discharged into the left brain through the edge of the left eye, causing no discomfort other than blurry vision in the (...) left eye. DBS was performed due to the short duration of efficacy for oral medication. Because the bullet was on the left subthalamic nucleus electrode trajectory and the patient's right limb was primarily stiff, the patient received globus pallidus interna -DBS implantation in the left hemisphere and STN-DBS implantation in the right hemisphere. During a 6-month postoperative follow-up, the patient's PD symptoms were effectively managed with no noticeable discomfort. (shrink)

Plants are considered as archetypes of the ramification phenomenon but numerous elementary processes occur in the elaboration of the shaping of each species. This paper aims to identify the part ascribed to different mechanisms in the morphogenesis of a Thallophyte, the red alga Antihamnion plumula.Agonistic-antagonistic models (Bernard-Weil, 1988) can be applied to this alga whose thallus includes two different kinds of whorls, pleuridian and cladomian. In each whorl the agonistic and antagonistic effects are expressed by the full development (S) of (...) the two branches and by their symmetry rate (R) respectively. Variations in S and R show the existence of particular pleuridian whorls having an intermediary dissymmetry and a rhythmic arrangement similarly to that of the cladomian whorls. A unilateral change of the system (removal of a lateral cladome) induces a transitory destabilisation mainly manifested by the stimulating ascendant flow throughout the thallus. (shrink)

The acquisition and evolution of speech production, discourse and communication can be negatively impacted by brain malformations. We describe, for the first time, a case of developmental dynamic dysphasia (DDD) in a right-handed adolescent boy (subject D) with cortical malformations involving language-eloquent regions (inferior frontal gyrus) in both the left and the right hemispheres. Language evaluation revealed a markedly reduced verbal output affecting phonemic and semantic fluency, phrase and sentence generation and verbal communication in everyday life. Auditory comprehension, repetition, naming, (...) reading and spelling were relatively preserved, but executive function was impaired. Multimodal neuroimaging showed a malformed cerebral cortex with atypical configuration and placement of white matter tracts bilaterally and abnormal callosal fibers. Dichotic listening showed right hemisphere dominance for language and functional magnetic resonance imaging (fMRI) additionally revealed dissociated hemispheric language representation with right frontal activation for phonology and bilateral dominance for semantic processing. Moreover, subject D also had congenital mirror movements (CMM), defined as involuntary movements of one side of the body that mirror intentional movements of the other side. Transcranial magnetic stimulation and fMRI during voluntary unimanual (left and right) hand movements showed bilateral motor cortex recruitment and tractography revealed a lack of decussation of bilateral corticospinal tracts. Genetic testing aimed to detect mutations that disrupt the development of commissural tracts correlating with CMM (e.g., Germline DCC mutations) was negative. Overall, our findings suggest that DDD in subject D resulted from the underdevelopment of the left inferior frontal gyrus with limited capacity for plastic reorganization by its homologous counterpart in the right hemisphere. Corpus callosum anomalies probably contributed to hinder interhemispheric connectivity necessary to compensate language and communication deficits after left frontal involvement. (shrink)

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, (...) psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression. (shrink)

It has been well documented that the auditory system in the superior temporal cortex is responsible for processing basic auditory sound features, such as sound frequency and intensity, while the prefrontal cortex is involved in higher-order auditory functions, such as language processing and auditory episodic memory. The temporal auditory cortex has vast forward anatomical projections to the prefrontal auditory cortex, connecting with the lateral, medial, and orbital parts of the prefrontal cortex. The connections between the auditory cortex and the prefrontal (...) cortex thus help in localizing, recognizing, and comprehending external auditory inputs. In addition, the medial prefrontal cortex is believed to be a core region of episodic memory retrieval and is one of the most important regions in the default mode network. However, previous neural evidence with regard to the comparison between basic auditory processing and auditory episodic memory retrieval mainly comes from fMRI studies. The specific neural networks and the corresponding critical frequency bands of neuronal oscillations underlying the two auditory functions remain unclear. In the present study, we reported results of direct cortical stimulations during stereo-electro-encephalography recording in a patient with drug-resistant epilepsy. Electrodes covered the superior temporal gyrus, the operculum and the insula cortex of bilateral hemispheres, the prefrontal cortex, the parietal lobe, the anterior and middle cingulate cortex, and the amygdala of the left hemisphere. Two types of auditory hallucinations were evoked with direct cortical stimulations, which were consistent with the habitual seizures. The noise hallucinations, i.e., “I could hear buzzing noises in my head,” were evoked with the stimulation of the superior temporal gyrus. The episodic memory hallucinations “I could hear a young woman who was dressed in a red skirt saying: What is the matter with you?,” were evoked with the stimulation of MPFC. The patient described how she had met this young woman when she was young and that the woman said the same sentence to her. Furthermore, by analyzing the high gamma power induced by direct electrical stimulation, two dissociable neural networks underlying the two types of auditory hallucinations were localized. Taken together, the present results confirm the hierarchical processing of auditory information by showing the different involvements of the primary auditory cortex vs. the prefrontal cortex in the two types of auditory hallucinations. (shrink)

Background: Treating medication-refractory freezing of gait in Parkinson’s disease remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus deep brain stimulation. Pedunculopontine nucleus region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS.Methods: In this clinical trial, five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop (...) class='Hi'>stimulation. Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes. (shrink)

Deep Brain Stimulation is an invasive device-based neuromodulation technique that allows the therapeutic direct stimulation of subcortical and deep cortical structures following the surgical placement of stimulating electrodes. DBS is approved by the U.S. Federal Drug Administration for the treatment of movement disorders and obsessive-compulsive disorder, while new indications, including Major Depressive Disorder, are in experimental development. We report the case of a patient with MDD who received DBS to the ventral internal capsule and ventral striatum bilaterally and (...) presented with 2 weeks of voltage-dependent Tourette-like symptoms including brief transient episodes of abrupt-onset and progressively louder coprolalia and stuttered speech; tic-like motor behavior in his right arm and leg; rushes of anxiety, angry prosody, angry affect; and moderate amnesia without confusion. We describe the results of the inpatient neuropsychiatric workup leading to the diagnosis of iatrogenic voltage-dependent activation of cortico-subcortical circuits and discuss insights into the pathophysiology of Tourette as well as safety considerations raised by the case. (shrink)

Patients with advanced Alzheimer's disease experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD underwent (...) surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324. (shrink)

