Neonatal Tactile Stimulation Downregulates Dendritic Spines in Layer V Pyramidal Neurons of the WAG/Rij Rat Somatosensory Cortex.

Objective: The aim of our study is to examine the effects of neonatal tactile stimulations on the brain structures that previously defined as the focus of epilepsy in the Wistar-Albino-Glaxo from Rijswijk (WAG/Rij) rat brain with genetic absence epilepsy. Methods: In the present research, morphology and density of dendritic spines were analyzed in layer V pyramidal neurons of the somatosensory cortex (SoCx) of WAG/Rij rats (nonstimulated control, tactile-stimulated, and maternal separated rats) and healthy Wistar (nonepileptic) rats. To achieve this, a Golgi-Cox method was used. Results: Dendritic spine number in layer V of the SoCx has been detected significantly higher in adult WAG/Rij rats at postnatal day 150 in comparison to nonepileptic adult control Wistar rats (p < 0.001). Moreover, quantitative analyses of dendrite structure in adult WAG/Rij rats showed a decrease in dendrite spine density of pyramidal neurons of SoCx which occurred in early neonatal exposure to maternal separation (MS) and tactile stimulation (TS) (p < 0.001). Conclusions: Our findings provide the first evidence that tactile stimulations during the early postnatal period have a long-term impact on dendrite structure in WAG/Rij rat's brain and demonstrate that neonatal tactile stimulation can regulate dendritic spines in layer V in pyramidal neurons of SoCx in epileptic brains.

Tactile stimulation of young WAG/Rij rats prevents development of depression but not absence epilepsy.

Investigations in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats that are susceptible to genetic absence epilepsy have demonstrated that environmental modifications affect absence seizures. Previously, we showed that neonatal tactile stimulations produce disease-modifying effect on genetically determined absence epilepsy and associated depression in Wag/Rij rats. The study presented here examined the effect of TS during late ontogenesis (adolescence and young adulthood) on epilepsy and depression outcomes in this genetically epileptic rat strain. On postnatal day (PND) 38, male WAG/Rij rats randomly were assigned to either the tactile stimulation (TS), handled or control group (unhandled) with 8 animals in each group. Following a 7-day adaptation period to their new surroundings, the animals were submitted to tactile stimulation from PND 45 to PND 90, five days per week, for 5 min daily. The tactile-stimulated rat was removed from its cage, placed on the experimenter's lap, and had its neck and back gently stroked by the researcher. The handled rats were taken to another cage and left alone for 5 min daily from PND 45 to PND 90. The control rats were left undisturbed in their home cage, except for regular cage cleaning. After PND 90, all rats were left undisturbed until behavioral testing and EEG recording. When the animals were 7 months old, they were subjected to the sucrose consumption test (SCT) and the forced swimming test (FST). Electroencephalogram (EEG) recordings were made at 8 months of age in order to measure electroencephalographic seizure activity, thus, the spike-wave discharges (SWDs). Tactile-stimulated rats showed increased sucrose consumption and number of approaches to the sucrose solution in the SCT when compared with the handled and control rats. In the FST, rats in TS group showed lower immobility time and greater immobility latency, active swimming time and diving frequency than the handled and control rats. The duration and the number of seizures were not different amongst the groups. The data obtained suggest that TS in young rats is able to prevent depression in WAG/Rij rats.

HEP® (Homeostasis-Enrichment-Plasticity) Approach Changes Sensory-Motor Development Trajectory and Improves Parental Goals: A Single Subject Study of an Infant with Hemiparetic Cerebral Palsy and Twin Anemia Polycythemia Sequence (TAPS).

BACKGROUND: Early intervention (EI) for infants identified as being at high risk for cerebral palsy (CP), or who have been diagnosed with it, is critical for promotion of postnatal brain organization. The aim of this study was to explore the effectiveness of the Homeostasis-Enrichment-Plasticity (HEP) Approach, which is a contemporary EI model that applies the key principles of enriched environment paradigms and neuronal plasticity from experimental animal studies to ecological theories of human development on the motor development, sensory functions, and parental goals of an infant with twin anemia polycythemia sequence (TAPS) and CP. METHODS: An AB phase with follow-up single case study design which consisted of multiple baseline assessments with the Peabody Developmental Motor Scales-2 (PDMS-2) and the Test of Sensory Functions in Infants (TSFI) was used. Non-overlapping confidence intervals analysis was used for pre-post PDMS-2 scores. The measurement of progress toward goals and objectives was conducted using the Goal Attainment Scale (GAS). The HEP Approach intervention consisted of 12 one-hour sessions implemented over a period of 3 months, where a physical therapist provided weekly clinic-based parental coaching. RESULTS: Results found a stable baseline during Phase A and improvement in response to the HEP Approach intervention during Phase B in both the PDMS-2 and TSFI according to 2SD Band analysis. The confidence intervals for the PDMS-2 scores also indicated a significant improvement after HEP intervention. The scores for both the PDMS-2 and the TSFI were consistent or showed improvement throughout the Follow-Up phase. A GAS t-score of 77.14 indicated that the infant exceeded intervention goal expectations. CONCLUSIONS: Although our findings suggest that the HEP Approach intervention has promise in enhancing sensory functions, motor skill outcomes, and parental goals in an infant with TAPS and CP, further research is required to validate and apply these results more broadly.

