bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral and neural evidence of increased attention to the bottom half of the face in deaf signers
Authors: Mitchell Teresa V. , Letourneau Susan M. , Maslin Melissa C.T.
Published: December 2019

Purpose: This study examined the effects of deafness and sign language use on the distribution of attention across the top and bottom halves of faces. Methods: In a composite face task, congenitally deaf signers and typically hearing controls made same/different judgments of the top or bottom halves of faces presented with the halves aligned or spatially misaligned, while event-related potentials (ERPs) were recorded. Results: Both groups were more accurate when judging misaligned than aligned faces, which indicates holistic face processing. Misalignment affected all ERP components examined, with effects on the N170 resembling those of face inversion. Hearing adults were similarly accurate when judging the top and bottom halves of the faces, but deaf signers were more accurate when attending to the bottom than the top. Attending to the top elicited faster P1 and N170 latencies for both groups; within the deaf group, this effect was greatest for individuals who produced the highest accuracies when attending to the top. Conclusions: These findings dovetail with previous research by providing behavioral and neural evidence of increased attention to the bottom half of the face in deaf signers, and by documenting that these effects generalize to a speeded task, in the absence of gaze shifts, with neutral facial expressions.
Modulatory effects of locomotor training on extensor spasticity in individuals with motor-incomplete spinal cord injury
Authors: Manella Kathleen J. , Field-Fote Edelle C.
Published: December 2019

Purpose: Sparse data exist about effects of locomotor training on spasticity in individuals with spinal cord injury (SCI). We investigated changes in spastic responses in individuals with motor-incomplete SCI (MISCI) associated with locomotor training and examined properties of a biomechanical measure of clonus severity, plantar flexor reflex threshold angle (PF RTA). Methods: In 18 individuals with chronic MISCI, we assessed biomechanical and electrophysiologic measures of extensor spasticity and their relationship with walking speed before and after 12 weeks of body-weight supported locomotor training. Measures included PF RTA, plantar flexor (ankle clonus) and quadriceps spasm duration, soleus H-reflex, and ankle muscle electromyography. PF RTA validity was assessed by measuring PF RTA and clonus duration in 40 individuals with SCI and 10 non-disabled individuals. Results: Locomotor training was associated with decreased PF RTA (p = 0.06), ankle clonus (p = 0.09) and quadriceps spasm (p = 0.05). PF RTA discriminated between non-disabled individuals and individuals with SCI and was moderately correlated with walking speed, soleus H/M ratio, and quadriceps spasm duration. Conclusions: In persons with spastic paresis due to MISCI, locomotor training was associated with decreased spasticity as measured by decreased plantar flexor excitability, ankle clonus, and quadriceps spasm.
Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia: clinical and physiological effects
Authors: Kimberley Teresa Jacobson , Borich Michael R. , Arora Sanjeev , Siebner Hartwig R.
Published: December 2019

Purpose: The ability of low-frequency repetitive transcranial magnetic stimulation (rTMS) to enhance intracortical inhibition has motivated its use as a potential therapeutic intervention in focal hand dystonia (FHD). In this preliminary investigation, we assessed the physiologic and behavioral effects of multiple sessions of rTMS in FHD. Methods: 12 patients with FHD underwent five daily-sessions of 1 Hz rTMS to contralateral dorsal premotor cortex (dPMC). Patients held a pencil and made movements that did not elicit dystonic symptoms during rTMS. We hypothesized that an active but non-dystonic motor state would increase beneficial effects of rTMS. Five additional patients received sham-rTMS protocol. The area under curve (AUC) of the motor evoked potentials and the cortical silent period (CSP) were measured to assess changes in corticospinal excitability and intracortical inhibition, respectively. Behavioral measures included pen force and velocity during handwriting and subjective report. Results: Multiple-session rTMS strengthened intracortical inhibition causing a prolongation of CSP after 3 days of intervention and pen force was reduced at day 1 and 5, leaving other measures unchanged. 68% of patients self-reported as ‘responders’ at day 5, and 58% at follow-up. Age predicted responders. Conclusions: A strong therapeutic potential of this rTMS paradigm in FHD was not supported but findings warrant further investigation.
Hippocampal neurotrophins after stimulation of the basolateral amygdala, and memory improvement in lesioned rats
Authors: Mercerón-Martínez Daymara , Almaguer-Melian William , Serrano Teresa , Lorigados Lourdes , Pavón Nancy , Bergado Jorge A.
Published: December 2019

Purpose: To investigate a possible role of neurotrophins in the memory improving effect of stimulating the basolateral amygdala. Methods: The BDNF and NGF levels were measured in the hippocampus of fimbria-fornix lesioned male rats after four days of training in the water maze and stimulation of the basolateral amygdala. Results: The behavioral results confirm that daily post-training stimulation of the amygdala improves the learning abilities of the lesioned animals. BDNF increased in lesioned and trained animals, but stimulating the basolateral amygdala induces a significantly greater increase. NGF showed a slight (but significant) increase in fimbria-fornix lesioned and trained animals, but stimulating the amygdala does not produce a further increase. In separate groups of animals we measured the levels of both neurotrophins in acute experiments, after 2 and 24 hours of stimulating the amygdala. BDNF was significantly increased at both times, while NGF showed again only slight increases (significant at 24 h). Conclusions: These results suggest that the BDNF response to amygdala stimulation might be of functional importance in the observed learning improvement. The changes in NGF are most likely due to the accumulation of this protein after removal of the septal axons.
The (pro)renin receptor / ATP6ap2 is expressed in the murine hippocampus by adult and newly generated neurons
Authors: Schäfer S.T. , Peters J. , von Bohlen und Halbach O.
Published: December 2019

