One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence‐specific implicit learning

Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence‐specific learning. Thirty‐three participants were assigned to one of three groups of repetitive transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence‐specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence‐specific learning with 1 Hz rTMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow‐up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation‐induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence‐specific learning of a visuomotor task and offer converging evidence for competing memory systems.     

Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study

Objective:  To investigate neural activity in prefrontal cortex and amygdala during bipolar depression.
Methods:  Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second-level random effects analysis.
Results:  Random effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between-group difference, however, was not significant.
Conclusions:  Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder.     

Dorsal premotor activity and connectivity relate to action selection performance after stroke

Compensatory activation in dorsal premotor cortex (PMd) during movement execution has often been reported after stroke. However, the role of PMd in the planning of skilled movement after stroke has not been well studied. The current study investigated the behavioral and neural response to the addition of action selection (AS) demands, a motor planning process that engages PMd in controls, to movement after stroke. Ten individuals with chronic, left hemisphere stroke and 16 age‐matched controls made a joystick movement with the right hand under two conditions. In the AS condition, participants moved right or left based on an abstract, visual rule; in the execution only condition, participants moved in the same direction on every trial. Despite a similar behavioral response to the AS condition (increase in reaction time), brain activation differed between the two groups: the control group showed increased activation in left inferior parietal lobule (IPL) while the stroke group showed increased activation in several right/contralesional regions including right IPL. Variability in behavioral performance between participants was significantly related to variability in brain activation. Individuals post‐stroke with relatively poorer AS task performance showed greater magnitude of activation in left PMd and dorsolateral prefrontal cortex (DLPFC), increased left primary motor cortex‐PMd connectivity, and decreased left PMd‐DLPFC connectivity. Changes in the premotor‐prefrontal component of the motor network during complex movement conditions may negatively impact the performance and learning of skilled movement and may be a prime target for rehabilitation protocols aimed at improving the function of residual brain circuits after stroke. Hum Brain Mapp 37:1816–1830, 2016. © 2016 Wiley Periodicals, Inc .     

Neural circuitry underlying voluntary suppression of sadness.

BACKGROUND: The ability to voluntarily self-regulate negative emotion is essential to a healthy psyche. Indeed, a chronic incapacity to suppress negative emotion might be a key factor in the genesis of depression and anxiety. Regarding the neural underpinnings of emotional self-regulation, a recent functional neuroimaging study carried out by our group has revealed that the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex are involved in voluntary suppression of sexual arousal. As few things are known, still, with respect to the neural substrate underlying volitional self-regulation of basic emotions, here we used functional magnetic resonance imaging to identify the neural circuitry associated with the voluntary suppression of sadness. METHODS: Twenty healthy female subjects were scanned during a Sad condition and a Suppression condition. In the Sad condition, subjects were instructed to react normally to sad film excerpts whereas, in the Suppression condition, they were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. RESULTS: Transient sadness was associated with significant loci of activation in the anterior temporal pole and the midbrain, bilaterally, as well as in the left amygdala, left insula, and right ventrolateral prefrontal cortex (VLPFC) (Brodmann area [BA] 47). Correlational analyses carried out between self-report ratings of sadness and regional blood oxygen level dependent (BOLD) signal changes revealed the existence of positive correlations in the right VLPFC (BA 47), bilaterally, as well as in the left insula and the affective division of the left anterior cingulate gyrus (BA 24/32). In the Suppression condition, significant loci of activation were noted in the right DLPFC (BA 9) and the right orbitofrontal cortex (OFC) (BA 11), and positive correlations were found between the self-report ratings of sadness and BOLD signal changes in the right OFC (BA 11) and right DLPFC (BA 9). CONCLUSIONS: These results confirm the key role played by the DLPFC in emotional self-regulation. They also indicate that the right DLPFC and right OFC are components of a neural circuit implicated in voluntary suppression of sadness.     