PurposeTo explore the changes of cerebral blood flow and fractional anisotropy in stroke patients with motor dysfunction after repetitive transcranial magnetic stimulation treatment, and to better understand the role of rTMS on motor rehabilitation of subcortical stroke patients from the perfusion and structural level.Materials and MethodsIn total, 23 first-episode acute ischemic stroke patients and sixteen healthy controls were included. The patients were divided into the rTMS and sham group. The rehabilitation assessments and examination of perfusion and structural MRI were (...) performed before and after rTMS therapy for each patient. Voxel-based analysis was used to detect the difference in CBF and FA among all three groups. The Pearson correlation analysis was conducted to evaluate the relationship between the CBF/FA value and the motor scales.ResultsAfter rTMS, significantly increased CBF was found in the ipsilesional supplementary motor area, postcentral gyrus, precentral gyrus, pons, medulla oblongata, contralesional midbrain, superior cerebellar peduncle, and middle cerebellar peduncle compared to that during the prestimulation and in the sham group, these fasciculi comprise the cortex-pontine-cerebellum-cortex loop. Besides, altered CBF in the ipsilesional precentral gyrus, postcentral gyrus, and pons was positively associated with the improved Fugl-Meyer assessment scores. Significantly decreased FA was found in the contralesional precentral gyrus, increased FA was found in the ipsilesional postcentral gyrus, precentral gyrus, contralesional supplementary motor area, and bilateral cerebellum, these fasciculi comprise the corticospinal tract. The change of FMA score was positively correlated with altered FA value in the ipsilesional postcentral gyrus and negatively correlated with altered FA value in the contralesional precentral gyrus.ConclusionOur results suggested that rTMS could facilitate the motor recovery of stroke patients. High frequency could promote the improvement of functional activity of ipsilesional CPC loop and the recovery of the microstructure of CST. (shrink)

Bidirectional deep brain stimulation (DBS) platforms have enabled a surge in hours of recordings in naturalistic environments, allowing further insight into neurological and psychiatric disease states. However, high amplitude, high frequency stimulation generates artifacts that contaminate neural signals and hinder our ability to interpret the data. This is especially true in psychiatric disorders, for which high amplitude stimulation is commonly applied to deep brain structures where the native neural activity is miniscule in comparison. Here, we characterized artifact (...) sources in recordings from a bidirectional DBS platform, the Medtronic Summit RC + S, with the goal of optimizing recording configurations to improve signal to noise ratio (SNR). Data were collected from three subjects in a clinical trial of DBS for obsessive-compulsive disorder. Stimulation was provided bilaterally to the ventral capsule/ventral striatum (VC/VS) using two independent implantable neurostimulators. We first manipulated DBS amplitude within safe limits (2–5.3 mA) to characterize the impact of stimulation artifacts on neural recordings. We found that high amplitude stimulation produces slew overflow, defined as exceeding the rate of change that the analog to digital converter can accurately measure. Overflow led to expanded spectral distortion of the stimulation artifact, with a six fold increase in the bandwidth of the 150.6 Hz stimulation artifact from 147–153 to 140–180 Hz. By increasing sense blank values during high amplitude stimulation, we reduced overflow by as much as 30% and improved artifact distortion, reducing the bandwidth from 140–180 Hz artifact to 147–153 Hz. We also identified artifacts that shifted in frequency through modulation of telemetry parameters. We found that telemetry ratio changes led to predictable shifts in the center-frequencies of the associated artifacts, allowing us to proactively shift the artifacts outside of our frequency range of interest. Overall, the artifact characterization methods and results described here enable increased data interpretability and unconstrained biomarker exploration using data collected from bidirectional DBS devices. (shrink)

The purpose of this study is to assess the efficacy of transcranial direct current stimulation in patients with treatment-refractory trigeminal neuralgia and examine the utility of neuroimaging methods in identifying markers of such efficacy. Six patients with classical TN refractory to maximal medical treatment, underwent tDCS. All patients underwent pre- and posttreatment functional magnetic resonance imaging during block-design tasks as well as single-shell diffusion MRI acquisition. The precise locations of tDCS electrodes were identified by neuronavigation. Five therapeutic tDCS sessions (...) were carried out for each patient with either anodic or cathodic applications. The Numeric Rating Scale of pain and the Headache Disability Index were used to score the subjective efficacy of treatment. Altered activity of regional sites was identified by fMRI and associated changes in the spinothalamocortical sensory tract were measured by the dMRI indices of fractional anisotropy and mean diffusivity. Fiber counts of the bilateral trigeminal root entry zone were performed as an added measure of fiber loss or recovery. All patients experienced a significant reduction in pain scores with a substantial decline in HDI in the number of contralateral sensory fibers in the STCT with either anodic or cathodic tDCS treatment in four of the six patients. A significant reduction in FA was observed in the ipsilateral REZ in the posttreatment phase in five of the six patients. Preliminary evidence suggests that navigated tDCS presents a promising method for alleviating the pain of TN. Different patterns of activation manifested by anodic and cathodic stimulation require further elaboration to understand their implication. Activation and attenuation of responses at various sites may provide further avenues for condition treatment. (shrink)

Deep Brain Stimulation (DBS) is an effective treatment for advanced Parkinson’s disease. However, identifying stimulation parameters, such as contact and current amplitudes, is time-consuming based on trial and error. Directional leads add more stimulation options and render this process more challenging with a higher workload for neurologists and more discomfort for patients. In this study, a sweet spot-guided algorithm was developed that automatically suggested stimulation parameters. These suggestions were retrospectively compared to clinical monopolar reviews. A cohort (...) of 24 Parkinson’s disease patients underwent bilateral DBS implantation in the subthalamic nucleus at our center. First, the DBS’ leads were reconstructed with the open-source toolbox Lead-DBS. Second, a sweet spot for rigidity reduction was set as the desired stimulation target for programming. This sweet spot and estimations of the volume of tissue activated were used to suggest (i) the best lead level, (ii) the best contact, and (iii) the effect thresholds for full therapeutic effect for each contact. To assess these sweet spot-guided suggestions, the clinical monopolar reviews were considered as ground truth. In addition, the sweet spot-guided suggestions for best lead level and best contact were compared against reconstruction-guided suggestions, which considered the lead location with respect to the subthalamic nucleus. Finally, a graphical user interface was developed as an add-on to Lead-DBS and is publicly available. With the interface, suggestions for all contacts of a lead can be generated in a few seconds. The accuracy for suggesting the best out of four lead levels was 56%. These sweet spot-guided suggestions were not significantly better than reconstruction-guided suggestions (p = 0.3). The accuracy for suggesting the best out of eight contacts was 41%. These sweet spot-guided suggestions were significantly better than reconstruction-guided suggestions (p < 0.001). The sweet spot-guided suggestions of each contact’s effect threshold had a mean error of 1.2 mA. On an individual lead level, the suggestions can vary more with mean errors ranging from 0.3 to 4.8 mA. Further analysis is warranted to improve the sweet spot-guided suggestions and to account for more symptoms and stimulation-induced side effects. (shrink)

