The influence of rTMS over the left dorsolateral prefrontal cortex on Stroop task performance

Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive processing. Neuroimaging studies have shown the engagement of the left dorsolateral prefrontal cortex (DLPFC) in executive functioning, and more specifically during selective attention. In the present study, the influence of high-frequency rTMS over the left DLPFC on Stroop task performance in healthy female volunteers was investigated. As expected, reaction time on both the incongruent and congruent trials decreased significantly after stimulation, and there was no difference with regard to the Stroop interference effect. Mood remained unchanged after rTMS. Such a pattern is consistent with the role of the left DLPFC in implementing top–down attentional control.     

Theta burst stimulation of dorsolateral prefrontal cortex modulates pathological language switching: A case report

Although different lesion and neuroimaging studies had highlighted the importance of the dorsolateral prefrontal cortex (DLPFC) in language switching, the nature of this higher cortical disorder of communication and its neural correlates have not been clearly established. To further investigate the functional involvement of the DLPFC, we used transcranial magnetic stimulation (TMS) given as theta burst stimulation (TBS) in a bilingual patient showing pathologic language switching after an ischemic stroke involving the left frontal lobe. Inhibitory and excitatory TBS were applied to the left DLPFC, to the right DLPFC, or to an occipital cortical control site. A short-lasting interruption of the pathological language switching occurred after excitatory left DLPFC stimulation, while inhibitory left DLPFC TBS transiently increased the number of utterances produced in the unwanted second language. Effects were non-significant after right DLPFC and occipital TBS. Our findings suggest that left DLPFC is actively involved in language switching. TMS techniques may help in understanding the neural bases of bilingualism.     

Anodal tDCS of dorsolateral prefontal cortex during an Implicit Association Test

Anodal stimulation of dorsolateral prefrontal cortex by transcranial Direct Current Stimulation (tDCS) has been shown to enhance performance on working memory tasks. However, it is not yet known precisely which aspects of working memory – a broad theoretical concept including short-term memory and various executive functions – are involved in such effects. In the current study, we aimed to determine whether tDCS would reduce bias effects on an Implicit Association Test, in which subjects must respond either congruently or incongruently to pre-existing evaluative associations. Such biases reflect a conflict between automatic associations and executive function, and tDCS was hypothesized to cause a shift in this balance in favor of executive function. The results clearly contradicted this hypothesis: tDCS did improve reaction times, but in the congruent rather than incongruent mapping condition. We conclude that DLPFC tDCS does not directly improve the ability to overcome bias; previous findings concerning working memory enhancement appear to reflect effects on a different component of executive function.     

Comparison of human infants and rhesus monkeys on Piaget's AB task: evidence for dependence on dorsolateral prefrontal cortex

Summary This paper reports evidence linking dorsolateral prefrontal cortex with one of the cognitive abilities that emerge between 7.5–12 months in the human infant. The task used was Piaget's Stage IV Object Permanence Test, known as AB (pronounced A not B). The AB task was administered (a) to human infants who were followed longitudinally and (b) to intact and operated adult rhesus monkeys with bilateral prefrontal and parietal lesions. Human infants displayed a clear developmental progression in AB performance, i.e., the length of delay required to elicit the AB error pattern increased from 2–5 s at 7.5–9 months to over 10 s at 12 months of age. Monkeys with bilateral ablations of dorsolateral prefrontal cortex performed on the AB task as did human infants of 7.5–9 months; i.e., they showed the AB error pattern at delays of 2–5 s and chance performance at 10 s. Unoperated and parietally operated monkeys succeeded at delays of 2, 5, and 10 s; as did 12 month old human infants. AB bears a striking resemblance to Delayed Response, the classic test for dorsolateral prefrontal function in the rhesus monkey, and indeed performance on AB and Delayed Response in the same animals in the present study was fully comparable. These findings provide direct evidence that AB performance depends upon dorsolateral prefrontal cortex in rhesus monkeys and indicates that maturation of dorsolateral prefrontal cortex may underlie the developmental improvement in AB performance of human infants from 7.5–12 months of age. This improvement marks the development of the ability to hold a goal in mind in the absence of external cues, and to use that remembered goal to guide behavior despite the pull of previous reinforcement to act otherwise. This confers flexibility and freedom to choose and control what one does.     