An fMRI investigation of working memory and sadness in females with bipolar disorder: a brief report

Objective: Functional magnetic resonance imaging (fMRI) studies have documented abnormalities in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex in bipolar disorder in the context of working memory tasks. It is increasingly recognized that DLPFC regions play a role in mood regulation and the integration of emotion and cognition. The purpose of the present study was to investigate with fMRI the interaction between acute sadness and working memory functioning in individuals with bipolar disorder. Methods: Nine depressed individuals with DSM‐IV bipolar I disorder (BP‐I) and 17 healthy control participants matched for age, gender, education, and IQ completed a 2‐back working memory paradigm under no mood induction, neutral state, or acute sadness conditions while undergoing fMRI scanning. Functional MRI data were analyzed with SPM2 using a random‐effects model. Results: Behaviorally, BP‐I subjects performed equally well as control participants on the 2‐back working memory paradigm. Compared to control participants, individuals with BP‐I were characterized by more sadness‐specific activation increases in the left DLPFC (BA 9/46) and left dorsal anterior cingulate (dACC). Conclusions: Our study documents sadness‐specific abnormalities in the left DLPFC and dACC in bipolar disorder that suggest difficulties in the integration of emotion (sadness) and cognition. These preliminary findings require further corroboration with larger sample sizes of medication‐free subjects.     

Functional magnetic resonance imaging in schizophrenia: cortical response to motor stimulation

Previous functional magnetic resonance imaging (fMRI) studies suggest that motor system abnormalities are present in schizophrenia. However, these studies have often produced conflicting or ambiguous findings. The purpose of this study was to ascertain whether activation differences could be identified in stable schizophrenic patients on the basis of BOLD measures in two motor regions, the primary motor cortex, Brodmann area 4 (BA4) and the premotor and supplementary motor area, Brodmann area 6 (BA6). Twenty-one schizophrenic patients and 21 healthy control subjects were studied with BOLD fMRI methods during a sequential finger tapping task. Statistical parametric maps were generated for each subject, and anatomic regions were automatically defined using an anatomic atlas. Compared with controls, the schizophrenic patients showed a significant reduction in contralateral activation for both BA4 and BA6 (P<0.001), and in ipsilateral activation in BA4 (P=0.007) and BA6 (P=0.002). In healthy controls, the coactivation in the ipsilateral cortex is reduced in comparison with the contralateral cortex for right and left handed tasks. In BA4, this reduction is significant for right (P=0.007) and left (P=0.003) finger tapping. Similar results were obtained for BA6. Further analyses are necessary to evaluate the activation in other motor system regions.     

Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence.

BACKGROUND: When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. METHODS: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (< or = 1.5 hours abstinence) and abstinence (> or = 14 hours abstinence) conditions. RESULTS: Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. CONCLUSIONS: We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.     

Neurofunctional correlates of eye to hand motor transfer

This work investigates the transfer of motor learning from the eye to the hand and its neural correlates by using functional magnetic resonance imaging (fMRI) and a sensorimotor task consisting of the continuous tracking of a virtual target. In pretraining evaluation, all the participants (experimental and control group) performed the tracking task inside an MRI scanner using their right hand and a joystick. After which, the experimental group practiced an eye‐controlled version of the task for 5 days using an eye tracking system outside the MRI environment. Post‐training evaluation was done 1 week after the first scanning session, where all the participants were scanned again while repeating the manual pretraining task. Behavioral results show that the training in the eye‐controlled task produced a better performance not only in the eye‐controlled modality (motor learning) but also in the hand‐controlled modality (motor transfer). Neural results indicate that eye to hand motor transfer is supported by the motor cortex, the basal ganglia and the cerebellum, which is consistent with previous research focused on other effectors. These results may be of interest in neurorehabilitation to activate the motor systems and help in the recovery of motor functions in stroke or movement disorder patients.     

The context of uncertainty modulates the subcortical response to predictability

Implicit motor learning tasks typically involve comparisons of subject responses during a sequence versus a random condition. In neuroimaging, brain regions that are correlated with a sequence are described, but the temporal relationship of sequence versus nonsequence conditions is often not explored. We present a functional magnetic resonance imaging (fMRI) study describing activation related to sequential predictability in an implicit sensorimotor learning task and the history (context) dependence of these effects. Participants regarded four squares displayed horizontally across a screen and pressed a button when any one of the four targets was illuminated in a particular color. A repeating spatial sequence with varying levels of predictability was embedded within a random color presentation. Both the right dorsolateral prefrontal cortex (R DLPFC) and right caudate displayed a positive correlation to increasing predictability, whereas the left posterior parietal cortex (L PPC) displayed a negative correlation. However, the activation changes within the caudate were significant when transitioning from high predictability to low predictability but not for the reverse case, suggesting a sensitivity not only to predictability but to order effects as well. These results support the hypothesized relationship between basal ganglia and visuomotor sequential learning, but demonstrate the importance of context upon sequence learning.     

