Frontal lobes and attention: processes and networks, fractionation and integration.

The frontal lobes (FL), are they a general adaptive global capacity processor, or a series of fractionated processes? Our lesion studies focusing on attention have demonstrated impairments in distinct processes due to pathology in different frontal regions, implying fractionation of the "supervisory system." However, when task demands are manipulated, it becomes evident that the frontal lobes are not just a series of independent processes. Increased complexity of task demands elicits greater involvement of frontal regions along a fixed network related to a general activation process. For some task demands, one or more anatomically distinct frontal processes may be recruited. In other conditions, there is a bottom-up nonfrontal/frontal network, with impairment noted maximally for the lesser task demands in the nonfrontal automatic processing regions, and then as task demands change, increased involvement of different frontal (more "strategic") regions, until it appears all frontal regions are involved. With other measures, the network is top-down, with impairment in the measure first noted in the frontal region and then, with changing task demands, involving a posterior region. Adaptability is not just a property of FL, it is the fluid recruitment of different processes anywhere in the brain as required by the current task.     

Frontal lobes, basal ganglia, temporal lobes--three sites for schizophrenia?

This special issue of the Schizophrenia Bulletin focuses on three brain areas hypothesized to play a role in the etiology of schizophrenia--the frontal lobes, the basal ganglia, and the temporal lobes. Contributors to the issue review evidence from brain-imaging, post-mortem, and psychopharmacological studies that support the involvement of each of these important brain areas in schizophrenia. It is concluded that theories emphasizing cortical/subcortical interconnections rather than a single brain area provide the greatest challenge, and also the greatest promise, to schizophrenia researchers.     

Frontal lobes pathology and dementia. An appraisal of the contribution of Leonardo Bianchi

This paper which was inspired by Leonardo Bianchi's work, published in English a hundred years ago, summarizes the main features of frontal dementias, with particular emphasis on Pick's Disease (PiD) and on Frontal Lobe Dementia (FLD). We intend to examine on one hand whether these behavioral changes follow pathology strictly limited to the frontal lobes and on the other hand whether these changes truly constitute a dementia. Currently available data suggest the following conclusions:

Frontal hypometabolism does not explain inhibitory dysfunction in Alzheimer disease

A series of tasks assessing inhibitory processes was administered to patients with Alzheimer disease and control subjects. Two groups of patients with Alzheimer disease were examined: patients with hypometabolism restricted to the posterior (temporal and parietal) cerebral areas and patients with hypometabolism in both posterior and anterior (frontal) cerebral areas. The performances of the patients with Alzheimer disease were inferior to those of control subjects on all inhibitory tasks, but the two groups of patients obtained similar scores. These data indicate that frontal lobe hypometabolism is not necessary to produce inhibitory impairment in Alzheimer disease. Consequently, inhibitory dysfunction could be the consequence of a (partial) disconnection process between posterior and anterior cerebral areas.     

Disruption of inhibitory control of memory following lesions to the frontal and temporal lobes

A group of patients with lesions to the frontal lobes, a group with lesions to the temporal lobes, and groups of non-brain damaged controls took part in three experiments. The first experiment used directed forgetting (DF) by items, the second DF by lists, and the third retrieval induced forgetting (RIF). Frontal patients with right side lesions could not intentionally inhibit but all frontal patients showed normal RIF. Temporal patients with left side lesions had abnormal DF by lists and all the temporal patients had abnormal RIF. These findings are explained in terms of impairment to executive thought avoidance control processes in frontal patients and impaired knowledge access to long-term memory in temporal patients.     

Frontal lobe function in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further.     

Frontal lobe function,sleep loss and fragmented sleep

Recent experimental studies involving total sleep loss, sleep reduction and clinically related sleep fragmentation report impaired performance on tasks of frontal lobe or executive function, including measures of verbal fluency, creativity and planning skills. Severity of sleep disturbance in obstructive sleep apnoea syndrome (OSAS) is correlated with level of executive impairment, with some residual impairment despite treatment (continuous positive airway pressure – CPAP). Executive impairment appears to be more closely related to hypoxaemic events rather than daytime sleepiness. Studies of electroencephalographic (EEG) changes throughout the course of sleep and following sleep deprivation as well as functional neuroimaging and psychophysiological changes (event-related potentials – ERPs) following sleep deprivation provide further indication of the relative importance of the frontal regions of the brain to sleep. However, neurocognitive studies present many inconsistencies, task classification is often ambiguous and, in the absence of any unifying explanation at the level of cognitive mechanisms, the overall picture is one of a disparate range of impairment following sleep loss and sleep fragmentation. Poorly defined concepts of frontal lobe function, executive function, memory and attention, using tasks largely developed with more severe deficit levels in mind, create further difficulties in interpreting current findings.     