The Homeostasis-Enrichment-Plasticity (HEP®) Approach for Premature Infants with Developmental Risks: A Pre-Post Feasibility Study.

Background: The environmental enrichment (EE) framework has inspired several early intervention (EI) approaches. This study evaluated the feasibility, safety, caregiver acceptance, and satisfaction of implementing the HEP Approach intervention, a novel EI model based on the EE paradigm. Outcome measures for motor development, individual functional goals, sensory functions, caregiver-provided environmental affordances, and motivation for movement were examined. Methods: A pre-post-study design examined 18 premature infants (<33 weeks six days gestation) with a corrected age of 4-10 months. A 21-item Likert scale survey assessed the feasibility, safety, acceptability, and satisfaction of implementing the HEP Approach intervention. The Peabody Developmental Motor Scales-2, Test of Sensory Functions in Infants, Affordances in the Home Environment for Motor Development, and Infant Movement Motivation Questionnaire were used for outcomes. The goal attainment scale measured progress toward parent goals. The HEP Approach consisted of 12 one-hour sessions implemented over three months. Results: Most participating parents found the HEP Approach intervention feasible, safe, acceptable, and satisfactory. GAS scores demonstrated significant gains with a mean t-score of 67.75 (SD = 2.00). Results found significant improvement (p ≤ 0.05) in all outcome measures. Conclusions: Results suggest that the HEP Approach intervention is safe, feasible, and acceptable to implement. Outcome measures were meaningful and sensitive in identifying improved motor development, individualized parental goals, sensory functions, caregivers' use of environmental opportunities, and movement motivation in premature at-risk infants. Results suggest further studies on the HEP Approach are feasible, and highlight the potential of this intervention to inspire and guide future research in this field.

Turkish Translation/Cultural Adaptation and Psychometric Analyses of the Affordances in the Home Environment for Motor Development-Infant Scale (AHEMD-IS).

In this study we translated the Affordances in the Home Environment for Motor Development-Infant Scale (AHEMD-IS) into Turkish, adapted the instrument culturally, examined its psychometric properties within a Turkish population, and identified its limitations. We administered the AHEMD-IS to families of 65 premature or full-term Turkish infants and repeated this testing for 17 families after one-two weeks to establish test-retest reliability. We calculated the Intraclass Correlation Coefficient (ICC) and Cronbach alpha coefficient to assess reliability, and we evaluated test validity using the Spearman's correlation coefficient and correlations with the Bayley-III motor development score. The Cronbach Alpha coefficient of the questionnaire was 0.846, and, for test-retest reliability, the ICC score was 0.830. The Turkish AHEMD-IS total score was moderately correlated with the Bayley-III fine motor development score (r = 0.469, p < 0.001), the Bayley-III gross motor development score (r = 0.533, p < 0.001), and the Bayley-III total motor development score (r = 0.526, p < 0.001). The Turkish version of the AHEMD-IS was found to be valid and reliable for children born prematurely or at full-term. The use of this questionnaire in Turkey will facilitate the creation of a home environment that will support motor development in children between 3-18 months of age.

Evaluation of Ayres Sensory Integration® Intervention on Sensory Processing and Motor Function in a Child with Rubinstein-Taybi Syndrome: A Case Report.

