الفهرس 
Anatomy and functions of the frontal lobesOnly 14 pages are availabe for public view
 |  | from | 16 |  |  |
| | | from | 16 | | |
Abstract
Summary
Scientific understanding of the frontal lobes has greatly advanced, with the fields of neuropsychology, neuroimaging , and neuroscience all contributing to a rapidly changing perspective on the role of the frontal lobes in behavior and cognition. Not only are these advances important for understanding the neuroanatomy, neurophysiology, and neurochemistry of frontal lobe function, but they have also altered clinical approaches to the evaluation of patients with frontal lobe disorders.
The advents of functional neuroimaging and advances in the neurosciences have revolutionized understanding of the functional neuroanatomy of psychiatric disorders. Neurosurgical treatment of psychiatric disorders has been influenced by evolving neurobiological models of symptom generation.
The frontal regions of the brain control behaviors including planning and organization, motivation for goal-directed activity, weighing consequences of future actions and impulse inhibition, known collectively as executive functions.
The prefrontal cortex can be broadly subdivided into the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and medial prefrontal cortex (MPFC).
The medial prefrontal cortex including the anterior cingulate handles monitoring, evaluation, motivation, attention (vigilance), and switching. The dorsolateral prefrontal cortex plays a role in central executive and working memory. The orbitofrontal cortex is implicated in executive function and decision-making, exerts an inhibitory action on the activity of the anterior cingulated and is involved in the control of emotional, motivational, cognitive flexibility and social behavior.
The anterior cingulate is intimately involved in motivated behavior, and the principal behavioral product of anterior cingulate dysfunction is an amotivational apathetic state.
The frontal-cortical areas of the brain oversee behavioral control through executive functions. Executive functions include abstract thinking, motivation, planning, attention to tasks and inhibition of impulsive responses.
Executive functions are often invoked to override responses that have been automatically elicited. The frontal lobe executive functions receive input from all sensory modalities, integrate memories and using working memory of temporary information, assemble reward and valuation information with timing of events to carry out planned behaviors.
Impulsive behaviors result from impaired executive functions since they include actions that are poorly conceived, prematurely expressed, unduly risky or inappropriate to the situation, which often result in undesirable consequences.
Impulsivity is a feature of damage to the frontal lobe and an “acquired sociopathic” syndrome has been described following ventromedial frontal lobe lesions. This has lead to suggestions that impaired ventromedial frontal lobe function may contribute to poor impulse control in antisocial personality disorders.
The dorsal lateral prefrontal cortex and orbital frontal cortex is associated with behavioral regulation owing to its unique capacity to maintain and integrate sensory, affective, and associative information. These functions allow representation of expected outcomes, information that can in turn be used to guide behavior.
Damage to the orbital frontal cortex results in loss of this critical behavioral guide, producing profound deficits in self-regulation, as was first documented in the famous case of Phineas Gage, a railway worker who survived the passage of a tamping rod through his orbital frontal cortex after an accidental explosion. While the personality changes, especially disinhibition and increased inappropriate behavior (impulsiveness) that Gage experienced are the most frequently cited consequence of his injury, the physician who documented Gage’ case, John Harlow, also noted that Gage lost his ability to assign appropriate monetary value to objects. This deficit is consistent with the view that an essential function of the orbital frontal cortex is the flexible assignment of value to environmental stimuli, which critically determines how such stimuli influence our actions.
People with orbitofrontal cortex lesions are more impulsive compared to both normal controls and people with non-OFC frontal cortex damage, as measured by self-report and by cognitive/behavioral tasks.
The prefrontal cortex, including orbitofrontal gyri and the anterior cingulated cortex are important for executive functions. When properly functioning, the frontal lobes equip individuals with the capacity to use past experience and knowledge to make sense of current behavior and to guide future selection of responses from their behavioral repertoire.
The dorsolateral prefrontal circuit underlies executive function, which includes the control of attention, as well as the sustained organization of behavior to solve complex problems.
