Left Prefrontal Regions Research Articles

Striatal Dopamine and Working Memory

Recent studies have emphasized the importance of dopamine projections to the prefrontal cortex (PFC) for working memory (WM) function, although this system has rarely been studied in humans in vivo. However, dopamine and PFC activity can be directly measured with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), respectively. In this study, we examined WM capacity, dopamine, and PFC function in healthy older participants in order to test the hypothesis that there is a relationship between these 3 factors. We used the PET tracer 6-[18F]fluoro-L-m-tyrosine to measure dopamine synthesis capacity in the striatum (caudate, putamen), and event-related fMRI to measure brain activation during different epochs (cue, delay, probe) of a WM task. Caudate (but not putamen) dopamine correlated positively with WM capacity, whereas putamen (but not caudate) dopamine correlated positively with motor speed. In addition, delay-related fMRI activation in a left inferior prefrontal region was related to both caudate dopamine and task accuracy, suggesting that this may be a critical site for the integration of WM maintenance processes. These results provide new evidence that striatal dopaminergic function is related to PFC-dependent functions, particularly brain activation and behavioral performance during WM tasks.

Aberrant connectivity of lateral prefrontal networks in presymptomatic Huntington's disease

In clinically presymptomatic individuals with the Huntington's disease (HD) gene mutation, functional neuroimaging data have suggested a dysfunction of multiple cortical and subcortical regions including the prefrontal and parietal cortex, as well as the striatum. Although it has been hypothesized that these activation differences most likely reflect aberrant corticostriatal circuits, the functional coupling of neural networks associated with cognitive performance has not been investigated so far. In this study, we used functional magnetic resonance imaging (fMRI) and multivariate analytic techniques to investigate memory-related patterns of functional connectivity in healthy controls ( n = 16) and pre-HD individuals ( n = 16). Independent component analyses (ICA) revealed distinct bilateral frontostriatal and frontoparietal networks that were activated during a verbal working memory paradigm in both healthy controls and pre-HD subjects. Compared with healthy controls, pre-HD individuals exhibited lower functional connectivity in left lateral prefrontal and parietal regions as well as in the bilateral putamen. Functional connectivity indices in the left putamen were negatively correlated with the CAG repeat size and the UHDRS behavioral score, and positively correlated with the predicted years to manifest symptom onset. The connectivity of the right putamen was negatively correlated with the UHDRS motor score. In pre-HD individuals, these results suggest an early frontostriatal and frontoparietal deficit of dissociable functional networks associated with executive processing.

Action‐Based Model of Dissonance: A Review of Behavioral, Anterior Cingulate, and Prefrontal Cortical Mechanisms

AbstractResearch and theoretical developments on the theory of cognitive dissonance are reviewed. After this critical review, we present the action‐based model of dissonance, which accepts the original theory's proposal that a sufficient cognitive inconsistency causes dissonance and extends the original theory by proposing why cognitive inconsistency prompts dissonance. Finally, we present results from behavioral and physiological experiments examining predictions derived from the action‐based model. In particular, this evidence converges with recent neuroscience evidence in suggesting that the anterior cingulate cortex and left prefrontal cortical region are involved in conflict detection and resolution, respectively.

