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PubMed2001

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo (1)H-MRS study of the Stroop Color-Word task.

The neurobiology of cognitive interference is unknown. Previous brain imaging studies using the Stroop Color-Word (SCW) task indicate involvement of the cingulate cortex cognitive division. The present study examines interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectroscopy in the right and left anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, orbitofrontal cortex and thalamus) and cognitive interference (as measured by the SCW task) in 15 normal subjects. The results show that brain chemistry depends on cognitive interference levels (high vs low). Reduction of NAA levels was demonstrated in the right ACC (ie, cognitive midsupracallosal division) of high interference subjects, as compared to the low interference group (P < 0.01, two-tailed t-test). Chemical-cognitive relationships were analyzed by calculating correlations between regional NAA levels and the SCW task scores. Cognitive interference was highly correlated with the right anterior cingulate NAA (r = 0.76, P < 0.001), and was unrelated to other studied regional NAA, including the left ACC (P < 0.025; comparing the difference between r values in the right and left ACC). The interrelationships between NAA across brain regions were examined using correlation analysis (square matrix correlation maps), which detected different connectivity patterns between the two groups. These findings provide evidence of ACC involvement in cognitive interference suggesting a possibility of neuronal reorganization in the physiological mechanism of interference (most likely due to genetically predetermined control of the number of neurons, dendrites and receptors, and their function). We conclude that spectroscopic brain mapping of NAA, the marker of neuronal density and function, to the SCW task measures differentiates between high and low interference in normal subjects. This neuroimaging/cognitive tool may be useful for documentation of interference in studying cognitive control mechanisms, and in diagnosis of neuropsychiatric disorders where dysfunction of cingulate cortex is expected.

Adult↗

PubMedDate not supplied

Direct comparison of episodic encoding and retrieval of words: an event-related fMRI study.

Functional magnetic resonance imaging (fMRI) was used to compare directly episodic encoding and retrieval. During encoding, subjects studied visually presented words and reported via keypress whether each word represented a pleasant or unpleasant concept (intentional, deep encoding). During the retrieval phase, subjects indicated (via keypress) whether visually presented words had previously been studied. No reliable differences were found during the recognition phase for words that had been previously studied and those that had not been studied. Areas preferentially active during encoding (relative to retrieval) included left superior frontal cortex, medial frontal cortex, left superior temporal cortex, posterior cingulate, left parahippocampal gyrus, and left inferior frontal gyrus. Regions more active in retrieval than encoding included bilateral inferior parietal cortex, bilateral precuneus, right frontal polar cortex, right dorsolateral prefrontal cortex, and right inferior frontal/insular cortex.

Adult↗

PubMed2001

Separate neural correlates for the mnemonic components of successive discrimination and working memory tasks.

We have used positron emission tomography to map the mnemonic components of two tasks at the extremes of the visual short-term/ working memory spectrum. The successive discrimination task requires only storage of a single item for very short time (ultra-short- term memory), while the 2back task requires both maintenance (i.e. storage and rehearsal) and manipulation of several items (working memory). We tested whether or not the storage component, common to the two tasks, engaged the same cerebral regions. To remove unnecessary confounds, we reduced the cues available to the subjects to a single elementary attribute, the orientation of a grating presented in central vision. This prevented subjects from using verbal strategies or vestibular cues and allowed equating of difficulty among tasks. Ultra-short-term memory for orientation engaged a large expanse of occipito-temporal cortex with a rate-dependent antero-posterior gradient: a fast trial rate engaged posterior regions, a slow trial rate anterior regions. On the other hand, working memory for orientation involved the left inferior parietal cortex, left dorsolateral prefrontal cortex and a left superior frontal sulcus region, and to a lesser degree the symmetrical right superior frontal region and a left superior parietal region. Direct comparison of the two orientation memory networks confirmed their functional segregation. We conclude that at least the storage of orientation information engages distinct regions depending on whether or not short-term memory/working memory involves rehearsal and/or manipulative processes.

Adult↗

PubMed1999

Ipsilesional line bisection bias in patients with chronic parietal lesions.

