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Does subthalamic nucleus stimulation affect the frontal limbic areas? A single-photon emission computed tomography study using a manual anatomical segmentation method.

Among the basal ganglia nuclei, the subthalamic nucleus (STN) is considered to play a major role in output modulation. The STN represents a relay of the motor cortico-basal ganglia-thalamo-cortical circuit and has become the standard surgical target for treating Parkinson's patients with long-term motor fluctuations and dyskinesia. But chronic bilateral stimulation of the STN produces cognitive effects. According to animal and clinical studies, the STN also appears to have direct or indirect connections with the frontal associative and limbic areas. This prospective study was conducted to analyse regional cerebral blood flow changes in single-photon emission computed tomography imaging of six Parkinson's patients before and after STN stimulation. We particularly focused on the dorsolateral prefrontal cortex and the frontal limbic areas using a manual anatomical MRI segmentation method. We defined nine regions of interest, segmenting each MR slice to quantify the regional cerebral blood flow on pre- and postoperative SPECT images. We normalised the region-of-interest-based measurements to the entire brain volume. The patients showed increased activation during STN stimulation in the dorsolateral prefrontal cortex bilaterally and no change in the anterior cingulate and orbito-frontal cortices. In our study, STN stimulation induced activation of premotor and associative frontal areas. Further studies are needed to underline involvement of the STN with the so-called limbic system.

Antiparkinson Agents↗

Working memory maintenance contributes to long-term memory formation: neural and behavioral evidence.

Theories of human memory have led to conflicting views regarding the relationship between working memory (WM) maintenance and episodic long-term memory (LTM) formation. Here, we tested the prediction that WM maintenance operates in two stages, and that processing during the initial stage of WM maintenance promotes successful LTM formation. Results from a functional magnetic resonance imaging study showed that activity in the dorsolateral prefrontal cortex and hippocampus during the initial stage of WM maintenance was predictive of subsequent LTM performance. In a behavioral experiment, we demonstrated that interfering with processing during the initial stage of WM maintenance impaired LTM formation. These results demonstrate that processing during the initial stage of WM maintenance directly contributes to successful LTM formation, and that this effect is mediated by a network that includes the dorsolateral prefrontal cortex and the hippocampus.

Adult↗

Prefrontal representation of stimulus attributes during delay tasks. II. The role of behavioral significance.

Rhesus monkeys were trained to perform two visual discrimination tasks with delayed response. In both tasks, the response depended on the color of the cue, a lighted circle in the center of a panel. Red and green guided one task, yellow and blue the other. In the course of performance, a fifth color (violet), non-relevant and inconsequential, was presented at random in the same location as the cues. All 5 stimuli were of equal brightness. Many cells in the dorsolateral prefrontal cortex (sulcus principalis and superior convexity) treated the relevant cues differently than the irrelevant stimulus. In general, cellular reactions to that stimulus were of lesser magnitude than the reactions to the cues. Cell reaction differences as a function of stimulus significance outnumbered and overshadowed differences as a function of cue-color or any other task variable. The results indicate that, during visual delay tasks, units in the dorsolateral prefrontal cortex differentiate stimuli by their behavioral significance, as well as by other stimulus attributes, including color. Because the motivational evaluation of sensory stimuli is an integral part of the cognitive processes in delay tasks (together with short-term memory and motor set), these results support the notion that the prefrontal cortex integrates motivational inputs into the structure of behavioral action.

Animals↗

Learning of sequences of finger movements and timing: frontal lobe and action-oriented representation.

