1. Emotional Disturbances between and during Epileptic Seizures Παρουσίαση: Μαρία Νικήτα 8 Ιουνίου 2012 Συγκίνηση και Νόηση

2. Partial Epilepsies – Emotional Disturbances Seizures have a focal onset – do not spread through the entire brain ex. Temporal lobe epilepsy – Frontal lobe epilepsy ~50% of temporal lobe epileptics  interictal emotional disturbances  fear, anxiety, depression, schizophrenic episodes During focal seizures  modification of behaviour and emotional state  intense agitation, screaming, facial expressions of rage, fear or anger

3. Precise anatomical origins of seizures that produce ictal and interictal emotional behaviour  not fully understood Mechanisms by which the epileptic discharges provoke these clinical phenomena  unknown Why + How

4. Long-term Amygdala Kindling in Rats as a Model for the Study of Interictal Emotionality in Temporal Lobe Epilepsy Kalynchuk, 2000

5. Animal Model - - Kindling model of temporal lobe epilepsy Kindling model of temporal lobe epilepsy  animal model of interictal changes in emotional behaviour  facilitate the study… Kindling  periodic administration of initially subconvulsive stimulations to certain brain structures results in the development and progressive intensification of limbic motor seizures Most often modeled  changes in fear and anxiety-like behaviour Rats kindled by amygdala stimulation  valid models of human partial seizures

6. Short-term Amygdala Kindling Enough stimulations (15-25  rats) to induce 3 consecutive generalized convulsions. Alterations in interictal emotional behaviour  related to changes in fear or anxiety-like behaviour (monkeys, cats, rats) + : assess behavioural changes at a stage in kindling before after-discharges become generalized – : animals partially kindled  findings may not directly relate to temporal lobe epilepsy / results not consistent / does not relate closely enough to the chronic epileptic state

7. Long-term Amygdala Kindling 100 stimulations in rats  well kindled but not displaying spontaneous seizures which would confound the behavioral testing Powerful model for the study of the interictal fear and anxiety Kindled rats: freeze in an unfamiliar open field resist being captured from an unfamiliar open field attempt escape from an unfamiliar elevated plus maze engage in active defensive behavior in a resident-intruder paradigm 20  60  100 stimulations  defensive reactions increase final stimulation of 100  defensive reactions persist > 2mo greater defensive reactions in amygdala- and hippocampal- kindled than in caudate-kindled rats

8. Kindling – Human Temporal Lobe Epilepsy Diversity of interictal emotionality  patient’s environment, cerebral hemisphere of epileptic focus, structural lesions, pharmacological treatment

9. Acute Alteration of Emotional Behaviour in Epileptic Seizures is related to Transient Desynchrony in Emotion-Regulation Networks Bartolomei et al., 2005

10. Methods (1) – Hypothesis 3 patients with partial drug-resistant epilepsy – seizures included intense emotional behavioral alterations as the main clinical semiology electrodes were placed to record from the: Hypothesis: the emergence of ictal emotional behaviour may correspond to acute dysfunction of the normal synchrony of emotional networks (  modification in the interactions between brain structures that take place during the first few seconds of the seizure) frontal lobecingulate gyrus dorsolateral prefrontal cortex orbitofrontal cortexpremotor regions amygdalatemporal pole

11. Methods (2)

12. EEG ictal period compared with an EEG period remote from the seizure onset Methods (3) Interdependencies (synchrony) between brain regions known to be involved in “emotional networks”

13. Most constant feature observed in 3 patients  decorrelation between orbitofrontal cortex and amygdala, just before the emergence of emotional behavior change Results (1)

14. Davidson et al., 2000: OFC, Amygdala  involved in the regulation of anger and aggressive behaviour Results (2) Davidson et al., 2000: inhibitory connection from OFC to the amygdala is 1mechanism underlying the suppression of negative emotion Blair, 2001: lesions of the OFC produce symptoms characterized by aggression and impulsivity Propose  occurrence of intense ictal emotional behaviour disturbance in frontal lobe seizures is related to a disruption of the normal mechanisms of emotional regulation, in particular those governed by the functional connections between OFC and amygdala.

15. Further research has to be made on ictal and interictal emotional disturbances Overall Conclusions Animal models facilitate the study of the interictal emotional disturbances, but caution must be exercised in directly applying the results of studies on animals to the human epileptic condition Interictal emotional disturbances can be more troublesome for patients than the seizures themselves