Uri Alyagon

Fear-related pictures deteriorate the performance of university students with high fear of snakes or spiders

Despite research regarding emotional processing, it is still unclear whether fear-evoking stimuli are processed when they are irrelevant and when attention is oriented elsewhere. In this study, 63 healthy university students with high fear from snakes or spiders participated in two different experiments. In an emotional modification of the spatial cueing task, 31 subjects (5 males) were asked to detect a target letter while ignoring a neutral or fear-related distracting picture. The distribution of attention was independently manipulated by a spatial cue that preceded the appearance of the picture and the target letter. In an emotional modification of the cognitive load paradigm, 32 subjects (4 males) were asked to discriminate between two target letters, while ignoring a central neutral or fear-related picture, and additional 1, 3, or 5 distracting letters that created a varied attentional load. Fear-related pictures interfered with the performance of highly fearful participants, even when the pictures were presented outside the focus of attention and when the task taxed attentional resources. We suggest that highly fearful individuals process fear-related information automatically, either inattentively or with prioritized attention capture over competing items, leading to deteriorated cognitive performance. Different results were shown in healthy individuals while processing negative—but not phobic—pictures, suggesting that emotional processing depends on the fear value of the stimulus for a specific observer.

Prelimbic Stimulation Ameliorates Depressive-Like Behaviors and Increases Regional BDNF Expression in a Novel Drug-Resistant Animal Model of Depression.

BACKGROUND Approximately one third of all major depression patients fail to respond to conventional pharmacological antidepressants, and brain stimulation methods pose a promising alternative for this population. Recently, based on repeated multifactorial selective inbreeding of rats for depressive-like behaviors, we introduced a novel animal model for MDD. Rats from this Depressive Rat Line (DRL) exhibit inherent depressive-like behaviors, which are correlated with lower levels of brain-derived neurotrophic factor (BDNF) in specific brain regions. In addition, DRL rats do not respond to antidepressant medication but respond to electroconvulsive treatment, and they can thus be utilized to test the effectiveness of brain stimulation on hereditary, medication-resistant depressive-like behaviors. OBJECTIVE To test the effect of sub-convulsive electrical stimulation (SCES) of the prelimbic cortex, using TMS-like temporal pattern of stimulation, on depressive-like behaviors and regional BDNF levels in DRL rats. METHODS SCES sessions were administered daily for 10 days through chronically implanted electrodes. Temporal stimulation parameters were similar to those used in TMS for major depression in human patients. Depressive-like behaviors were assayed after treatment, followed by brain extraction and regional BDNF measurements. RESULTS SCES normalized both the depressive-like behaviors and the reduced BDNF levels observed in DRL rats. Correlation analyses suggest that changes in specific behaviors are mediated, at least in part, by BDNF expression in reward-related brain regions. CONCLUSIONS Brain stimulation is effective in a drug-resistant, inherited animal model for depression. BDNF alterations in specific regions may mediate different antidepressant effects.

Right Prefrontal Deep Tms Effects On Attention Symptoms: Behavioral Outcomes and Electrophysiological Correlates

Introduction Despite its high prevalence, the validated treatment for ADHD is chronic administration of psychostimulants, which is associated with side effects and occasionally not tolerated. Deep TMS using special coil designs for targeting neural networks linked with neuropsychiatric disorders, may become a viable alternative. Objectives Comparison of rTMS treatment using deep, figure-8 and sham coils on ADHD symptoms. Methods In the current randomized, sham-controlled study, adult ADHD patients received 15 daily sessions of high-frequency rTMS directed to the right prefrontal cortex (rPFC), using either deep, figure-8, or a sham coil. ADHD symptoms and cognitive alterations were assessed using the CAARS-INV, self–report questionnaires and performance tests. Additionally, the stop signal task (SST) combined with EEG measures was used to asses behavioural inhibition and ERPs. EEG responses to an inhibitory protocol of paired TMS pulses over the rPFC were measured before and after treatments. A healthy control group was evaluated at baseline for comparison. Results Several ADHD symptoms were improved in patients that received dTMS but not standard figure-8 or sham treatment (p=0.007, CAARS; p=0.014, SST). Differences between ADHD patients and healthy controls were demonstrated in ERPs during the SST, and in response to single and paired TMS pulses. The lower amplitudes of ERPs in patients correlated with ADHD symptoms and behavioural inhibition measures. Conclusions Repeated stimulation of deep areas in the rPFC has therapeutic potential, where rPFC excitability is impaired in ADHD patients. Ongoing analysis attempts to establish the neurophysiological measures as predictors and biomarkers for effectiveness of dTMS treatment.

