Biomedical subjects

T W Robbins

Publications and source records attributed to T W Robbins.

At least 37 records · Page 2Linked to original sources

PubMed2004

The specificity of clinical characteristics in adults with attention-deficit/hyperactivity disorder: a comparison with patients with borderline personality disorder.

Characteristics of DSM-IV attention-deficit/hyperactivity disorder (ADHD) in adults can also be found as part of other psychiatric disorders. This study investigated the specificity of adult ADHD features in relation to patients with borderline personality disorder (BPD), a syndrome which shares some of its intrinsic features with ADHD and often co-occurs with ADHD. A group of 20 adult patients selected on the basis of a diagnosis of ADHD and 20 patients selected on the basis of a diagnosis of BPD were assessed by the self-report Attention Deficit Scales for Adults (ADSA). The two groups were matched for age, verbal IQ and gender. Of the nine ADSA scales, seven showed significant inter-group differences, in particular involving attention, organisation and persistence. The 'Consistency/Long-Term' scale, which mainly reflects impaired task and goal persistence, was the best discriminator between the groups. Furthermore, ratings on this scale correlated significantly with the error score of a computer-administered task of spatial working memory, the performance of which has been reported to be impaired in patients with ADHD. The results provide further validation for the ADSA scales and support a previous claim that 'long-term consistencies', i.e., related to task and goal persistence, is 'the centrepiece behavioural issue' for adults with ADHD.

Adult↗

PubMed2004

Region specific changes in forebrain 5-hydroxytryptamine1A and 5-hydroxytryptamine2A receptors in isolation-reared rats: an in vitro autoradiography study.

The neurochemical correlates of the behavioural consequences of isolation rearing of rats are complex and involve many neurotransmitters, including the serotonergic system. Impaired functioning of the ascending serotonergic system has been implicated in many neuropsychiatric syndromes, including attention deficit hyperactivity disorder and schizophrenia. In the present investigation serotonergic function was assessed using in vitro receptor autoradiography. The 5-hydroxytryptamine(2A) (5-HT(2A)) receptor antagonist [(3)H]ketanserin and the 5-HT(1A) receptor antagonist, [(3)H]WAY100, 635 were used to compare 5-HT receptor subtype densities in the forebrains of socially and isolation-reared rats. Regions of highest receptor density were observed in the frontal cortex for 5-HT(2A) receptors and in the frontal cortex, dorsal hippocampus and lateral septum for 5-HT(1A) receptors. In isolation-reared rats, 5-HT(2A) receptor binding site densities were significantly increased by between 36 and 67% in the prelimbic, motor and cingulate cortices compared with socially reared controls. By contrast, 5-HT(1A) receptor binding site densities were significantly reduced by 22% in the prelimbic cortex, and significantly increased by between 10 and 50% in the motor cortex, somatosensory cortex, dentate gyrus and CA fields of the hippocampus. These data demonstrate that isolation-rearing produces significant effects on forebrain 5-HT(1A) and 5-HT(2A) receptor densities in the adult rat. It is hypothesised that altered serotonergic function, particularly in the hippocampus and prefrontal cortex, may underlie some of the behavioural abnormalities associated with isolation-rearing.

Animals↗

PubMed2004

The neuropsychology of ventral prefrontal cortex: decision-making and reversal learning.

Converging evidence from human lesion, animal lesion, and human functional neuroimaging studies implicates overlapping neural circuitry in ventral prefrontal cortex in decision-making and reversal learning. The ascending 5-HT and dopamine neurotransmitter systems have a modulatory role in both processes. There is accumulating evidence that measures of decision-making and reversal learning may be useful as functional markers of ventral prefrontal cortex integrity in psychiatric and neurological disorders. Whilst existing measures of decision-making may have superior sensitivity, reversal learning may offer superior selectivity, particularly within prefrontal cortex. Effective decision-making on existing measures requires the ability to adapt behaviour on the basis of changes in emotional significance, and this may underlie the shared neural circuitry with reversal learning.