The current study investigated whether an ipsilesional bias in line bisection, a conventional measure for diagnosing hemispatial neglect, persists even in the absence of this syndrome in patients with chronic lesions restricted to posterior association cortex or dorsolateral prefrontal cortex. Both left and right hemisphere parietal lesions produced ipsilesional bisection errors, and to a comparable degree. Patients with lesions in frontal cortex, on the other hand, did not show a consistent bias. We conclude that chronic parietal lesions produce an ipsilesional bias in line bisection, even in the absence of other clinical signs of neglect, and that left hemisphere lesions can affect line bisection to the same degree as right hemisphere lesions.

Adult↗

PubMed2004

Regional brain activity in women grieving a romantic relationship breakup.

OBJECTIVE: Separation from loved ones commonly leads to grief reactions. In some individuals, grief can evolve into a major depressive episode. The brain regions involved in grief have not been specifically studied. The authors studied brain activity in women actively grieving a recent romantic relationship breakup. It was hypothesized that while remembering their ex-partner, subjects would have altered brain activity in regions identified in sadness imaging studies: the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex. METHOD: Nine right-handed women whose romantic relationship ended within the preceding 4 months were studied. Subjects were scanned using blood-oxygen-level-dependent functional magnetic resonance imaging while they alternated between recalling a sad, ruminative thought about their loved one (grief state) and a neutral thought about a different person they knew an equally long time. RESULTS: Acute grief (grief minus neutral state) was associated with increased group activity in posterior brain regions, including the cerebellum, posterior brainstem, and posterior temporoparietal and occipital brain regions. Decreased activity was more prominent anteriorly and on the left and included the anterior brainstem, thalamus, striatum, temporal cortex, insula, and dorsal and ventral anterior cingulate/prefrontal cortex. When a more lenient statistical threshold for regions of interest was used, additional increases were found in the lateral temporal cortex, supragenual anterior cingulate/medial prefrontal cortex, and right inferomedial dorsolateral prefrontal cortex, all of which were adjacent to spatially more prominent decreases. In nearly all brain regions showing brain activity decreases with acute grief, activity decreases were greater in women reporting higher grief levels over the past 2 weeks. CONCLUSIONS: During acute grief, subjects showed brain activity changes in the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex, consistent with the hypothesis. Subjects with greater baseline grief showed greater decreases in all these regions except for the cerebellum. Further imaging studies are needed to understand the relationship between normal sadness, grief, and depression.

Brain↗

PubMed2005

Structural brain correlates of unconstrained motor activity in people with schizophrenia.

Avolition affects quality of life in chronic schizophrenia. We investigated the relationship between unconstrained motor activity and the volume of key executive brain regions in 16 male patients with schizophrenia. Wristworn actigraphy monitors were used to record motor activity over a 20 h period. Structural magnetic resonance imaging brain scans were parcellated and individual volumes for anterior cingulate cortex and dorsolateral prefrontal cortex extracted. Patients'total activity was positively correlated with volume of left anterior cingulate cortex. These data suggest that the volume of specific executive structures may affect (quantifiable) motor behaviours, having further implications for models of the 'will' and avolition.

Adult↗

PubMed1995

Functional MRI during word generation, using conventional equipment: a potential tool for language localization in the clinical environment.

OBJECTIVE: To test the accuracy of bilateral language mapping using a standard clinical magnetic resonance (MR) imaging device during word generation. DESIGN: A study of normal volunteers. SETTING: Volunteers from the Washington, DC, area. PARTICIPANTS: Nine normal, right-handed, native English speakers (four women, five men, mean age 31 years). INTERVENTIONS: During four MR acquisition periods, subjects would alternately rest and silently generate words. Sagittal MR images covered the middle and inferior frontal gyri, insulae, and part of the temporal and parietal lobes bilaterally. MAIN OUTCOME MEASURES: (1) Anatomic maps of task-related signal changes obtained by comparing, in each voxel, the signal during word generation and rest periods, and (2) analysis of the time course of the signal. RESULTS: Maximum responses were in the left hemisphere, mainly in the frontal lobe (Broca's area, premotor cortex, and dorsolateral prefrontal cortex) but also in posterior regions such as Wernicke's area. In agreement with previous studies, some degree of task-related changes was present in a subset of the corresponding regions in the right hemisphere. CONCLUSION: Despite certain limitations, it is possible, using widely available MR equipment, to obtain results consistent with previous studies. The technique may have important implications for assessment of cognitive functions in patients with neurologic disorders in a clinical environment.

