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Brain : a Journal of Neurology Feb 2015Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be...
Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be combined with electroencephalography to index long-interval cortical inhibition, a measure of GABAergic receptor-mediated inhibitory neurotransmission from the frontal and motor cortex. In previous studies we have reported that schizophrenia is associated with inhibitory deficits in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder. The main objective of the current study was to replicate and extend these initial findings by evaluating long-interval cortical inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia compared to patients with obsessive-compulsive disorder. A total of 111 participants were assessed: 38 patients with schizophrenia (average age: 35.71 years, 25 males, 13 females), 27 patients with obsessive-compulsive disorder (average age: 36.15 years, 11 males, 16 females) and 46 healthy subjects (average age: 33.63 years, 23 females, 23 males). Long-interval cortical inhibition was measured from the dorsolateral prefrontal cortex and motor cortex through combined transcranial magnetic stimulation and electroencephalography. In the dorsolateral prefrontal cortex, long-interval cortical inhibition was significantly reduced in patients with schizophrenia compared to healthy subjects (P = 0.004) and not significantly different between patients with obsessive-compulsive disorder and healthy subjects (P = 0.5445). Long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex were also significantly greater in patients with schizophrenia compared to patients with obsessive-compulsive disorder (P = 0.0465). There were no significant differences in long-interval cortical inhibition across all three groups in the motor cortex. These results demonstrate that long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex are specific to patients with schizophrenia and are not a generalized deficit that is shared by disorders of severe psychopathology.
Topics: Adult; Anatomy, Cross-Sectional; Antipsychotic Agents; Electroencephalography; Electromyography; Female; Humans; Inhibition, Psychological; Male; Motor Cortex; Obsessive-Compulsive Disorder; Prefrontal Cortex; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Transcranial Magnetic Stimulation
PubMed: 25524710
DOI: 10.1093/brain/awu360 -
Neurology and Therapy Jun 2021Precise stereotactic targeting of the dorsolateral motor part of the subthalamic nucleus (STN) is paramount for maximizing clinical effectiveness and preventing side... (Review)
Review
Precise stereotactic targeting of the dorsolateral motor part of the subthalamic nucleus (STN) is paramount for maximizing clinical effectiveness and preventing side effects of deep brain stimulation (DBS) in patients with advanced Parkinson's disease. With recent developments in magnetic resonance imaging (MRI) techniques, direct targeting of the dorsolateral part of the STN is now feasible, together with visualization of the motor fibers in the nearby internal capsule. However, clinically relevant discrepancies were reported when comparing STN borders on MRI to electrophysiological STN borders during microelectrode recordings (MER). Also, one should take into account the possibility of a 3D inaccuracy of up to 2 mm of the applied stereotactic technique. Pneumocephalus and image fusion errors may further increase implantation inaccuracy. Even when implantation has been successful, suboptimal lead anchoring on the skull may cause lead migration during follow-up. Meticulous pre- and intraoperative imaging is therefore indispensable, and so is postoperative imaging when the effects of DBS deteriorate during follow-up. Thus far, most DBS centers employ MRI targeting, multichannel MER, and awake test stimulation in STN surgery, but randomized trials comparing surgery under local versus general anesthesia and additional studies comparing MER-STN borders to high-field MRI-STN may change this clinical practice. Further developments in imaging protocols and improvements in image fusion processes are needed to optimize placement of DBS leads in the dorsolateral motor part of the STN in Parkinson's disease.
PubMed: 33565018
DOI: 10.1007/s40120-021-00233-8 -
Indian Journal of Psychiatry Apr 2013Schizophrenia is a disorder with variable outcome and the ability to predict the outcome has important clinical utility. Neurological soft signs (NSS) and dorsolateral...