Animals↗

PubMed2004

Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder.

BACKGROUND: It is now accepted that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. However, relative to the considerable literature concerning the profile of neurocognitive deficits associated with this disorder in childhood, equivalent investigations in adult populations have been less common. The current study examined cognitive function in adults diagnosed with ADHD employing well-validated neuropsychological tasks. METHOD: Nineteen adult patients who satisfied DSM-IV criteria for ADHD and 19 matched (gender, age and verbal IQ), non-clinical control subjects were recruited. Patients were either unmedicated or had abstained from a psychostimulant medication regime for at least 24 h prior to neurocognitive assessment. A functionally wide-ranging test battery was administered. RESULTS: Relative to controls, ADHD adults performed significantly worse on spatial working memory, planning, and attentional-set shifting tests and were significantly slower to respond to target stimuli on the go/no-go task. In contrast, the two subject groups performed equivalently on decision-making and pattern/spatial recognition memory assessments. CONCLUSIONS: The demonstration of neuropsychological dysfunction in the adult ADHD cohort provides some support for the validity of this diagnosis in adulthood. In particular, there is broad consistency between the cognitive profile revealed in the current investigation and that previously demonstrated in a study of medication-naïve ADHD children. There is evidence that frontostriatal function is especially disrupted.

Adult↗

PubMed2004

Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability.

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.

Adult↗

PubMed2004

Impaired spatial working memory in adults with attention-deficit/hyperactivity disorder: comparisons with performance in adults with borderline personality disorder and in control subjects.

OBJECTIVE: This study investigated a previous claim that working memory may be 'particularly impaired' in adult attention-deficit/hyperactivity disorder (ADHD), compared with other psychiatric disorders which affect frontal lobe-mediated executive functions. METHOD: Performance on spatial working memory (SWM) and two additional tasks were investigated for adult patients selected on the basis of DSM-IV ADHD (n = 19), adult patients selected on the basis of borderline personality disorder (BPD) (n = 19), and non-clinical control subjects (n = 19). Groups were matched for age, verbal IQ and gender. RESULTS: Analysis of variance showed that the ADHD group had significant impairment of SWM performance relative to the non-clinical controls. Although there was a trend towards impairment in the BPD group relative to non-clinical controls, this did not reach significance. CONCLUSION: The results are consistent with the claim that aspects of working memory are 'particularly impaired' in adult ADHD. Also, the BPD group had a longer deliberation time for one of the additional tasks, compared with the ADHD group, which indicated that the patient groups may have different patterns of neuropsychological impairments.

Adult↗

PubMed2003

Diazepam produces disinhibitory cognitive effects in male volunteers.

RATIONALE: Diazepam has well known amnestic and sedative effects but effects on fronto-executive function remain largely uninvestigated, especially on neuropsychologically validated tests of risk taking and orbitofrontal cortex function. OBJECTIVES: We aimed to determine the impact of diazepam on a variety of executive tasks. METHODS: The effects of 5, 10 and 20 mg of diazepam on a battery of neuropsychological tests were investigated using a randomised, double blind, placebo-controlled design. Seventy-five adult men were recruited. The Rogers et al. (1999b) test of risk-taking was given along with tasks from the CANTAB battery. RESULTS: Diazepam impaired performance on the Tower of London test of planning, without influencing visual pattern recognition memory. Subjects who had taken diazepam made more risky choices on the risk-taking task. On two speeded reaction time tasks diazepam impaired discrimination sensitivity and increased the bias to respond. CONCLUSIONS: In contrast to the well-known sedative effects of diazepam, we demonstrate disinhibitory effects on two speeded reaction time tasks. Our results show that diazepam can impair performance on reaction time tasks both by impairing sensitivity and by increasing the bias to respond. Furthermore diazepam impaired performance on tests of planning and risky decision making that depend predominantly on dorsolateral and orbitofrontal regions of the prefrontal cortex, respectively.

