Abigail Livny

New developments in brain research of internet and gaming disorder

There is evidence that the neural mechanisms underlying Internet Gaming Disorder (IGD) resemble those of drug addiction. Functional Magnetic Resonance Imaging (fMRI) studies of the resting state and measures of gray matter volume have shown that Internet game playing was associated with changes to brain regions responsible for attention and control, impulse control, motor function, emotional regulation, sensory-motor coordination. Furthermore, Internet game playing was associated with lower white matter density in brain regions that are involved in decision-making, behavioral inhibition and emotional regulation. Videogame playing involved changes in reward inhibitory mechanisms and loss of control. Structural brain imaging studies showed alterations in the volume of the ventral striatum that is an important part of the brains reward mechanisms. Finally, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and lower dopamine transporter and dopamine receptor D2 occupancy indicating sub-sensitivity of dopamine reward mechanisms.

Brain Imaging Studies on the Cognitive, Pharmacological and Neurobiological Effects of Cannabis in Humans: Evidence from Studies of Adult Users

Cannabis is the most widely used illicit drug worldwide. Regular cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, psychotic symptoms and neurocognitive impairments and their neural mechanisms need to be examined. This review summarizes and critically evaluates brain-imaging studies of cannabis in recreational and regular cannabis users between January 2000 and January 2016. The search has yielded eligible 103 structural and functional studies. Regular use of cannabis results in volumetric, gray matter and white matter structural changes in the brain, in particular in the hippocampus and the amygdala. Regular use of cannabis affects cognitive processes such as attention, memory, inhibitory control, decision-making, emotional processing, social cognition and their associated brain areas. There is evidence that regular cannabis use leads to altered neural function during attention and working memory and that recruitment of activity in additional brain regions can compensate for it. Similar to other drugs of abuse, cannabis cues activated areas in the reward pathway. Pharmacological studies showed a modest increase in human striatal dopamine transmission after administration of THC in healthy volunteers. Regular cannabis use resulted in reduced dopamine transporter occupancy and reduced dopamine synthesis but not in reduced striatal D2/D3 receptor occupancy compared with healthy control participants. Studies also showed different effects of Δ-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on emotion, cognition and associated brain regions in healthy volunteers, whereby CBD protects against the psychoactive effects of THC. Brain imaging studies using selective high-affinity radioligands for the imaging of cannabinoid CB1 receptor availability in Positron Emission Tomography (PET) showed downregulation of CB1 in regular users of cannabis. In conclusion, regular use of the cannabinoids exerts structural and functional changes in the human brain. These changes have profound implications for our understanding of the neuropharmacology of cannabis and its effects on cognition, mental health and the brain.

Cognitive Deficits Post-Traumatic Brain Injury and Their Association with Injury Severity and Gray Matter Volumes

Traumatic brain injury (TBI) is known to have a substantial though highly variable impact on cognitive abilities. Due to the wide range of cognitive abilities among healthy individuals, an objective assessment of TBI-related cognitive loss requires an accurate measurement of pre-morbid cognitive performance. To address this problem, we recruited 50 adults who sustained a TBI and had performed a cognitive baseline assessment in adolescence as part of the aptitude tests mandated by the Israeli Defense Forces. This group was matched with non-injured controls (n = 35). Pre- and post-injury cognitive assessments consisted of three domains-namely, verbal abstraction, mathematical reasoning, and non-verbal abstract reasoning (from the Wechsler Adult Intelligence Scale-Third Edition). The difference between post- and pre-injury scores was calculated as a measure of domain-specific cognitive decline. Voxel-based regression was used to correlate cognitive decline with modulated gray matter probability maps controlling for age, Glasgow Coma Scale, and total intracranial volume. Using objectively assessed cognitive scores, we found that abstract reasoning declined in both moderate-severe and mild TBI patients, whereas verbal abstraction declined only in the moderate-severe group. Mathematical reasoning was not affected by TBI. In the TBI patients, non-verbal abstract reasoning post-pre-injury change scores were negatively correlated with the volume of the insula. We conclude that access to pre-morbid neuropsychological data may have facilitated the discovery of the effects of mild TBI on abstract reasoning, as well as a significant correlation between TBI-related decline in this cognitive domain and the volume of the bilateral insula, both of which had not been appreciated in the past.