(140) Voxel based morphometry analysis of patients with chronic neuropathic pain

Complex regional pain syndrome (CRPS) is a debilitating chronic neuropathic pain condition. Central mechanisms have been proposed to play a role in the generation and maintenance of many chronic pain conditions. In this study we investigated regional gray matter volume (GMV) differences between CRPS patients and controls by performing voxelbased morphometry (VBM) analyses on high-resolution T1 magnetic resonance images. Eighteen right-handed patients with right upper extremity CRPS (mean age 41.7 11.3 (SD)) meeting IASP criteria for CRPS were matched with 25 right-handed controls (age 35.0 14.0). Statistical Parametrical Mapping 5 (SPM5) software and tools provided by Dr. Christian Gaser were used to process the data. Gray matter (GM) images were then submitted to an analysis of covariance (ANCOVA) regressing out age and total GMV (p 0.01 corrected). We found that CRPS patients, compared to controls, had significantly reduced GM in the cingulate to precuneus and increased GM in the right occipital cerebellar region. At a more lenient threshold, we found increased GM in the left lateral prefrontal region and the midbrain including periaqueductal gray. A second analysis (CRPS: n15, age 43.7 9.1 RH females with right upper-extremity CRPS; Controls: n15, age 41.6 12.8, RH females) showed similar trends. The increase in cerebellar volume may be due to repeated painful stimuli being processed through the cerebellothalamo-cortical pathways. Increases in periaqueductal gray may represent continued increased inhibitory activity in patients with chronic pain. The posterior cingulate and the precuneus are thought to be involved in the experience of pain -the posterior cingulate through the encoding of pain intensity, and the precuneas through emotional learning and integrative tasks. The areas of decreased GM are shown in functional studies to be hyperactive in pain patients adds further support to the theory that CRPS induces structural abnormalities in the human brain.

The capacity constraint in the prefrontal and parietal regions for coordinating dual arithmetic tasks

Using a dual-serial-arithmetic paradigm, we examined whether a capacity limitation constrains the neural activation that underlies dual-task performance. Six conditions were run in the experiment (the baseline, single-addition, single-subtraction, dual-addition, dual-subtraction, and the dual-operation condition). In the baseline condition, participants were asked to remember the initial pair of numbers and ignore subsequent stimuli. In the single-addition and single-subtraction conditions, participants had to calculate a running total over a series of stimuli. In the dual-addition and dual-subtraction conditions, they had to do two arithmetic tasks involving the same operand (e.g., + 2 and + 7, − 3 and − 5). Participants performed one addition and one subtraction task (e.g., + 2 and − 7, − 3 and + 5) in the dual-operation condition. The functional magnetic resonance imaging results showed strict left prefrontal and parietal regions in the single-addition condition and bilateral activation in the single-subtraction condition. Greater activation in the prefrontal and parietal regions was observed in both the dual-operation condition and the dual-addition condition in comparison to the single-addition condition. No greater activation was observed in either the dual-operation condition or dual-subtraction condition in comparison to the single-subtraction condition. These results suggest a constraint imposed by a limit in capacity for the neural activity subserving dual-task performance when one of the tasks places high resource demands on the executive network.

Physiologically Patterned Weak Magnetic Fields Applied Over Left Frontal Lobe Increase Acceptance of False Statements as True

Fifty men and women were exposed to only one of four experimentally generated magnetic fields over the left prefrontal region (above the eyebrow) or to a sham field immediately after the words “true” or “false” were presented following statements of definitions of words for a “foreign language”. Three of the patterns (25 Hz, 50 Hz, or burst-firing) with intensities between 1 and 10 microT were presented for 1 s during the refutation process (immediately after the offset of “true” or “false”) for specific statements from a total of 28 statements. The fourth pattern was a variable approximately 7–10 Hz (10 nT) field generated from the circuitry that was present continuously during the entire experiment. When the statements were presented again, the groups who had received the burst-firing (“limbic”) or 25 Hz pulsed magnetic fields during the refutation process accepted about twice the number of false statements as true compared to those exposed to the 50 Hz field or sham-field conditions. The treatments did not significantly affect the numbers of true statements accepted as false. These results suggest that the appropriately pulsed magnetic field during the refutation process of what one has been told or has heard can increase the probability a person will accept a false statement as true.