Adult↗

PubMed2003

Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity.

It is becoming increasingly apparent that multiple functions of the frontal cortex such as inhibitory control and executive attention are likely sustained by its functionally distinct and interacting sub-regions but the precise localization of dissociable executive processes has proved difficult and controversial. In the present series of studies, we investigated the behavioural effects of bilateral excitotoxic lesions of different regions of the rat neocortex in the 5-choice serial reaction time task. Whereas lesions of the dorsal anterior cingulate cortex (ACC) impaired performance of the task as revealed by a reduction in discriminative accuracy, lesions made to distinct ventral regions of the frontal cortex showed selective deficits in inhibitory measures of control. Specifically, the infralimbic lesion produced increases in premature responding that was accompanied by fast response latencies. By comparison, the orbitofrontal lesion showed perseverative tendencies particularly when the inter-trial interval was made long and unpredictable, a challenge that would normally promote premature responding instead. These different behavioural effects following dorsal and ventral lesions of the rodent frontal cortex signifies the integrity of the frontal cortex in multiple executive mechanisms that work independently and complementarily by which performance is optimized. Furthermore, these data provide new insights into the functional organization of the rodent frontal cortex with a particular emphasis on localization of function.

Animals↗

PubMed2003

Lesions of the medial prefrontal cortex or nucleus accumbens core do not impair inhibitory control in rats performing a stop-signal reaction time task.

The 'stop-signal' task measures the ability to inhibit a response that has already been initiated, i.e. the ability to stop. Human subjects who have been classified as 'impulsive', for example, those with attention-deficit/hyperactivity disorder (ADHD), are slower to react to the stop signal, and are often less sensitive to changes in the timing of signals to stop. Imaging studies have implicated fronto-striatal circuitry in the mediation of this form of response control. We report inhibition functions on the stop-signal reaction time (SSRT) task for normal rats, and following damage to the medial prefrontal cortex or to the nucleus accumbens core. Neither group of excitotoxic lesions produced significant deficits on task performance. Subsequent treatment with D-amphetamine (0.3 and 1.0mg/kg) resulted in quicker go-trial reaction times (mRT) overall, but had no significant effect on SSRT. Neither medial prefrontal cortex nor nucleus accumbens lesions had any differential effects on performance following D-amphetamine. These results are discussed with respect to the fronto-striatal circuitry involved in the mediation of behavioural inhibition.

Animals↗

PubMed2003

Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance.

BACKGROUND: Recent evidence suggests that an abnormal response to performance feedback may contribute to the wide-ranging neuropsychological deficits typically associated with depressive illness. The present research sought to determine whether the inability of depressed patients to utilize performance feedback advantageously is equally true for accurate and misleading feedback. METHOD: Patients with major depression and matched controls completed: (1) a visual discrimination and reversal task that featured intermittent and misleading negative feedback; and (2) feedback and no-feedback versions of a computerised test of spatial working memory. In the feedback version, negative feedback was accurate, highly informative, and could be used as a mnemonic aid. RESULTS: On the Probability Reversal task, depressed patients were impaired in their ability to maintain response set in the face of misleading negative feedback as shown by their increased tendency to switch responding to the 'incorrect' stimulus following negative reinforcement, relative to that of controls. Patients' ability to acquire and reverse the necessary visual discrimination was unimpaired. On the Spatial Working Memory task, depressed patients made significantly more between-search errors than controls on the most difficult trials, but their ability to use negative feedback to facilitate performance remained intact. CONCLUSIONS: The present results suggest that feedback can have different effects in different contexts. Misleading, negative feedback appears to disrupt the performance of depressed patients, whereas negative but accurate feedback does not. These findings are considered in the context of recent studies on reinforcement systems and their associated neurobiological substrates.

Adult↗

PubMed2003

Inhibitory control in rats performing a stop-signal reaction-time task: effects of lesions of the medial striatum and d-amphetamine.