Transvertebral magnetic stimulation (TVMS) of the human lumbar spinal cord can evoke bilateral rhythmic leg movements, as in walking, supposedly through the activation of spinal locomotor neural circuitry. However, an appropriate stimulus intensity that can effectively drive the human spinal locomotor circuitry to evoke walking-like movements has not been determined. To address this issue, TVMS was delivered over an intervertebral space of the lumbar cord (L1–L3) at different stimulus intensities (10–70% of maximum stimulator output) in healthy human adults. (...) In a stimulus intensity-dependent manner, TVMS evoked two major patterns of rhythmic leg movements in which the left-right movement cycles were coordinated with different phase relationships: hopping-like movements, in which both legs moved in the same direction in phase, and walking-like movements, in which both legs moved alternatively in anti-phase; uncategorized movements were also observed which could not be categorized as either movement type. Even at the same stimulation site, the stimulus-evoked rhythmic movements changed from hopping-like movements to walking-like movements as stimulus intensity was increased. Different leg muscle activation patterns were engaged in the induction of the hopping- and walking-like movements. The magnitude of the evoked hopping- and walking-like movements was positively correlated with stimulus intensity. The human spinal neural circuitry required a higher intensity of magnetic stimulation to produce walking-like leg movements than to produce hopping-like movements. These results suggest that TVMS activates distinct neural modules in the human spinal cord to generate hopping- and walking-like movements. (shrink)

Galvanic vestibular stimulation is a non-invasive method of electrically stimulating the vestibular system. We investigated whether the application of GVS can alter the learning of new functional mobility and manual control tasks and whether learning can be retained following GVS application. In a between-subjects experiment design, 36 healthy subjects performed repeated trials, capturing the learning of either a functional mobility task, navigating an obstacle course on a compliant surface with degraded visual cues or a manual control task, using a (...) joystick to null self-roll tilt against a pseudo-random disturbance while seated in the dark. In the “learning” phase of trials, bilateral, bipolar GVS was applied continuously. The GVS waveform also differed between subjects in each task group: white noisy galvanic vestibular stimulation at 0.3 mA high-level random GVS at 0.7 mA, or with the absence of stimulation. Following the “learning” trials, all subjects were blindly transitioned to sham GVS, upon which they immediately completed another series of trials to assess any aftereffects. In the functional mobility task, we found nGVS significantly improved task learning. Further, improvements in learning the functional mobility task with nGVS were retained, even once the GVS application was stopped. The benefits in learning with nGVS were not observed in the manual control task. High level GVS tended to inhibit learning in both tasks, but not significantly so. Even once the high-level stimulation was stopped, the impaired performance remained. Improvements in learning with nGVS may be due to increased information throughput resulting from stochastic resonance. The benefit of nGVS for functional mobility, but not manual control nulling, may be due to the multisensory, strategic, motor coordination, or spatial awareness aspects of the former task. Learning improvements with nGVS have the potential to benefit individuals who perform functional mobility tasks, such as astronauts, firefighters, high performance athletes, and soldiers. (shrink)

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson’s disease (PD).Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) (...) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively.Results: Pearson’s correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R2 = 0.283, p = 0.016) but not on the non-tremor total score (R2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R2′ = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R2 = 0.290, p = 0.021), but not on the total score (R2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R2′ = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor.Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response. (shrink)

BackgroundIn Parkinson's disease, the side of motor symptoms onset may influence disease progression, with a faster motor symptom progression in patients with left side lateralization. Moreover, worse neuropsychological outcomes after subthalamic nucleus deep brain stimulation have been described in patients with predominantly left-sided motor symptoms. The objective of this study was to evaluate if the body side of motor symptoms onset may predict motor outcome of bilateral STN-DBS.MethodsThis retrospective study included all consecutive PD patients treated with bilateral (...) STN-DBS at Grenoble University Hospital from 1993 to 2015. Demographic, clinical and neuroimaging data were collected before and 1 year after surgery. The predictive factors of motor outcome at one-year follow-up, measured by the percentage change in the MDS-UPDRS-III score, were evaluated through univariate and multivariate linear regression analysis.ResultsA total of 233 patients were included with one-year follow-up after surgery [143 males ; 121 right body onset; 112 left body onset; mean age at surgery, 55.31 ± 8.44 years; mean disease duration, 11.61 ± 3.87]. Multivariate linear regression analysis showed that the left side of motor symptoms onset did not predict motor outcome.ConclusionsIn this retrospective study, the body side of motor symptoms onset did not significantly influence the one-year motor outcome in a large cohort of PD patients treated with bilateral STN-DBS. (shrink)

ObjectiveThe effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging.MethodA total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 Hz rTMS, 100% (...) resting motor threshold, and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation and regional homology at 0.01–0.08 Hz, 0.01–0.027 Hz, and 0.027–0.073 Hz.ResultsAfter cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01–0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01–0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area.ConclusionRepetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice. (shrink)

Objective: Deep brain stimulation targeted to the ventral intermediate nucleus of the thalamus is effective for motor symptoms in essential tremor, but there is limited data on cognitive outcomes. We examined cognitive outcomes in a large cohort of ET DBS patients.Methods: In a retrospective analysis, we used repeated-measures ANOVA testing to examine whether the age of tremor onset, age at DBS surgery, hemisphere side implanted with lead, unilateral vs. bilateral implantations, and presence of surgical complications influenced the cognitive (...) outcomes. Neuropsychological outcomes of interest were verbal memory, executive functioning, working memory, language functioning, visuospatial functioning, and general cognitive function.Results: We identified 50 ET DBS patients; 29 males; the mean age of tremor onset was 35.84 years with a median age of 38 years. The mean age at DBS was 68.18 years. There were 37 unilateral 30 left, seven right, and 13 bilateral brain implantations. In the subgroup analysis, there was a significant interaction between assessment and age of tremor onset ; F = 4.47; p = 0.043 for working memory. The post hoc testing found improvements for younger onset ET. Similarly, there was a significant interaction between assessment and complications vs. no complications subgroups; F = 4.34; p = 0.043 for verbal memory with worsening scores seen for ET patients with complications. The remaining tests were not significant.Conclusion: In this large cohort of ET patients with, DBS was not accompanied by a significant decline in many cognitive domains. These outcomes were possibly related to the selection of patients with normal cognitive functioning before surgery, unilateral DBS implantations for the majority, and selection of patients with optimal response to DBS. (shrink)

Motor training to improve walking and balance function is a common aspect of rehabilitation following motor-incomplete spinal cord injury. Evidence suggests that moderate- to high-intensity exercise facilitates neuroplastic mechanisms that support motor skill acquisition and learning. Furthermore, enhancing corticospinal drive via transcranial direct current stimulation may augment the effects of motor training. In this pilot study, we investigated whether a brief moderate-intensity locomotor-related motor skill training circuit, with and without tDCS, improved walking and balance outcomes in persons with MISCI. (...) In addition, we examined potential differences between within-day and between-day effects of MST. Twenty-six adults with chronic MISCI, who had some walking ability, were enrolled in a 5-day double-blind, randomized study with a 3-day intervention period. Participants were assigned to an intensive locomotor MST circuit and concurrent application of either sham tDCS or active tDCS. The primary outcome was overground walking speed measured during the 10-meter walk test. Secondary outcomes included spatiotemporal gait characteristics, peak trailing limb angle, intralimb coordination, the Berg Balance Scale, and the Falls Efficacy Scale-International questionnaire. Analyses revealed a significant effect of the MST circuit, with improvements in walking speed, cadence, bilateral stride length, stronger limb TLA, weaker limb ACC, BBS, and FES-I observed in both the MST+tDCSsham and MST+tDCS groups. No differences in outcomes were observed between groups. Between-day change accounted for a greater percentage of the overall change in walking outcomes. In persons with MISCI, brief intensive MST involving a circuit of ballistic, cyclic locomotor-related skill activities improved walking outcomes, and selected strength and balance outcomes; however, concurrent application of tDCS did not further enhance the effects of MST.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT03237234]. (shrink)