A Case of Oral Spelling Behavior: Another Environmental Dependency Syndrome

To present the case of a woman with a probable vascular dementia and a unique oral spelling behavior (OSB). Our aim was to better characterize the mechanisms underlying OSB in this patient with advanced cognitive and noncognitive deficits. Different kind of language deficits have been described in dementias and other related diseases. Other nonaphasic acquired communication disorders include a heterogeneous group of verbal impairment that are mainly due to attentional and executive impairments. We describe the neurolinguistic and neuropsychologic analysis of an 88-year-old woman with spontaneous OSB. Computed tomography-scan at the time of the clinical analysis is also presented. OSB occurred preferentially in spontaneous discourse, manifested in other language tasks, concerned all lexical categories, and was not accompanied by spelling deficit although language was not intact and disclosed foreign accent syndrome. Environmental dependency syndrome or utilization behavior was prominent and concerned various sensorimotor activities. We postulate that OSB was not secondary to a linguistic or more specifically to a spelling deficit but to another variant of environmental dependency syndrome and probably associated with a cortico-subcortical lesion including the left prefrontal region.

Functional Magnetic Resonance Imaging and Working Memory in Adolescents with Gestational Cocaine Exposure

To assess the effect of gestational cocaine exposure on the prefrontal cortex (PFC) with functional magnetic resonance imaging (fMRI). Using an n-back task, we obtained fMRI with a 3T Siemens scanner on 49 adolescents, 25 who were exposed to cocaine and 24 who were not exposed. The primary outcome was PFC activation during task performance. Five functionally derived regions of interest (ROI) were defined; in addition, 2 a priori anatomical ROIs were generated for Brodmann regions 10 and 46. Of the 49 adolescents who underwent imaging, data from 17 who were exposed to cocaine and 17 who were not exposed were in the final analysis. Groups had similar performance on the n-back task (P >/= .4), with both showing a fewer number of correct responses on the 2-back than the 1-back (P < .001), indicating increased demands on working memory with greater task difficulty. In functionally derived ROIs, imaging results showed increased activation for both groups in the 2-back versus the 1-back condition. In anatomical ROIs, both groups showed greater activation in the 2-back versus the 1-back condition, with activation in the non-exposed group proportionally greater for the left prefrontal region (P = .05). In this sample of adolescents, participants who were exposed to cocaine and participants who were not exposed were similar in performance on an executive function task and in fMRI activation patterns during task performance.

A Regions-of-Interest Volumetric Analysis of Mobility Limitations in Community-Dwelling Older Adults

In community-dwelling older adults, greater mobility impairment is associated with greater burden of diffuse brain structural abnormalities, such as higher white matter hyperintensities. This study examined the association between gray matter volumes of regions related to motor control, gait, and balance and whether this association is independent of burden of white matter hyperintensities. A random sample of 327 participants of the Cardiovascular Health Study (78.3 +/- 4.1 years old, 57% women) contributed brain magnetic resonance imaging (MRI) and mobility data. A brain imaging automated method measured gray matter volume in cerebellum, basal ganglia, and prefrontal and parietal cortex in both hemispheres. Gait speed was measured while walking 15 feet at usual pace. Standing balance was assessed by timing tandem stance. Associations between each region's volume and gait speed or balance were measured before and after adjustment for demographics, head size, cardiovascular risk factors, and 0-9 grading scores of white matter hyperintensities. Smaller left cerebellum and left prefrontal regions were associated with slower gait, independently of covariates and of white matter hyperintensities. Smaller right putamen, right posterior superior parietal cortex, and both left and right cerebellum were associated with balance difficulty, independently of covariates and white matter hyperintensities. Smaller gray matter volumes in regions crucial for motor control are associated with slower gait and poorer balance, and the association appears to be independent of other diffuse brain abnormalities such as white matter hyperintensities.

Findings of proton magnetic resonance spectometry in the dorsolateral prefrontal cortex in adolescents with first episodes of psychosis

Knowledge of the neurobiology of early onset psychosis is limited. We used proton magnetic resonance spectroscopy to investigate the possible existence of dorsolateral prefrontal brain biochemical abnormalities in adolescents with psychosis and to determine possible differential effects related to specific psychotic diagnoses. We measured the ratios of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) to water in two groups of adolescents with a first episode of psychosis (schizophrenia n = 8; non-schizophrenia n = 15) and in 32 healthy controls matched for age, gender, and years of education. Proton magnetic resonance spectroscopy at 1.5 T was used to study two 6.75-cc voxels placed in the left and right dorsolateral prefrontal region. The schizophrenia patients presented statistically significant reductions in NAA/water levels in the left dorsolateral prefrontal voxel as compared with non-schizophrenia patients and healthy controls. No significant differences were detected between groups for NAA/water in the right dorsolateral prefrontal voxel or for Cho/water and Cr/water levels in any hemisphere. A reduction of the NAA/water level in the left dorsolateral prefrontal region may be selectively present at the onset of psychosis during adolescence in patients who later progress to schizophrenia, but not in those who later progress to other psychotic disorders.