The dorsal lateral prefrontal cortex is essential to draw attention to important factors and to actively select goals. The medial prefrontal/cingulate circuit is critical for feedback monitoring and motivation, with lesions producing profound apathy.
Cases of frontotemporal dementia with orbital frontal cortex pathology are also marked by compulsive consummatory behaviors; including hyperphagia, gambling, and substance abuse.
The frontal lobes supervise cognitive tasks, such as memory, attention, and response selection. Intact control of response selection fundamentally underpins adaptive decision-making. Thus, decision-making impairments may be considered evidence of executive impairment.
Reciprocal connections between frontal-cortical brain regions, hippocampal–amygdala limbic brain areas and striatal regions regulate goal-directed behavior.
The frontal regions of the brain weigh consequences of future actions with the decisional balance requiring attention and activation of multiple brain circuits. The prefrontal cortex (dorsal lateral prefrontal cortex), includes as well as projects to anterior cingulate cortex (ACC) and the OFC with all 3 projecting to the ventral striatum (VS) a dopamine rich area important for expression of behaviors. dlPFC, ACC and OFC all contribute to executive functions and inhibition of impulses.
Researchers have suggested that the MFC, plays an important role in mentalizing . they proposed that the MFC is important for monitoring action, person perception, inferences about others’ thoughts, and outcomes related to punishments and rewards.
About possible neural correlates of mentalizing, the MFC, the superior temporal sulcus, the temporal–parietal junction, and the temporal poles (adjacent to the amygdala) are candidates serving social cognitive functions.
In contrast to the MFC, the lateral FC (LFC) is responsible for non-emotion-related cognitive processes. The literature suggests that the LFC is a key neural substrate of cognitive control for inhibiting a prepotent behavior, selecting a novel behavior, and selecting a response option when competition exists between more than one.
In clinical studies, damage to the LFC is associated with impaired selection of plans for behavior. Such patients are unable to choose between possible alternatives, preferring well-practiced behaviors regardless of context.
A growing body of evidence from both neuroimaging and lesion studies has shown that the prefrontal cortex plays an important role in ToM. Impairment in social cognition or decision making has long been recognized as a commonly observed effect of prefrontal cortex damage. Many studies have shown that patients with both sided lesions of the ventromedial prefrontal cortex (VMPC) develop severe impairment in the theory of mind (ToM), social behaviors, or decision making.
The VMPC is a part of the neural circuit for mind reading, and the social impairment of patients with VMPC lesions is due to a deficit in the ToM. Those Patients were able to correctly analyze abstract social situations, but behaved inappropriately when they responded to real-life situations. For instance, such patients typically do not respond to signals of whether the other person is interested in what they are saying or whether they are on the right topic during a social conversation.
A neuropsychological study demonstrated that, compared with patients with VMPC lesions, patients with DLPC performed well on the affective ToM. However, results from a neuroimaging study showed that the ToM task activated the right DLPC besides the temporoparietal junction on both sides and the right inferior parietal lobule (IPL) more than the non-ToM task, regardless of task modality
Patients with aneurysmal subarachnoid hemorrhage secondary to ruptured anterior communicating artery aneurysms showed no significant difference in speed or quality of their decision making compared with healthy controls (HC), but exhibited increased risk-taking behavior and simple impulsivity.
However, it wasfound that both the VMPC and DLPC damage groups were impaired on IGT. A neuroimaging study also showed that DLPC was involved in choosing between “safe” and “risky” responses when subjects were performing the Risky-Gains task. Hence, conflicting evidence exists on the role of DLPC and VMPC in the decision-making process. Previous studies showed the impairments in decision making might be related to the executive function or the mood state of individuals. Other studies implied that decision making abilities might be related to social and emotional cognition.
Apathy with impaired motivation and indifference has most strongly been associated with damage to anterior cingulate cortex (ACC). Neuroimaging studies have found apathy in AD patients to be correlated with hypoperfusion in frontotemporal regions; apathetic stroke patients showed reduced regional cerebral blood flow in the right dorsolateral prefrontal cortex and the left frontotemporal regions.
