The frontal cortex and memory for temporal order

Patients with unilateral frontal- or temporal-lobe excisions and normal control subjects made relative-recency decisions about objects presented sequentially. Several objects within each series were presented in the context of actions to be performed using them, such as "squeeze the sponge", whereas others had only to be named. Both left and right frontal-lobe groups were impaired on order judgements for named items, but their performance was normal for action items. The results suggest that providing salient and distinctive items, involving meaningful actions and multimodal cues, helps compensate for deficits in memory for temporal information associated with frontal-lobe damage.     

Role of frontal versus temporal cortex in verbal fluency as revealed by voxel-based lesion symptom mapping.

Category and letter fluency tasks have been used to demonstrate psychological and neurological dissociations between semantic and phonological aspects of word retrieval. Some previous neuroimaging and lesion studies have suggested that category fluency (semantic-based word retrieval) is mediated primarily by temporal cortex, while letter fluency (letter-based word retrieval) is mediated primarily by frontal cortex. Other studies have suggested that both letter and category fluency are mediated by frontal cortex. We tested these hypotheses using voxel-based lesion symptom mapping (VLSM) in a group of 48 left-hemisphere stroke patients. VLSM maps revealed that category and letter fluency deficits correlate with lesions in temporal and frontal cortices, respectively. Other regions, including parietal cortex, were significantly implicated in both tasks. Our findings are therefore consistent with the hypothesis that temporal cortex subserves word retrieval constrained by semantics, whereas frontal regions are more critical for strategic word retrieval constrained by phonology.     

Vasopressin metabolite neuropeptide facilitates simultaneous temporal processing

Rats were trained on a peak-interval timing procedure in which auditory, tactile, and visual stimuli signaled 3 different fixed-interval schedules (15, 30, and 60 s) that were presented simultaneously in a hierarchical fashion. Administration of vasopressin metabolite neuropeptide [pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2, 0.3 microgram/kg i.p.] had two main effects on performance. With repeated exposure the temporal criterion for each of the intervals shifted leftward on the time scale in a proportional manner, and the probability of attention to each of the intervals increased proportionally. The conclusion is that vasopressin metabolite neuropeptide facilitates simultaneous temporal processing by increasing the speed of mental processes involved in memory storage and divided attention. These results indicate that a major metabolite of arginine vasopressin that is devoid of endocrine and pressor activity can produce facilitation of cognitive processes in animals.     

Laminar degeneration of frontal and temporal cortex in Parkinson disease dementia

Neurological Sciences - To investigate cortical laminar degeneration in Parkinson’s disease (PD) with dementia (PDD). Changes in density of α-synuclein-immunoreactive Lewy bodies (LB),...     

Functional neuroanatomy of speech processing within the temporal cortex

The phonemic structure of the maternal language determines the way of perceiving speech signals. A typical example is that native Japanese listeners map two English phonemes, /r/ and /l/, onto the same /R/. This perceptual assimilation of speech sounds has been associated with the left and/or right posterior perisylvian region, but the precise functional anatomy is unknown. Using functional magnetic resonance imaging and a repetition priming paradigm, we identified three subregions in the left temporal cortex: an anterior division sensitive to language-specific phonological knowledge, and a midlateral and a posterior division related to other vocal stimuli features. Dynamic causal modeling supports the scheme by which the anterior pathway processes perceptual assimilation; the posterior pathway processes lexico-semantic information.     

Continuous processing in macaque frontal cortex during visual search

A central issue in mental chronometry is whether information is transferred between processing stages such as stimulus evaluation and response preparation in a continuous or discrete manner. We tested whether partial information about a stimulus influences the response stage by recording the activity of movement-related neurons in the frontal eye field of macaque monkeys performing a conjunction visual search and a feature visual search with a singleton distractor. While movement-related neurons were activated maximally when the target of the search array was in their movement field, they were also activated for distractors even though a saccade was successfully made to the target outside the movement field. Most importantly, the level of activation depended on the properties of the distractor, with greater activation for distractors that shared a target feature or were the target during the previous session during conjunction search, and for the singleton distractor during feature search. These results support the model of continuous information processing and argue against a strictly discrete model.     

Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer's disease

OBJECTIVE: Delusional thoughts are common in patients with Alzheimer's disease and contribute prominently to morbidity. The pathophysiologic underpinnings for delusions in Alzheimer's disease are not well understood. In this study the authors examined the relationship between delusional thoughts and regional cortical metabolism in patients with Alzheimer's disease. METHOD: Twenty-five patients with probable Alzheimer's disease were included. None was taking psychotropic medication. Severity of delusions and other neuropsychiatric symptoms was assessed by using a semistructured interview and the Neurobehavioral Rating Scale just before the imaging procedure. [(18)F]Fluorodeoxyglucose positron emission tomography was used to measure resting cerebral glucose metabolic rates in the cortical lobes and in anatomically defined subregions of the frontal and temporal cortexes. RESULTS: A linear regression model, controlling for the effects of cognitive deficits, revealed a significant relationship between severity of delusional thought and the metabolic rates in three frontal regions: the right superior dorsolateral frontal cortex (Brodmann's area 8), the right inferior frontal pole (Brodmann's area 10), and the right lateral orbitofrontal region (Brodmann's area 47). Bivariate partial correlation analysis indicated that severity of delusions was associated with hypometabolism in additional prefrontal and anterior cingulate regions. Robust relationships with metabolism in regions of the temporal cortex were not apparent. CONCLUSIONS: Dysmetabolism in specific regions of the right prefrontal cortex may be associated with delusional thought in Alzheimer's disease. Delusions appear to reflect the pathophysiologic state of particular cortical regions. Activity across distributed neuronal networks and the specific content of delusional thoughts may modulate these relationships.     

fMRI identifies the right inferior frontal cortex as the brain region where time interval processing is altered by negative emotional arousal

The reason why human beings are inclined to overestimate the duration of highly arousing negative events remains enigmatic. The issue about what neurocognitive mechanisms and neural structures support the connection between time perception and emotion was addressed here by an event‐related neuroimaging study involving a localizer task, followed by the main experiment. The localizer task, in which participants had to categorize either the duration or the average color of visual stimuli aimed at identifying the neural structures constitutive of a duration‐specific network. The aim of the main experiment, in which participants had to categorize the presentation time of either neutral or emotionally negative visual stimuli, was to unmask which parts of the previously identified duration‐specific network are sensitive to emotionally negative arousal. The duration‐specific network that we uncovered from the localizer task comprised the cerebellum bilaterally as well as the orbitofrontal, the anterior cingulate, the anterior insular, and the inferior frontal cortices in the right hemisphere. Strikingly, the imaging data from the main experiment underscored that the right inferior frontal cortex (IFC) was the only region within the duration‐specific network whose activity was increased in the face of emotionally negative pictures compared to neutral ones. Remarkably too, the extent of neural activation induced by emotionally negative pictures (compared to neutral ones) in this region correlated with a behavioral index reflecting the extent to which emotionally negative pictures were overestimated compared to neutral ones. The results are discussed in relation to recent models and studies suggesting that the right anterior insular cortex/IFC is of central importance in time perception. Hum Brain Mapp 36:981–995, 2015. © 2014 Wiley Periodicals, Inc.     

Contribution of subregions of human frontal cortex to novelty processing

Novelty processing was studied in patients with lesions centered in either OFC or lateral pFC (LPFC). An auditory novelty oddball ERP paradigm was applied with environmental sounds serving as task irrelevant novel stimuli. Lesions to the LPFC as well as the OFC resulted in a reduction of the frontal Novelty P3 response, supporting a key role of both frontal subdivisions in novelty processing. The posterior P3b to target sounds was unaffected in patients with frontal lobe lesions in either location, indicating intact posterior cortical target detection mechanisms. LPFC patients displayed an enhanced sustained negative slow wave (NSW) to novel sounds not observed in OFC patients, indicating prolonged resource allocation to task-irrelevant stimuli after LPFC damage. Both patient groups displayed an enhanced NSW to targets relative to controls. However, there was no difference in behavior between patients and controls suggesting that the enhanced NSW to targets may index an increased resource allocation to response requirements enabling comparable performance in the frontal lesioned patients. The current findings indicate that the LPFC and OFC have partly shared and partly differential contributions to the cognitive subcomponents of novelty processing.     

A computational model of information processing in the frontal cortex and basal ganglia

Performance on the Wisconsin Card Sort Test (WCST) of patients with schizophrenia, Parkinson's disease (PD), and Huntington's disease (HD) was simulated by a neural network model constructed on principles derived from neuroanatomic loops from the frontal cortex through the basal ganglia and thalamus. The model provided a computational rationale for the empirical pattern of perseverative errors associated with frontal cortex dysfunction and random errors associated with striatal dysfunction. The model displayed perseverative errors in performance when the gain parameter of the activation function in units representing frontal cortex neurons was reduced as an analog of reduced dopamine release. Random errors occurred when the gain parameter of the activation function in units representing striatal neurons was reduced, or when the activation level was itself reduced as an analog of a striatal lesion. The model demonstrated that the perseveration of schizophrenic, Huntington's, and demented Parkinsonian patients may be principally due to ineffective inhibition of previously learned contextual rules in the frontal cortex, while the random errors of Parkinson's and Huntington's patients are more likely to be due to unsystematic errors of matching in the striatum. The model also made specific, empirically falsifiable predictions that can be used to explore the utility of these putative mechanisms of information processing in the frontal cortex and basal ganglia.     