Purpose: The (pro)renin receptor ((P)RR) is receptor that has been shown to be involved in developmental processes. Adult neurogenesis shares many similarities with fetal and embryonic neuronal development, but is restricted to some brain areas, including the hippocampus. We therefore investigated the expression of the (P)RR within the adult hippocampal formation and investigated whether (P)PR is expressed by adult and newly generated neurons in the dentate gyrus. Methods: (P)PR protein expressing cells in the hippocampus were analyzed using immunohistochemistry. Double-labeling with markers for adult neurogenesis was used to investigate whether newly formed cells also express (P)PR. Results: (P)PR is expressed by neuronal cells with the hippocampus. (P)RR protein is expressed during different stages of adult neurogenesis within the dentate gyrus (DG). (P)RR is not expressed by Sox2 positive neuronal stem cells, but by doublecortin positive cells located both in the subgranular zone and the granular layer of the DG. Conclusions: The results indicate that (P)PR is mainly expressed by adult neurons in the hippocampus as well as in late stages of adult neurogenesis within the hippocampus. However, to clarify the involvement of this receptor in adult hippocampal neurogenesis and neuronal cell differentiation in detail, functional analyses needed to be performed.
Diffusion tensor imaging predicts the outcome of constraint-induced movement therapy in chronic infarction patients with hemiplegia: A pilot study
Authors: Marumoto Kohei , Koyama Tetsuo , Hosomi Masashi , Takebayashi Takashi , Hanada Keisuke , Ikeda Sayaka , Kodama Norihiko , Domen Kazuhisa
Published: December 2019

Purpose: To test whether diffusion tensor imaging could evaluate potential motor capability of patients with chronic cerebral infarction. Methods: We used constraint-induced movement therapy (CIMT) as a rehabilitation, which reveals potential motor capability. We also investigated the relationship between the outcome of CIMT and the ratio between fractional anisotropy values (rFA) in affected and unaffected sites of the corticospinal tract before CIMT. Imaging was performed in cerebral infarction patients (n = 14) and the rFA of the posterior limb of internal capsule (PLIC) was measured before CIMT. Patients were evaluated before and after CIMT using the Fugl-Meyer (F-M) assessment, Wolf Motor Function Test, Action Research Arm Test, and Motor Activity Log and association between PLIC- rFA and these scores was determined. Results: All patients showed an improvement in mobility following the 10-day CIMT session. Strong positive correlation was found only between F-M after CIMT and PLIC-rFA (r = 0.8098, p = 0.0004). A strong linear relationship was observed after CIMT. Conclusion: These data support PLIC-rFA as a new marker of the CIMT-induced improvement in motor function (F-M).
Androgen treatment and recovery of function following recurrent laryngeal nerve injury in the rat
Authors: Brown Todd J. , Pittman Amy L. , Monaco Gina N. , Benscoter Brent J. , Mantravadi Avinash V. , Akst Lee M. , Jones Kathryn J. , Foecking Eileen M.
Published: December 2019

Purpose: To investigate the effects of the androgen testosterone propionate (TP), on regeneration of the recurrent laryngeal nerve (RLN) after unilateral crush injury using assessment of vocal fold mobility (VFM) as a measure of behavioral recovery. Methods: 48 adult male rats underwent standardized crush injury of left RLN and received treatment in the form of 2 silastic capsules containing TP or controls receiving a blank capsule (untreated). Direct laryngoscopic assessment of vocal cord mobility was performed before, immediately following and 1, 2, 3, 4, 5 or 6 weeks post injury. Results: Treatment with TP enhanced the recovery of full VFM following crush injury of the RLN compared to controls. There was statistically significant improvement in VFM seen at the 1 and 2 week time points (p < 0.05). By 4 weeks TP-treated rats displayed a 100% recovery of VFM function, compared to only 50% by the control group. Conclusions: TP enhances RLN functional recovery following a crush injury, which further supports its potential general applicability as a therapeutic agent in peripheral nerve injury.
Allogenic umbilical cord blood therapy combined with erythropoietin for patients with severe traumatic brain injury: Three case reports
Authors: Min Kyunghoon , Song Junyoung , Lee Ji Hyun , Kang Myung Seo , Jang Su Jin , Kim Sang Heum , Kim MinYoung
Published: December 2019