Apathy has several dimensions; components of the apathetic syndrome are motoric, cognitive, affective, emotional and motivational. Motoric apathy is manifested by diminished motor activity, reduced gesturing, and diminished verbal output. Cognitive apathy is manifested by decreased curiosity and altered interest in learning, deducing, and drawing logical conclusions. Affective apathy includes diminished vocal inflection and reduced facial expression of internal emotional states. Emotional apathy is evidenced by reduced social interest, diminished affection, and compromised enthusiasm. Motivational apathy includes reduced initiation and poor maintenance of implemented activities. Independence and anatomical and neurobiological correlates of these different forms of apathy have not been determined.
Apathy may be distinguished from depression by the absence of dysphoric mood symptoms such as sadness, guilt, hopelessness, and helplessness. The difference in mood states, dysphoric versus emotionally indifferent, is the most useful characteristic in making a differential diagnosis between apathy and depression. Apathy can be thought of as a syndrome of primary motivational loss and diminished emotional reactivity, while depression reflects a syndrome of mood disturbance.
The mechanisms of apathy are not fully understood, though most theories suggest it involves disruption of the frontal-subcortical neural circuit. This circuit begins with the anterior cingulate cortex, and continues to the ventral striatum, the globus pallidus, and the thalamus, before looping back to the anterior cingulate cortex. It has been hypothesized that neuropathological changes and alterations in regional chemistry, especially acetylcholine, dopamine, and serotonin, in this circuit, are responsible for the clinical manifestation of apathy.
Apathy with impaired motivation and indifference has most strongly been associated with damage to anterior cingulate cortex (ACC). Apathy occurs with degenerative, ischemic, neoplastic, and infectious conditions affecting the anterior cingulate cortex, nucleus accumbens, globus pallidus, thalamus, or connecting white matter tracts. Apathy is particularly striking in some patients with frontotemporal dementia, individuals with thalamic stroke, and persons with human immunodeficiency virus (HIV) encephalopathy.
In the most extreme cases, damage to the ACC results in akinetic mutism, and a complete loss of initiation and motivation. Single photon emission computed tomography (SPECT) studies of patients with Alzheimer’s disease found that apathy was strongly and inversely correlated with right anterior cingulate activity or with a bilateral reduction in cingulate activity.
Functional neuroimaging research has demonstrated that psychomotor retardation in depression is associated with decreased blood flow in the dorsolateral prefrontal cortex, left prefrontal cortex, angular gyrus, and the anterior cingulated. However, and despite its long observed prevalence in MDD, the characterization, clinical significance and the biological correlates of psychomotor retardation are poorly understood.
Increased knowledge and understanding of psychomotor retardation in major depressive disorder may lead to further research and better informed diagnosis in regards to psychomotor retardation. Also, Investigations into psychomotor retardation in the context of diseases co-morbid with MDD could bring increased understanding to its biological underpinnings and lead to better diagnosis.
As regarding the biological correlates of psychomotor retardation in MDD Experts have postulated that psychomotor changes in depression correlate with specific neurocircuitry in the prefrontal cortex and basal ganglia.
A positron emission tomography (PET) study examined subjects with both depression and Huntington’s disease compared to subjects with only Huntington’s disease and healthy controls. Regional cerebral glucose metabolism was measured using 2-[18F]- fluoro-2-deoxy-D-glucose. The results indicated that subjects with both MDD and Huntington’s had orbital frontal-inferior prefrontal cortex hypometabolism compared to the other subjects. This metabolic pattern is similar to that in patients with both MDD and Parkinson’s disease. These findings suggest that the paralimbic regions of the frontal lobes may be associated with mood and movement disorders. A later study with single photon emission computed tomography (SPECT) with 99mTchexamethylpropylene amine oxime, found that in 13 subjects with severe depression, the severity of psychomotor retardation was negatively correlated with prefrontal, frontal and temporal perfusion.
Future investigations of psychomotor retardation could produce numerous benefits such as further insights regarding the biology of mood disorders and enhanced treatment planning for patients with psychomotor retardation.