Background: In prior reports, we described the design and initial performance of a fully implantable, bi-directional neural interface system for use in deep brain and other neurostimulation applications. Here we provide an update on the chronic, long-term neural sensing performance of the system using traditional 4-contact leads and extend those results to include directional 8-contact leads.Methods: Seven ovine subjects were implanted with deep brain stimulation leads at different nodes within the Circuit of Papez: four with unilateral leads in the (...) anterior nucleus of the thalamus and hippocampus; two with bilateral fornix leads, and one with bilateral hippocampal leads. The leads were connected to either an Activa PC+S® or Percept PC°ledR deep brain stimulation and recording device. Spontaneous local field potentials, evoked potentials, LFP response to stimulation, and electrode impedances were monitored chronically for periods of up to five years in these subjects.Results: The morphology, amplitude, and latencies of chronic hippocampal EPs evoked by thalamic stimulation remained stable over the duration of the study. Similarly, LFPs showed consistent spectral peaks with expected variation in absolute magnitude dependent upon behavioral state and other factors, but no systematic degradation of signal quality over time. Electrode impedances remained within expected ranges with little variation following an initial stabilization period. Coupled neural activity between the two nodes within the Papez circuit could be observed in synchronized recordings up to 5 years post-implant. The magnitude of passive LFP power recorded from directional electrode segments was indicative of the contacts that produced the greatest stimulation-induced changes in LFP power within the Papez network.Conclusion: The implanted device performed as designed, providing the ability to chronically stimulate and record neural activity within this network for up to 5 years of follow-up. (shrink)

Individuals with substance use disorders exhibit risk-taking behaviors, potentially leading to negative consequences and difficulty maintaining recovery. Non-invasive brain stimulation techniques such as transcranial direct current stimulation have yielded mixed effects on risk-taking among healthy controls. Given the importance of risk-taking behaviors among substance-using samples, this study aimed to examine the effects of tDCS on risk-taking among a sample of adults using cannabis. Using a double-blind design, 27 cannabis users [M age = 32.48, 41% female] were randomized, receiving (...) one session of active or sham tDCS over the bilateral dorsolateral prefrontal cortex. Stimulation parameters closely followed prior studies with anodal right dlPFC and cathodal left dlPFC stimulation. Risk-taking—assessed via a modified Cambridge Gambling Task—was measured before and during tDCS. Delay and probability discounting tasks were assessed before and after stimulation. No significant effects of stimulation on risk-taking behavior were found. However, participants chose the less risky option ∼86% of the trials before stimulation which potentially contributed to ceiling effects. These results contradict one prior study showing increased risk-taking among cannabis users following tDCS. There was a significant increase in delay discounting of a $1000 delayed reward during stimulation for the sham group only, but no significant effects for probability discounting. The current study adds to conflicting and inconclusive literature on tDCS and cognition among substance-using samples. In conclusion, results suggest the ineffectiveness of single session dlPFC tDCS using an established stimulation protocol on risk-taking, although ceiling effects at baseline may have also prevented behavior change following tDCS. (shrink)

The heterogeneity of transcranial direct current stimulation protocols and clinical profiles may explain variable results in modulating excitability in the motor cortex after stroke. However, the cortical electrical effects induced by different tDCS protocols remain unclear. Here, we aimed to compare rhythm changes in electroencephalography induced by three tDCS position protocols and the association between tDCS effects and clinical factors in stroke. Nineteen patients with chronic ischemic stroke underwent four experimental sessions with three tDCS protocols [anodal, cathodal, and (...) class='Hi'>bilateral ] and a sham protocol, according to a single-blind randomized crossover design. Resting-state EEG was acquired before and after each protocol. First, a paired-sample t-test was used to examine the difference in spectral power between pre- and post-stimulation. Then, linear and quadratic regression models were used separately to describe the association between the clinical factors of stroke and changes in spectral power which was significantly different between pre- and post-tDCS. Finally, repeated measures analysis of variance with lesion hemisphere, stimulation protocol, and the location was performed to investigate the effects of tDCS over time. The induced effect of tDCS was mainly reflected in the alpha rhythms. The alpha power was increased by atDCS, especially low-alpha, in localized areas of the central and distant areas of the frontal and parietal lobes. Bi-tDCS also affected alpha power but in a smaller area that mainly focused on high-alpha rhythms. However, ctDCS and sham had no significant effects on any EEG rhythm. The clinical factors of time since stroke and motor impairment level were related to the change in high-alpha induced by atDCS and bi-tDCS following quadratic regression models. The above-mentioned modulation effect lasted for 20 min without attenuation. In conclusion, our findings provide evidence that the alpha rhythm of EEG is modulated differently by different tDCS protocols and that high alpha is affected by clinical characteristics such as post-stroke time and motor deficits, which is of great significance for understanding the modulation effect of different tDCS protocols on stroke and the guidance of protocols to promote motor recovery following stroke. (shrink)

The ventrolateral prefrontal cortex plays a pivotal role in cognitive reappraisal. Previous studies suggested a functional asymmetry of the bilateral VLPFC, but the evidence is still insufficient during cognitive reappraisal. In this study, we conducted an online single-pulse transcranial magnetic stimulation to investigate the causal and distinct roles of the left and right VLPFC in reappraisal. Participants were instructed to reappraise or attend to pictures depicting social exclusion scenarios while the spTMS was applied over the left or right (...) VLPFC of the participants’ brains. The results showed that spTMS of either the left or the right VLPFC would increase reappraisal difficulty. Meanwhile, the outcome of reappraisal significantly deteriorated when the right VLPFC was temporally interrupted by spTMS, while the verbal fluency during oral reporting of the reappraisal strategy was significantly reduced when the left VLPFC was interrupted by spTMS. Taken together, these findings provide causal evidence for the involvement of left and right VLPFC with distinct roles: while the left VLPFC is responsible for the linguistic especially semantic process of generating and selecting appraisals according to the goal of emotion regulation, the right VLPFC plays a critical role in inhibiting inappropriate negative emotions and thoughts generated by the effective scenarios. These findings deepen our understanding of the neurocognitive mechanism of emotion regulation. (shrink)