Adult↗

PubMed2002

Changes in regional cerebral blood flow caused by deep-brain stimulation of the subthalamic nucleus in Parkinson's disease.

UNLABELLED: The aim of this study was to investigate the effect of deep-brain stimulation of the subthalamic nucleus (STN) on regional cerebral blood flow (rCBF) throughout the entire brain volume in patients with Parkinson's disease and to evaluate which of the brain areas showing an rCBF increase during STN stimulation related significantly to the improvement in motor function. METHODS: Ten consecutive Parkinson's disease patients (6 men, 4 women; mean age +/- SD, 59 +/- 8 y) with bilateral STN stimulators underwent 3 rCBF SPECT examinations at rest: the first preoperatively and the second and third postoperatively (follow-up, 4.8 +/- 1.4 mo) with STN stimulators on and off, respectively. The motor unified Parkinson's disease rating scale, the Hoehn and Yahr disability scale, and the Schwab and England activities-of-daily-living scale were used to evaluate the clinical state under each condition. Statistical parametric mapping was used to investigate rCBF during STN stimulation in comparison with rCBF preoperatively and with STN stimulators off. Also evaluated with statistical parametric mapping was the relationship between rCBF and individual motor scores used as covariates of interest. RESULTS: STN stimulation significantly changed rCBF in the right pre-supplementary motor area (pre-SMA), anterior cingulate cortex, and dorsolateral prefrontal cortex and in the medial Brodmann's area 8 (BA8) as defined in the atlas of Talairach and Tournoux (P < 0.05 corrected for multiple comparisons). The rCBF in these areas increased from the preoperative condition to the stimulators-on condition and decreased again after the stimulators were switched off. A significant correlation was detected between the improvement in motor scores and the rCBF increase only in the right pre-SMA and in the anterior cingulate motor area (P < 0.005, uncorrected). CONCLUSION: According to the topographic organization of the primate STN, our study shows that stimulation of the STN leads to rCBF increases in the motor (pre-SMA), associative, and limbic territories (anterior cingulate) in the frontal cortex. The significant correlation between motor improvement and rCBF increase in the pre-SMA and the anterior cingulate motor area reinforces the hypothesis that STN stimulation in parkinsonian patients can potentiate the cortical areas participating in higher-order aspects of motor control.

Brain↗

PubMed2004

[The neurofunctional foundation of cognitive rigidity in attention deficit hyperactivity disorder: some preliminary findings].

INTRODUCTION: It has been proposed that there is an impairment in cognitive flexibility in children with attention deficit hyperactivity disorder (ADHD). The Wisconsin card sorting test (WCST) is the most widely used neuropsychological test for assessing this process. Previous studies have reported the presence of a subgroup of children with ADHD which has a low cognitive flexibility. In addition this subgroup showed a high resistance to the treatment with stimulant medication. OBJECTIVES: The aim of this study was to examine whether there were different patterns of brain magnetic activity in different subgroups of ADHD, during the performance of a cognitive flexibility task, such as WCST. PATIENTS AND METHODS: We recruited a sample of 18 children, divided into three groups according to DSM IV R diagnostic criteria. Here we present preliminary data based on a subsample of nine children. Brain magnetic activity was registered while the children performed the WCST by means of Magnetoencephalography (MEG). This is a non invasive neuroimaging technique with a high spatio temporal resolution. RESULTS: Preliminary results showed that ADHD mixed group had a higher rate of perseverative responses. In addition, a different pattern of brain magnetic activity was noted in this group, showing less activation in anterior cingulate cortex and dorsolateral prefrontal cortex in the left hemisphere during the first 400 ms. CONCLUSIONS: MEG seems to be an useful tool to describe the brain network that subserves cognitive flexibility in different groups of children. It could have important repercussions in the classification of ADHD, both neuropsychologically and pharmacologically.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

[Neuropsychological and neuropathological interactions in affective and cognitive geriatric syndromes].