Prefrontal and striatal activation during sequence learning in geriatric depression.

BACKGROUND: Frontostriatal dysfunction is a primary hypothesis for the neurocognitive changes of depression in late life. The aim of the present study was to test this hypothesis with the use of functional magnetic resonance imaging (fMRI) tasks that are known to engage the prefrontal and neostriatal cognitive circuits. METHODS: Twenty-three elderly subjects (mean age, 69.9 years) participated: 11 subjects with a current major depressive episode and 12 nondepressed elderly control subjects. Subjects underwent fMRI while performing a concurrent implicit and explicit sequence learning task. Region of interest (ROI)-based analyses were conducted, focusing on the dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, and the neostriatum. RESULTS: As expected, both the control and depressed subjects learned the sequence during both implicit and explicit conditions. During explicit learning, decreased prefrontal activation was found in the depressed subjects, along with increased striatal activation. The increased striatal activity in the depressed subjects was due to increased activity on the trials that violated the sequence. During implicit learning, no significant differences were found between the groups in the identified ROIs. CONCLUSIONS: The increased striatal activation on trials that violated the sequence demonstrates a greater response to negative feedback for depressed compared with control subjects. Our observations of significant differences in both prefrontal and striatal regions in the depressed elderly subjects relative to elderly control subjects supports the frontostriatal dysfunction hypothesis of late-life depression.     

rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study

A recent fMRI study showed that dorsolateral prefrontal cortex (DLPFC) exerts an inhibitory control on pain pathways in humans. We investigated whether high-frequency rTMS over left DLPFC could ameliorate chronic migraine. Treatment consisted of 12 rTMS sessions, delivered in alternate days over left DLPFC. Sham rTMS was used as placebo. Eleven patients were randomly assigned to the rTMS (n=6) or to the placebo (n=5) treatment. Measures of attack frequency, headache index, number of abortive medications (outcome measures) were recorded in the month before, during and in the month after treatment. Subjects treated by rTMS showed a significant reduction of the outcome measures during and in the month after the treatment as compared to the month before treatment. No significant differences in the outcome measures were observed in the placebo group. High-frequency rTMS over left DLPFC was able to ameliorate chronic migraine. This is in agreement with the suggested role of DLPFC in pain control.     

Site‐specific effects of mental practice combined with transcranial direct current stimulation on motor learning

Mental practice can induce significant neural plasticity and result in motor performance improvement if associated with motor imagery tasks. Given the effects of transcranial direct current stimulation (tDCS) on neuroplasticity, the current study tested whether tDCS, using different electrode montages, can increase the neuroplastic effects of mental imagery on motor learning. Eighteen healthy right‐handed adults underwent a randomised sham‐controlled crossover experiment to receive mental training combined with either sham or active anodal tDCS of the right primary motor cortex (M1), right supplementary motor area, right premotor area, right cerebellum or left dorsolateral prefrontal cortex (DLPFC). Motor performance was assessed by a blinded rater using: non‐dominant handwriting time and legibility, and mentally trained task at baseline (pre) and immediately after (post) mental practice combined with tDCS. Active tDCS significantly enhances the motor‐imagery‐induced improvement in motor function as compared with sham tDCS. There was a specific effect for the site of stimulation such that effects were only observed after M1 and DLPFC stimulation during mental practice. These findings provide new insights into motor imagery training and point out that two cortical targets (M1 and DLPFC) are significantly associated with the neuroplastic effects of mental imagery on motor learning. Further studies should explore a similar paradigm in patients with brain lesions.     