Motor sequence learning involves learning of a sequence of effectors with which to execute a series of movements and learning of a sequence of timings at which to execute the movements. In this study, we have segregated the neural correlates of the two learning mechanisms. Moreover, we have found an interaction between the two learning mechanisms in the frontal areas, which we claim as suggesting action-oriented coding in the frontal lobe. We used positron emission tomography and compared three learning conditions with a visuo-motor control condition. In two learning conditions, the subjects learned either a sequence of finger movements with random timing or a sequence of timing with random use of fingers. In the third condition the subjects learned to execute a sequence of specific finger movements at specific timing; we argue that it was only in this condition that the motor sequence was coded as an action-oriented representation. By looking for condition by session interactions (learning vs. control conditions over sessions), we have removed nonspecific time effects and identified areas that showed a learning-related increment of activation during learning. Learning of a finger sequence was associated with an increment of activation in the right intraparietal sulcus region and medial parietal cortex, whereas learning of a timing sequence was associated with an increment of activation in the lateral cerebellum, suggesting separate mechanisms for learning effector and temporal sequences. The left intraparietal sulcus region showed an increment of activation in learning of both finger and timing sequences, suggesting an overlap between the two learning mechanisms. We also found that the mid-dorsolateral prefrontal cortex, together with the medial and lateral premotor areas, became increasingly active when subjects learned a sequence that specified both fingers and timing, that is, when subjects were able to prepare specific motor action. These areas were not active when subjects learned a sequence that specified fingers or timing alone, that is, when subjects were still dependent on external stimuli as to the timing or fingers with which to execute the movements. Frontal areas may integrate the effector and temporal information of a motor sequence and implement an action-oriented representation so as to perform a motor sequence accurately and quickly. We also found that the mid-dorsolateral prefrontal cortex was distinguished from the ventrolateral prefrontal cortex and anterior fronto-polar cortex, which showed sustained activity throughout learning sessions and did not show either an increment or decrement of activation.

Adult↗

Co-ordination within and between verbal and visuospatial working memory: network modulation and anterior frontal recruitment.

Attention switching between items being stored and manipulated in working memory (WM) is proposed to be an elementary executive function. Experiment 1 reveals a similar attentional limitation within and between verbal and visuospatial WM and identifies a supramodal switching process required for switching between WM items. By using functional magnetic resonance imaging, Experiment 2 investigated brain activation correlates of parametrically varied attention switching within and between these two WM modalities. Attention switching activation was broadly distributed, was quite similar across the three conditions, and, in almost all areas, increased with increasing switching demand, indicating that attention switching recruits and modulates the entire WM network. Dorsolateral prefrontal cortex was implicated in both within- and between-modality attention switching, but no significant activation was found in ventrolateral areas, supporting dorsal-ventral process models of prefrontal organization. A functional dissociation between anterior frontal and dorsolateral prefrontal cortex was found with the former being more activated when switching attention between modalities was required. The data challenge the notion of an anatomically separate attention switching executive function, but suggest that anterior frontal areas are recruited for the additional demand of coordinating the verbal and visuospatial WM slave systems.

Adolescent↗

Effects of single-pulse transcranial magnetic stimulation over the prefrontal and posterior parietal cortices during memory-guided saccades in humans.

1. We used single-pulse transcranial magnetic stimulation (TMS) to explore the temporal organization of the cortical control of memory-guided saccades in eight humans. The posterior parietal cortex (PPC) or the dorsolateral prefrontal cortex (DPFC), which are both known to be involved in the control of such saccades, were stimulated on the right side at different time intervals after the presentation of a flashed lateral visual target. The memorization delay was 2,000 ms. Single pulses were applied at 160, 260, and 360 ms after the flashed target, during the period of 700 and 1,500 ms, and finally at 2,100 ms, i.e., 100 ms after the extinguishing of the central fixation point. The effects of TMS were evaluated by calculating the percentage of error in amplitude (PEA) and latency of memory-guided saccades. The PEA was determined for the primary saccade (motor aspect) and the final eye position, i.e., after the end saccade (mnemonic aspect). Stimulation over the occipital cortex at the same time intervals served as control experiments. 2. After PPC stimulation, a significant increase in the PEA of the primary saccade and final eye position existed for contralateral saccades, compared with the PEA without stimulation, when stimulation was applied 260 ms after target presentation, but not at other time intervals. There was no significant effect on ipsilateral saccades. Latency was significantly increased bilaterally when stimulation was performed 2,100 ms after target presentation. 3. After prefrontal stimulation, a significant increase in the PEA of the primary saccade and final eye position existed for contralateral saccades, when stimulation was applied between 700 and 1,500 ms after target presentation, but not at other time intervals. There was no significant effect on ipsilateral saccades. Latency was not affected by prefrontal TMS at any stimulation times. 4. Occipital stimulation resulted in no significant effect on the PEA and latency of ipsilateral or contralateral saccades, in particular including the application at 260 ms after target presentation or during the memorization phase. 5. From these results it may be concluded that the observed effects of TMS on saccade accuracy were specific to the stimulated region and specific to the stimulation time. The PPC seems to be involved in the preparation of saccade amplitude, during the early phase of the paradigm, i.e., the sensorimotor processing period, whereas the DPFC could play a role during the later phase of the paradigm, i.e., the memorization period. Therefore in humans these results support the experimental findings suggesting that sensorimotor integration is controlled by the PPC and spatial memory by the DPFC. Furthermore, our results suggest that the PPC, although not the DPFC, plays a role in saccade triggering.