The stop-signal task measures the ability to inhibit a response that has already been initiated, that is, the ability to stop. Imaging studies have implicated frontostriatal circuitry in the mediation of this form of response control. The authors report inhibition functions of normal rats and those with medial striatal damage performing the stop-signal task. Excitotoxic lesions of the medial striatum produced significant deficits on task performance, including increased omissions on the go task and flattened inhibition function, possibly as a result of increased reaction-time mean and variability. Medial striatal lesions also significantly slowed stop-signal reaction time. Subsequent treatment with d-amphetamine removed (0.3 mg/kg) or exacerbated (1.0 mg/kg) this deficit.

Animals↗

PubMed2003

Subdissociative dose ketamine produces a deficit in manipulation but not maintenance of the contents of working memory.

We investigated the effects of subdissociative dose ketamine on executive processes during a working memory task. A total of 11 healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. They attended on three occasions, receiving intravenous infusions of placebo, a lower ketamine dose, and a higher ketamine dose. On each occasion, they underwent a series of tasks engaging working memory function in verbal and visuo-spatial domains. Further tasks explored aspects of long-term memory, planning, attention, and perceptual processing. With respect to working memory/executive function, a highly specific pattern of impairment was observed. Impairments were seen only at the higher dose of ketamine and restricted to a subgroup of the verbal working memory tasks: While visuo-spatial working memory showed no evidence of impairment, and while simple maintenance processes during verbal working memory were also unimpaired, higher dose ketamine produced a significant impairment in the manipulation of information within working memory. This process-specific effect of ketamine was reflected in a drug-by-task interaction. The specificity of this ketamine effect suggests that the earliest effect of NMDA receptor blockade is in higher order control of executive function rather than in more basic maintenance processes.

Adolescent↗

PubMed2003

Individual differences in prefrontal cortical activation on the Tower of London planning task: implication for effortful processing.

Solving challenging ('effortful') problems is known to involve the dorsal and dorsolateral prefrontal cortex in normal volunteers, although there is considerable individual variation. In this functional magnetic resonance imaging study, we show that healthy subjects with different levels of performance in the Tower of London planning task exhibit different patterns of brain activation. All subjects exhibited significant bilateral activation in the dorsolateral prefrontal cortex, the anterior and posterior cingulate areas and the parietal cortex. However, 'standard performers' (performance < 70% correct) and 'superior performers' (performance >70% correct) differed in the patterns of activation exhibited. Superior performers showed a significantly more spatially extended activation in the left dorsolateral prefrontal cortex than did standard performers, whereas the latter group tended to show increased activation of the anterior cingulate region.

Adolescent↗

PubMed2003

Inhibition of subliminally primed responses is mediated by the caudate and thalamus: evidence from functional MRI and Huntington's disease.