Long-Term Variability in Glycemic Control Is Associated With White Matter Hyperintensities in APOE4 Genotype Carriers With Type 2 Diabetes

OBJECTIVE We assessed whether the apolipoprotein ε4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA1c SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS WMH volume was generated from structural T1 and fluid-attenuated inversion recovery MRI in each subject. The analysis included 124 subjects; 27 (21.8%) had one or more APOE4 alleles. RESULTS HbA1c variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA1c, number of follow-up years, and a composite of cardiovascular risk factors, but not in noncarriers (r = −0.04, P = 0.71; P for interaction = 0.050). CONCLUSIONS The results suggest that the APOE4 genotype affects the relationship of long-term glycemic control with WMH load so that APOE4 carriers may be more vulnerable to the insults of poor control.

Haptoglobin 1-1 Genotype Modulates the Association of Glycemic Control With Hippocampal Volume in Elderly Individuals With Type 2 Diabetes

Recent evidence suggests that glycemic control is associated with cognitive function in older patients with type 2 diabetes who are carriers of the haptoglobin (Hp) 1-1 genotype compared with noncarriers. We assessed whether poor glycemic control in Hp 1-1 carriers is more strongly associated with smaller hippocampal volume than in noncarriers. Hippocampal volume was generated from high-resolution structural T1 MRI obtained for 224 participants (28 Hp 1-1 carriers [12.5%] and 196 noncarriers [87.5%]) from the Israel Diabetes and Cognitive Decline (IDCD) study, who had a mean (SD) number of years in the Maccabi Healthcare Services (MHS) registry of 8.35 (2.63) and a mean (SD) HbA1c level of 6.66 (0.73)% [49 mmol/mol]. A stronger negative association between right hippocampal volume and HbA1c was found in patients with the Hp 1-1 genotype, with a 0.032-mL decrease in right hippocampal volume per 14% increase in HbA1c (P = 0.0007) versus a 0.009-mL decrease in Hp 1-1 noncarriers (P = 0.047), after adjusting for total intracranial volume, age, sex, follow-up years in the registry, and cardiovascular factor (interaction, P = 0.025). This indicates that 29.66% of the total variance in right hippocampal volume is explained by HbA1c levels among Hp 1-1 carriers and that 3.22% is explained by HbA1c levels among Hp 1-1 noncarriers. Our results suggest that the hippocampus of Hp 1-1 carriers may be more vulnerable to the insults of poor glycemic control.

Age Modulates the Association of Caffeine Intake With Cognition and With Gray Matter in Elderly Diabetics

Background The association between caffeine and cognitive performance has not been tested in older individuals with type 2 diabetes (T2D). Its association with brain volume in T2D has been tested only in animals. Methods We examined the association of caffeine with cognitive function and brain volume in a sample of elderly diabetics participating in the Israel Diabetes and Cognitive Decline Study (n = 638) and the moderating effect of age on this association. In a subsample (n = 185) with magnetic resonance imaging, we also examined these associations with gray and white matter volumes (GM/WM). Results Using linear regression adjusting for cognition-related covariates, we found that higher caffeine intake was associated with better function in overall cognition (p = .018), attention/working memory (p = .002), executive functioning (p = .047), and semantic categorization (p = .026). Interaction analyses of caffeine intake with age were significant for semantic categorization (p = .025), and approached significance for overall cognition (p = .066). This association was driven by the older group (above-median) for whom the association of caffeine intake with semantic categorization (p = .001), attention/working memory (p = .007), executive functioning (p = .005), and overall cognition (p = .002) were significant. In the magnetic resonance imaging subsample, there was an interaction (p = .034) of caffeine intake with age for GM volume; in the older group, higher caffeine intake was associated with greater GM volume (β = .198, p = .033). Conclusions Caffeine intake may have a beneficial role in cognitive functioning of elderly adults with T2D, which may be moderated by age. Greater GM volume may be a mechanism underlying the association of higher caffeine intake with better cognitive function.

