Prefrontal Cortex

1. Prefrontal Cortex Catherine McGuane Janice Herbert Mackenzie Halter Kelly Zepf Lajasha Brooke

2. Background Movie • http://youtu.be/j2A1nZwE4ac?t=5m25s

3. Structure Mackenzie Halter

4. Location • Anterior of the frontal lobe • In front of motor and premotor areas • Brodmann areas 8-11, 44-47 • Input from the dorsomedial nucleus of the thalamus and brainstem arousal systems • Blood supply from the anterior cerebral artery and middle cerebral artery

5. Development • Does not fully develop until around age 25 • Brain develops fromthe back of the brain forward • Less white matter (myelin) in young adults • Myelin: fatty substance that covers axons, speeds up brain’s communication

6. Definition #1 • Granular frontal cortex: this areas has a cortical granular layer IV • based on cytoarchitectonics • Layer 4 in the subdivision of the mammalian cortex into 6 layers • Jacobsen (1935) used this definition of the prefrontal cortex as granular to distinguish the the prefrontal area from the agranular motor and premotor areas • Nonprimates have a prefrontal cortex but no cortical granular layer IV

7. Definition #2 • Projection zone of the mediodorsal nucleus of the thalamus • Rose and Woolsey (1948) showed that this area projected to mediodorsal nucleus of thalamus in both primates and nonprimates, but termed area as “orbitofrontal zone” • Akret (1964) used prefrontal cortex to define the structures in this area as homologous • Projections of mediodorsal nucleus of thalamus not restricted to granular frontal cortex • Prefrontal cortex as region of cortex that has stronger connection with mediodorsal nucleus than any other thalamic nucleus

8. Definition #3 • Part of the frontal cortex whose electrical stimulation does not evoke movements • David Ferrier (1890) • The electrically “silent” frontal cortex has granular and non-granular areas

9. 3 Divisions • Dorsolateral Prefrontal Cortex (DLPFC) • Ventromedial Prefrontal Cortex • Orbitofronal Cortex (OFC) • All differ in cytoarchitecture

10. Dorsolateral Prefrontal Cortex • Brodmann areas 9-12, 45-46and superior part of 47 • Receive blood supply from the middle cerebral artery • Connected to orbitofrontal cortex, thalamus, dorsal caudate nucleus, hippocampus, and posterior temporal, parietal, occipital areas (areas involved with attention, cognition, action) • Input from dopaminergic cells in tegmentum • Last to myelinate in the human brain

11. Ventromedial Frontal Cortex • Brodmann area 10 • Anterior Prefrontal Cortex, Rostral Prefrontal Cortex, Frontopolar Prefrontal Cortex • Sometimes part of the cingulate cortex • Sometimes refers to areaabove medial orbitofrontalcortex, sometimes broad area in ventral medial region of prefrontal cortex • Connects to regions involved with emotion, medial longitudinal fasciculus in white matter of the STS, multisensory areas of STS, ventral region of insula, amygdala, anterior STS

12. Orbitofrontal Cortex • Brodmann area 10, 11, 47 in humans; 11, 12, 13 in non-human primates • Receives projections from magnocellular medial nucleus and mediodorsal thalamus • Connects with primary sensory and association cortices, limbic systems,nucleus accumbens • Input from temporal lobe, amygdala, gustatory cortex, somatosensory cortex, olfactory cortex, dopaminergic cells in tegmentum • Projects to hypothalamus and amygdala

13. Pyramidal Neurons • Type of neuron found in the brain • Found by Santiago Ramón y Cajal • Triangular shape of soma, cell body • Single axon and dendritic spines • Primary excitation units of mammalian prefrontal cortex • Many different sensory modalities, so process many different types of input • Located on cerebral cortex (outer layer) • Implicated for cognitive ability

14. Executive and Cognitive Functions Kelly Zepf

15. Studies of Fuster and Goldman-Rakic • Joaquin M. Fuster is a neuroscientist whose research has made a major contributions to the understanding of neural structures involving cognition and behavior. • Patricia Goldman-Rakic was an American neuroscientist/neurobiologist known for her study of the frontal lobe and her work on the cellular basis of working memory. • Emphasized the fundamental ability of the prefrontal cortex to represent information not currently in the environment • Central role: create the “mental sketch pad”

16. Goldman-Rakic: “Mental Sketch Pad” • Representational knowledge used to intelligently guide thought, action, and emotion, including the inhibition of inappropriate thoughts, distraction, actions, and feelings. • Allowing us abstract reasoning, high order decision making, working memory, and thoughtful regulation of attention, behavior and emotion.

17. Fuster’s Findings • Prefrontal ability allows the wedding of past to future • Allowing both cross-temporal and cross-modal associations in the creation of goal-directed, and perception-action cycles

18. Dynamic Filtering Theoryby Shimamura • The PFC is presumed to act as a high-level gating or filtering mechanism that enhances goal-directed activations and inhibits irrelevant activations • The filtering mechanism: enables executive control at various levels of processing, including selecting, maintaining, updating, and rerouting activations • Also used to explain emotion regulation

19. Integrative Theory of Prefrontal Cortex Functionby Miller and Cohen • Arises from the work of Fuster and Goldman-Rakic • Theorize that “cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represents goals and means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task”

20. Top-Down Processing • When behavior is guided by internal states or intentions • According to Miller and Cohen, “The PFC is critical in situations when the mappings between sensory inputs, thoughts, and actions either are weakly established relative to other existing ones or are rapidly changing” • This can be showed in Wisconsin Card Sorting Test

21. Wisconsin Card Sort Subjects engaging in this task are instructed to sort cards according to the shape, color, or number of symbols appearing on them The thought is that any given card can be associated with a number of actions and no single stimulus-response mapping will work. Humans with damage to the PFC are able to sort the card in the initial simple tasks, but unable to do so as the rules of classification change.