Adult↗

Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions.

Damage to the orbitofrontal cortex (OFC) in humans has been associated with disinhibited or socially inappropriate behaviour and emotional changes. Some of the changes may be related to difficulty in responding correctly to rewards and punishers, in that these patients have difficulty in learning to correct their choice of a visual stimulus when it is no longer associated with reward. We extend this fundamental approach by investigating the relationship between frontal dysfunction and impulsive behaviour, the behavioural, emotional and personality changes seen in patients with prefrontal cortex damage, and thus in addition illuminate the cognitive and biological processes that are impaired in impulsive people. OFC patients (n = 23) performed more impulsively on both self-report and cognitive/behavioural tests of impulsivity, reported more inappropriate 'frontal' behaviours, and performed worse on a stimulus-reinforcement association reversal task, than non-OFC prefrontal cortex lesion control (n = 20) and normal control (n = 39) participants. Further, OFC patients experienced more subjective anger than non-OFC and normal participants, and less subjective happiness than normals; and had a faster subjective sense of time (overestimated and underproduced time intervals) than normal controls, while non-OFC patients did not differ from normals. Finally, both OFC and non-OFC patients were less open to experience than normal participants. There were no differences between OFC patients, non-OFC lesion patients and normal controls on all other personality traits, most notably extraversion. In a spatial working memory task, the non-OFC group, most of whom had dorsolateral prefrontal cortex lesions, were impaired in that they repeatedly returned to previously chosen empty locations ('within errors'), whereas OFC patients were not impaired on this measure. Thus there is a dissociation between the effects of OFC damage which does not affect this measure of spatial working memory but does affect impulsive and inappropriate behaviour, reversal, personality, time perception and emotion; and dorsolateral prefrontal cortex damage which does affect this measure of spatial working memory, but not impulsive and inappropriate behaviour, reversal, personality, time perception and emotion. The effects of OFC damage on impulsive and related behaviours described here have implications for understanding impulsive behaviour.

Adolescent↗

Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism?

This study tested the hypothesis that dorsolateral prefrontal cortex deficits contribute to both working memory and long-term memory disturbances in schizophrenia. It also examined whether such deficits were more severe for verbal than nonverbal stimuli. Functional magnetic resonance imaging was used to assess cortical activation during performance of verbal and nonverbal versions of a working memory task and both encoding and recognition tasks in 38 individuals with schizophrenia and 48 healthy controls. Performance of both working memory and long-term memory tasks revealed disturbed dorsolateral prefrontal cortex activation in schizophrenia, although medial temporal deficits were also present. Some evidence was found for more severe cognitive and functional deficits with verbal than nonverbal stimuli, although these results were mixed.

Adult↗

Neurophysiological signatures of Stanford Neuromodulation Therapy in treatment resistant depression.

Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder. Stanford Neuromodulation Therapy (SNT), a high-dose intermittent theta-burst transcranial magnetic stimulation protocol, produces rapid antidepressant effects, but its neurophysiological mechanisms remain unclear. Here, we used longitudinal TMS-EEG to characterize the progressive neurophysiological changes induced by SNT, assess their site-specificity, and explore whether baseline neural markers are associated with clinical response. We conducted a double-blind, randomized, sham-controlled trial at Stanford University (2017-2018; analysis August 2024-October 2025) in 24 TMS-na&#xef;ve participants with TRD (Montgomery-&#xc5;sberg Depression Rating Scale &#x2265;20; &#x2265;1 failed antidepressant trial). Participants were randomized to active (n&#x2009;=&#x2009;12) or sham (n&#x2009;=&#x2009;12) SNT, consisting of 10 sessions per day over 5 consecutive days targeting the left dorsolateral prefrontal cortex (90,000 pulses). TMS-EEG was acquired at two baseline sessions, before and after each treatment session, and at 1-month follow-up (14 TMS-EEG sessions in total). Active SNT progressively reduced cortical excitability at the treatment site, with significant decreases by day 3 in the early window component (-27.9%; P&#x2009;<&#x2009;0.01), while no changes were observed at the vertex control site. Site-specific comparisons confirmed early window reductions only at the left dorsolateral prefrontal cortex (t&#x2082;&#x2082; = -3.82; P&#x2009;<&#x2009;0.001). SNT also selectively decreased estimated medial prefrontal source activity consistent with the subgenual anterior cingulate cortex (sgACC) across sessions (F&#x2081;&#x2083;,&#x2082;&#x2082;&#x2082; = 4.93; P&#x2009;<&#x2009;0.001), with effects persisting at 1-month follow-up. In an exploratory analysis in the active group (n&#x2009;=&#x2009;12), higher baseline estimated sgACC source activity was associated with greater clinical improvement (r = -0.67; P&#x2009;=&#x2009;0.023); although promising, the latter preliminary finding requires replication in larger, adequately powered samples before predictive utility can be established. These findings indicate that SNT induces progressive, site-specific cortical modulation and selective downstream effects on estimated sgACC source activity. Early cortical excitability changes represent candidate neurophysiological markers of SNT response, while the observed association between baseline sgACC activity and clinical outcome, while preliminary, motivates prospective investigation of subcortical source activity as a potential predictor of treatment response in larger trials. ClinicalTrials.gov Identifier: NCT03068715.

Journal Article↗

Maintenance versus manipulation in verbal working memory revisited: an fMRI study.

Working memory (WM) is the ability to keep a limited amount of information "on line" for immediate use during short intervals. Verbal WM has been hypothesized to consist of neuroanatomically segregated components, i.e., maintenance (storage, rehearsal, and matching) and manipulation (reordering or updating), corresponding to ventrolateral and dorsolateral prefrontal cortex. Previous imaging studies of maintenance vs manipulation processes in WM have produced inconsistent results, which may have been due to methodological issues such as low statistical power and the use of insertion (subtraction) designs. In the present functional magnetic resonance imaging study we used parametric versions of both a prototypical maintenance task (Sternberg) and a prototypical manipulation task (n-letter back task) in 21 healthy subjects. Increased signal correlated with load common for both tasks was found in bilateral dorsolateral and anterior prefrontal, left ventrolateral prefrontal, and bilateral parietal regions. Workload x task interactions were found in bilateral dorsolateral prefrontal cortex for manipulation vs maintenance, but also for responding vs encoding (storage) in the maintenance task. Therefore, our data support a functional rather than a neuroanatomical distinction between maintenance and manipulation, given our finding that these tasks differentially activate virtually identical systems.

Adult↗

Obsessive-compulsive disorder among schizophrenic patients: an exploratory study using functional magnetic resonance imaging data.

Despite the growing research on the etiology of obsessive-compulsive disorder (OCD), and schizophrenia, the clinical distinction between the two disorders is not clearly understood. In the present investigation, we sought to better understand the relationship between OCD and psychotic disorders by examining functional magnetic resonance imaging (fMRI) data from a group of schizophrenic patients with varying degrees of OCD symptomatology, based on results of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the National Institute of Mental Health (NIMH) rating scales of OCD. While subjects performed a cognitive challenge paradigm that included a verbal fluency task, activation data from the left dorsolateral prefrontal cortex were collected and analyzed. We hypothesized that the fMRI signal patterns in schizophrenic patients with high levels of OCD symptomatology would differ from that of schizophrenic patients with a low level of OCD. For the group as a whole, no significant relationship was found for scores of either rating scale and fMRI signal change; however, a significant association was found for a subgroup of patients. For these schizophrenics, there was a negative relationship between OCD symptomatology and activation of the left dorsolateral prefrontal cortex. These results support the suggestion of several researchers that a relationship between OCD severity and neurophysiological activity exists in schizophrenia.