Influence of transcranial direct current stimulation of the dorsolateral prefrontal cortex on pain related emotions: A study using electroencephalographic power spectrum analysis

Pain is a multidimensional experience with sensory-discriminative, cognitive-evaluative and affective-motivational components. Emotional factors such as unpleasantness or anxiety are known to have influence on pain in humans. The aim of this single-blinded, cross over study was to evaluate the effects of transcranial direct current stimulation (tDCS) on emotional aspects of pain in pain alleviation. Fifteen subjects (5 females, 10 males) volunteered to participate in this study. In an oddball paradigm, three categories of 20 pictures (unpleasant, neutral, and pleasant) served as rare target pictures from the International Affective Picture System (IAPS). The power of the delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–25 Hz), and gamma (30–40 Hz) frequency bands in the three categories were measured using electroencephalography during an oddball paradigm at pre- and post-anodal or sham tDCS above the left dorsolateral prefrontal cortex (DLPFC). Results showed that the beta band power was significantly increased, and the alpha band power was significantly decreased during unpleasant pictures after anodal tDCS compared with sham tDCS. Furthermore, regarding unpleasant pictures, subjective reports of Self Assessment Manikin (SAM) for emotional valence after anodal tDCS showed a significant decrease of unpleasantness. Therefore, emotional aspects of pain may be effectively alleviated by tDCS of the left DLPFC as was shown not only by subjective evaluation, but also by objective observation of cerebral neural activity. This processing may be mediated by facilitation of the descending pain inhibitory system through enhancing neural activity of the left DLPFC.     

Altered MHC class I expression in dorsolateral prefrontal cortex of nonsmoker patients with schizophrenia

Schizophrenia (SZ) is a psychiatric disease with plausible neurodevelopmental etiology. Although genetic studies show significant association of immune molecules loci such as major histocompatibility complex (MHC) class I with SZ, it is not clear whether these immune molecules are involved in the pathology observed in SZ brains. MHC class I and the classical pathway components of complement system (C1q and C3) have been shown to regulate brain neuronal maturation and function. We have examined the expression of MHC class I and complement protein C3 in two frontal cortical regions of postmortem brains of SZ patients. Since cigarette smoking may modulate MHC class I protein expression and a higher rate of smoking is observed in SZ patients, we studied the expression of MHC class I and C3 in relation to the presence of smoking. We found that MHC class I protein expression is reduced in the dorsolateral prefrontal cortex (DLPFC) but not in the orbitofrontal cortex (OFC) of nonsmoker SZ patients. We did not observe SZ-associated changes in C3 mRNA expression. Our exploratory research suggests a potential involvement of MHC class I in SZ and implies that smoking might modulate its expression.     

Activity of primate orbitofrontal and dorsolateral prefrontal neurons: task-related activity during an oculomotor delayed-response task

The orbitofrontal cortex (OFC) has strong reciprocal connections to the dorsolateral prefrontal cortex (DLPFC), which is known to participate in spatial working memory processes. However, it is not known whether or not the OFC also participates in spatial working memory and whether the OFC and DLPFC contribute equally to this process. To address these issues, we collected single-neuron activity from both areas while a monkey performed an oculomotor delayed-response task, and compared the characteristics of task-related activities between the OFC and DLPFC. All of the task-related activities observed in the DLPFC were also observed in the OFC. However, the proportion and response characteristics of task-related activities were different between the two areas. While most delay-period activity observed in the DLPFC was directionally selective and showed tonic sustained activation, most delay-period activity observed in the OFC was omni-directional and showed gradually increasing activity. Reward-period activity was predominant among task-related activities in the OFC. The proportion of neurons showing reward-period activity was significantly higher in the OFC than in the DLPFC. These results suggest that, although both the OFC and DLPFC participate in spatial working memory processes, the OFC is related more to the expectation and the detection of reward delivery, while the DLPFC is related more to the temporary maintenance of spatial information and its processing.     

Transcranial magnetic stimulation (TMS) applied to left dorsolateral prefrontal cortex disrupts verbal working memory performance in humans

Working memory refers to the temporary maintenance and processing of information and involves executive processes that manipulate the contents of the working memory. The role of the executive function in the human left dorsolateral prefrontal cortex (LDLPFC) was explored using transcranial magnetic stimulation (TMS) after confirming the LDLPFC activation using fMRI. We applied double-pulse TMS having a 100-ms inter-pulse interval to LDLPFC immediately after the subjects finished reading the sentences of the reading span test (RST) task, an efficient measure of verbal working memory, in which dual tasks that include both sentence comprehension and word maintenance are required. Using eight normal participants, we found a significant deterioration of performance, i.e., decreased number of correctly reported words, in RST due to TMS stimulation of LDLPFC. Evidence suggests that transient functional disruption of the LDLPFC impairs performance in the maintenance processing of the RST task.     