Schizophrenia is a disorder with variable outcome and the ability to predict the outcome has important clinical utility. Neurological soft signs (NSS) and dorsolateral prefrontal cortex volumes have been described as trait markers for schizophrenia and their relation to long-term outcome in schizophrenia has not been well studied. The aim of this study was to examine the correlation between baseline dorsolateral prefrontal lobe (DLPFL) volume and NSS scores to clinical and functional outcome variables in a cohort of schizophrenia patients who were anti-psychotic naïve at baseline. Fourteen anti-psychotic naive schizophrenia patients whose baseline magnetic resonance imaging scans, NSS scores and positive and negative signs and symptoms scale (PANSS) scores (assessed in drug naïve state) were available were reevaluated after a mean follow-up period of 74.2±24.2 months. The clinical outcome variables measured was PANSS. The social and functional outcome was assessed comprehensively by the socio occupational functioning scale and the Strauss Carpenter outcome scale. The DLPFL, volume was measured from the baseline scans using the region of interest method. Statistical analysis was done using the paired samples t-test and the Pearson's correlation co-efficient. The results showed that smaller left DLPFL volume and greater primitive reflexes at baseline predicted greater negative symptoms and poorer functional outcome on follow-up. This study also demonstrates the clinical utility of NSS as a simple bedside tool in assessing schizophrenia patients.
PubMed: 23825842
DOI: 10.4103/0019-5545.111445 -
Journal of Clinical Medicine Jul 2021The present study had three main aims: (1) to explore the possible relationships between the two dimensions of negative symptoms (NS) with the three frontal behavioral...
The present study had three main aims: (1) to explore the possible relationships between the two dimensions of negative symptoms (NS) with the three frontal behavioral syndromes (dorsolateral, orbitofrontal and the anterior or mesial cingulate circuit) in patients with schizophrenia; (2) to determine the influence of sociodemographic and clinical variables on the severity of the two dimensions of NS (expressive deficits and disordered relationships/avolition); and (3) to explore the possible relationships between the two dimensions of NS and social functioning. We evaluated a group of 33 patients with schizophrenia with a predominance of NS using the self-reported version of the Frontal System Behavior scale. To quantify the severity of NS, the Assessment of Negative Symptoms (SANS) scale was used. The results revealed that the two dimensions of NS correlate positively with the behavioral syndrome of dorsolateral prefrontal origin. Regarding the influence of sociodemographic and clinical variables, in patients with a long evolution the NS of the expressive deficits dimension were less severe than in patients with a short evolution. A negative correlation was found between the severity of NS of the disordered relationships/avolition dimension and perceived social functioning. Our results show the importance of differentiating between the two dimensions of NS to characterize better their possible frontal etiology and impact on clinical course and social functioning.
PubMed: 34362200
DOI: 10.3390/jcm10153417 -
NeuroImage Dec 2022Intergenerational sustainability requires people of the present generation to make sacrifices today to benefit others of future generations (e.g. mitigating climate...
Intergenerational sustainability requires people of the present generation to make sacrifices today to benefit others of future generations (e.g. mitigating climate change, reducing public debt). Individuals vary greatly in their intergenerational sustainability, and the cognitive and neural sources of these interindividual differences are not yet well understood. We here combined neuroscientific and behavioral methods by assessing interindividual differences in cortical thickness and by using a common-pool resource paradigm with intergenerational contingencies. This enabled us to look for objective, stable, and trait-like neural markers of interindividual differences in consequential intergenerational behavior. We found that individuals behaving sustainably (vs. unsustainably) were marked by greater cortical thickness of the dorsomedial and dorsolateral prefrontal cortex. Given that these brain areas are involved in perspective-taking and self-control and supported by mediation analyses, we speculate that greater cortical thickness of these brain areas better enable individuals to take the perspective of future generations and to resist temptations to maximize personal benefits that incur costs for future generations. By meeting recent calls for the contribution of neuroscience to sustainability research, it is our hope that the present study advances the transdisciplinary understanding of interindividual differences in intergenerational sustainability.