A pilot study of a novel therapeutic approach to obesity: CNS modification by N.I.R. H.E.G. neurofeedback

BACKGROUND & AIMS Despite the thorough mapping of brain pathways involved in eating behavior, no treatment aimed at modulating eating dysregulation from its neurocognitive root has been established yet. We aimed to evaluate the effect of N.I.R. H.E.G. (Near Infra-Red Hemoencephalography) neurofeedback training on appetite control, weight and food-related brain activity. METHODS Six healthy male participants with overweight or mild obesity went through 10 N.I.R. H.E.G. neurofeedback sessions designed to practice voluntary activation of the prefrontal cortex. Weight, eating behavior, appetite control and brain activity related to food and self-inhibition based on fMRI were evaluated before and after neurofeedback training. RESULTS Our study group demonstrated a positive trend of increased self-control and inhibition related to food behavior, reduced weight and increased activation during an fMRI response-inhibition task (Go-No-Go - GNG) in the predefined region of interest (ROI): superior orbitofrontal cortex (sOFC). CONCLUSIONS N.I.R. H.E.G. holds a promising potential as a feasible neurofeedback platform for modulation of cortical brain circuits involved in self-control and eating behavior and should be further evaluated and developed as a brain modifying device for the treatment and prevention of obesity.

ASSOCIATION OF STRUCTURAL RETINAL MARKERS WITH BRAIN STRUCTURE IN ASYMPTOMATIC INDIVIDUALS AT HIGH RISK FOR ALZHEIMER’S DISEASE

P3-217 ASSOCIATIONOF STRUCTURALRETINAL MARKERS WITH BRAIN STRUCTURE IN ASYMPTOMATIC INDIVIDUALS AT HIGH RISK FOR ALZHEIMER’S DISEASE Inbal Sharvit-Ginon, Michal Schnaider Beeri, Abigail Livny, Aron Weller, Ifat Sher, Ygal Rotenstreich, Ramit Ravona-Springer, Bar Ilan University, Ramat Gan, Israel; Sheba Medical Center, Ramat Gan, Israel; Department of Diagnostic Imaging and The Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat-Gan, Israel; Tel Aviv University, Tel Aviv, Israel. Contact e-mail: Ramit.Ravona@sheba.health. gov.il

Functional Plasticity in the Absence of Structural Change

This work presents a case of a young woman with apraxia and a severe body scheme disorder, 10 years after a childhood frontal and occipitoparietal brain injury. Despite specific limitations, she is independent in performing all activities of daily living. A battery of tests was administered to evaluate praxis and body representations. Specifically, the Hand Laterality Test was used to compare RS’s dynamic body representation to that of healthy controls (N = 14). Results demonstrated RS’s severe praxis impairment, and the Hand Laterality Test revealed deficits in accuracy and latency of motor imagery, suggesting a significant impairment in dynamic body representation. However, semantic and structural body representations were intact. These results, coupled with frequent use of verbalizations as a strategy, suggest a possible ventral compensatory mechanism (top-down processing) for dorsal stream deficits, which may explain RS’s remarkable recovery of activities of daily living. The link between praxis and dynamic body representation is discussed.

Haptoglobin genotype modulates the relationships of glycemic control with white matter hyperintensities in elderly with type 2 diabetes

P1-202 HAPTOGLOBIN GENOTYPE MODULATES THE RELATIONSHIPS OF GLYCEMIC CONTROLWITH WHITE MATTER HYPERINTENSITIES IN ELDERLY WITH TYPE 2 DIABETES Abigail Livny, Ramit Ravona-Springer, Anthony Heymann, Tammar Kushnir, Galia Tsarfaty, Leeron Rabinov, Reut Moran, Michal Beeri, Department of Diagnostic Imaging and The Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat-Gan, Israel; Department of Psychiatry and The Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat Gan, Israel; Maccabi Health Services, Tel-Aviv, Israel; Diagnostic Imaging Department, ShebaMedical Center, Ramat-Gan, Israel; The Joseph SagolNeuroscienceCenter, ShebaMedical Center, Ramat Gan, Israel; Department of PsychiatryMount Sinai School ofMedicine, New York, NY, USA; School of Psychology, The Interdisciplinary Center, Hertzlia, Israel. Contact e-mail: abigail.livnyezer@gmail.com