Processing in prefrontal cortex underlies tactile direction discrimination: An fMRI study of a patient with a traumatic spinal cord lesion

We have investigated cortical processing of tactile direction discrimination (TDD) in a patient with unilateral tactile disturbance due to spinal cord lesion. The patient R.A. (male, 45 years old), suffers from a traumatic dorsal column lesion at the level of Th XI–XII on the right side. He was instructed to report the direction of 2 mm long skin pull stimulations applied in a proximal or distal direction on his right or left lower legs during functional magnetic resonance imaging (fMRI). Although R.A. considered himself to have nearly normal tactile sensibility, testing showed severely disturbed TDD on his right leg whereas results were within the range of healthy subjects on his left leg. For both legs TDD activated an extensive cortical network that included opercular parietal area 1 (OP1) of the second somatosensory cortex (S2), as has previously been observed in healthy subjects. However, dorsolateral prefrontal cortex (DLPFC) and anterior insular cortex (AIC) were only activated for the unaffected (left) leg where TDD was normal. A revisit of previously published data showed that healthy subjects consistently had TDD-related activations in DLPFC and AIC. However, in several healthy subjects AIC, but not DLPFC, was also activated for skin pull stimulations per se without the TDD task. Thus, the patient's data, in conjunction with the previous results from healthy subjects, suggest that DLPFC processing is important for tactile decision making based on proper tactile input.     

Development of brain stimulation reward in the medial prefrontal cortex: Facilitation by prior electrical stimulation of the sulcal prefrontal cortex

Electrical stimulation of the medial prefrontal cortex (MC) in rats delivered daily for seven days causes a marked improvement in the rate of acquisition of a self-stimulation response. In the present experiment, we looked at whether we could get the same facilitatory effect on self-stimulation of the MC by delivering pre-training stimulation to other points in the brain anatomically related to the MC. Electrical stimulation of the lateral hypothalamus was without effect. However, electrical stimulation of the sulcal prefrontal cortex (SC) either contralateral or ipsilateral to the MC electrode did facilitate acquisition of self-stimulation of the MC. Thus the SC and MC would appear to be part of the same substrate controlling the development of positive reinforcement in the MC.     

Effects of repetitive transcranial magnetic stimulation over dorsolateral prefrontal and posterior parietal cortex on memory-guided saccades

We investigated the role of the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in a visuospatial delayed-response task in humans. Repetitive transcranial magnetic stimulation (20 Hz, 0.5 s) was used to interfere temporarily with cortical activity in the DLPFC and PPC during the delay period. Omnidirectional memory-guided saccades with a 3-s delay were used as a quantifiable motor response to a visuospatial cue. The question addressed was whether repetitive transcranial magnetic stimulation (rTMS) over the DLPFC or PPC during the sensory of memory phase affects accuracy of memory-guided saccades. Stimulation over the primary motor cortex served as control. Stimulation over the DLPFC significantly impaired accuracy of memory-guided saccades in amplitude and direction. Stimulation over the PPC impaired accuracy of memory-guided saccades only when applied within the sensory phase (50 ms after cue offset), but not during the memory phase (500 ms after cue offset). These results provide further evidence for a parieto-frontal network controlling performance of visuospatial delayed-response tasks in humans. It can be concluded that within this network the DLPFC is mainly concerned with the mnemonic respresentation and the PPC with the sensory representation of spatially defined perceptual information. Received: 22 April 1996/Accepted: 16 June 1997     

Assessing functioning of the prefrontal cortical subregions with auditory evoked potentials in sleep-wake cycle

Our previously observations showed that the amplitude of cortical evoked potentials to irrelevant auditory stimulus (probe) recorded from several different cerebral areas was differentially modulated by brain states. At present study, we simultaneously recorded auditory evoked potentials (AEPs) from the dorsolateral prefrontal cortex (DLPFC) and the ventromedial prefrontal cortex (VMPFC) in the freely moving rhesus monkey to investigate state-dependent changes of the AEPs in the two subregions of prefrontal cortex. AEPs obtained during passive wakefulness (PW), active wakefulness (AW), slow wave sleep (SWS) and rapid-eye-movement sleep (REM) were compared. Results showed that AEPs from two subregions of prefrontal cortex were modulated by brain states. Moreover, a significantly greater increase of the peak-to-peak amplitude (PPA) of N1-P1 complexes appears in the DLPFC during PW compared to that during AW. During REM, the PPA of N1-P1 complexes presents a contrary change in the two subregions with significant difference: a significant increase in the DLPFC and a slight decrease in the VMPFC compared to that during AW. These results indicate that the modulation of brain states on AEPs from two subregions of the prefrontal cortex investigated is also not uniform, which suggests that different subregions of the prefrontal cortex have differential functional contributions during sleep-wake cycle.     