Although schizophrenia is widely considered to be caused by a biological disturbance of brain function, how this might translate into the symptoms of the disorder is poorly understood.
However, with growing recognition of the importance of negative symptoms in the course and outcome of schizophrenia, as well as advances in neuro-imaging techniques, there has been a growing body of literature exploring the structural and functional brain correlates of negative symptoms as well as brain regions that may be critical in the development of specific negative symptoms.
So, numerous structural and functional imaging studies have been carried out in efforts to uncover the neurobiological substrates of the negative symptoms of schizophrenia. Although findings are not entirely consistent, these investigations collectively offer valuable insights into the potential neurobiological underpinnings of negative symptoms. The collective evidence suggests that negative symptoms are related to a hypoactive frontal lobe, and in particular to dysfunction within the OFC, ventrolateral prefrontal cortex, ventral striatum, DLPFC and some areas of the temporal lobe.
Dopamine has figured prominently in hypotheses around the pathophysiology of schizophrenia, with the suggestion that negative symptoms are related to a cortical hypodopaminergic state; however, neurochemical data supporting this and a link with negative symptoms has not been forthcoming. In contrast, a growing body of evidence has underscored the importance of reward prediction and the role of dopaminergic signaling in the ventral striatum as one component of a complex motivation system.
Across the schizophrenia spectrum there have been very few neurobiological investigations of negative symptoms, although those that have been conducted suggest involvement of similar brain regions to those implicated in schizophrenia.
There are significant advances in the understanding of negative symptoms in schizophrenia over the last several decades, a shift that has highlighted their critical role in functional outcomes. However, the respective roles of cortical and subcortical neurobiological abnormalities in negative symptoms are, at best, rudimentary.
The value of multimodal imaging studies in this regard cannot be overstated, with opportunities to concurrently evaluate structural and functional correlates of negative symptoms on multiple levels, from regional metabolic and blood flow changes to specific neurochemical involvement in the processes under investigation. At the same time, further advances in these technologies that currently limit the questions asked, as is currently the case regarding the PFC and D1 activity.
Decades of research have established the critical role of the prefrontal cortex in memory, and the impairments following frontal lesions have been better characterized in recent years.
Frontal lobe lesions lead to a variety of subtle but noticeable memory impairments, particularly in the strategic control of encoding and retrieval. Frontal patients perform poorly on many long-term memory tasks, including free recall, cued recall, and source and temporal order memory. They also show increased susceptibility to interference and have difficulty with strategy implementation at encoding and retrieval, which extends to the organization and monitoring of retrieval from remote memory.
The MPFC serves as a key structure for AM retrieval in young adults, since it is strongly involved in the conscious re-experience of our personal past and supports the interaction of emotional, self-referential and time processing rather than any of these cognitive processes alone. Those data especially contribute to the understanding of how emotions, self-referential processing and AM might be related to each other.
Prospective memory defined as the ability to carry out a delayed intended action, refers to a type of memory that allows maintaining and retrieving future plans, goals and activities, which is a crucial ability for human everyday life. Functional imaging studies that have been performed using tasks checking the prospective memory have shown consistent activation in rostral PFC (in Brodmann area [BA] 10), but also in more posterior prefrontal regions and in non frontal regions. It therefore appears that the rostral PFC is often activated by prospective memory tasks.
from a clinical perspective, the efficacy of PM rehabilitation is important for improving quality of life (QOL) in patients with brain damage. Prospective memory is a new and useful window to better understand rostral patients’ problems and to explore the cognitive processes that depend on rostral prefrontal cortex. Nevertheless, it is likely that prospective memory is not the only crucial component that could explain the difficulties of patients with frontopolar damage.
The focus has been on the role of the PFC in strategic and effortful control of encoding and retrieval, leading many to propose that the PFC is critical for recollection. It is now apparent that this is not always the case. At least for item recognition, the lateral prefrontal cortex is necessary for familiarity, but not recollection. With respect to familiarity, neuroimaging studies have found lateral PFC activation at both encoding and retrieval which tracks recognition confidence, suggesting this region is sensitive to familiarity.