Background: Eye movement desensitization and reprocessing [EMDR] is an innovative, evidence-based and effective psychotherapy for post-traumatic stress disorder [PTSD]. As with other psychotherapies, the effectiveness of EMDR contrasts with a limited knowledge of its underlying mechanism of action. In its relatively short life as a therapeutic option, EMDR has not been without controversy, in particular regarding the role of the bilateral stimulation as an active component of the therapy. The high prevalence of EMDR in clinical practice and the (...) dramatic increase in EMDR research in recent years, with more than 26 randomized controlled trials published to date, highlight the need for a better understanding of its mechanism of action. Methods: We conducted a thorough systematic search of studies published until October 2017, using PubMed, ScienceDirect, Web of Knowledge and Scopus databases that examined the mechanism of action of EMDR or provided conclusions within the framework of current theoretical models of EMDR functioning. Results: Seventy-five studies were selected for review and classified into three overarching models; (i) psychological models (ii) psychophysiological models and (iii) neurobiological models. The evidence available from each study was analysed and discussed. Results demonstrated a reasonable empirical support for the working memory hypothesis and for the physiological changes associated with successful EMDR therapy. Recently, more sophisticated structural and functional neuroimaging studies using high resolution structural and temporal techniques are starting to provide preliminary evidence into the neuronal correlates before, during and after EMDR therapy. Discussion: Despite the increasing number of studies that published in recent years, the research into the mechanisms underlying EDMR therapy are still in its infancy. Studies in well-defined clinical and non-clinical populations, larger sample sizes and tighter methodological control are further needed in order to establish firm conclusions. (shrink)

Antisocial behavior and prosocial behavior in the condition of inequality have long been observed in daily life. Understanding the neurological mechanisms and brain regions associated with antisocial and prosocial behavior and the development of new interventions are important for reducing violence and inequality. Fortunately, neurocognitive research and brain imaging research have found a correlation between antisocial or prosocial behavior and the prefrontal cortex. Recent brain stimulation research adopting transcranial direct current stimulation or transcranial magnetic stimulation has shown (...) a causal relationship between brain regions and behaviors, but the findings are mixed. In the present study, we aimed to study whether stimulation of the DLPFC can change participants’ antisocial and prosocial behavior in the condition of inequality. We integrated antisocial and prosocial behavior in a unified paradigm. Based on this paradigm, we discussed costly and cost-free antisocial and prosocial behavior. In addition, we also measured participants’ disadvantageous and advantageous inequality aversion. The current study revealed an asymmetric effect of bilateral stimulation over the DLPFC on costly antisocial behavior, while such an effect of antisocial behavior without cost and prosocial behavior with and without cost were not observed. Moreover, costly antisocial behavior exhibited by men increased after receiving right anodal/left cathodal stimulation and decreased after receiving right cathodal anodal/left anodal stimulation compared with the behavior observed under sham stimulation. However, subjects’ inequality aversion was not influenced by tDCS. (shrink)

New York Times best-selling author offers a groundbreaking approach to activate the subconscious brain to set yourself free from your past and create a terrific future. Can you remember a time in your life when you felt absolutely confident, happy, and free? Imagine what your life would be like if you could live in that space... In this book, Dr. Mike Dow shares a groundbreaking, life-changing program he created: Subconscious Visualization Technique (SVT). Now, if you think the subconscious brain is (...) some woo-woo pseudoscience, prepare to have your mind blown. The cutting-edge research, protocol, and audio tracks Mike offers will help you speak directly to your subconscious brain and tap into your greatest strengths, gifts, and resources. His program, the first of its kind, starts with cognitive behavioral therapy (CBT), then incorporates various types of subconscious tools: mindfulness, guided visualization, audio-visual entrainment, and bilateral stimulation of the brain and body. Your subconscious can change the way you digest food, help you access memories and repressed feelings, boost your immune system, and activate mindbody healing so that you don't have to constantly treat your symptoms. Some examples of syndromes that SVT can treat include chronic pain, fibromyalgia, leaky gut, irritable bowel syndrome (IBS), migraines, anxiety disorders, and more! SVT helps you access the best parts of yourself and move into your true self. In short, your subconscious brain can change your life!" -- ONIX annotation. (shrink)

Introduction: Motor evoked potentials (MEPs) to transcranial magnetic stimulation are known to be susceptible to several sources of variability. However, conflicting evidences on individual characteristics in relatively small sample sizes have been reported. We investigated the effect of age, height, and sex on MEPs of the motor cortex and spinal roots in a large cohort. Methods: A total of 587 subjects clinically and neuroradiologically intact were included. MEPs were recorded during mild tonic contraction through a circular coil applied over (...) the “hot spot” of the first dorsal interosseous and tibialis anterior muscles, bilaterally. Central motor conduction time (CMCT) was estimated as the difference between MEP cortical latency and the peripheral motor conduction time by cervical or lumbar magnetic stimulation. Peak-to-peak MEP amplitude to cortical stimulation and right-to-left difference of each parameter were also measured. Results: After Bonferroni correction, general linear (multiple) regression analysis showed that both MEP cortical latency and peripheral motor conduction time at four limbs positively correlated with age and height. At lower limbs, an independent effect of sex on the same measures was also observed (with females showing smaller values than males). CMCT correlated with both age (negatively) and height (positively) when analyzed by a single regression; however, with a multiple regression analysis this significance disappeared, due to the correction for the multicollinearity within the dataset. Conclusions: Physical individual features need to be considered for a more accurate and meaningful MEPs interpretation. Both in clinical practice and in research setting, patients and controls should be matched for age, height, and sex. (shrink)

IntroductionDeep brain stimulation is an effective treatment for advanced Parkinson’s disease with the targeting bilateral subthalamic nucleus or globus pallidus internus. So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS.Materials and MethodsSeventeen patients with Parkinson’s disease who underwent unilateral GPi-DBS were selected. We conducted comparison analyses between scores obtained 6–42 months pre- and postoperatively using the following measurement tools: the Movement Disorder Society (...) Unified Parkinson’s Disease Rating Scale part III, the Hoehn and Yahr stage, the presence/absence of dyskinesia, Mini-Mental State Examination, Frontal Assessment Battery, Geriatric Depression Scale, levodopa equivalent dose, and cerebral blood flow by single photon emission computed tomography. Patient backgrounds were compared between four cohorts with favorable and unfavorable postoperative outcome.ResultsSignificant improvement was observed postoperatively in the following: total MDS-UPDRS Part III scores during the off period, contralateral scores, ipsilateral scores, and axial scores. Similarly, the Hoehn and Yahr stages during the off period, and GDS also showed significant decrease. In contrast, LED, MMSE, and FAB remained unchanged while the number of patients who scored positive for dyskinesia decreased by 40%. Abnormal cerebral blood flow preoperatively seen in the cerebral cortex had normalized in the total score-based good responder cohort. In the ipsilateral score-based good responder cohort, cerebral blood flow increased in the contralateral frontal lobe including in the premotor cortex, contralateral to the DBS. Compared to the poor responders, postoperative good responders demonstrated significantly higher preoperative MMSE scores.DiscussionUnilateral GPi-DBS therapy was effective in improving contralateral, ipsilateral, and axial motor symptoms of patients with advanced PD; in particular, it was found to be especially beneficial in PwPD whose cognitive function was unimpaired; the treatment efficacy rivaled that of bilateral counterparts up till at least 6 months postoperatively. Finally, normalization of preoperative abnormalities in cerebral blood flow and increased cerebral blood flow in the contralateral frontal lobe indicated the beneficial potential of this therapy on ipsilateral motor symptoms. (shrink)