Abnormal Parietal Cortex Activation During Working Memory in Schizophrenia: Verbal Phonological Coding Disturbances Versus Domain-General Executive Dysfunction

Objective: The goal of this study was to determine whether the regions of the prefrontal and parietal cortices showing abnormal activation among individuals with schizophrenia during working memory tasks are associated with either 1) phonological coding processes that may be specific to verbal tasks (i.e., ventral prefrontal and parietal cortices) or 2) domain-general executive processes engaged by verbal and nonverbal tasks (i.e., dorsal prefrontal and parietal cortices). Method: The participants were 57 medicated individuals with schizophrenia and 120 healthy subjects. Functional magnetic resonance imaging was used to scan all participants during performance of verbal and nonverbal 2-back working memory tasks. Results: In the healthy subjects there was similar bilateral dorsal prefrontal and inferior parietal cortex activation for both the verbal and nonverbal working memory tasks, but greater left ventral prefrontal and parietal cortex activation during verbal compared to nonverbal working memory. Individuals with schizophrenia showed bilateral deficits in dorsal frontal and parietal activation during both verbal and nonverbal working memory tasks. They also demonstrated the typical pattern of greater activity for verbal, as compared to nonverbal, working memory in ventral prefrontal and parietal regions, although they showed less verbal superiority in a left ventral prefrontal region. Conclusions: These results support the hypothesis that working memory deficits in individuals with schizophrenia reflect deficits in activation of brain regions associated with the central executive components of working memory rather than domain-specific storage buffers.

Abnormal Parietal Cortex Activation During Working Memory in Schizophrenia: Verbal Phonological Coding Disturbances Versus Domain-General Executive Dysfunction

The goal of this study was to determine whether the regions of the prefrontal and parietal cortices showing abnormal activation among individuals with schizophrenia during working memory tasks are associated with either 1) phonological coding processes that may be specific to verbal tasks (i.e., ventral prefrontal and parietal cortices) or 2) domain-general executive processes engaged by verbal and nonverbal tasks (i.e., dorsal prefrontal and parietal cortices). The participants were 57 medicated individuals with schizophrenia and 120 healthy subjects. Functional magnetic resonance imaging was used to scan all participants during performance of verbal and nonverbal 2-back working memory tasks. In the healthy subjects there was similar bilateral dorsal prefrontal and inferior parietal cortex activation for both the verbal and nonverbal working memory tasks, but greater left ventral prefrontal and parietal cortex activation during verbal compared to nonverbal working memory. Individuals with schizophrenia showed bilateral deficits in dorsal frontal and parietal activation during both verbal and nonverbal working memory tasks. They also demonstrated the typical pattern of greater activity for verbal, as compared to nonverbal, working memory in ventral prefrontal and parietal regions, although they showed less verbal superiority in a left ventral prefrontal region. These results support the hypothesis that working memory deficits in individuals with schizophrenia reflect deficits in activation of brain regions associated with the central executive components of working memory rather than domain-specific storage buffers.