This paper reviews recent empirical findings related to depressive moods and cognitive functions in elderly persons. Vascular depression and major depression in Alzheimer disease (AD) are particularly common among elderly persons and, therefore, are discussed in light of the interactions among the cognitive deficits, the depressed moods and the neuropathologies. Functional imaging studies with depressed patients in several therapeutic or cognitive challenges have revealed that depression may involve impaired reciprocal interactions among the several important cognitive brain areas such as the hippocampus, anterior cingulate cortex and dorsolateral prefrontal cortex. Such impairment may be produced by the small ischemic changes in the subcortical areas of the frontal cortex in vascular depression and by the particular neurodegenerative processes in major depression in AD.

Adult↗

PubMed2005

[Neuropsychology of attention deficit hyperactivity disorder: relevant theories and empirical studies].

There is a rapidly accumulating body of knowledge related to the neurobiology of Attention Deficit Hyperactivity Disorder (ADHD) stemming from multidisciplinary neuropsychological and neuroimaging studies. This paper is a review of recent knowledge in the context of neuropsychological theory and research in this area. The final section of the article introduces animal models on the subject. It has been emphasized that the controversy regarding the results of neuropsychological studies is semantic rather than substantive. The semantic issue here is believed to be that the term "attention" has to be related to more than one anatomical network among several brain regions. ADHD, which has many cognitive and behavioral dimensions like attention deficit, hyperactivity and impulsivity, has a heterogeneous nature reflecting the neurobiological basis related to parallel information processing models. Based on clinical and neuropsychological data it has been stated that both the orbitofrontal cortex and dorsolateral prefrontal cortex are functionally disturbed in ADHD. However, whether these functional disturbances are related to the prefrontal cortex or other brain regions associated however primarily with this cortex is yet unclear. Dopamine and epinephrine as neurochemical factors and the frontal lobe and basal ganglia as anatomical factors have been found to be especially responsible. Valid endophenotypic features should be determined in order to specify genetic subtypes of neuropsychiatric syndromes. A review of the literature leads us to the conclusion that tests used to assess attentional components like the executive control network and behavioral inhibition could determine valid endophenotypes.

Animals↗

PubMed1991

The role of the inferior prefrontal convexity in performance of delayed nonmatching-to-sample.

Findings in an earlier study (Bachevalier, J. and Mishkin, M. Behav. Brain Res. 20, 249-261, 1986) indicated that ventromedial prefrontal cortex, which receives thalamic projections from the limbo-diencephalic system, is critical for visual recognition; whereas the dorsolateral prefrontal cortex, which receives no such thalamic projections, makes little or no contribution to this type of memory. In the present study, we examined the role in recognition of another prefrontal area outside the thalamic projection zone of the limbo-diencephalic system, namely, the inferior prefrontal convexity. In the first experiment, monkeys with lesions of this cortex (Group IC) were found to be impaired in relearning delayed nonmatching-to-sample (DNMS), but not on the subsequent DNMS performance test in which memory demands were greatly increased. In a second experiment, monkeys with combined lesions of the inferior and dorsolateral prefrontal cortex (Group LAT) were also found to be impaired in relearning DNMS, but in this case they were impaired, in addition, on the subsequent performance test. Neither group (IC or LAT) showed retardation in acquiring visual discrimination habits. Analysis of the DNMS behavior of both groups suggested that their deficits on this task were due not to a loss in recognition memory, but to various forms of perseverative interference. The results support the view that the inferior prefrontal convexity, like the dorsolateral prefrontal cortex, lies outside the limbo-diencephalic memory system not only anatomically but also functionally.

Animals↗

PubMed2003

Metabolic changes after repetitive transcranial magnetic stimulation (rTMS) of the left prefrontal cortex: a sham-controlled proton magnetic resonance spectroscopy (1H MRS) study of healthy brain.