Adult↗

Executive function deficits associated with symptoms of schizotypy and obsessive-compulsive disorder.

Research suggests that executive dysfunction is seen both in disorders of the schizophrenia constellation and in obsessive-compulsive disorder (OCD), but that the patterns of executive deficits may differ. While disorders of the schizophrenia spectrum reflect impairment of functions such as integration of cognitive activities, a tendency to perseverate, and a failure to notice details (e.g. impairment associated with the dorsolateral prefrontal cortex), OCD may involve problems of impulse control and regulation of behavior, and an inability to maintain cognitive set (e.g. impairment associated with the orbitofrontal cortex). The present study examined differences between high-scorers on a measure of schizotypy, high-scorers on a measure of OCD, high-scorers on both schizotypy and OCD and a control group in performance on executive function tests. As expected, the OCD group demonstrated relative deficits on measures thought to reflect orbitofrontal functioning. However, contrary to expectations, the schizotypal group did not demonstrate deficits on neuropsychological tests thought to reflect dorsolateral prefrontal cortex functioning, and the combined group showed no executive impairment.

Adolescent↗

Impact of expected reward on neuronal activity in prefrontal cortex, frontal and supplementary eye fields and premotor cortex.

In several regions of the macaque brain, neurons fire during delayed response tasks at a rate determined by the value of the reward expected at the end of the trial. The activity of these neurons might be related either to the internal representation of the appetitive value of the expected reward or to motivation-dependent variations in the monkey's level of motor preparation or motor output. According to the first interpretation, reward-related activity should be most prominent in areas affiliated with the limbic system. According to the second interpretation, it should be most prominent in areas affiliated with the motor system. To distinguish between these alternatives, we carried out single-neuron recording while monkeys performed a memory-guided saccade task in which a visual cue presented early in each trial indicated whether the reward would be large or small. Neuronal activity accompanying task performance was monitored in the dorsolateral prefrontal cortex (PFC), the frontal eye field (FEF), a transitional zone caudal to the frontal eye field (FEF/PM), premotor cortex (PM), the supplementary eye field (SEF), and the rostral part of the supplementary motor area (SMAr). The tendency for neuronal activity to increase after cues that predicted a large reward became progressively stronger in progressively more posterior areas both in the lateral sector of the frontal lobe (PFC < FEF < FEF/PM < PM) and in the medial sector (SEF < SMAr). The very strong reward-related activity of premotor neurons was presumably attributable to the monkey's motivation-dependent level of motor preparation or motor output. This finding points to the need to determine whether reward-related activity in other nonlimbic brain areas, including dorsolateral prefrontal cortex and the dorsal striatum, genuinely represents the value of the expected reward or, alternatively, is related to motivational modulation of motor signals.

Action Potentials↗

Electrical stimulation of cortical-caudate pairs during delayed successive visual discrimination in monkeys.

The anterodorsal head of the caudate nucleus is the recipient of efferent projections from the dorsolateral prefrontal cortex while the tail of the caudate receives fibers originating in inferotemporal cortex. In order to investigate whether anatomically related members of these two systems are also functionally related, monkeys were trained on a delayed successive visual discrimination task. Electrical stimulation was administered during varied portions of individual trials to determine when in each trial performance was most disturbed as a function of the structure stimulated. Comparisons of stimulation effects allowed for examination of both functional dissociation and functional equivalence. Performance was maximally impaired when a 2 sec train of stimulation was applied to the principal sulcus region of dorsolateral prefrontal cortex or to the anterodorsal head of the caudate nucleus early during the delay or was delivered to posterior inferotemporal cortex or the tail of the caudate during cue presentation. No significant differences were seen between stimulation performance curves drawn for two members of each anatomically related system. Thus it appears that the anatomical systems may be functionally dissociated while the anatomically related structures within these systems show a functional equivalence; however the nature of this equivalence is uncertain. The theoretical functional relationship of the cortical-caudate pairs is also considered.