Objective: To report the safety and efficacy of a novel therapeutic trial with umbilical cord blood (UCB) and concomitant recombinant human erythropoietin (rhEPO), which was tried for three cases of severe traumatic brain injury (TBI) in rehabilitation. Design: Case series. Setting: University hospital setting. Participants: Three patients with TBI over 6-months post-injury. Interventions: Intravascular administration of allogenic UCB and injection of rhEPO, and rehabilitation therapy. Outcomes: For safety, adverse events, symptom, vital signs, blood chemistry, and hematologic study; for efficacy, modified Barthel index, motor assessment scale, Fugl-Meyer assessment of upper extremity, motor-free visual perception test, mini-mental screening examination, and brain images. Results: There were no serious adverse events and the participants showed improvements during the follow-up periods in various aspects. Patient 1 demonstrated improvements in motor and cognitive function. Diffusion tensor images showed increased nerve fibers. Patient 2 displayed improvements in activities of daily living. In Patient 3, neurogenic fever vanished and Brain PET revealed increased glucose metabolism at basal ganglia, thalami, and cerebellum. Conclusions: The allogenic UCB therapy combined with rhEPO in the present study was safe and suggested potential therapeutic efficacy for patients with TBI. Controlled clinical trials are now needed to document efficiacy and safety in a larger patient sample.
Visual outcome of patients following NAION after treatment with adjunctive fluocortolone
Authors: Prokosch Verena , Thanos Solon
Published: December 2019

Purpose: Nonarteriitic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden loss of vision, which particularly affects individuals older than 50 years. Up to now there is no treatment that is effective at reversing or limiting the course of this disease. To study the short- and long-term effects of fluocortolone (FC) on the visual outcome of patients with acute NAION compared to standard treatment with pentoxifylline (PFX). Methods: A prospective, quasirandomized intervention trial was conducted involving 60 patients with acute-onset NAION. Patients in the comparison (PFX) group (n = 30) received PFX intravenously and per os for 7 days and then per os for a further 6 months, which is a standard treatment. Patients in the intervention (PFX + FC) group (n = 30) received the standard treatment plus 1 mg/kg FC for 5 days, with a subsequent stepwise dose reduction over time. As a primary outcome measure, the best corrected visual acuity (BCVA) was determined at the initial baseline consultation (i.e., before treatment), and at 3 days and 6 months after therapy onset. Visual field (VF) was analyzed using standard automated perimetry at the initial baseline examination and at 6 month after therapy onset. Changes in BCVA and visual field in the PFX and PFX + FC groups were compared and analyzed statistically. Results: Treatment with FC resulted in a significant improvement in BCVA. Patients receiving FC in acute NAION were more likely to experience improvement and less likely to have worsened visual acuity (mean BCVA scores: at baseline, 0.22; after 3 days and 6 months of treatment, 0.33 and 0.43, respectively) than PFX patients (mean BCVA scores: at baseline, 0.33; after 3 days and 6 months of treatment, 0.33 and 0.28, respectively; p < 0.002 and 0.001). The beneficial effect was even more marked 6 months after therapy onset. Remarkably, patients with a baseline BCVA score of >=0.05 profited significantly by FC treatment (p < 0.006 and 0.001), whereas those with a baseline BCVA score of <0.05 did not (p < 0.4). PFX did not improve BCVA. However, VF did not show any significant improvement due to FC therapy. Conclusion: This is the first prospective randomized intervention trial that demonstrates the distinctive beneficial effects of FC in terms of the visual outcome of patients with NAION compared to standard treatment with only PFX. FC significantly improves both short- and long-term visual acuity in patients with moderate BCVA impairment due to recent onset of NAION, while VF did not show any significant improvement; however, PFX did neither enhance BCVA nor VF. Administration of FC should be seriously considered for the treatment of NAION whenever there are no contraindications.
Motor neuron target selectivity and survival after prolonged axotomy
Authors: Robinson Grant A. , Madison Roger D.
Published: December 2019

Purpose: After a cut peripheral nerve is repaired, motor neurons usually regenerate across the lesion site, however they often enter an inappropriate Schwann cell tube and may be directed to an inappropriate target organ such as skin, resulting in continued loss of function. In fact, only about 10% of adults who receive a peripheral nerve repair display full functional recovery. The reasons for this are many and complex, however one aspect is whether the motor neuron has undergone a prolonged period of axotomy prior to nerve repair. Previous studies have suggested a deleterious effect of prolonged axotomy. Methods: We examined the influence of prolonged axotomy on target selectivity using a cross-reinnervation model of rat obturator motor neurons regrowing into the distal femoral nerve, with its normal bifurcating pathways to muscle and skin. Results: Surprisingly, we found that a prolonged period of axotomy resulted in an increase in motor neuron regeneration accuracy. In addition, we found that regeneration accuracy could be increased even further by a simple surgical manipulation of the distal terminal nerve pathway to skin. Conclusions: These results suggest that under certain conditions prolonged axotomy may not be detrimental to the final accuracy of motor neuron regeneration and highlight that a simple manipulation of terminal nerve pathways may be one approach to increase such regeneration accuracy.
Towards a more precise neurophysiological assessment of cognitive functions in patients with disorders of consciousness
Authors: Kotchoubey B. , Veser S. , Real R. , Herbert C. , Lang S. , Kübler A.
Published: December 2019