Immunohistochemical and biochemical evidence for the putative inhibitory neurotransmitters histamine and GABA in lobster olfactory lobes

As an initial effort to investigate possible inhibitory interactions in the olfactory system of the spiny lobster, studies were conducted to identify and localize the putative inhibitory neurotransmitters histamine and GABA in the olfactory lobe. Biochemical studies demonstrated that olfactory lobe tissue was capable of synthesizing histamine from radioactive histidine and GABA from glutamic acid. Immunohistochemistry was used to localize histamine and GABA in brain sections, by using either avidin-biotin conjugated peroxidase or fluorescein conjugated secondary antibody. Specific histamine-like and GABA-like immunoreactivity was found in soma clusters of olfactory interneurons, adjacent to the olfactory lobe. Small, putative glial cells displaying intense histamine-like immunoreactivity were found interspersed among the glomeruli of the lobe. The accessory lobe exhibited moderate immunostaining for both histamine and GABA. Positive immunostaining for histamine and GABA was also found in the olfactory lobes, with a predominance of staining in the outer caps of the glomeruli, which are thought to be the regions where the primary afferent terminals contact the processes of second-order olfactory neurons. These findings collectively implicate inhibition at the first synaptic level of the olfactory pathway in the spiny lobster.     

Frontal lobe phosphorus metabolism and neuropsychological function in aging and in alzheimer's disease

³¹P Magnetic resonance spectroscopy of the frontal lobe was performed in 17 patients with Alzheimer's disease (AD), 8 elderly controls (EC), and 17 young controls (YC). The phosphocreatine/inorganic phosphate (PCr/Pi) ratio in AD (2.32 ± 0.26 SD) was significantly lower than in EC (2.65 ± 0.41). In AD patients, a correlation was observed between the PCr/Pi ratio and the dementia rating scale (r = ?0.50, p = 0.04). A significant positive correlation between PCr/Pi ratio and age was observed in both AD (r = 0.67, p 0.003) and YC (r = 0.63, p 0.006) groups, however, suggesting caution in interpretation of this ratio in AD. We did not find differences between AD, EC, or YC in any other spectroscopic measure. A significant sex difference in the phosphomonoester/phosphodiester ratio (PME/PDE) ratio was observed in AD brain. Females had a lower PME/PDE ratio than males.     

Cortical inhibitory function in cervical dystonia

Objective

To assess the specificity of cortical inhibitory deficits in cervical dystonia patients.

Frontal lobe function in Korsakoff and non-Korsakoff alcoholics: planning and spatial working memory

Groups of Korsakoff (KS) and non-Korsakoff alcoholics (ALC) and a group of normal volunteers, matched for age and verbal IQ, were tested on traditional neuropsychological tests of frontal lobe function and on computerized tests of planning (the Tower of London task) and spatial working memory. KS demonstrated deficits on the planning task which could not be explained by abnormalities of memory, including spatial span, or by visuoperceptive disturbances. KS were also impaired on the spatial working memory task, in part because of the failure to adopt an organized strategy. ALC exhibited fewer impairments which could not be attributed to deficits in either planning or spatial working memory. On Nelson's modified Wisconsin Card Sorting Task, KS and ALC achieved fewer categories than controls but only KS made perseverative errors. The data suggest that in the alcoholic Korsakoff's syndrome there is a specific disturbance of frontal-lobe function in addition to amnesia. The impairment seen in chronic alcoholics without Korsakoff's syndrome, on the other hand, do not reflect specific frontal dysfunction.     

Epilepsy and the frontal lobes

Although the frontal lobes contain a large proportion of the total cerebral cortex in human brain, the epilepsies arising in this region are less studied and less well characterised than epilepsies arising in the mesial temporal lobe. Detailed studies of seizure semiology have identified a number of patterns of frontal lobe seizure, but with inconsistency across studies, and with limited evidence that specific patterns arise in specific discrete frontal lobe regions. In contrast to mesial temporal lobe epilepsy, there is no consistent pattern of cognitive impairment seen in patients with frontal lobe epilepsy, although some evidence exists to support the notion that cognitive function may be impaired. Given the rich interconnectivity between frontal lobes and many other brain regions, it is not surprising to find functional deficits in the frontal lobes in patients with epilepsy arising in other sites; this is best studied in patients with temporal lobe epilepsy. Current concepts in epilepsy suggest that epilepsies hitherto regarded as idiopathic generalised (rather than focal) may in fact have a focal origin of seizure activity; this may be supported by increasing evidence for focal structural and functional frontal lobe abnormalities in idiopathic generalised epilepsies.     

Apraxia and the parietal lobes

The widely held belief in a central role of left parietal lesions for apraxia can be traced back to Liepmann's model of a posterior to anterior stream converting mental images of intended action into motor execution. Although this model has undergone significant changes, its modern descendants still attribute the parietal contribution to the existence of mental representations of intended movements which precede and direct their motor execution. They predict that pantomime of tool use should be particularly vulnerable to parietal lesions. A review of clinical studies contradicts these assumptions: The impact of parietal lobe damage on pantomime of tool use is inconstant if not absent altogether. The domains of action which are most affected by left parietal damage are the imitation of meaningless gestures and, although probably only in the context of additional more widespread brain damage, actual use of tools and objects.I hypothesize that imitation of meaningless gestures and use of tool and objects depend on left parietal lobe integrity because of their demands on categorical apprehension of spatial relationships between multiple objects or between multiple parts of objects. For use of tools and objects the spatial relationships are between the hand, the tool, its recipient, and the material it acts upon. Categorical apprehension concentrates on features of these relations which determine mechanical interactions. For imitation of meaningless gestures, categorical apprehension of demonstrated gesture results in “body part coding” which reduces the visual appearance of the demonstrated gestures to simple spatial relationships between a limited set of discrete body parts. The hypothesis that the role of the left parietal lobe in apraxia concerns categorical apprehension of spatial relationships fits well with more general theories of parietal lobe function and hemisphere asymmetries.