Modulating neural oscillations by transcranial static magnetic field stimulation of the dorsolateral prefrontal cortex: A crossover,double‐blind,sham‐controlled pilot study

Transcranial static magnetic field stimulation (tSMS) is a novel non‐invasive brain stimulation technique that has been shown to locally increase alpha power in the parietal and occipital cortex. We investigated if tSMS locally increased alpha power in the left or right prefrontal cortex, as the balance of left/right prefrontal alpha power (frontal alpha asymmetry) has been linked to emotional processing and mood disorders. Therefore, altering frontal alpha asymmetry with tSMS may serve as a novel treatment to psychiatric diseases. We performed a crossover, double‐blind, sham‐controlled pilot study to assess the effects of prefrontal tSMS on neural oscillations. Twenty‐four right‐handed healthy participants were recruited and received left dorsolateral prefrontal cortex (DLPFC) tSMS, right DLPFC tSMS, and sham tSMS in a randomized order. Electroencephalography data were collected before (2 min eyes‐closed, 2 min eyes‐open), during (10 min eyes‐open), and after (2 min eyes‐open) stimulation. In contrast with our hypothesis, neither left nor right tSMS locally increased frontal alpha power. However, alpha power increased in occipital cortex during left DLPFC tSMS. Right DLPFC tSMS increased post‐stimulation fronto‐parietal theta power, indicating possible relevance to memory and cognition. Left and right DLPFC tSMS increased post‐stimulation left hemisphere beta power, indicating possible changes to motor behavior. Left DLPFC tSMS also increased post‐stimulation right frontal beta power, demonstrating complex network effects that may be relevant to aggressive behavior. We concluded that DLPFC tSMS modulated the network oscillations in regions distant from the location of stimulation and that tSMS has region specific effects on neural oscillations.     

Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study

BackgroundPrefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia.Objective/Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity.MethodsWe enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition.ResultsOf the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p = 0.0157; max z-score = 4.7) and neighboring BA46 (p = 0.019; max z-score = 4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p = 0.02; max z-score = 3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r = 0.83, p = 0.004).ConclusionsSubjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.     

Distinct prefrontal activations in processing sequence at the sentence and script level: an fMRI study

Neuropsychological studies have shown that the prefrontal cortex is important in planning and monitoring everyday behaviour. In this study, using functional magnetic resonance imaging (fMRI), we investigated whether specific prefrontal regions are involved in processing a sequence of actions. Subjects were required to perform two different tasks: Script-event order and Sentence-word order. Script sequence and word sequence processing were found to activate partially overlapping areas which are known to be implicated in language processing. In addition, the Script-task activated a large area in the dorsolateral prefrontal cortex (Brodmann area 6 and 8, BA 6 and 8), in both the left and right hemispheres, as well as the left supplementary motor area and left angular gyrus (BA 39). Our results suggest that these prefrontal areas may be more specifically involved in the process of analysing sequential links in the action domain.     

Functional magnetic resonance imaging in schizophrenia: cortical response to motor stimulation

Previous functional magnetic resonance imaging (fMRI) studies suggest that motor system abnormalities are present in schizophrenia. However, these studies have often produced conflicting or ambiguous findings. The purpose of this study was to ascertain whether activation differences could be identified in stable schizophrenic patients on the basis of BOLD measures in two motor regions, the primary motor cortex, Brodmann area 4 (BA4) and the premotor and supplementary motor area, Brodmann area 6 (BA6). Twenty-one schizophrenic patients and 21 healthy control subjects were studied with BOLD fMRI methods during a sequential finger tapping task. Statistical parametric maps were generated for each subject, and anatomic regions were automatically defined using an anatomic atlas. Compared with controls, the schizophrenic patients showed a significant reduction in contralateral activation for both BA4 and BA6 (P<0.001), and in ipsilateral activation in BA4 (P=0.007) and BA6 (P=0.002). In healthy controls, the coactivation in the ipsilateral cortex is reduced in comparison with the contralateral cortex for right and left handed tasks. In BA4, this reduction is significant for right (P=0.007) and left (P=0.003) finger tapping. Similar results were obtained for BA6. Further analyses are necessary to evaluate the activation in other motor system regions.     

Basal ganglia-thalamocortical circuitry disruptions in schizophrenia during delayed response tasks.