Autobiographical memory of the recent past following frontal cortex or temporal lobe excisions

Previous research has raised questions regarding the necessity of the frontal cortex in autobiographical memory and the role that it plays in actively retrieving contextual information associated with personally relevant events. Autobiographical memory was studied in patients with unilateral excisions restricted to the frontal cortex or temporal lobe involving the amygdalo-hippocampal region and in normal controls using an event-sampling method. We examined accuracy of free recall, use of strategies during retrieval and memory for specific aspects of the autobiographical events, including temporal order. Patients with temporal lobe excisions were impaired in autobiographical recall. By contrast, patients with frontal cortical excisions exhibited normal autobiographical recall but were less likely to use temporal order spontaneously to organize event retrieval. Instruction to organize retrieval by temporal order failed to improve recall in temporal lobe patients and increased the incidence of plausible intrusion errors in left temporal patients. In contrast, patients with frontal cortical excisions now surpassed control subjects in recall of autobiographical events. Furthermore, the retrieval accuracy for the temporal order of diary events was not impaired in these patients. In a subsequent cued recall test, temporal lobe patients were impaired in their memory for the details of the diary events and their context. In conclusion, a basic impairment in autobiographical memory (including memory for temporal context) results from damage to the temporal lobe and not the frontal cortex. Patients with frontal excisions fail to use organizational strategies spontaneously to aid retrieval but can use these effectively if instructed to do so.     

Projections from the superior temporal sulcus to the agranular frontal cortex in the macaque

The aim of this study was to investigate the organization of the projections from the superior temporal sulcus (STS) to the various areas forming the agranular frontal cortex. Injections of retrograde neuronal tracers were made in the various agranular areas, in nine macaque monkeys. The results showed that two rostral premotor areas, F6 (pre-SMA) and F7, and the ventrorostral part of area F2 (F2vr) are targets of projections from the upper bank of the STS (uSTS). F6 and the dorsorostral part of F7 (supplementary eye field, SEF) are targets of projections from the rostral part of the uSTS, corresponding to the so-called 'superior temporal polysensory area' (STP). In contrast, the ventral part of area F7 (not including the SEF) and F2vr are targets of afferents from the caudal part of the uSTS. Ventral F7 is the target of weak afferents from the caudalmost and dorsalmost part of the uSTS (area 7a), whilst F2vr is the target of projections from a relatively more rostral and ventral sector of the uSTS, close to the fundus of the sulcus. This sector should correspond to area MST. In conclusion, F6 and SEF receive high order information from STP, whereas ventral F7 and F2vr receive information from areas of the dorsal visual stream.     

Alterations in Alzheimer's disease-associated protein in Alzheimer's disease frontal and temporal cortex.

Alzheimer's disease (AD)-associated protein is present in brain and cerebrospinal fluid of patients with AD but not in adult, nondemented, normal controls. This protein may represent an abnormal epitope of the "tau" microtubule-associated protein and has been detected before the appearance of senile plaques and neurofibrillary tangles. The amount of AD-associated protein in the frontal and temporal cortices in 93 cases of neuropathologically confirmed AD was compared with the amount that was present in 20 cases without AD. The amount of AD-associated protein was significantly increased in the cases of AD for both brain regions compared with that in the cases without AD. The presence of high levels of this protein is a useful adjunct, postmortem marker of the presence of AD and may eventually lead to tests that allow early detection of individuals at risk for this disease.     