Blindsight, the ability to blindly discriminate wavelength and other aspects of stimuli in a blind field, sometimes occurs in people with lesions to striate (V1) cortex. There is currently no consensus on whether qualitative color information of the sort that is normally computed by double opponent cells in striate cortex is indeed computed in blindsight but doesn’t reach awareness, perhaps owing to abnormal neuron responsiveness in striate or extra-striate cortical areas, or is not computed at all. The existence of primesight, (...) the experience of colored afterimages in blindsight, has been taken to suggest that qualitative color information is computed either in pre-striate or striate cortical areas but is not broadcast to working memory. I argue here that a recent study in which color phosphenes were induced in a blindsighter using bilateral transcranial magnetic stimulation indicates that computations necessary for conscious color vision are lost in blindsight. Owing to this loss, the neural responsiveness in extrastriate cortical areas is abnormal and hence is unable to give rise to color awareness. Blindsight is thus degraded vision in which the computations necessary for conscious color vision have been lost. (shrink)

Background Neuroimaging and lesion studies suggested that the dorsolateral prefrontal and posterior parietal cortices mediate visual metacognitive awareness. The causal evidence provided by non-invasive brain stimulation, however, is inconsistent. -/- Objective/hypothesis Here we revisit a major figure discrimination experiment adding a new Kanizsa figure task trying to resolve whether bilateral continuous theta-burst transcranial magnetic stimulation (cTBS) over these regions affects perceptual metacognition. Specifically, we tested whether subjective visibility ratings and/or metacognitive efficiency are lower when cTBS is applied (...) to these two regions in comparison to an active control region. -/- Methods A within-subjects design including three sessions spaced by one-week intervals was implemented. In each session, every participant was administered bilateral cTBS to either prefrontal, control or parietal cortices. Two concurrent tasks were performed, a real and an illusory figure task, stabilising objective performance with use of an adaptive staircase procedure. -/- Results When performing the replicated task, cTBS was found insufficient to disrupt neither visibility ratings nor metacognitive efficiency. However, with use of Kanizsa style illusory figures, cTBS over the dorsolateral prefrontal, but not over the posterior parietal cortex, was observed to significantly diminish metacognitive efficiency. -/- Conclusion(s) Real and illusory figure tasks demonstrated different cTBS effects. A possible explanation is the involvement of the prefrontal cortex in the creation of expectations, which is necessary for efficient metacognition. Failure to replicate previous findings for the real figure task, however, cannot be said to support, conclusively, the notion that these brain regions have a causal role in metacognitive awareness. This inconsistent finding may result from certain limitations of our study, thereby suggesting the need for yet further investigation. (shrink)

One-third of all human lives end in early death from poverty-related causes. Most of these premature deaths are avoidable through global institutional reforms that would eradicate extreme poverty. Many are also avoidable through global health-system reform that would make medical knowledge freely available as a global public good. The rules should be redesigned so that the development of any new drug is rewarded in proportion to its impact on the global disease burden (not through monopoly rents). This reform would bring (...) drug prices down worldwide close to their marginal cost of production and would powerfully stimulate pharmaceutical research into currently neglected diseases concentrated among the poor. Its feasibility shows that the existing medical-patent regime (trade-related aspects of intellectual property rights—TRIPS—as supplemented by bilateral agreements) is severely unjust—and its imposition a human-rights violation on account of the avoidable mortality and morbidity it foreseeably produces. (shrink)

BackgroundResponsive neurostimulation has been utilized as a treatment for intractable epilepsy. The RNS System delivers stimulation in response to detected abnormal activity, via leads covering the seizure foci, in response to detections of predefined epileptiform activity with the goal of decreasing seizure frequency and severity. While thalamic leads are often implanted in combination with cortical strip leads, implantation and stimulation with bilateral thalamic leads alone is less common, and the ability to detect electrographic seizures using RNS System (...) thalamic leads is uncertain.ObjectiveThe present study retrospectively evaluated fourteen patients with RNS System depth leads implanted in the thalamus, with or without concomitant implantation of cortical strip leads, to determine the ability to detect electrographic seizures in the thalamus. Detailed patient presentations and lead trajectories were reviewed alongside electroencephalographic analyses.ResultsAnterior nucleus thalamic leads, whether bilateral or unilateral and combined with a cortical strip lead, successfully detected and terminated epileptiform activity, as demonstrated by Cases 2 and 3. Similarly, bilateral centromedian thalamic leads or a combination of one centromedian thalamic alongside a cortical strip lead also demonstrated the ability to detect electrographic seizures as seen in Cases 6 and 9. Bilateral pulvinar leads likewise produced reliable seizure detection in Patient 14. Detections of electrographic seizures in thalamic nuclei did not appear to be affected by whether the patient was pediatric or adult at the time of RNS System implantation. Sole thalamic leads paralleled the combination of thalamic and cortical strip leads in terms of preventing the propagation of electrographic seizures.ConclusionThalamic nuclei present a promising target for detection and stimulation via the RNS System for seizures with multifocal or generalized onsets. These areas provide a modifiable, reversible therapeutic option for patients who are not candidates for surgical resection or ablation. (shrink)

Central sensitization refers to the increased responsiveness of nociceptive neurons in the central nervous system after repeated or sustained peripheral nociceptor activation. It is hypothesized to play a key role in the development of chronic pain. A hallmark of central sensitization is an increased sensitivity to noxious mechanical stimuli extending beyond the injured location, known as secondary hyperalgesia. For its ability to modulate the transmission and the processing of nociceptive inputs, attention could constitute a promising target to prevent central sensitization (...) and the development of chronic pain. It was recently shown that the experimental induction of central sensitization at both forearms of healthy volunteers using bilateral high-frequency electrocutaneous stimulation (HFS), can be modulated by encouraging participants to selectively focus their attention to one arm, to the detriment of the other arm, resulting in a greater secondary hyperalgesia on the attended arm as compared to the unattended one. Given the potential value of the question being addressed, we conducted a preregistered replication study in a well-powered independent sample to assess the robustness of the effect, i.e., the modulatory role of spatial attention on the induction of central sensitization. This hypothesis was tested using a double-blind, within-subject design. Sixty-seven healthy volunteers performed a task that required focusing attention toward one forearm to discriminate innocuous vibrotactile stimuli while HFS was applied on both forearms simultaneously. Our results showed a significant increase in mechanical sensitivity directly and 20 min after HFS. However, in contrast to the previous study, we did not find a significant difference in the development of secondary hyperalgesia between the attended vs. unattended arms. Our results question whether spatial selective attention affects the development of secondary hyperalgesia. Alternatively, the non-replication could be because the bottom-up capture of attention caused by the HFS-mediated sensation was too strong in comparison to the top-down modulation exerted by the attentional task. In other words, the task was not engaging enough and the HFS pulses, including those on the unattended arm, were too salient to allow a selective focus on one arm and modulate nociceptive processing. (shrink)

We add evidence in support of Corballis's gestural theory of language. Using transcranial magnetic stimulation, we found that productive and receptive linguistic tasks excite the motor cortices for both hands. This indicates that the language and the hand motor systems are still tightly linked in modern man. The bilaterality of the effect, however, implies that lateralisation is a secondary issue.