Purpose: To analyze the principles that guide inference of covert cognitive functions and consciousness in patients with extremely severe brain damage on the basis of neurophysiological test results. Methods: (1) A quantitative analysis of a range of possible inferences based on neurophysiological findings in low- and non-responsive patients; (2) a logical analysis of the various possible orders of application of neurophysiological tests in such patients. Results: Surprisingly, improvement of neurophysiological test qualities contributes to the improvement of diagnostic results less than some other factors, such as the structure of the patient population, the quality of the previous clinical diagnosis, and the variability of the methods used. Conclusions: A sequential decision procedure is suggested. Different test paradigms should be combined most effectively to arrive at a reliable evaluation of cognitive functions in this patient population.
Effects of balance and gait rehabilitation in cerebellar disease of vascular or degenerative origin
Authors: Nardone Antonio , Turcato Anna Maria , Schieppati Marco
Published: December 2019

Purpose: To investigate whether the response to rehabilitation differs between patients with abnormalities of balance and gait due to vascular or to degenerative cerebellar disease. Methods: We reviewed the outcome of 27 cerebellar patients. Fourteen patients with vascular and 13 with degenerative cerebellar disease underwent a 3-week inpatient physical therapy program for 5 days/week, 90 min/day, focused on balance and gait. Body sway area during quiet stance with eyes open and eyes closed, and gait velocity, stride length, cadence and step width were recorded. The Berg Balance Scale (BBS) and Functional Independence Measure (FIM) were administered. All tests were performed before and after treatment. Results: Before treatment, both groups showed comparable values in all sway and gait variables and in BBS. FIM score was higher in degenerative than vascular patients. After treatment, a significant reduction of body sway area was observed under both visual conditions in both groups. Gait velocity, stride length and step width improved more in the vascular than in the degenerative patient group. BBS improved in both groups. FIM improved to a larger extent in the vascular patients. Conclusion: Short-term treatment may not be sufficient to produce definite improvement in locomotion in degenerative as much as occurs in vascular patients, even if clinical and functional signs of balance improve in both groups.
Effect of fish oil supplementation in a rat model of multiple mild traumatic brain injuries
Authors: Wang Tao , Van Ken C. , Gavitt Brian J. , Grayson J. Kevin , Lu Yi-Cheng , Lyeth Bruce G. , Pichakron Kullada O.
Published: December 2019

Purpose: Repetitive mild traumatic brain injury (TBI) is a major military and sports health concern. The purpose of this study was to determine if a diet rich in omega-3 fatty acids would reduce cognitive deficits and neuronal cell death in a novel fluid percussion rat model of repetitive mild TBIs. Methods: Thirty-two Sprague-Dawley rats were assigned to either an experimental rat chow enhanced with 6% fish oil (source of omega-3 fatty acids) or a control rat chow. Both rat chows contained equivalent quantities of calories, oil, and nutrients. After four weeks, both groups received mild repetitive bilateral fluid percussion TBIs on two sequential days. Pre-injury diets were resumed, and the animals were monitored for two weeks. On post-injury days 10–14, Morris Water Maze testing was performed to assess spatial learning and cognitive function. Animals were euthanized at 14 days post-injury to obtain specimens for neurohistopathology. Results: There was no difference in pre-injury weight gain between groups. Post-injury, animals on the fish oil diet lost less weight and recovered their weight significantly faster. By 14 days, the fish oil diet group performed significantly better in the Morris Water Maze. Neurohistopathology identified a non-significant trend toward a higher density of hippocampal neurons in the fish oil diet group. Conclusions: Pre-injury dietary supplementation with fish oil improves recovery of body weight and provides a small improvement in cognitive performance in a rat model of multiple mild TBIs.
Transcranial Direct Current Stimulation (tDCS) for sleep disturbances and fatigue in patients with post-polio syndrome
Authors: Acler Michele , Bocci Tommaso , Valenti Diana , Turri Mara , Priori Alberto , Bertolasi Laura
Published: December 2019

Purpose: Post-polio syndrome develops about 20–40 years after acute paralytic poliomyelitis, and manifests with progressively deteriorating muscle strength and endurance. Here, we assessed whether transcranial direct current stimulation (tDCS) improves sleep and fatigue symptoms in patients with post-polio syndrome. Methods: We enrolled 32 patients with a diagnosis of post-polio syndrome. tDCS (1.5 mA, 15 min) was delivered by a direct current stimulator connected to three electrodes: two anodal electrodes on the scalp over the right and left pre-motor cortex and the other above the left shoulder (cathode). 16 patients received anodal tDCS and the remainder sham tDCS. We evaluated changes induced by tDCS (daily for five days a week, for three weeks) on clinical scales (Short Form Health Survey [SF-36], Piper Fatigue Scale [PFS], Fatigue Severity Scale [FSS], 101-Point Numerical Rating [PNR-101], Hamilton Rating Scale for Depression [HRSD], Pittsburgh Sleep Quality Index [PSQI]) at baseline (T0) and three weeks later (T1). Results: At T1 SF-36 sub-items physical functioning, role physical, vitality, social functioning and role emotional improved significantly more in patients who received tDCS (p < 0.01) than in sham-treated patients. Also, PSQI scores improved more in treated patients (p < 0.05, two-way ANOVA with “stimulation” and “time” as factors: p < 0.01). tDCS-induced benefits were more pronounced in patients who were younger at primary infection (p < 0.05). Conclusion: Anodal tDCS over the pre-motor areas for fifteen days improved sleep and fatigue symptoms in patients with post-polio syndrome. tDCS could be a non-invasive and valuable new tool for managing post-polio patients.
Neural correlates of training-induced improvements of calculation skills in patients with brain lesions
Authors: Claros-Salinas Dolores , Greitemann Georg , Hassa Thomas , Nedelko Violetta , Steppacher Inga , Harris Joseph Allen , Schoenfeld Mircea Ariel
Published: December 2019