Metabolic and electric brain patterns during pleasant and unpleasant emotions induced by music masterpieces

Brain correlates comparing pleasant and unpleasant states induced by three dissimilar masterpiece excerpts were obtained. Related emotional reactions to the music were studied using Principal Component Analysis of validated reports, fMRI, and EEG coherent activity. A piano selection by Bach and a symphonic passage from Mahler widely differing in musical features were used as pleasing pieces. A segment by Prodromidès was used as an unpleasing stimulus. Ten consecutive 30 s segments of each piece alternating with random static noise were played to 19 non-musician volunteers for a total of 30 min of auditory stimulation. Both brain approaches identified a left cortical network involved with pleasant feelings (Bach and Mahler vs. Prodromidès) including the left primary auditory area, posterior temporal, inferior parietal and prefrontal regions. While the primary auditory zone may provide an early affective quality, left cognitive areas may contribute to pleasant feelings when melodic sequences follow expected rules. In contrast, unpleasant emotions (Prodromidès vs. Bach and Mahler) involved the activation of the right frontopolar and paralimbic areas. Left activation with pleasant and right with unpleasant musical feelings is consistent with right supremacy in novel situations and left in predictable processes. When all musical excerpts were jointly compared to noise, in addition to bilateral auditory activation, the left temporal pole, inferior frontal gyrus, and frontopolar area were activated suggesting that cognitive and language processes were recruited in general responses to music. Sensory and cognitive integration seems required for musical emotion.

Sex Differences in Neural Responses to Disgusting Visual Stimuli: Implications for Disgust-Related Psychiatric Disorders

A majority of patients with disgust-related psychiatric disorders such as animal phobias and contamination-related obsessive-compulsive disorder are women. The aim of this functional magnetic resonance imaging (fMRI) study was to examine possible sex differences in neural responses to disgust-inducing stimuli that might help explain this female predominance. Thirty-four healthy adult volunteers (17 women, all right-handed) were scanned while viewing alternating blocks of disgusting and neutral pictures from the International Affective Picture System. Using a partially-silent fMRI sequence, the participants rated their level of discomfort after each block of pictures. Skin conductance responses (SCR) were measured throughout the experiment. All participants completed the Disgust Scale. Both women and men reported greater subjective discomfort and showed more SCR fluctuations during the disgusting picture blocks than during the neutral picture blocks. Women and men also demonstrated a similar pattern of brain response to disgusting compared with neutral pictures, showing activation in the anterior insula, ventrolateral and dorsolateral prefrontal cortices, and visual regions. Compared with men, women had significantly higher disgust sensitivity scores, experienced more subjective discomfort, and demonstrated greater activity in left ventrolateral prefrontal regions. However, these differences were no longer significant when disgust sensitivity scores were controlled for. In healthy adult volunteers, there are significant sex-related differences in brain responses to disgusting stimuli that are irrevocably linked to greater disgust sensitivity scores in women. The implications for disgust-related psychiatric disorders are discussed.

Prefrontal White Matter Lesions and Prefrontal Task Impersistence in Depressed and Nondepressed Elders

Poor task persistence is often observed among depressed individuals, and may be associated with some of the same frontal regions that are involved in depression. The current study explored the association between white-matter lesion volume in prefrontal cortex and noncompletion rates on a complex neurocognitive task among older adults in a treatment study for depression. Older adults in treatment for depression (n=83) and nondepressed (n=47) elders were administered the Stockings of Cambridge subtest (SoC) of the Cambridge Automated Neuropsychological Testing Battery (CANTAB) and completed a brain magnetic resonance imaging scan as part of an ongoing research study. Noncompletion of the SoC occurred in approximately 19% of depressed participants (16/83) and only 2% of nondepressed participants (1/47), which was statistically significant. In multivariate models, failure to complete the SoC was consistently and significantly associated with greater volume of white matter lesions in the anterior-most region of prefrontal cortex, particularly in the left hemisphere, and with greater age. Although SoC completion was not significantly associated with depression severity, noncompletion rates were significantly higher among unremitted individuals and those with comorbid anxiety at study entry. The inability to initiate behavior sufficient to sustain a complex neurocognitive task is a characteristic of geriatric depression which may be associated with integrity of left-prefrontal regions. Future research should investigate whether task impersistence is a construct that generalizes to other neurocognitive tasks, and if it is associated with other adverse outcomes in geriatric depression related to cerebrovascular pathology, such as poor treatment response.