Introduction: Electroconvulsive therapy is a commonly used brain stimulation treatment for treatment-resistant or severe depression. This study was planned to find the effects of ECT on brain connectivity by conducting a systematic review and coordinate-based meta-analysis of the studies performing resting state fMRI in patients with depression receiving ECT.Methods: We systematically searched the databases published up to July 31, 2020, for studies in patients having depression that compared resting-state functional connectivity before and after a course of pulse wave ECT. (...) Meta-analysis was performed using the activation likelihood estimation method after extracting details about coordinates, voxel size, and method for correction of multiple comparisons corresponding to the significant clusters and the respective rsFC analysis measure with its method of extraction.Results: Among 41 articles selected for full-text review, 31 articles were included in the systematic review. Among them, 13 articles were included in the meta-analysis, and a total of 73 foci of 21 experiments were examined using activation likelihood estimation in 10 sets. Using the cluster-level interference method, one voxel-wise analysis with the measure of amplitude of low frequency fluctuations and one seed-voxel analysis with the right hippocampus showed a significant reduction in the left cingulate gyrus and a significant increase in the right hippocampus with the right parahippocampal gyrus, respectively. Another analysis with the studies implementing network-wise resting state functional connectivity showed a significant increase in bilateral posterior cingulate cortex. There was considerable variability as well as a few key deficits in the preprocessing and analysis of the neuroimages and the reporting of results in the included studies. Due to lesser studies, we could not do further analysis to address the neuroimaging variability and subject-related differences.Conclusion: The brain regions noted in this meta-analysis are reasonably specific and distinguished, and they had significant changes in resting state functional connectivity after a course of ECT for depression. More studies with better neuroimaging standards should be conducted in the future to confirm these results in different subgroups of depression and with varied aspects of ECT. (shrink)

The human brain’s ongoing activity is characterized by intrinsic networks of coherent fluctuations, measured for example with correlated functional magnetic resonance imaging signals. So far, however, the brain processes underlying this ongoing blood oxygenation level dependent (BOLD) signal orchestration and their direct relevance for human behavior are not sufficiently understood. In this study, we address the question of whether and how ongoing BOLD activity within intrinsic occipital networks impacts on conscious visual perception. To this end, backwardly masked targets were presented (...) in participants’ left visual field only, leaving the ipsi-lateral occipital areas entirely free from direct effects of task throughout the experiment. Signal time courses of ipsi-lateral BOLD fluctuations in visual areas V1 and V2 were then used as proxies for the ongoing contra-lateral BOLD activity within the bilateral networks. Magnitude and phase of these fluctuations were compared in trials with and without conscious visual perception, operationalized by means of subjective confidence ratings. Our results show that ipsilateral BOLD magnitudes in V1 were significantly higher at times of peak response when the target was perceived consciously. A significant difference between conscious and non-conscious perception with regard to the pre-target phase of an intrinsic-frequency regime suggests that ongoing V1 fluctuations exert a decisive impact on the access to consciousness already before stimulation. Both effects were absent in V2. These results thus support the notion that ongoing slow BOLD activity within intrinsic networks covering V1 represents localized processes that modulate the degree of readiness for the emergence of visual consciousness. (shrink)

Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations. The treatment of cancer with (...) immune checkpoint inhibitors aims to reverse the progression to tolerance of cancer, and achieve an immunogenic, rather than tolerogenic, homeostasis. Broadening the efficacy and durability of checkpoint inhibitors focuses on reversing tolerance and stimulating immunogenicity in the cancer, host, and environment. Two examples of important physiological states of tolerance that may inform tolerance of cancer are microbial infection and placental reproduction. These states of tolerance result from bilateral shaping of host and non‐self, akin to immunoediting in cancer, and offer reliable models to study the immune tolerance paradigm. (shrink)

We present evidence disputing the hypothesis that memories are processed or consolidated in REM sleep. A review of REM deprivation (REMD) studies in animals shows these reports to be about equally divided in showing that REMD does, or does not, disrupt learning/memory. The studies supporting a relationship between REM sleep and memory have been strongly criticized for the confounding effects of very stressful REM deprivation techniques. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and (...) selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep. The MAOIs virtually abolish REM sleep, and the TCAs and SSRIs have been shown to produce immediate (40–85%) and sustained (30–50%) reductions in REM sleep. Despite marked suppression of REM sleep, these classes of antidepressants on the whole do not disrupt learning/memory. There have been a few reports of patients who have survived bilateral lesions of the pons with few lingering complications. Although these lesions essentially abolished REM sleep, the patients reportedly led normal lives. Recent functional imaging studies in humans have revealed patterns of brain activity in REM sleep that are consistent with dream processes but not with memory consolidation. We propose that the primary function of REM sleep is to provide periodic endogenous stimulation to the brain which serves to maintain requisite levels of central nervous system (CNS) activity throughout sleep. REM is the mechanism used by the brain to promote recovery from sleep. We believe that the cumulative evidence indicates that REM sleep serves no role in the processing or consolidation of memory. Key Words: antidepressant drugs; brain stem lesions; dreams; functional imaging; memory consolidation; REM deprivation; REM sleep; theta rhythm. (shrink)

The integration of event-related potential and functional magnetic resonance imaging helps to obtain and study neural networks with high temporal and spatial resolution. EEG/fMRI data proves that in the visual tristimulus oddball paradigm, two P300 potentials induced by target stimulation and novel stimulation are detected at the frontal-middle, center, and mid-apical electrodes. Previous studies have shown that P3a and P3b have different spatial distributions of brain activation, but it is unclear whether they have the same neural mechanism. The (...) purpose of this study is to determine the neuropsychological mechanisms of P3a and P3b, as well as the spatiotemporal differences in neurodynamics between the two ERP subcomponents. In a group of 25 subjects, P300 ERP induced by target stimulation and novel stimulation can be detected at the Fz, Cz, and Pz electrodes. At Cz and Fz, compared with P3b related to the target stimulus, the P3a related to the novel stimulus has a higher amplitude and the waveform declines more slowly. But at Pz, P3b has a higher amplitude than P3a. P3a appeared earlier than P3b at Cz and Fz, but the opposite phenomenon was observed at the Pz electrode. The activated brain regions of P3a included the left frontal-parietal lobe region, left anterior wedge lobe region, and right insula, while the target-driven P3b was significantly associated with BOLD changes in the bilateral fusiform gyrus, the left frontal region, and the bilateral insula. The results showed that the integration of the spatial and temporal information of the two imaging modes, namely, ERP and fMRI, proves the existence of the different brain function processes of the two P300 subcomponents. Through the analysis of the composition of P300, the results further proved that the top-down and bottom-up processing processes have played a role in the occurrence of attention capture. It is just that the modulation effects of the two processing mechanisms are different in different tasks. Therefore, it should be noted that the captured neural mechanism is not a single top-down or bottom-up processing process but should be the result of the interaction between the two. (shrink)