Rapid transcranial magnetic stimulation is being increasingly used in the treatment of psychiatric disorders, especially major depression. However, its mechanisms of action are still unclear. The aim of this study was to assess metabolic changes by proton magnetic resonance spectroscopy following high-frequency rapid transcranial magnetic stimulation (20 Hz), both immediately after a single session and 24 h after a series of five consecutive sessions. Twelve healthy volunteers were enrolled in a prospective single-blind, randomized study [sham (n = 5) vs. real (n = 7)]. Three brain regions were investigated (right, left dorsolateral prefrontal cortex, left anterior cingulate cortex). A single as well as a series of consecutive rapid transcranial magnetic stimulations affected cortical glutamate/glutamine levels. These effects were present not only close to the stimulation site (left dorsolateral prefrontal cortex), but also in remote (right dorsolateral prefrontal cortex, left cingulate cortex) brain regions. Remarkably, the observed changes in glutamate/glutamine levels were dependent on the pre-transcranial magnetic stimulation glutamate/glutamine concentration, i.e. the lower the pre-stimulation glutamate/glutamine level, the higher the glutamate/glutamine increase observed after short- or long-term stimulation (5 days). In general, the treatment was well tolerated and no serious side-effects were reported. Neither transient mood changes nor significant differences in the outcome of a series of neuropsychological test batteries after real or sham transcranial magnetic stimulation occurred in our experiment. In summary, these data indicate that rapid transcranial magnetic stimulation may act via stimulation of glutamatergic prefrontal neurons.

Adult↗

PubMed1998

Lesions of the caudal area of rabbit medial prefrontal cortex impair trace eyeblink conditioning.

The dorsolateral prefrontal cortex of the primate is an area known to be important for memory. Since the discovery of a homologous area in subprimate mammals, the caudal medial prefrontal cortex, rabbits have become useful in the investigation of working memory. The subprimate prefrontal cortex is intimately interconnected with the hippocampus, which is also recognized for its role in learning and memory. In addition, the hippocampus and prefrontal cortex have been shown to be similarly involved in a variety of tasks. Therefore, we hypothesized that the caudal medial prefrontal cortex of the rabbit would be necessary for acquisition of the hippocampally dependent trace eyeblink conditioning task. A total of 16 young rabbits (Oryctolagus cuniculus) received bilateral aspiration lesions of the prefrontal cortex. Six of the lesioned subjects were unable to acquire the trace eyeblink conditioning task, but were unimpaired when tested subsequently in the hippocampally independent delay conditioning task. The lesions of these 6 subjects either were limited to or extended into the caudal medial prefrontal cortex. In the remaining 10 subjects, which were not impaired in trace conditioning, the lesions were limited to the rostral pole. Our results support our original hypothesis and provide further evidence of the involvement of the subprimate caudal medial prefrontal cortex in learning.

Animals↗

PubMed1998

A review of differences between basal ganglia and cerebellar control of movements as revealed by functional imaging studies.

The role of the basal ganglia and cerebellum in the control of movements is unclear. We summarize results from three groups of PET studies of regional CBF. The results show a double dissociation between (i) selection of movements, which induces differential effects in the basal ganglia but not the cerebellum, and (ii) sensory information processing, which involves the cerebellum but not the basal ganglia. The first set of studies concerned motor learning of a sequence of finger movements; there was a shift of activation in the anterior-posterior direction of the basal ganglia which paralleled changes in the motor areas of the frontal cortex. During new learning, the dorsolateral prefrontal cortex and striatum (caudate nucleus and anterior putamen) were activated. When subjects had to select movements, the premotor cortex and mid-putamen were activated. With automatic (overlearned) movements, the sensorimotor cortex and posterior putamen were activated. When subjects paid attention to overlearned actions, activation shifted back to the dorsolateral prefrontal cortex and striatum. The cerebellum was not activated when subjects made new decisions, attended to their actions or selected movements. These results demonstrate components of basal ganglia-(thalamo)-cortical loops in humans. According to earlier studies in animals we propose that the basal ganglia may be concerned with selecting movements or the selection of appropriate muscles to perform a movement selected by cortical areas (e.g. premotor cortex). Secondly, a visuomotor co-ordination task was examined. In the absence of visual control over arm movements, subjects were required to use a computer mouse to either generate new lines or to re-trace lines on a computer screen. The neocerebellum (hemispheres of the posterior lobe, cerebellar nuclei and cerebellar vermis), not the basal ganglia, was more engaged when lines were re-traced (compared with new line generation). Animal experiments have shown that error detection (deviation from given lines) and correction occurs during line re-tracing but not line generation. Our data suggest that the neocerebellum (not the basal ganglia) is involved in monitoring and optimizing movements using sensory (proprioceptive) feedback. Thirdly, the relative contribution of sensory information processing to the signal during active/passive execution of a motor task (flexion and extension of the elbow) was examined; it was found that 80-90% of the neocerebellar signal could be attributed to sensory information processing. The basal ganglia were not involved in sensory information processing. They may be concerned with movement/ muscle selection (efferent motor component); the neocerebellum may be concerned with monitoring the outcome (afferent sensory component) and optimizing movements using sensory (feedback) information.