The Rubinstein-Taybi Syndrome (RSTS) literature is limited about sensory integration, which is a foundational neurological function of the central nervous system that may affect the development of cognitive, social, and motor skills. The aim of this case report was to investigate the effects of Ayres Sensory Integration® (ASI) intervention on processing and integrating sensations, motor functions and parental goals of 3-year-old child with RSTS. Analysis of assessment data reviewed before and after treatment. Assessment collected by interview, Sensory Profile (SP), Sensory Processing Measure-Preschool (SPM-P) Home, Peabody Developmental Motor Scales-2 (PDMS-2), Gross Motor Function Measurement-88 (GMFM-88), and Gross Motor Function Classification System (GMFCS). Progress toward goals and objectives was measured with Goal Attainment Scale (GAS). ASI intervention was implemented 3 times per week for 8 weeks. At pre-intervention, SP and SPM-P Home revealed prominent sensory processing and integration difficulties in this case. PDMS-2 scores indicated the child was far behind his peers in fine and gross motor areas. In addition, systematic observations determined that the child's GMFCS level was III. After 8 weeks of ASI intervention significant improvements were found in parent reports of sensory processing in the areas of vestibular, tactile, and oral functioning on the Sensory Profile. Gains in functional motor skills were found on the GMFM-88 and the GMFCS. Consistent with these results, significant gains at or above expected levels of performance were found on GAS goals which reflected the family's main concerns for social participation, feeding, play, and movement. There are limited studies on sensory processing and integration in children with RSTS. This case report identified sensory processing and integration difficulties for the first time in a child with RSTS. Results also provide preliminary support for the positive effects of ASI intervention on sensory processing, functional motor skills, and parental goals of a child with RSTS.

Effects of Postnatal Caffeine Exposure on Absence Epilepsy and Comorbid Depression: Results of a Study in WAG/Rij Rats.

The present study aims to investigate effect of early caffeine exposure on epileptogenesis and occurrence of absence seizures and comorbid depression in adulthood. For this purpose, Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats were enrolled in a control and two experimental groups on the 7th day after the delivery. The rats in experimental groups received either 10 or 20 mg/kg caffeine subcutaneously while animals in control group had subcutaneous injections of 0.9% saline. The injections started at postnatal day 7 (PND7) and were continued each day for 5 days. At 6-7 months of age, electroencephalogram (EEG) recordings and behavioral recordings in the forced swimming test, sucrose consumption/preference test and locomotor activity test were carried out. At 6 months of age, 10 mg/kg and 20 mg/kg caffeine-treated WAG/Rij rats showed increased immobility latency and active swimming duration in forced swimming test when compared with the untreated controls. In addition, 20 mg/kg caffeine treatment decreased immobility time. In sucrose preference/consumption tests, WAG/Rij rats in 10 mg/kg caffeine group demonstrated higher sucrose consumption and preference compared to untreated controls. The rats treated with 20 mg/kg caffeine showed higher sucrose preference compared to control rats. The exploratory activity of rats in the 10 mg/kg caffeine-treated group was found to be higher than in the 20 mg/kg caffeine-treated and control groups in the locomotor activity test. At 7 months of age, caffeine-treated animals showed a decreased spike-wave discharge (SWD) number compared to the control animals. These results indicate that postnatal caffeine treatment may decrease the number of seizure and depression-like behaviors in WAG/Rij rats in later life. Caffeine blockade of adenosine receptors during the early developmental period may have beneficial effects in reducing seizure frequency and depression-like behaviors in WAG/Rij rat model.

Neonatal Tactile Stimulations Affect Genetic Generalized Epilepsy and Comorbid Depression-Like Behaviors.

Recent studies suggest that development of absence epilepsy and comorbid depression might be prevented by increased maternal care of the offspring, in which tactile stimulation induced by licking/grooming and non-nutritive contact seem to be crucial. In this study, we aimed to evaluate the effect of neonatal tactile stimulations (NTS) on absence epilepsy and depression-like behaviors in adulthood. Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat pups with a genetic predisposition to absence epilepsy were divided into tactile stimulation (TS) group, deep touch pressure (DTP) group, maternal separation (MS) group or control group. Between postnatal day 3 and 21, manipulations (TS, DTP, and MS) were carried out for 15 min and three times a day. Animals were submitted to locomotor activity, sucrose consumption test (SCT) and forced swimming test (FST) at five months of age. At the age of six months, the electroencephalogram (EEG) recordings were conducted in order to quantify the spike-wave discharges (SWDs), which is the hallmark of absence epilepsy. The TS and DTP groups showed less and shorter SWDs in later life in comparison to maternally separated and control rats. SWDs' number and total duration were significantly reduced in TS and DTP groups whereas mean duration of SWDs was reduced only in DTP group (p < 0.05). TS and DTP also decreased depression-like behaviors measured by SCT and FST in adult animals. In the SCT, number of approaches was significantly higher in TS and DTP groups than the maternally separated and control rats. In the FST, while the immobility latency of TS and DTP groups was significantly higher, only TS group showed significantly decreased immobility and increased swimming time. The results showed that NTS decreases both the number and length of SWDs and the depression-like behaviors in WAG/Rij rats probably by increasing arousal level and causing alterations in the level of some neurotrophic factors as well as in functions of the neural plasticity in the developing rat's brain.