Topics: Humans; Prefrontal Cortex; Dorsolateral Prefrontal Cortex; Brain; Magnetic Resonance Imaging
PubMed: 36202158
DOI: 10.1016/j.neuroimage.2022.119664 -
Schizophrenia Research May 2022Clozapine (CLZ) demonstrates a unique clinical efficacy relative to other antipsychotic drugs. Previous work has linked the plasma ratio of CLZ and its major metabolite,...
Clozapine (CLZ) demonstrates a unique clinical efficacy relative to other antipsychotic drugs. Previous work has linked the plasma ratio of CLZ and its major metabolite, N-desmethylclozapine (NDMC), to an inverse relationship with cognition via putative action on the cholinergic system. However, neuroimaging correlates of CLZ/NDMC remain unknown. Here, we examined changes in basal forebrain functional connectivity with the dorsolateral prefrontal cortex, and secondly, cognition in relation to the CLZ/NDMC ratio. A cohort of nineteen chronically ill participants with treatment-resistant schizophrenia (TRS) undergoing 12 weeks of CLZ treatment were included. Measures of cognition and plasma CLZ/NDMC ratios were obtained in addition to resting-state functional neuroimaging scans, captured at baseline and after 12 weeks of CLZ treatment. We observed a significant correlation between basal forebrain-DLPFC connectivity and CLZ/NDMC ratios across CLZ treatment (p = 0.02). Consistent with previous findings, we also demonstrate a positive relationship between CLZ/NDMC ratio and working memory (p = 0.03). These findings may reflect the action of CLZ and NDMC on the muscarinic cholinergic system, highlighting a possible neural correlate of cognition across treatment.
Topics: Antipsychotic Agents; Basal Forebrain; Cholinergic Agents; Clozapine; Dorsolateral Prefrontal Cortex; Humans; Schizophrenia; Schizophrenia, Treatment-Resistant
PubMed: 35381515
DOI: 10.1016/j.schres.2022.03.014 -
Neuropsychologia Jan 2008We used neuropsychological tasks to investigate integrity of brain circuits linking orbitofrontal cortex and amygdala (orbitofrontal-amygdala), and dorsolateral...
We used neuropsychological tasks to investigate integrity of brain circuits linking orbitofrontal cortex and amygdala (orbitofrontal-amygdala), and dorsolateral prefrontal cortex and hippocampus (dorsolateral prefrontal-hippocampus), in 138 individuals aged 7-18 years, with and without autism. We predicted that performance on orbitofrontal-amygdala tasks would be poorer in the Autism group compared to the Non-Autism group regardless of intellectual level (verbal mental age, VMA) and that performance on dorsolateral prefrontal-hippocampus tasks would be associated primarily with intellectual level. Predicted differences between Autism and Non-Autism groups on orbitofrontal-amygdala tasks were present but greater in individuals with higher VMA. On dorsolateral prefrontal-hippocampus tasks, poorer performance by the Autism compared to the Non-Autism group was found at all VMA levels. Group differences suggest both brain circuits are impaired in autism, but performance on all tasks is also associated with intellectual level.
Topics: Adolescent; Autistic Disorder; Avoidance Learning; Child; Discrimination, Psychological; Female; Frontal Lobe; Humans; Limbic System; Male; Memory; Neuropsychological Tests; Pattern Recognition, Visual; Photic Stimulation; Space Perception
PubMed: 17936314
DOI: 10.1016/j.neuropsychologia.2007.08.017 -
The Journal of Comparative Neurology Nov 2008To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an...
To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed nonmatching to sample, or DNMS) and a spatial (delayed nonmatching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-second delay, suggesting disrupted retention of the general task rules; however, this impairment was transient, and long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a nonmatching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals.
Topics: Animals; Behavior, Animal; Dogs; Female; Humans; Learning; Male; Memory Disorders; Prefrontal Cortex; Psychomotor Performance; Spatial Behavior
PubMed: 18792072
DOI: 10.1002/cne.21821 -
Journal of Integrative Neuroscience May 2022The prefrontal cortex (PFC) has been reported to be related to memory function. Especially, the dorsolateral PFC (DLPFC) is a substantial neural structure in short-term...