Answering the missed call: Initial exploration of cognitive and electrophysiological changes associated with smartphone use and abuse

Background Smartphone usage is now integral to human behavior. Recent studies associate extensive usage with a range of debilitating effects. We sought to determine whether excessive usage is accompanied by measurable neural, cognitive and behavioral changes. Method Subjects lacking previous experience with smartphones (n = 35) were compared to a matched group of heavy smartphone users (n = 16) on numerous behavioral and electrophysiological measures recorded using electroencephalogram (EEG) combined with transcranial magnetic stimulation (TMS) over the right prefrontal cortex (rPFC). In a second longitudinal intervention, a randomly selected sample of the original non-users received smartphones for 3 months while the others served as controls. All measurements were repeated following this intervention. Results Heavy users showed increased impulsivity, hyperactivity and negative social concern. We also found reduced early TMS evoked potentials in the rPFC of this group, which correlated with severity of self-reported inattention problems. Heavy users also obtained lower accuracy rates than nonusers in a numerical processing. Critically, the second part of the experiment revealed that both the numerical processing and social cognition domains are causally linked to smartphone usage. Conclusion Heavy usage was found to be associated with impaired attention, reduced numerical processing capacity, changes in social cognition, and reduced right prefrontal cortex (rPFC) excitability. Memory impairments were not detected. Novel usage over short period induced a significant reduction in numerical processing capacity and changes in social cognition.

Interhemispheric cortico-cortical paired associative stimulation of the prefrontal cortex jointly modulates frontal asymmetry and emotional reactivity

BACKGROUND As advances in neuroimaging further our understanding of the brains functional connectivity, neuropsychology has moved away from a regional approach of attributing behavior to a specific region towards a network approach, attributing behavior to interconnected regions. A prime example of this is the suggested relevance of frontal asymmetry of the lateral prefrontal cortex (LPFC) in emotional processing. Yet, while neuroimaging defines relevant networks, it can only establish correlations and not causality. OBJECTIVE We address this deficiency by applying cortico-cortical paired associative stimulation (ccPAS) to twenty-seven healthy, human participants (both genders represented equally). ccPAS involves TMS applied to two brain regions contemporaneously, changing the connectivity via Hebbian mechanisms. METHODS We evaluate modifications in connectivity following ccPAS between the right and left LPFC that are dependent on the direction of ccPAS, i.e., which hemisphere is stimulated first. Participants performed an emotional reactivity task, assessed by measuring attentional bias, and brain activity was recorded with electroencephalogram (EEG) both at rest and in response to TMS pulses. RESULTS We find that ccPAS modulates attentional bias bidirectionally depending on the order of stimulation. Furthermore, this modulation is accompanied by a change in frontal asymmetry. Measuring the direction of the information flow using TMS evoked potentials provides evidence that ccPAS strengthens inhibition from the hemisphere stimulated first to the hemisphere stimulated second. CONCLUSIONS Our findings provide causal evidence for the role of frontal asymmetry in emotional processing and establish ccPAS combined with the EEG measures as a tool to causally characterize functionality of neuronal circuits.

Deep transcranial magnetic stimulation of the anterior cingulate cortex in obsessive compulsive disorder patients

Objective: Evaluate whether dTMS targeting the medial prefrontal and the anterior cingulate cortices influences symptom severity in obsessive compulsive disorder (OCD). Background: Converging evidence points toward the involvement of a dysfunctional cortico-striato-thalamo-cortical (CSTC) circuit in OCD. Transcranial magnetic stimulation (TMS) has been applied to treat and investigate OCD. However, conventional TMS coils lack the ability to target the CSTC circuits directly and treatment protocols for OCD showed diversified results. The use of dTMS coils allows direct stimulation of deeper neuronal pathways relative to those affected by conventional TMS coils. We evaluated whether dTMS targeting the medial prefrontal and the anterior cingulate cortices may influence symptom severity. Methods: Forty OCD patients were treated with either dTMS H7/ HAC high (20 Hz) or low (1 Hz) stimulation frequencies or sham coil daily for five weeks in a double blind controlled study. OCD symptoms were provoked in each patient in order to activate the OCD circuitry before treatment. EEG measurements were taken at baseline and at the end of treatment. Results: The active 20 Hz dTMS group improved significantly in YBOCS score compared to the 1 Hz and sham groups (26 vs. 6% reduction), {t (93) = -2.29 (p = 0.0243)} with three month durability. EEG evoked responses over the anterior cingulate cortex correlated with clinical response, providing an objective measure, or biomarker of dTMS efficacy. Conclusions: High frequency dTMS treatment with the H7 coil, targeting the medial prefrontal and anterior cingulate cortices, is a promising therapeutic intervention in OCD. Disclosure: Drs. Zangen, Alyagon and Tendler have a financial interest in Brainsway.