How necessary are the stripes of a tiger?: Diagnostic and characteristic features in an fMRI study of word meaning

This study contrasted two approaches to word meaning: the statistically determined role of high-contribution features like striped in the meaning of complex nouns like “tiger” typically used in studies of semantic memory, and the contribution of diagnostic features like parent's brother that play a critical role in the meaning of nominal kinds like “uncle.” fMRI monitored regional brain activity while participants read complex noun descriptions consisting of statistically high-contribution and low-contribution features; and nominal kind descriptions consisting of diagnostic and characteristic features. We found different patterns of activation depending on the type of noun and the type of feature contributing to the noun. Complex nouns recruited significantly greater bilateral superior temporal and left prefrontal activation compared to nominal kind nouns, while nominal kind nouns activated bilateral medial parietal and right inferior parietal regions more than complex nouns. Moreover, features making a statistically high contribution to complex noun meaning activated right inferior frontal cortex relative to low-contribution features, while diagnostic features of nominal kinds activated left dorsolateral prefrontal and right parietal regions more than characteristic features. These findings are consistent with the hypothesis that at least two different neural mechanisms appear to support word meaning: one driven by a statistically determined approach to feature knowledge, and the other sensitive to the qualitatively critical role that a specific diagnostic feature plays in word meaning.

Functional connectivity of the prefrontal cortex in Huntington’s disease

Background: Huntington’s disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions. Aim: To assess the functional connectivity between prefrontal brain regions in patients...

A High-Resolution Single Photon Emission Computed Tomography Study of Verbal Recognition Memory in Alzheimer’s Disease

Background: In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer’s disease (AD) subjects on a verbal recognition memory task. Methods: Eighteen early AD and 10 matched healthy control subjects underwent split-dose ^99mTc-HMPAO (Ceretec^®) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. Results: In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippocampus. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippocampus. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. Conclusions: Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.

Orthographic Distinctiveness and Semantic Elaboration Provide Separate Contributions to Memory

Orthographic distinctiveness and semantic elaboration both enhance memory. The present behavioral and functional magnetic resonance imaging (fMRI) studies examined the relationship between the influences of orthographic distinctiveness and semantic elaboration on memory, and explored whether they make independent contributions. As is typical for manipulations of processing levels, words studied during semantic encoding were better remembered than words studied during nonsemantic encoding. Notably, orthographically distinct words were better recalled and received more remember responses on recognition memory tests than orthographically common words regardless of encoding task, suggesting that orthographic distinctiveness has an additive effect to that of semantic elaboration on memory. In the fMRI study, orthographic distinctiveness and semantic elaboration engaged separate networks of brain regions. Semantic elaboration modulated activity in left inferior prefrontal and lateral temporal regions. In contrast, orthographic distinctiveness modulated activity in distinct bilateral inferior prefrontal, extrastriate, and parietal regions. Orthographic distinctiveness and semantic elaboration appear to have separate behavioral and functional-anatomic contributions to memory.

Age-related functional recruitment for famous name recognition: An event-related fMRI study

Recent neuroimaging research shows that older adults exhibit recruitment, or increased activation on various cognitive tasks. The current study evaluated whether a similar pattern also occurs in semantic memory by evaluating age-related differences during recognition of Recent (since the 1990s) and Enduring (1950s to present) famous names. Fifteen healthy older and 15 healthy younger adults performed the name recognition task with a high and comparable degree of accuracy, although older adults had slower reaction time in response to Recent famous names. Event-related functional MRI showed extensive networks of activation in the two groups including posterior cingulate, right hippocampus, temporal lobe and left prefrontal regions. The Recent condition produced more extensive activation than the Enduring condition. Older adults had more extensive and greater magnitude of activation in 15 of 20 regions, particularly for the Recent condition (15 of 15; 7 of 15 also differed for Enduring); young adults did not show greater activation magnitude in any region. There were no group differences for non-famous names, indicating that age differences are task-specific. The results support and extend the existing literature to semantic memory tasks, indicating that older adult brains use functional recruitment to support task performance, even when task performance accuracy is high.