BACKGROUND
The prefrontal cortex (PFC) has been reported to be related to memory function. Especially, the dorsolateral PFC (DLPFC) is a substantial neural structure in short-term memory. In this study, using diffusion tensor tractography (DTT), we investigated the relationship between short-term memory impairment and the DLPFC injury in patients with mild traumatic brain injury (TBI).
METHODS
We recruited 46 consecutive chronic patients with mild TBI and 42 normal control subjects. Fractional anisotropy (FA) and fiber number (FN) of the prefronto-thalamic tracts were determined for both hemispheres.
RESULTS
Significant differences were detected in the FA value of the DLPFC and FN value of the prefronto-thalamic tracts in the patient and control groups ( < 0.05). However, no significant differences were detected in the ventrolateral PFC (VLPFC) and orbitofrontal cortex (OFC) between the patient and control groups ( > 0.05). In addition, the FN value of the DLPFC showed moderate positive correlation with short-term memory ( = 0.510, < 0.05). However, no significant correlations were detected between the short-term memory and the FA value of the DLPFC, and the FA and FN values of the VLPFC and OFC in the patient group ( > 0.05).
CONCLUSIONS
We found that the short-term memory impairment was closely associated with the DLPFC injury in patients with mild TBI. Our results suggest that the estimation of the DLPFC using DTT would be useful for patients with severity of short-term memory impairment following mild TBI.
Topics: Brain Concussion; Diffusion Tensor Imaging; Dorsolateral Prefrontal Cortex; Humans; Memory, Short-Term; Prefrontal Cortex
PubMed: 35633174
DOI: 10.31083/j.jin2103093 -
The Journal of Neuroscience : the... Oct 2015The role of neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of the midbrain in contributing to the elicitation of reward prediction errors during...
UNLABELLED
The role of neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of the midbrain in contributing to the elicitation of reward prediction errors during appetitive learning has been well established. Less is known about the differential contribution of these midbrain regions to appetitive versus aversive learning, especially in humans. Here we scanned human participants with high-resolution fMRI focused on the SN and VTA while they participated in a sequential Pavlovian conditioning paradigm involving an appetitive outcome (a pleasant juice), as well as an aversive outcome (an unpleasant bitter and salty flavor). We found a degree of regional specialization within the SN: Whereas a region of ventromedial SN correlated with a temporal difference reward prediction error during appetitive Pavlovian learning, a dorsolateral area correlated instead with an aversive expected value signal in response to the most distal cue, and to a reward prediction error in response to the most proximal cue to the aversive outcome. Furthermore, participants' affective reactions to both the appetitive and aversive conditioned stimuli more than 1 year after the fMRI experiment was conducted correlated with activation in the ventromedial and dorsolateral SN obtained during the experiment, respectively. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts.
SIGNIFICANCE STATEMENT
The role of the substantia nigra (SN) and ventral tegmental area (VTA) in appetitive learning is well established, but less is known about their contribution to aversive compared with appetitive learning, especially in humans. We used high-resolution fMRI to measure activity in the SN and VTA while participants underwent higher-order Pavlovian learning. We found a regional specialization within the SN: a ventromedial area was selectively engaged during appetitive learning, and a dorsolateral area during aversive learning. Activity in these areas predicted affective reactions to appetitive and aversive conditioned stimuli over 1 year later. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts.
Topics: Adult; Appetite; Avoidance Learning; Blinking; Computer Simulation; Conditioning, Classical; Emotions; Female; Heart Rate; Humans; Image Processing, Computer-Assisted; Male; Models, Biological; Motion; Nerve Net; Oxygen; Pupil; Respiration; Substantia Nigra; Taste; Young Adult
PubMed: 26490862
DOI: 10.1523/JNEUROSCI.2277-15.2015