Purpose: The loss of calculation skills due to brain lesions leads to a major reduction in the quality of life and is often associated with difficulties of returning to work and a normal life. Very little is known about the neural mechanisms underlying performance improvement due to calculation training during rehabilitation. The current study investigates the neural basis of training-induced changes in patients with acalculia following ischemic stroke or traumatic brain lesions. Methods: Functional hemodynamic responses (fMRI) were recorded in seven patients during calculation and perceptual tasks both before and after acalculia training. Results: Despite the heterogeneity of brain lesions associated with acalculia in our patient sample, a common pattern of training-induced changes emerged. Performance improvements were associated with widespread deactivations in the prefrontal cortex. These deactivations were calculation-specific and only observed in patients exhibiting a considerable improvement after training. Conclusion: These findings suggest that the training-induced changes in our patients rely on an increase of frontal processing efficiency.
After vs. priming effects of anodal transcranial direct current stimulation on upper extremity motor recovery in patients with subacute stroke
Authors: Fusco Augusto , Iosa Marco , Venturiero Vincenzo , De Angelis Domenico , Morone Giovanni , Maglione Luisa , Bragoni Maura , Coiro Paola , Pratesi Luca , Paolucci Stefano
Published: December 2019

Purpose: Transcranial direct current stimulation (tDCS) of the motor cortex seems to be effective in improving motor performance in patients with chronic stroke, while some recent findings have reported conflicting results for the subacute phase. We aimed to verify whether upper extremity motor rehabilitation could be enhanced by treatment with tDCS administered before a rehabilitative session. Methods: Hand dexterity and force in 16 individuals with subacute stroke were assessed before (T0) and after anodal stimulation (T1) and after a successive session of motor rehabilitation (T2) in a double-blind, randomized, sham-controlled, crossover trial. To confirm the value of the device as a specific effector, behavioral tests were also administered. Results: Anodal and sham stimulation plus rehabilitation significantly improved manual dexterity (repeated-measure Anova: A-tDCS: p = 0.005; S-tDCS: p = 0.042). Post hoc analysis revealed a significant stimulation effect only for A-tDCS (p = 0.013 between T0 and T1) and not for S-tDCS, whereas the rehabilitation effect (between T1 and T2) was not significant in either group. Hand force and behavioral features were unchanged. Conclusions: Anodal brain stimulation improves hand dexterity but does not increase the effectiveness of the rehabilitation directly. These results suggest the presence of aftereffects, not priming effects, of A-tDCS superimposed onto motor learning phenomena.
Chronic neurodegenerative consequences of traumatic brain injury
Authors: Chauhan Neelima B.
Published: December 2019

Traumatic brain injury (TBI) is a serious public health concern and a major cause of death and disability worldwide. Each year, an estimated 1.7 million Americans sustain TBI of which ~52,000 people die, ~275,000 people are hospitalized and 1,365,000 people are treated as emergency outpatients. Currently there are ~5.3 million Americans living with TBI. TBI is more of a disease process than of an event that is associated with immediate and long-term sensomotor, psychological and cognitive impairments. TBI is the best known established epigenetic risk factor for later development of neurodegenerative diseases and dementia. People sustaining TBI are ~4 times more likely to develop dementia at a later stage than people without TBI. Single brain injury is linked to later development of symptoms resembling Alzheimer's disease while repetitive brain injuries are linked to later development of chronic traumatic encephalopathy (CTE) and/or Dementia Pugilistica (DP). Furthermore, genetic background of ß-amyloid precursor protein (APP), Apolipoprotein E (ApoE), presenilin (PS) and neprilysin (NEP) genes is associated with exacerbation of neurodegenerative process after TBI. This review encompasses acute effects and chronic neurodegenerative consequences after TBI.
Effects of intravitreal injection of a Rho-GTPase inhibitor (BA-210), or CNTF combined with an analogue of cAMP, on the dendritic morphology of regenerating retinal ganglion cells
Authors: Drummond Eleanor S. , Rodger Jennifer , Penrose Marissa , Robertson Donald , Hu Ying , Harvey Alan R.
Published: December 2019