Basal Ganglia↗

PubMed1998

Common pattern of cortical pathology in childhood-onset and adult-onset schizophrenia as identified by proton magnetic resonance spectroscopic imaging.

OBJECTIVE: Multislice proton magnetic resonance spectroscopic imaging (1H-MRSI) permits simultaneous acquisition and mapping of signal intensities of N-acetyl-containing compounds (mainly N-acetylaspartate, NAA), choline-containing compounds (CHO), and creatine plus phosphocreatine (CRE) from multiple whole-brain slices consisting of small single-volume elements. Previous 1H-MRSI studies of adult patients with schizophrenia showed small NAA relative signals in the hippocampal area and in the dorsolateral prefrontal cortex in comparison with healthy subjects. As part of a program to address the pathophysiological continuity between childhood-onset and adult-onset schizophrenia, the authors performed 1H-MRSI of patients with childhood-onset schizophrenia to specifically test whether the hippocampal area and dorsolateral prefrontal cortex show the same abnormalities as seen in adult-onset schizophrenia. METHOD: A 1.5-T nuclear magnetic resonance machine was used to test 14 patients (mean age, 16.4 years) and 14 comparison subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions. RESULTS: The patients showed significantly lower NAA/CRE ratios bilaterally in the hippocampal area and the dorsolateral prefrontal cortex than the comparison subjects. There were no significant differences in CHO/CRE or in NAA ratios in any other area sampled. CONCLUSIONS: The present study shows that patients with childhood-onset schizophrenia have smaller than normal regional NAA relative signals, suggesting neuronal damage or malfunction in the hippocampal area and dorsolateral prefrontal cortex. These differences were similar in magnitude to those found in patients with adult-onset schizophrenia. The present data extend other evidence of a biological continuum between childhood- and adult-onset schizophrenia.

Adolescent↗

PubMed2003

Up-regulation of the D1 dopamine receptor-interacting protein, calcyon, in patients with schizophrenia.

BACKGROUND: The dopamine hypothesis remains a prominent influence on research into the pathogenesis of schizophrenia, yet the presence of consistent schizophrenia-linked abnormalities in the presynaptic components of the dopamine system or in dopamine receptors still remains a matter of debate. The present study focuses on a recently recognized group of dopamine receptor-interacting proteins as possible novel sites of dysfunction in schizophrenia. Specifically, we examined whether the D1 dopamine receptor-interacting protein calcyon and the D2 dopamine receptor-interacting proteins filamin-A and spinophilin are affected in the dorsolateral prefrontal cortex of patients with schizophrenia. METHODS: Slot blots of dorsolateral prefrontal cortical tissue were used to compare the levels of the 3 proteins of interest in control, schizophrenic, bipolar, and major depression groups (n = 15 per group). The nonschizophrenic psychiatric groups were included to determine the specificity of the detected abnormalities. RESULTS: The dorsolateral prefrontal cortex in schizophrenic patients displayed nearly twice the normal levels of calcyon, whereas filamin-A and spinophilin levels were unaltered. Patients with bipolar disorder or major depression showed no changes in all 3 proteins examined. CONCLUSION: Our findings provide the first evidence that abnormalities in the dopamine system of patients with schizophrenia may lie in altered levels of dopamine receptor-interacting proteins.

Animals↗

PubMed1998

A developmental approach to severe depression.

Reduced rapid-eye-movement (REM) sleep latency and increased REM sleep activity are associated not only with increased risk of recurrent depressive episodes but also with shortened time to the onset of subsequent episodes. Increased REM sleep activity might be a sign of attempt to excite the photic-responsive brain regions during the night, and there is a negative correlation between regional blood flow in the dorsolateral prefrontal cortex and REM sleep. The relative deactivation of the dorsolateral prefrontal cortex as a result of a developmental abnormality could explain the increased REM sleep activity during the first half of the night and the subsequent terminal insomnia among depressed subjects.

Animals↗