BACKGROUND: Schizophrenia is characterized by executive functioning deficits, presumably mediated by prefrontal cortex dysfunction. For example, schizophrenia participants show performance deficits on ocular motor delayed response (ODR) tasks, which require both inhibition and spatial working memory for correct performance. METHODS: The present functional magnetic resonance imaging (fMRI) study compared neural activity of 14 schizophrenia and 14 normal participants while they performed ODR tasks. RESULTS: Schizophrenia participants generated: 1) more trials with anticipatory saccades (saccades made during the delay period), 2) memory saccades with longer latencies, and 3) memory saccades of decreased accuracy. Increased blood oxygenation level-dependent (BOLD) signal changes were observed in both groups in ocular motor circuitry (e.g., supplementary eye fields [SEF], lateral frontal eye fields [FEF], inferior parietal lobule [IPL], cuneus, and precuneus). The normal, but not the schizophrenia, group demonstrated BOLD signal changes in dorsolateral prefrontal regions (right Brodmann area [BA] 9 and bilateral BA 10), medial FEF, insula, thalamus, and basal ganglia. Correlations between percentage of anticipatory saccade trials and BOLD signal changes were more similar between groups for subcortical regions and less similar for cortical regions. CONCLUSIONS: These results suggest that executive functioning deficits in schizophrenia may be associated with dysfunction of the basal ganglia-thalamocortical circuitry, evidenced by decreased prefrontal cortex, basal ganglia, and thalamus activity in the schizophrenia group during ODR task performance.     

Neural correlates of switching set as measured in fast, event-related functional magnetic resonance imaging

Attentional switching has shown to involve several prefrontal and parietal brain regions. Most cognitive paradigms used to measure cognitive switching such as the Wisconsin Card Sorting Task (WCST) involve additional cognitive processes besides switching, in particular working memory (WM). It is, therefore, questionable whether prefrontal brain regions activated in these conditions, especially dorsolateral prefrontal cortex (DLPFC), are involved in cognitive switching per se, or are related to WM components involved in switching tasks. Functional magnetic resonance imaging (fMRI) was used to examine neural correlates of pure switching using a paradigm purposely designed to minimize WM functions. The switching paradigm required subjects to switch unpredictably between two spatial dimensions, clearly indicated throughout the task before each trial. Fast, event-related fMRI was used to compare neural activation associated with switch trials to that related to repeat trials in 20 healthy, right-handed, adult males. A large cluster of activation was observed in the right hemisphere, extending from inferior prefrontal and pre- and postcentral gyri to superior temporal and inferior parietal cortices. A smaller and more caudal cluster of homologous activation in the left hemisphere was accompanied by activation of left dorsolateral prefrontal cortex (DLPFC). We conclude that left DLPFC activation is involved directly in cognitive switching, in conjunction with parietal and temporal brain regions. Pre- and postcentral gyrus activation may be related to motor components of switching set.     

Primary motor and premotor cortex in implicit sequence learning - evidence for competition between implicit and explicit human motor memory systems

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1‐AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd‐AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1‐AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd‐AtDCS during practice attenuated offline stabilization compared with M1‐AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition.     

Alterations in functional activation in euthymic bipolar disorder and schizophrenia during a working memory task

Dysfunctions in prefrontal cortical networks are thought to underlie working memory (WM) impairments consistently observed in both subjects with bipolar disorder and schizophrenia. It remains unclear, however, whether patterns of WM‐related hemodynamic responses are similar in bipolar and schizophrenia subjects compared to controls. We used fMRI to investigate differences in blood oxygen level dependent activation during a WM task in 21 patients with euthymic bipolar I, 20 patients with schizophrenia, and 38 healthy controls. Subjects were presented with four stimuli (abstract designs) followed by a fifth stimulus and required to recall whether the last stimulus was among the four presented previously. Task‐related brain activity was compared within and across groups. All groups activated prefrontal cortex (PFC), primary and supplementary motor cortex, and visual cortex during the WM task. There were no significant differences in PFC activation between controls and euthymic bipolar subjects, but controls exhibited significantly increased activation (cluster‐corrected P < 0.05) compared to patients with schizophrenia in prefrontal regions including dorsolateral prefrontal cortex (DLPFC). Although the bipolar group exhibited intermediate percent signal change in a functionally defined DLPFC region of interest with respect to the schizophrenia and control groups, effects remained significant only between patients with schizophrenia and controls. Schizophrenia and bipolar disorder may share some behavioral, diagnostic, and genetic features. Differences in the patterns of WM‐related brain activity across groups, however, suggest some diagnostic specificity. Both patient groups showed some regional task‐related hypoactivation compared to controls across the brain. Within DLPFC specifically, patients with schizophrenia exhibited more severe WM‐related dysfunction than bipolar subjects. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.