Purpose: In adult rats, intravitreal injections of the Rho-GTPase inhibitor C3 transferase (BA-210), or a cocktail of recombinant ciliary neurotrophic factor (CNTF) and a cyclic AMP analogue (CPTcAMP), increase retinal ganglion cell (RGC) survival and axonal regeneration. Here we examined whether these treatments also affect the dendritic architecture of regrowing RGCs. Methods: In Fischer F344 rats, one optic nerve was cut and an autologous peripheral nerve graft was sutured onto it. Rats then received intravitreal injections (4 μl) of saline, BA-210 or CNTF + CPTcAMP four and eleven days after the PN graft surgery. After 5 weeks, regenerating RGCs were retrogradely labelled with fluorogold (FG) and in living wholemounts the dendritic trees of FG labelled RGCs were visualised by intracellular injection of 2% Lucifer Yellow. Results: Injection of BA-210 or CNTF + CPTcAMP resulted in significantly more regenerating RGCs with abnormal dendritic morphologies, including abnormally long looping processes. Compared to saline-injected regenerating controls, RGCs in BA-210 injected eyes had significantly smaller dendritic field areas and sparser dendrites, while in CNTF + CPTcAMP injected eyes there was increased branching of more distal dendrites. Conclusions: While both intraocular treatments enhance RGC axonal regrowth, they also induce significant changes in RGC dendritic morphology. It remains to be determined if such changes alter the function of the regenerating neuronal population.
Brain control of functional reach in healthy adults and stroke survivors
Authors: Daly Janis J. , Hrovat Ken , Holcomb John , Pundik Svetlana
Published: December 2019

Purpose: Recovery of the most basic shoulder-flexion/elbow-extension components of functional reach is critical for effective arm function following stroke. In order to understand the mechanisms of motor recovery, it is important to characterize the pattern of brain activation during the reach task. Methods: We evaluated 11 controls and 23 moderately to severely impaired chronic stroke survivors (>6 months), with impaired shoulder flexion and elbow extension. Measures were acquired for Arm Motor Ability Test (AMAT) and functional Magnetic Resonance Imaging (fMRI) during the basic shoulder/elbow reach. Results: First, in controls, lateralization of fMRI signal during the reach task was less pronounced in comparison to other tasks, and even further diminished after stroke (p < 0.05). Second, for the stroke group, centroid locations, for specific ipsilesional (contralateral to working limb) motor-sensory regions and for contralesional (ipsilateral to working arm) somatosensory and SMA regions, were significantly more distant from the centroid location of average healthy controls (p < 0.05). Third, both greater activation volume and greater degree of signal intensity were correlated with better motor function in stroke survivors. Conclusions: These findings can be useful in guiding the development of more targeted brain training methods for recovery of impaired reach coordination.
Bone marrow-derived mononuclear cell transplantation in spinal cord injury patients by lumbar puncture
Authors: Suzuki Yoshihisa , Ishikawa Namiko , Omae Kaoru , Hirai Tatsuya , Ohnishi Katsunori , Nakano Norihiko , Nishida Hidetaka , Nakatani Toshio , Fukushima Masanori , Ide Chizuka
Published: December 2019

Purpose: This study was conducted to assess the safety and feasibility of intrathecal transplantation of autologous bone marrow-derived mononuclear cells for the treatment of patients with spinal cord injury. Methods: Ten patients were included in the study. Approximately 120 ml of bone marrow aspirate was obtained from bilateral iliac bone of patients with spinal cord injury. Isolation of mononuclear cells was performed using Ficoll density-gradient centrifugation. Bone marrow mononuclear cells were transplanted into cerebrospinal fluid by lumbar puncture. Functional tests were performed prior to the cell transplantation and six months after cell transplantation. The patients were carefully observed for up to six months. Results: In 5 patients with AIS A prior to cell transplantation, 1 patient converted to AIS B six months after cell transplantation. In 5 patients with AIS B, 1 patient converted to AIS D and 2 patients to AIS C. MRI did not show any complication. Two patients showed slight anemia after aspiration of bone-marrow cells, which returned to normal level within a several weeks. Conclusion: The results of this study suggest that this method may be safe and feasible.
Current-modulated electrical stimulation as a treatment for peripheral nerve regeneration in diabetic rats
Authors: Lin Yu-Ching , Kao Chia-Hong , Cheng Yu-Kai , Chen Jia-Jin J. , Yao Chun-Hsu , Chen Yueh-Sheng
Published: December 2019

Purpose: To study if electrical stimulation (ES) can be a useful tool to improve functional recovery after neuronal injury in the peripheral nervous system. Methods: We studied the effects of 2 Hz of percutaneous ES at different intensities of 1, 10 and 20 mA on peripheral nerve regeneration in rats with diabetes induced by streptozotocin. Non-stimulated diabetic rats were used as the sham-controls. A10-mm gap was made in the rat sciatic nerve by suturing the stumps into silicone rubber tubes and stimulation was carried out every other day for 3 weeks starting 1 week after surgery. Results: After 4 weeks of recovery, the diabetic rats showed that ES of 1 mA or above could increase the cutaneous blood flow in their ipsilateral hindpaw to the injury. ES of 10 mA could improve the amplitude and the area of evoked muscle action potentials with faster target muscle reinnervation. ES of 10 mA could also ameliorate the calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn ipsilateral to the injury and the number of macrophages in the diabetic distal sciatic nerve. The impaired growth and maturation of regenerating axons in diabetic rat could be improved by ES of 10 mA or above. Conclusions: All these results lead to the conclusion that ES of 10 mA or above might be necessary to improve regeneration after a dissect lesion of the sciatic nerve in the diabetic rat.
Cognitive enhancers for the treatment of anxiety disorders
Authors: Hofmann Stefan G. , Fang Angela , Gutner Cassidy A.
Published: December 2019