Laminar distributions of neurons sensitive to acetylcholine, noradrenaline and dopamine in the dorsolateral prefrontal cortex of the monkey

Sensitivities of neurons to acetylcholine (ACh), noradrenaline (NA) and dopamine (DA) were investigated at different depths of the dorsolateral prefrontal cortex (PFC) in awake or halothane-anesthetized macaque monkeys, using microiontophoretic techniques with multi-barreled electrodes. The laminar locations of tested neurons (n = 403) were estimated by reconstructing electrode tracks based on the microlesion made by passing a current through the recording barrel, which contained a carbon fiber. Iontophoretically applied drugs induced excitatory or inhibitory responses. Neurons excited by ACh (n = 105) were located mainly in layers III and V, and those inhibited by ACh (n = 126) were in layers III and IV. The majority of the NA-sensitive neurons (n = 123) were NA-inhibited neurons (n = 100), and were found most often in layers III and IV. The ratio of DA-sensitive neurons (excited, n = 74; inhibited, n = 63) to tested neurons was higher in the deep layers than in the superficial ones. These results indicate that sensitivities of the PFC neurons to ACh, NA and DA are not uniform between cortical layers, suggesting that each of these substances may predominantly influence the neuronal activity of particular layers of the monkey PFC.     

Peripubertal refinement of the intrinsic and associational circuitry in monkey prefrontal cortex

The peripubertal elimination of axospinous synapses and dendritic spines in monkey prefrontal cortex suggests that this region undergoes substantial reorganization during late postnatal development. Understanding the functional impact of these maturational refinements requires knowledge of the specific presynaptic elements involved in these changes. Two potential sources of these presynaptic terminals are the intrinsic axon collaterals furnished by pyramidal cells within a region, and the associational axons that arise from pyramidal neurons in other cortical regions in the same hemisphere. In the adult, both of these types of axon terminals form synapses predominantly with dendritic spines on other pyramidal neurons, and thus they may be preferentially involved in the peripubertal pruning of axospinous synapses and dendritic spines. In order to test this hypothesis, iontophoretic injections of the anterograde tracer biotinylated dextran amine were made into the superficial layers of areas 9 or 46 of the prefrontal cortex of four prepubertal juvenile (14.9–21.5 months old) and three young adult macaque monkeys. Tangential reconstructions revealed a stripe-like pattern of labeled terminals for intrinsic and associational projections in both juvenile and adult animals. During puberty, the intrinsic circuitry underwent extensive topographic refinement, as demonstrated by a 42.7% decrease in stripe area and a 28.0% increase in gap distance between stripes. Furthermore, the mediolateral tangential spread of labeled stripes around the injection site decreased by 27.0%. In contrast, topographic refinement was not evident in the associational circuitry. In both layers 1 and 3, the densities of varicosities and branch points on labeled axons decreased by about 50% in intrinsic stripes during puberty, but only by approximately 30% in associational stripes.

These findings suggest that the spatial form and magnitude of peripubertal refinements in prefrontal cortical connectivity may be specific for certain neural elements.     

Catalepsy after microinjection of haloperidol into the rat medial prefrontal cortex

Summary To investigate the behavioural role of mesocortical dopamine innervation we performed bilateral microinjections of haloperidol into various parts of the rat frontal cortex and into adjacent subcortical forebrain structures. Haloperidol (2.5 g/ 0.5 l) locally injected into the medial prefrontal cortex or into the rostral part of the neostriatum resulted in the development of catalepsy as measured in the bar test. In contrast, injections of haloperidol into the nucleus accumbens, more caudal parts of the neostriatum, anterior cingulate cortex, rostral and lateral parts of the prefrontal cortex and into the lateral ventricles failed to induce catalepsy. It is concluded that blockade of dopamine receptors located in the rostral neostriatum and in the medial prefrontal cortex contributes to the development of haloperidol induced catalepsy.     

Neuroprotective effect of afobazole on rats with bilateral local photothrombosis of vessels in the prefrontal cortex

We studied the neuroprotective effect of a new selective anxiolytic afobazole on rats with bilateral focal ischemic stroke in the prefrontal cortex caused by photothrombosis. Intraperitoneal injection of 5 mg/kg afobazole 1 h after surgery and over the next 8 days (daily treatment) produced a neuroprotective effect. Afobazole was far superior to the reference cerebroprotective drug cavinton (4 mg/kg) by neuroprotective activity. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 167–169, February, 2008     

Retrospective and prospective coding of information: role of the medial prefrontal cortex

Summary Animals with sham-operations or medial prefrontal cortex lesions were trained in a task which required memory for short or long lists of items (spatial locations). On any one trial a rat is presented with 2, 4, 6, 8 or 10 items (spatial locations) on a 12-arm radial maze followed 15 min later by a win-shift test comprising a choice between a place previously visited and a novel place. Sham-operated animals showed an increase in errors as a function of set size (2 to 8 items) followed by a decrease in errors with a set size of 10 items suggesting the use of both retrospective and prospective memory codes. In contrast, animals with medial prefrontal cortex lesions made most of their errors for the longest list length reflecting an inability to shift from a retrospective to prospective memory code. The results are interpreted as support for a medial prefrontal cortex role in mediating a prospective code perhaps via knowlege systems based on temporal information.