Animals↗

Evidence for a compromised dorsolateral prefrontal cortical parallel circuit in schizophrenia.

Evidence is reviewed that one of the cognitive-affective parallel circuits in the brain, the dorsolateral prefrontal circuit, is compromised at the level of anatomical, neuropathological and transmitter-related molecules in a subgroup of schizophrenic patients. The dorsolateral prefrontal cortex (DLPFC) comprises a key structure in this circuit. Data supporting a compromised DLPFC includes cognitive deficits, decreased regional metabolism and blood flow activation; disruption of cortical subplate activity (inferred from maldistribution of neurons from the cortical subplate which are required for the orderly neuronal migration during the second trimester and for connectivity of the thalamocortical neurons); decrease in major components of the cortical inhibitory neurotransmitter system; and alterations in the molecules critical for NMDA-receptor mediated neural transmission. Thus a great deal of evidence accumulated over the last decade has definitively implicated the dorsolateral prefrontal cortex in the pathophysiology of schizophrenia. Emerging data also confirms neuropathology in the mediodorsal nucleus of the thalamus that projects to the DLPFC. There is currently a consensus that schizophrenia involves epigenetic factors interacting with genetic information in the cells to produce abnormal molecules which when they are associated with abnormal circuits such as the DLPFC, may result in abnormal behavior. Thus, abnormal cortical connections and or altered neurotransmitter related molecules in the DLPFC could explain some of the prominent frontal cognitive disruptions seen in schizophrenia.

Animals↗

Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse.

BACKGROUND: Short-term depletion of plasma tryptophan has been shown to result in depressive relapse in patients with remission of major depression. Positron emission tomography and single photon emission computed tomography studies implicated the dorsolateral prefrontal cortex, orbitofrontal cortex, thalamus, and caudate nucleus in the pathogenesis of depression. The purpose of this study was to measure cerebral metabolic correlates of tryptophan depletion-induced depressive relapse. METHODS: Patients diagnosed as having major depression (N = 21) who clinically improved with serotonin reuptake inhibitors underwent 2 test days involving tryptophan depletion or placebo, followed 6 hours later by positron emission tomography scanning with fludeoxy-glucose F18. Brain metabolism was compared in patients with (n = 7) and without (n = 14) a tryptophan depletion-induced depressive relapse. RESULTS: Tryptophan depletion resulted in a decrease in brain metabolism in the middle frontal gyrus (dorsolateral prefrontal cortex), thalamus, and orbitofrontal cortex in patients with a depletion-induced depressive relapse (but not in patients without depletion-induced relapse). Decreased brain metabolism in these regions correlated with increased depressive symptoms. Baseline metabolism was increased in prefrontal and limbic regions in relapse-prone patients. CONCLUSION: Specific brain regions, including the middle frontal gyrus, thalamus, and orbitofrontal cortex, may mediate the symptoms of patients with major depression.

Antidepressive Agents↗

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans↗

Conditional associative memory for musical stimuli in nonmusicians: implications for absolute pitch.

A previous positron emission tomography (PET) study of musicians with and without absolute pitch put forth the hypothesis that the posterior dorsolateral prefrontal cortex is involved in the conditional associative aspect of the identification of a pitch. In the work presented here, we tested this hypothesis by training eight nonmusicians to associate each of four different complex musical sounds (triad chords) with an arbitrary number in a task designed to have limited analogy to absolute-pitch identification. Each subject under-went a functional magnetic resonance imaging scanning procedure both before and after training. Active condition (identification of chords)-control condition (amplitude-matched noise bursts) comparisons for the pretraining scan showed no significant activation maxima. The same comparison for the posttraining scan revealed significant peaks of activation in posterior dorsolateral prefrontal, ventrolateral prefrontal, and parietal areas. A conjunction analysis was performed to show that the posterior dorsolateral prefrontal activity in this study is similar to that observed in the aforementioned PET study. We conclude that the posterior dorsolateral prefrontal cortex is selectively involved in the conditional association aspect of our task, as it is in the attribution of a verbal label to a note by absolute-pitch musicians.

Acoustic Stimulation↗