Traditional treatments for anxiety disorders include cognitive-behavioral therapy and anxiolytic medications. Although these treatments are more effective than placebo, there is still considerable room for further improvement. Unfortunately, combining these different modalities is generally not substantially better than monotherapies. Recently, researchers have turned their attention toward translating preclinical research on the neural circuitry underlying fear extinction to clinical applications for the treatment of anxiety disorders with the goal to augment the learning process during exposure-based procedures with cognitive enhancers. This review examines d-cycloserine, cortisol, catecholamines, yohimbine, oxytocin, modafinil, as well as nutrients and botanicals as agents to augment treatment for anxiety disorders. D-cycloserine shows the most empirical support. Other promising agents include cortisol, catecholamines, yohimbine, and possibly oxytocin. Less support comes from studies that examined nutrients and botanicals, such as caffeine, nicotine, and omega-3 fatty acid. Limitations of the exiting literature and future research directions are discussed.
Incentive motivational salience and the human brain
Authors: Jensen Jimmy , Walter Henrik
Published: December 2019

In this paper the concept of incentive motivational salience is briefly described, pioneering studies on the subject of the mesolimbic motivational system are reviewed, and studies we have been involved in conducting which elaborate on this subject are discussed. In particular, we aim to show that the mesolimbic motivational system is recruited as a reaction to primary and secondary reinforcers as a function of salience, that is independent of valence. Furthermore, studies showing that both psychological and pharmacological interventions can affect the function of the mesolimbic motivational system and how its' dysfunction is related to psychopathological phenomena with an emphasis on psychosis are discussed.
Bipolar disorder: A neural network perspective on a disorder of emotion and motivation
Authors: Wessa Michèle , Kanske Philipp , Linke Julia
Published: December 2019

Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60–80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.
Psychobiology of social support: The social dimension of stress buffering
Authors: Ditzen Beate , Heinrichs Markus
Published: December 2019

Social integration and social support have a substantial influence on individual health and longevity, an effect assumed to be mediated through reduced stress reactivity in support recipients. However, considerable variability in individual responses to social support has been documented, suggesting that the beneficial effect of social support interacts with early experiences, genetically influenced differences in biological systems mediating social behavior, personality traits, and psychopathology. Here we outline the historical background of social support research, including epidemiological studies, laboratory studies, and field studies on the subject of social support and health, with regard to different psychobiological effector systems. Most recent research has focused on brain mechanisms which link social integration or social support with reduced neural threat responses. As numerous mental disorders are associated with considerable social impairment, understanding the potentially underlying mechanisms of neural plasticity in relation to social support, stress buffering and health in these disorders can help tailor new diagnostic and treatment strategies. Thus, theories of socially-driven emotional learning and memory, as presented in this review, might eventually lead to psychobiology-based treatment concepts for mental disorders involving social deficits.
Training-induced cerebral changes in the elderly
Authors: Degen Christina , Schröder Johannes
Published: December 2019

As the demographic shift towards an aging population prevails, the improvement and/or maintenance of cognitive functioning appear increasingly important. To date, the effectiveness of cognitive, cardiovascular and sensorimotor training approaches in older adults has been demonstrated frequently using neuropsychological and behavioral performance measures. We present an overview of selected studies applying modern imaging techniques (fMRI, PET) to assess practice-induced structural and functional changes in the brain. Structurally, practice is associated with volumetric increases. Functionally, reorganization of neural network recruitment, overall decreases and increases in activity levels are found. Thus, the human brain retains a high degree of plasticity in old age. Moreover, it seems that practice leads to more efficient processing, requiring less neural engagement to perform the same task. While the concept of economization finds widespread support in healthy populations, in patient groups this effect has proven to be absent or reversed. The concept of cognitive reserve and potentially compensatory mechanisms are discussed in this context.
Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry
Authors: Lang Peter J. , McTeague Lisa M. , Bradley Margaret M.
Published: December 2019