Masked prime tasks have shown that sensory information that has not been consciously perceived can nevertheless trigger the preactivation of a motor response. Automatic inhibitory control processes prevent such response tendencies from interfering with behaviour. The present study investigated the possibility that these inhibitory control processes are mediated by a cortico-striatal-pallidal-thalamic pathway by using a masked prime task with Huntington's disease patients (Experiment 1) and with healthy volunteers in a functional MRI (fMRI) study (Experiment 2). In the masked prime task, clearly visible left- or right-pointing target arrows are preceded by briefly presented and subsequently masked prime arrows. Participants respond quickly with a left or right key-press to each target. Trials are either compatible (prime and target pointing in the same direction) or incompatible (prime and target pointing in different directions). Prior behavioural and electrophysiological results show that automatic inhibition of the initially primed response tendency is reflected in a 'negative compatibility effect' (faster reaction times for incompatible trials than for compatible trials), and is shown to consist of three distinct processes (prime activation, response inhibition and response conflict) occurring within 300 ms. Experiment 1 tested the hypothesis that lesions of the striatum would interrupt automatic inhibitory control by studying early-stage Huntington's disease patients. Findings supported the hypothesis: there was a bimodal distribution for patients, with one-third (choreic) showing disinhibition, manifested as an absent negative compatibility effect, and two-thirds (non-choreic) showing excessive inhibition, manifested as a significantly greater negative compatibility effect than that in controls. Experiment 2 used fMRI and a region of interest (ROI) template-based method to further test the hypothesis that structures of the striatal-pallidal-thalamic pathway mediate one or more of the processes of automatic inhibitory control. Neither prime activation nor response conflict significantly engaged any ROIs, but the response inhibition process led to significant modulation of both the caudate and thalamus. Taken together, these experiments indicate a causal role for the caudate nucleus and thalamus in automatic inhibitory motor control, and the results are consistent with performance of the task requiring both direct and indirect striatal-pallidal-thalamic pathways. The finding that Huntington's disease patients with greater chorea were disinhibited is consistent with the theory that chorea arises from selective degeneration of striatal projections to the lateral globus pallidus, while the exaggerated inhibitory effect for patients with little or no chorea may be due to additional degeneration of projections to the medial globus pallidus.

Adult↗

PubMed2002

Nucleus accumbens dopamine depletion impairs both acquisition and performance of appetitive Pavlovian approach behaviour: implications for mesoaccumbens dopamine function.

The involvement of mesoaccumbens dopamine in adaptive learning and behaviour is unclear. For example, dopamine may act as a teaching signal to enable learning, or more generally modulate the behavioural expression, or selection, of an already-learned response. The present study investigated the involvement of the mesoaccumbens dopamine system in a fundamental form of learning: Pavlovian conditioning. In this case, the temporal association of a previously neutral visual stimulus and a biologically significant unconditioned stimulus (US), subsequently led to the production of the conditioned response (CR) of discriminated approach behaviour directed toward the conditioned stimulus (CS+), relative to a control (CS-) stimulus. 6-hydroxydopamine lesions of the nucleus accumbens (NAcc), leading to approximately 80% reductions in tissue dopamine, were made at varying time points in four experimental groups of rats, either before or subsequent to the acquisition of the CR. NAcc dopamine depletion produced long-term neuroadaptations in dopamine function 2 months after surgery, and profoundly impaired discriminated Pavlovian approach regardless of when the lesion was made. Thus, NAcc dopamine not only plays a role in conditioned behavioural activation, but also in making the appropriate discriminated response i.e. the direction of response. Further, acquisition lesions produced a far greater impact on discriminated approach than performance lesions. This difference in lesion-induced impairment implies that mesoaccumbens dopamine may play differential roles in the learning and performance of preparatory Pavlovian conditioning.

Animals↗

PubMed2002

Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity.

RATIONALE: Rats reared in social isolation exhibit hyperactivity and specific attentional disturbances in later adult life. These behavioural abnormalities may be relevant to impulsivity and other neuropsychiatric syndromes such as attention-deficit hyperactivity disorder and schizophrenia where disturbances in circuitry involving the prefrontal cortex have been identified. OBJECTIVE: To establish whether isolation-reared rats show a differential susceptibility to cognitive processes that depend on the prefrontal cortex and its monoaminergic innervation. METHODS: Rats were reared in isolation from postnatal day 28 or in social groups of four and trained on the five-choice serial reaction time task, which assesses spatially divided visual attention. Following a range of manipulations designed to tax visual attention and response control, in vivo microdialysis was used in conjunction with behavioural testing to assess dopamine (DA) and serotonin (5-HT) release in the prefrontal cortex, either under baseline conditions prior to task initiation, or during task performance. Subjects were challenged with amphetamine (0.125 mg/kg intravenously) every 15 min, commencing 15 min after the start of the task. RESULTS: Apart from being consistently slower to collect food rewards and showing more perseverative responses to an auditory distractor, isolates were unimpaired on accuracy, impulsivity and correct latency measures on the five-choice task. Basal levels of DA and 5-HT in the prefrontal cortex were also unaffected by isolation rearing. Amphetamine increased the speed of responding in control and isolation-reared animals and increased premature (impulsive) responding, but only in socially-reared animals. Cortical DA release increased to a similar extent in both groups following amphetamine challenge. By contrast, 5-HT release was attenuated in isolates under these conditions. CONCLUSIONS: These findings highlight a rather specific deficit in 5-HT release in the prefrontal cortex of isolation-reared rats, although this appears not to affect visual attentional function. Rather, these data may be relevant to reduced impulsiveness of isolation-reared rats on the five-choice task. These findings are important in the context of animal models of attentional disturbances in schizophrenia.