22. Miller and Cohen • The Prefrontal cortex plays a large role in guiding control of cognitive actions • They claim that, “depending on their target of influence, representations in the PFC can function variously as attention templates, rules, or goals by providing top-down bias signals to other parts of the brain that guide the flow of activity along the pathways needed to perform a task.” (Miller and Cohen)

23. Pre Frontal Cortex Function Facts • Since the prefrontal cortex is the brain center responsible for taking in data through the body's senses and deciding on actions, it is most strongly implicated in human qualities like consciousness, general intelligence, and personality. • Regulates thought in terms of both short-term and long-term decision making. • Allows humans to plan ahead and create strategies • Also to adjust actions or reactions in changing situations • Helps to focus thoughts, which enables people to pay attention, learn and concentrate on goals

24. Disorders Catherine McGuane

25. Damage to the Prefrontal Cortex • Phineas Gage • large iron rod through frontal lobe • retained normal memory, speech and motor skills, his personality changed radically • irritable, quick-tempered, and impatient. • Socially inappropriate at times • Patients with lesions in the prefrontal cortex may behave inap­propriately in public, violating social rules such as personal space maintenance, social contracts, or inappropriate verbalizations.

26. Disorders: Bipolar • Evidence for a failure in the prefrontal cortex modulation of anterior limbic structures such as amygdala resulting in emotional dysregulation in bipolar disorder. • Medial Prefrontal Cortex (MPFC) has been said to have connections to the limbic circuit and surrounding prefrontal cortical regions and has been suggested to contribute to the emotional regulation impairment in bipolar disorder. Effective connectivity between MPFC and amygdala has been shown to differentiate bipolar disorder from major depression patients.

27. Disorders: Autism • Autism impairs the development of social behavior, emotions and communication. The prefrontal cortex plays an important role in the early development of these skills and displays abnormal growth and function in children with autism. Studies conclude: • atypical architecture of neurons in the prefrontal cortex. This architecture may be a common neural defect that predisposes a child to developing autism. • In another experiment, the researchers found 67 percent more neurons in the prefrontal cortex of young boys (aged 2 to 16 years) with autism than in age-matched controls.

28. Present day examples Janice Herbert

29. Adolescents • The prefrontal cortex is one of the last regions of the brain to reach maturation during adolescents. • With an immature prefrontal cortex, even if teens understand that something is dangerous, they may still go ahead and engage in the risky behavior. • In other words, key areas of the brain are still under construction during the adolescent years, and are more sensitive to the toxic effects of drugs and alcohol.

30. Binge Drinking • University of California in San Diego compared the brain scans of teens who drink heavily with the scans of teens who don't. • Researchers believe this damage negatively affects attention span in boys, and girls' ability to comprehend and interpret visual information. • http://www.youtube.com/watch?v=g2gVzVIBc_g The red specks highlight where the integrity of the brain's white matter is significantly less in the teens who binge drink, compared to those who do not.

31. Treatments for teenagers • Group Counseling • Academic Education • Family Counseling • Medical Treatment

32. Addiction

34. STRESS • “Stress-induced alterations in prefrontal cortical” – Article, stress has have been implicated clinically in the pathogenesis of mental illness. • Treatment: Intervention strategies like meditation and other contemplative practices 

35. Research articles Lajasha Brooke

36. Impairment of social & moral behavior related to early damage in human prefrontal cortex • Steven Anderson, Antoine Bechara, Hanna Damasion, Daniel Tranel & Anotnio R. Damasio (1999, Nature) • Early prefrontal cortex lesions occurring before 16 months were investigated in two adults • Compares adults with early prefrontal cortex damage and adult onset prefrontal cortex damage • Early onset prefrontal damage resulted in a syndrome resembling psychopathy • Defective social and moral reasoning suggests that complex social conventions and moral rules had been impaired

37. Subjects • Data obtained from medical and school records, as well as legal documentations, interviews and clinical and experimental cognitive tasks • Patient A – 20 year old female • Run over by a vehicle at 15 months • First behavioral abnormalities noted at 3 years of age – unresponsive to verbal or physical punishment • Entered first treatment facility at age 14 • Patient B – 23 year old male • Resection of a right frontal tumor at 3 months • At age 9 – showed general lack of motivation, had limited social interaction and brief yet explosive outbursts of anger • Both patients raised in stable, middle-class family homes with no evidence of neurologic or psychiatric disease in family history

38. Neuropsychological Evidence • Patients were asked to perform several cognitive tasks designed to asses heir ability to plan and execute multistep procedures, reason through social dilemmas and generate appropriate responses to social situations • Wisconsin Card Sorting tests • Both subjects failed to show normal learning of rules and strategies from repeated experience and feedback • Moral reasoning tests • Patients demonstrated limited consideration of the social and emotional implications of decisions • Failed to identify the primary issues involved in social dilemmas • Generated few response options for interpersonal conflicts • Gambling Task – Decision making • Both patients failed to develop a preference for the advantageous response option • Failed to choose options with low immediate reward but positive long term gain • Persisted in choosing options which provided immediate reward but higher long term success

39. Results and Points for Further Research • Lesion in subject A was bilateral and involved the polar and ventromedial prefrontal sectors • Lesion in Subject B was unilateral located in the right prefrontal region, and involved in the polar sector both medially and dorsally • The lesions of both patients were located in sites whose damage is known to produce the emotional and decision making defects seen in the study results • Dysfunction in the medial prefrontal cortices can be caused by direct damage or white matter undercutting – point for further research