Research from the University of Florida Center for the Study of Emotion and Attention aims to develop neurobiological measures that objectively discriminate among symptom patterns in patients with anxiety disorders. From this perspective, anxiety and mood pathologies are considered to be brain disorders, resulting from dysfunction and maladaptive plasticity in the neural circuits that determine fearful/defensive and appetitive/reward behavior (Insel et al., 2010). We review recent studies indicating that an enhanced probe startle reflex during the processing of fear memory cues (mediated by cortico-limbic circuitry and thus indicative of plastic brain changes), varies systematically in strength over a spectrum-wide dimension of anxiety pathology—across and within diagnoses—extending from strong focal fear reactions to a consistently blunted reaction in patients with more generalized anxiety and comorbid mood disorders. Preliminary studies with functional magnetic resonance imaging (fMRI) encourage the hypothesis that fear/defense circuit dysfunction covaries with this same dimension of psychopathology. Plans are described for an extended study of the brain's motivation circuitry in anxiety spectrum patients, with the aim of defining the specifics of circuit dysfunction in severe disorders. A sub-project explores the use of real-time fMRI feedback in circuit analysis and as a modality to up-regulate circuit function in the context of blunted affect.
From assistance towards restoration with epidural brain-computer interfacing
Authors: Gharabaghi Alireza , Naros Georgios , Walter Armin , Grimm Florian , Schuermeyer Marc , Roth Alexander , Bogdan Martin , Rosenstiel Wolfgang , Birbaumer Niels
Published: December 2019

Purpose: Today's implanted brain-computer interfaces make direct contact with the brain or even penetrate the tissue, bearing additional risks with regard to safety and stability. What is more, these approaches aim to control prosthetic devices as assistive tools and do not yet strive to become rehabilitative tools for restoring lost motor function. Methods: We introduced a less invasive, implantable interface by applying epidural electrocorticography in a chronic stroke survivor with a persistent motor deficit. He was trained to modulate his natural motor-related oscillatory brain activity by receiving online feedback. Results: Epidural recordings of field potentials in the beta-frequency band projecting onto the anatomical hand knob proved most successful in discriminating between the attempt to move the paralyzed hand and to rest. These spectral features allowed for fast and reliable control of the feedback device in an online closed-loop paradigm. Only seven training sessions were required to significantly improve maximum wrist extension. Conclusions: For patients suffering from severe motor deficits, epidural implants may decode and train the brain activity generated during attempts to move with high spatial resolution, thus facilitating specific and high-intensity practice even in the absence of motor control. This would thus transform them from pure assistive devices to restorative tools in the context of reinforcement learning and neurorehabilitation.
Are cognitive interventions for Multiple Sclerosis effective and feasible?
Authors: Magalhães Rosana , Alves Jorge , Thomas Roger E. , Chiaravalloti Nancy , Gonçalves Óscar F. , Petrosyan Agavni , Sampaio Adriana
Published: December 2019

Purpose: Fifty percent of patients with Multiple Sclerosis (MS) are estimated to have cognitive impairments leading to considerable decline in productivity and quality of life. Cognitive intervention has been considered to complement pharmacological treatments. However, a lack of agreement concerning the efficacy of cognitive interventions in MS still exists. A systematic review and meta-analysis was conducted to assess the effects of cognitive interventions in MS. Methods: To overcome limitations of previous meta-analyses, several databases were searched only for Randomized Clinical Trials (RCTs) with low risk of bias. Results: Five studies (total of 139 participants) met our eligibility criteria. Although good completion and adherence rates were evident, we found no evidence of intervention effects on cognition or mood in post-intervention or follow-up assessments. Conclusions: This is the first meta-analysis assessing the effects of cognitive intervention in MS including only RCTs with comparable conditions. Research regarding efficacy, cost-effectiveness and feasibility is still in its infancy. Caution is advised when interpreting these results due to the small number of RCTs meeting the inclusion criteria. Considering the costs of disease, good completion and adherence rates of this approach, further research is warranted. Recommendations concerning improved research practices in the field are presented as well.
The effect of single session bi-cephalic transcranial direct current stimulation on gait performance in sub-acute stroke: A pilot study
Authors: Tahtis Vassilios , Kaski Diego , Seemungal Barry M.
Published: December 2019

Purpose: Non-invasive brain stimulation with transcranial direct current stimulation (tDCS) modulates cortical excitability and improves upper limb motor performance when applied to chronic stroke patients. The objective was to evaluate whether tDCS can influence gait function in sub-acute stroke patients. Methods: We assessed the effect of single session, bi-cephalic tDCS on gait performance in 14 subacute patients with stroke involving the cerebral hemisphere (2–8 weeks post-stroke) in a double-blinded, sham-controlled study. Patients were randomly allocated to receive either active (n = 7) or sham (n = 7) tDCS. The anodal electrode was placed on the scalp over the ipsilesional lower limb primary motor cortex and the cathode was placed over the contralesional leg motor cortex. Gait performance was measured using the Timed Up and Go test and the Performance Oriented Mobility Assessment before and after active or sham tDCS. Results: The tDCS group was significantly quicker in the Timed Up and Go test in the tDCS group, compared to the sham group (p = 0.018). The Performance Oriented Mobility Assessment was not different between groups (p = 0.897). Conclusions: This is the first study to examine the effects of tDCS on gait in stroke patients in the sub-acute stage. Active tDCS improved gait performance (Timed Up and Go) in stroke patients, despite no changes to limb biomechanics of the hemiparetic side (Performance Oriented Mobility Assessment), as compared to sham stimulation. These results suggest that tDCS could be used as a therapeutic adjunct for gait rehabilitation following stroke.