Amphetamine↗

PubMed2002

The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry.

RATIONALE: The developmental history and application of the 5-choice serial reaction time task (5CSRTT) for measuring effects of drugs and other manipulations on attentional performance (and stimulus control) in rats is reviewed. OBJECTIVES: The 5CSRTT has been used for measuring effects of systemic drug treatments and also central manipulations such as neurochemical lesions on various aspects of attentional control, including sustained, selective and divided attention--and is relevant to the definition of neural systems of attention and applications to human disorders such as attention deficit/hyperactivity disorder (ADHD) and Alzheimer's disease. METHODS: The 5CSRTT is implemented in a specially designed operant chamber with multiple response locations ('nine-hole box') using food reinforcers to maintain performance on baseline sessions (about 100 trials) at criterion levels of accuracy and trials completed. The 5CSRTT can be used for measuring various aspects of attentional control over performance with its main measures of accuracy, premature responding, correct response latencies and latency to collect earned food pellets. RESULTS: The data reviewed include studies mainly of systemic and intra-cerebral effects of adrenoceptor, dopamine receptor, serotoninergic receptor and cholinergic receptor agents. These are compared with investigations of effects of selective chemical neurotoxins and excitotoxins applied to discrete parts of the forebrain, in order to define the neural and neurochemical substrates of attentional function. Furthermore, these results are integrated with findings from in vivo microdialysis in freely moving rats or metabolic studies. CONCLUSIONS: The monoaminergic and cholinergic systems appear to play separable roles in different aspects of performance controlled by the 5CSRTT, in neural systems centred on the prefrontal cortex, cingulate cortex and striatum. These conclusions are considered in the methodological and theoretical context of other psychopharmacological studies of attention in animals and humans.

Acetylcholine↗

PubMed2002

The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers.

RATIONALE: Cognitive impairment is a common feature of depressive illness. While accumulating evidence suggests that brain serotonin (5-HT) pathways play an important role in the neurobiology of depression, the extent to which altered 5-HT function is responsible for the associated changes in cognition and emotion remains unclear. OBJECTIVE: The present study examined the effects of acute dietary depletion of tryptophan (TRP) on cognitive and affective processing in healthy volunteers and explored the putative role of 5-HT in the neuropsychology of depression. METHODS: We administered computerised cognitive tests to healthy control participants following ingestion of TRP-free and nutritionally balanced amino acid drinks in a double-blind, placebo-controlled, crossover design. RESULTS: The TRP-free amino acid mixture significantly lowered plasma total and free TRP concentrations relative to baseline values and produced selective deficits similar to those observed previously in cases of clinical depression. In particular, TRP depletion increased response times for happy but not sad targets in an affective go/no-go task and slowed responding in a visual discrimination and reversal learning task. These deficits were not due to a global sedative effect, as planning ability was unimpaired. CONCLUSIONS: The present data indicate that serotonergic factors may be more involved in the disrupted inhibitory and emotional processing characteristic of depression than in other aspects of executive function, such as planning ability. These findings support the recent proposal that serotonergic manipulation may have greater effects on tasks mediated by frontal circuitry that includes the orbitofrontal cortex than by dorsolateral prefrontal cortex circuitry.

Adult↗