We studied patients with left visual extinction following right hemisphere damage in a simple manual reaction time task using brief visual stimuli. With unilateral lateralized stimuli the patients showed a high proportion of unwanted, reflex-like saccades to either side of stimulation. In contrast, with bilateral stimuli there was an overall decrease in the proportion of unwanted saccades, and the vast majority of them were directed toward the ipsilesional side. The implications of these results for the Findlay & Walker (...) model are discussed. (shrink)

There are a limited number of neuroimaging investigations into motor control of the lumbopelvic musculature. Most investigation examining motor control of the lumbopelvic musculature utilize transcranial magnetic stimulation and focus primarily on the motor cortex. This has resulted in a dearth of knowledge as it relates to how other regions of the brain activate during lumbopelvic movement. Additionally, task-based functional connectivity during lumbopelvic movements has not been well elucidated. Therefore, we used functional magnetic resonance imaging to examine brain activation (...) and ROI-to-ROI task-based functional connectivity in 19 healthy individuals during the performance of three lumbopelvic movements: modified bilateral bridge, left unilateral bridge, and right unilateral bridge. The whole brain analysis found robust, bilateral activation within the motor regions of the brain during the bilateral bridge task, and contralateral activation of the motor regions during unilateral bridging tasks. Furthermore, the ROI-to-ROI analysis demonstrated significant connectivity of a motor network that included the supplemental motor area, bilateral precentral gyrus, and bilateral cerebellum regardless of the motor task performed. These data suggest that while whole brain activation reveals unique patterns of activation across the three tasks, functional connectivity is very similar. As motor control of the lumbopelvic area is of high interest to those studying low back pain, this study can provide a comparison for future research into potential connectivity changes that occur in individuals with LBP. (shrink)

The German problem dominated among the priorities of the Polish diplomacy after 1960. The stalemate was broken by the visit of the Prime Minister Józef Cyrankiewicz in Vienna in September 1965. Józef Cyrankiewicz’s visit in Austria highlighted new possibilities in Austrian-Polish relations. The old policy of Minister Adam Rapacki had been conceived in a difficult period and had no impact on the international environment. The article aims to characterises of the conditions for developing Polish-Austrian relations in the late 60s. The (...) articles poses several questions: how far policy towards Germany stimulated relations with Austria and how Polish authorities saw the possibilities of economic cooperation with Vienna and finally how they prepared for this cooperation. The difficult economic situation in Poland required resuming cooperation with the West. The meeting in Vienna developed further bilateral relations in a very positive way. The Minister Bruno Kreisky recognized in the Polish government both a partner and a neighbour to cooperate. Cyrankiewicz’s visit launched the ratification processes of many bilateral agreements which developed trade in the Eastern Europe. (shrink)

Executive functions are of vital importance in the process of active cognition, which is thought to be associated with the dorsolateral prefrontal cortex. As a valid brain stimulation technology, high-definition transcranial direct current stimulation has been used to optimize cognitive function in healthy adults. Substantial evidence indicates that short-term or single anodal tDCS sessions over the left DLPFC will enhance the performance of executive functions. However, the changes in performance and cortical activation of executive functions after modulation by (...) repeated anodal HD-tDCS is as yet unexplored. This study aims to examine changes in three core components of executive functions produced by nine HD-tDCS sessions, and to use functional near-infrared spectroscopy to bilaterally record DLPFC neural activity. A total of 43 participants were divided randomly into two study groups to complete nine interventions. Our results demonstrate that the enhancement of cognitive flexibility in the anodal group was significantly better than that in the sham group. Additionally, a Stroop effect-related decrease in oxygenated hemoglobin concentration in the DLPFC was observed in the anodal group but not the sham group. In conclusion, our study found that repeated anodal HD-tDCS sessions can significantly promote cognitive flexibility, one of the core components of executive function, and that alterations in DLPFC activation can enhance our understanding of the neuroplastic modifications modulated by HD-tDCS. (shrink)

Psychosis is associated with distorted perceptions and deficient bottom-up learning such as classical fear conditioning. This has been interpreted as reflecting imprecise priors in low-level predictive coding systems. Paradoxically, overly strong beliefs, such as overvalued beliefs and delusions, are also present in psychosis-associated states. In line with this, research has suggested that patients with psychosis and associated phenotypes rely more on high-order priors to interpret perceptual input. In this behavioural and fMRI study we studied two types of fear learning, i.e., (...) instructed fear learning mediated by verbal suggestions about fear contingencies and classical fear conditioning mediated by low level associative learning, in delusion proneness—a trait in healthy individuals linked to psychotic disorders. Subjects were shown four faces out of which two were coupled with an aversive stimulation while two were not in a fear conditioning procedure. Before the conditioning, subjects were informed about the contingencies for two of the faces of each type, while no information was given for the two other faces. We could thereby study the effect of both classical fear conditioning and instructed fear learning. Our main outcome variable was evaluative rating of the faces. Simultaneously, fMRI-measurements were performed to study underlying mechanisms. We postulated that instructed fear learning, measured with evaluative ratings, is stronger in psychosis-related phenotypes, in contrast to classical fear conditioning that has repeatedly been shown to be weaker in these groups. In line with our hypothesis, we observed significantly larger instructed fear learning on a behavioural level in delusion-prone individuals compared to non-delusion-prone subjects. Instructed fear learning was associated with a bilateral activation of lateral orbitofrontal cortex that did not differ significantly between groups. However, delusion-prone subjects showed a stronger functional connectivity between right lateral orbitofrontal cortex and regions processing fear and pain. Our results suggest that psychosis-related states are associated with a strong instructed fear learning in addition to previously reported weak classical fear conditioning. Given the similarity between nocebo paradigms and instructed fear learning, our results also have an impact on understanding why nocebo effects differ between individuals. (shrink)

Rumfitt has given two arguments that in unilateralist verificationist theories of meaning, truth collapses into correct assertibility. In the present paper I give similar arguments that show that in unilateral falsificationist theories of meaning, falsehood collapses into correct deniability. According to bilateralism, meanings are determined by assertion and denial conditions, so the question arises whether it succumbs to similar arguments. I show that this is not the case. The final section considers the question whether a principle central to Rumfitt's first (...) argument, ‘It is assertible that if and only if it is assertible that it is assertible that ’, is one that bilateralists can reject, and concludes that they cannot. It follows that the logic of assertibility and deniability, according to a result by Williamson, is the little known modal logic K4 studied by Sobociński. The paper ends with a plaidoyer for bilateralists to adopt this logic. (shrink)