Increase in HLA-DR immunoreactive microglia in frontal and temporal cortex of chronic schizophrenics

Glia play a major role in neuronal migration, synapse formation, and control of neurotransmission in the developing and mature nervous system. This study investigated whether chronic schizophrenia is associated with glial changes in 3 regions of the cerebral cortex: dorsolateral prefrontal cortex (Brodmann's area 9), the superior temporal gyrus (area 22), and the anterior cingulate gyrus (area 24). In a blind study, astroglia and microglia were identified immunocytochemically in frozen sections from postmortem schizophrenic and control brains. Astroglia and microglia were identified using antibodies to glial fibrillary acidic protein (GFAP) and class II human leucocyte antigen (HLA-DR) respectively. They were then quantified for each cortical layer. Significant differences were found in HLA-DR+ microglial numerical density in 2 of the areas. A 28% increase (p < 0.05) was found in area 9 in 8 schizophrenics (115 +/- 9 cells/mm2) compared with 10 controls (89 +/- 5 cells/mm2), when combining all cortical layers and both cerebral hemispheres. For area 22, there was a 57% increase (p < 0.01) in microglia in 7 schizophrenics (139 +/- 6 cells/mm2) compared with 10 controls (88 +/- 5 cells/mm2). In area 24 the same trend was evident, but the results did not reach significance. Microglial number was further analyzed for each cortical layer, which confirmed the overall pattern. For all areas, numerical density of astroglia showed no significant differences between schizophrenics and controls. Cortical thickness was measured in all areas and total neuronal numerical density was estimated for area 22. Again, no significant differences were found between schizophrenics and controls. This study demonstrates a specific increase in the numerical density of HLA-DR+ microglia in temporal and frontal cortex of chronic schizophrenics, not related to aging, which might be implicated in possible changes in cortical neuropil architecture in schizophrenia.     

Task-dependent modulation of regions in the left inferior frontal cortex during semantic processing

To distinguish areas involved in the processing of word meaning (semantics) from other regions involved in lexical processing more generally, subjects were scanned with positron emission tomography (PET) while performing lexical tasks, three of which required varying degrees of semantic analysis and one that required phonological analysis. Three closely apposed regions in the left inferior frontal cortex and one in the right cerebellum were significantly active above baseline in the semantic tasks, but not in the nonsemantic task. The activity in two of the frontal regions was modulated by the difficulty of the semantic judgment. Other regions, including some in the left temporal cortex and the cerebellum, were active across all four language tasks. Thus, in addition to a number of regions known to be active during language processing, regions in the left inferior frontal cortex were specifically recruited during semantic processing in a task-dependent manner. A region in the right cerebellum may be functionally related to those in the left inferior frontal cortex. Discussion focuses on the implications of these results for current views regarding neural substrates of semantic processing.     

Auditory-visual interaction in single cells in the cortex of the superior temporal sulcus and the orbital frontal cortex of the macaque monkey

Previous anatomical studies show that the cortex of the superior temporal sulcus and the orbital frontal cortex receive convergent corticocortical and thalamocortical projections which represent different sensory modalities. In the present experiments both intracellular and extracellular recordings were made in these cortical regions to determine if the individual cells receive polysensory information and if interactions between different medalities are a result of local convergence at the cortical cell. The results show that many neurons have visual receptive fields which are bilateral, include the fovea, and are sensitive to moving stimuli. Many of these neurons are also excited or inhibited by auditory stimuli. For both modalities a variety of ON or OFF excitatory and inhibitory effects was seen. The results further indicate that neurons in both regions show auditory-visual interactions and that at least some of these interactions are due to convergence at the cortical cell. For example, we found that auditory stimuli of a specific frequency had a powerful inhibitory effect on many of the neurons and that this inhibitory effect could negate the excitation caused by a visual stimulus. These types of interactions are related to the anatomical inputs and may be possible mechanism implicating each of these regions in attention and discrimination.     

Distractibility following simultaneous bilateral lesions of the superior colliculus or medial frontal cortex in the rat

Hooded rats with bilateral lesions of the superior colliculus or medial frontal cortex were compared with controls for locomotor guidance in shuttling back and forth between goal-doors at two opposite ends of a large arena. Colliculectomized rats accomplished this with great accuracy. When flashing distractor lights were introduced midway down the runway, frontal corticals and controls were severely disrupted but colliculars continued to run normally. This result was obtained both when all training occurred postoperatively (Experiment 1) and when runway performance had been stabilized preoperatively (Experiment 2), thus after a long or short postoperative recovery interval. The results offer support for previous studies with rats which have demonstrated sensory 'neglect' but good locomotor guidance after collicular ablation. Frontal corticals differed from controls only in terms of their elevated rate of repeat door-pressing upon postoperative resumption of testing in Experiment 2. Despite the similarity between effects reported elsewhere of collicular and frontal lesions made unilaterally, bilateral deficits clearly demonstrable after collicular ablation were absent here after frontal lesions. The results imply that the functional responsibilities of superior colliculus and frontal cortex in the rat are separable; at least, they have different rates of functional recovery.